strontium-radioisotopes and Bone-Neoplasms

Radium-223 dichloride (

Topics: Bone Neoplasms; Humans; Male; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Radionuclide Imaging; Radiopharmaceuticals; Radium; Samarium; Strontium Radioisotopes

This is an update of the review published in Issue 4, 2003. Bone metastasis cause severe pain as well as pathological fractures, hypercalcaemia and spinal cord compression. Treatment strategies currently available to relieve pain from bone metastases include analgesia, radiotherapy, surgery, chemotherapy, hormone therapy, radioisotopes and bisphosphonates.. To determine efficacy and safety of radioisotopes in patients with bone metastases to improve metastatic pain, decrease number of complications due to bone metastases and improve patient survival.. We sought randomised controlled trials (RCTs) in MEDLINE, EMBASE, CENTRAL, and the PaPaS Trials Register up to October 2010.. Studies selected had metastatic bone pain as a major outcome after treatment with a radioisotope, compared with placebo or another radioisotope.. We assessed the risk of bias of included studies by their sequence generation, allocation concealment, blinding of study participants, researchers and outcome assessors, and incomplete outcome data. Two review authors extracted data. We performed statistical analysis as an "available case" analysis, and calculated global estimates of effect using a random-effects model. We also performed an intention-to-treat (ITT) sensitivity analysis.. This update includes 15 studies (1146 analyzed participants): four (325 participants) already included and 11 new (821 participants). Only three studies had a low risk of bias. We observed a small benefit of radioisotopes for complete relief (risk ratio (RR) 2.10, 95% CI 1.32 to 3.35; Number needed to treat to benefit (NNT) = 5) and complete/partial relief (RR 1.72, 95% CI 1.13 to 2.63; NNT = 4) in the short and medium term (eight studies, 499 participants). There is no conclusive evidence to demonstrate that radioisotopes modify the use of analgesia with respect to placebo. Leucocytopenia and thrombocytopenia are secondary effects significantly associated with the administration of radioisotopes (RR 5.03; 95% CI 1.35 to 18.70; Number needed to treat to harm (NNH) = 13). Pain flares were not higher in the radioisotopes group (RR 0.74; 95% CI 0.27 to 2.06). There are scarce data of moderate quality when comparing Strontium-89 (. This update adds new evidence on efficacy of radioisotopes versus placebo,

Topics: Bone Neoplasms; Fractures, Bone; Humans; Hypercalcemia; Pain; Pain Measurement; Phosphorus Radioisotopes; Radioisotopes; Randomized Controlled Trials as Topic; Ruthenium Radioisotopes; Samarium; Spinal Cord Compression; Strontium Radioisotopes

The majority of patients with castration-resistant prostate cancer develop bone metastatic disease. It is often challenging to optimally palliate malignant bone pain. In case of multifocal pain due to diffuse osteoblastic metastases, treatment with bone-seeking radiopharmaceuticals can be considered.. This systematic review evaluates the efficacy of different bone-seeking radiopharmaceuticals for palliation of malignant bone pain from prostate cancer.. The PubMed (Medline) and Embase databases were searched for publications on 89-strontium-chloride ((89)Sr), 153-samarium-EDTMP ((153)Sm), 186-rhenium-HEDP ((186)Re), 188-rhenium-HEDP ((188)Re), and 223-radium-chloride ((223)Ra). Randomised controlled trials and prospective cohort studies were included. Metastatic bone pain had to be registered as outcome measure for prostate cancer patients separately.. This review included 36 articles of which 13 randomised trials and 23 prospective studies. Of all trials, 10 studies used (89)Sr, 7 (153)Sm, 12 (186)Re, 2 (188)Re, and 2 (223)Ra; three reported on a combination of different radionuclides. Only a few trials contained a blinding procedure and several studies contained incomplete follow-up or lack of intention-to-treat analysis. It was not possible to calculate a pooled estimate of pain response to treatment with any of the radionuclides because different definitions of pain response were used.. Overall, pain response percentages greater than 50-60% were seen with each radionuclide. Haematological toxicity was reported in 26 of the 36 studies and more than half of these trials stated no grade 3/4 leukopenia or thrombocytopenia occurred.. In this report we reviewed the efficacy of bone-seeking radionuclides for treating bone pain from metastatic prostate cancer. Overall, treatment with bone-seeking radionuclides resulted in pain responses greater than 50-60%.

Topics: Antineoplastic Agents; Bone Neoplasms; Cancer Pain; Etidronic Acid; Humans; Male; Organometallic Compounds; Organophosphorus Compounds; Palliative Care; Prospective Studies; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Radiopharmaceuticals; Radium; Randomized Controlled Trials as Topic; Strontium; Strontium Radioisotopes

The present review article aims to provide an overview of the available radionuclides for palliative treatment of bone metastases beyond (89)Sr and (153)Sm. In addition, it aims to review and summarize the clinical outcomes associated with the palliative treatment of bone metastases using different radiopharmaceuticals.. A literature search was conducted on Science Direct and PubMed databases (1990 - 2015). The following search terms were combined in order to obtain relevant results: "bone", "metastases", "palliative", "care", "therapy", "treatment", "radiotherapy", "review", "radiopharmaceutical", "phosphorus-32", "strontium-89", "yttrium-90", "tin-117m", "samarium-153", "holmium-166", "thulium-170", "lutetium-177", "rhenium-186", "rhenium-188" and "radium-223". Studies were included if they provided information regarding the clinical outcomes.. A comparative analysis of the measured therapeutic response of different radiopharmaceuticals, based on previously published data, suggests that there is a lack of substantial differences in palliative efficacy among radiopharmaceuticals. However, when the comparative analysis adds factors such as patient's life expectancy, radionuclides' physical characteristics (e.g. tissue penetration range and half-life) and health economics to guide the rational selection of a radiopharmaceutical for palliative treatment of bone metastases, (177)Lu and (188)Re-labeled radiopharmaceuticals appear to be the most suitable radiopharmaceuticals for treatment of small and medium/large size bone lesions, respectively.

Topics: Bone Neoplasms; Female; Humans; Male; Pain Management; Palliative Care; Radioisotopes; Radiopharmaceuticals; Samarium; Strontium Radioisotopes

Although patients with castration-resistant prostate cancer frequently have metastases to the bone, they have a relatively favorable prognosis. Therefore, it is important to keep or improve the level of patient's quality of life. The use of strontium-89 for the management of the pain from bone metastasis was approved in 2007 in Japan. A new bone-targeting radiopharmaceuticals using radium-223 is also promising, because a randomized trial showed an overall survival advantage of radium-223 in prostate patients with bone metastases. In this review, we summarize the role of targeted radionuclide therapy for castration-resistant prostate cancer, focusing on strontium-89 and radium-223.

Topics: Antineoplastic Agents; Bone Neoplasms; Humans; Male; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Radiopharmaceuticals; Radium; Strontium Radioisotopes

(99m)Tc-hydroxymethylene diphosphonate is not directly to Calcium of the bone matrix, but is binding to hydroxyapatite within the bone matrix. Strontium-89 is a member of family II A of the periodic table, same as Calcium, and is incorporated into bone matrix directly. It is very important that the the regions of the pain from bone metastases are present in the site of the abnormal uptake by bone metastases.

Topics: Bone Matrix; Bone Neoplasms; Humans; Nuclear Medicine; Radiopharmaceuticals; Strontium Radioisotopes; Technetium Tc 99m Medronate

The administration of a radionuclide in unsealed source whose radiation will destroy cells that have selectively accumulated product is called radiometabolic therapy. The management of bone pain is a major problem, particularly in cases of breast or prostate where the presence of metastases can remain compatible with long-term survival of cancer patients. In this context, the radiometabolic therapy reduces the pain secondary to bone metastases, in association or not with analgesics. This technique is rarely prescribed as first-line. It can also be combined with external beam radiotherapy or chemotherapy, if clinical conditions permit (due to the increased risk of hematologic toxicity). In this setting, the currently used substances are Metastron® and Quadramet®. Recently, a new product, radium chloride (or Alpharadin®) has shown efficacy in bone metastases from prostate cancer, particularly in terms of bone pain palliation, but also of increased overall survival. In addition, this product has virtually no hematologic toxicity.

Topics: Analgesics; Bone Neoplasms; Breast Neoplasms; Female; Humans; Male; Organometallic Compounds; Organophosphorus Compounds; Pain; Prostatic Neoplasms; Radiopharmaceuticals; Radium; Strontium; Strontium Radioisotopes

Bone is one of the organs to which cancer metastasizes most frequently. However, it is not a vital organ, therefore, survival after the occurrence of osseous metastasis is relatively favorable. Improvements of medical treatment bring prolonged survival to patients with osseous metastases. But this makes us to recognize the importance of quality of life (QOL) due to several factors, including pain. It is important for oncologists to know how to deal with such painful osseous metastases, as pain relief may enable patients to live their remaining lives to the fullest. Strontium-89 (89Sr) has been used worldwide as in Japan, while being reported to have positive effects on pain relief and QOL improvement in patients with osseous metastases. This review paper is aimed to present not only the history, roles, and medical characters of 89Sr, but also new aspects, such as how to use bone turnover markers, which location of osseous metastases is suitable for effective use of 89Sr.

Topics: Bone Neoplasms; Combined Modality Therapy; Humans; Neoplasm Metastasis; Osteolysis; Pain; Strontium Radioisotopes

The aim of the study was to assess the state of the art of the use of bone-seeking radiopharmaceuticals for palliation therapy of pain from bone metastases.. A systematic literature search was conducted about therapy with 89Sr-chloride and 153Sm-EDTMP between 2001-2011. The primary outcomes were efficacy and toxicity. Descriptive and quantitative data were extracted from each study, calculating event rates and odds ratio (OR) with 95% confidence intervals (CI) for pooled analysis. Subgroup analyses were performed.. Fifty-seven studies contributed to the systematic review. Forty-six studies used radiopharmaceuticals as a single agent, 15 investigated therapeutic combinations. Most of the studies included patients with prostate cancer. The overall efficacy of bone-seeking radiopharmaceuticals as single agents was 70%, whereas it was 74% when used in combination with other therapies. Complete response was reported in 27% of patients. Efficacy resulted to be 70% for prostate cancer and 79% for breast cancer. The overall toxicity of radiopharmaceuticals was 15%: the toxicity was 11% selecting only studies reporting on the use of radiopharmaceuticals as a single agent. No significant difference was found between bone-seeking radiopharmaceuticals and other oncological treatments regarding efficacy or toxicity. Reports of objective response outcomes suggest that bone-seeking radiopharmaceuticals have some cytotoxic activity, either alone or combination with chemotherapy.. This literature analysis emphasizes multiple evidences of high efficacy and low toxicity of bone seeking radiopharmaceuticals; moreover, this therapy may have a therapeutic potential beyond simple palliation of bone pain.

Topics: Bone Neoplasms; Comorbidity; Humans; Pain; Palliative Care; Radiation Injuries; Radiopharmaceuticals; Risk Factors; Samarium; Strontium Radioisotopes; Treatment Outcome

Treatment of multisite, sclerotic bone metastases is successfully performed by radionuclide therapy. Pain palliation is the most common aim for the treatment. Two radiopharmaceuticals are currently approved by the European Medicines Agency ((153)Sm-EDTMP and (89)Sr-Cl₂) whilst other radiopharmaceuticals are at different stages of development, or are approved in some European countries ((186)Re-HEDP, (117)Snm-DTPA and (223)Ra-Cl₂). The tissues at risk for the treatment are bone marrow and normal bone. A review of the methods applied for dosimetry for these tissues and for tumours is performed, including the calculation of S values (the absorbed dose per decay) and optimal procedures on how to obtain biodistribution data for each radiopharmaceutical. The dosimetry data can be used to individualise and further improve the treatment for each patient. Dosimetry for radionuclide therapy of bone metastases is feasible and can be performed in a routine clinical practice.

Topics: Bone Neoplasms; Humans; Pain; Palliative Care; Phosphorus Radioisotopes; Radiopharmaceuticals; Radiotherapy Planning, Computer-Assisted; Radium; Rhenium; Samarium; Strontium Radioisotopes; Tin Radioisotopes

This is an update of the review published in Issue 4, 2003. Bone metastasis cause severe pain as well as pathological fractures, hypercalcaemia and spinal cord compression. Treatment strategies currently available to relieve pain from bone metastases include analgesia, radiotherapy, surgery, chemotherapy, hormone therapy, radioisotopes and bisphosphonates.. To determine efficacy and safety of radioisotopes in patients with bone metastases to improve metastatic pain, decrease number of complications due to bone metastases and improve patient survival.. We sought randomised controlled trials (RCTs) in MEDLINE, EMBASE, CENTRAL, and the PaPaS Trials Register up to October 2010.. Studies selected had metastatic bone pain as a major outcome after treatment with a radioisotope, compared with placebo or another radioisotope.. We assessed the risk of bias of included studies by their sequence generation, allocation concealment, blinding of study participants, researchers and outcome assessors, and incomplete outcome data. Two review authors extracted data. We performed statistical analysis as an "available case" analysis, and calculated global estimates of effect using a random-effects model. We also performed an intention-to-treat (ITT) sensitivity analysis.. This update includes 15 studies (1146 analyzed participants): four (325 participants) already included and 11 new (821 participants). Only three studies had a low risk of bias. We observed a small benefit of radioisotopes for complete relief (risk ratio (RR) 2.10, 95% CI 1.32 to 3.35; Number needed to treat to benefit (NNT) = 5) and complete/partial relief (RR 1.72, 95% CI 1.13 to 2.63; NNT = 4) in the short and medium term (eight studies, 499 participants). There is no conclusive evidence to demonstrate that radioisotopes modify the use of analgesia with respect to placebo. Leucocytopenia and thrombocytopenia are secondary effects significantly associated with the administration of radioisotopes (RR 5.03; 95% CI 1.35 to 18.70; Number needed to treat to harm (NNH) = 13). Pain flares were not higher in the radioisotopes group (RR 0.74; 95% CI 0.27 to 2.06). There are scarce data of moderate quality when comparing Strontium-89 ((89)Sr) with Samarium-153 ((153)Sm), Rhenium-186 ((186)Re) and Phosphorus-32 ((32)P). We observed no significant differences between treatments. Similarly, we observed no differences when we compared different doses of (153)Sm (0.5 versus 1.0 mCi).. This update adds new evidence on efficacy of radioisotopes versus placebo, (89)Sr compared with other radioisotopes, and dose-comparisons of (153)Sm and (188)Re. There is some evidence indicating that radioisotopes may provide complete reduction in pain over one to six months with no increase in analgesic use, but severe adverse effects (leucocytopenia and thrombocytopenia) are frequent.

Topics: Bone Neoplasms; Fractures, Bone; Humans; Hypercalcemia; Pain; Pain Measurement; Phosphorus Radioisotopes; Radioisotopes; Randomized Controlled Trials as Topic; Ruthenium Radioisotopes; Samarium; Spinal Cord Compression; Strontium Radioisotopes

Radionuclide therapy has been an integral part of systemic treatment of patients with advanced and disseminated cancer for 50 years. Specific radioisotopes (b- or a-emitters) with selective concentration at sites of bone cancer damage are used in the treatment. Radioisotopes are an important addition to the armamentarium of clinicians who take care of patients with advanced cancer and painful cancer bone metastases (especially osteoblastic and mixed type). They offer a high degree of efficacy with minimal toxicity and simple administration, fulfilling the fundamental criteria for palliative treatment that should combine minimal patient discomfort and toxicity with maximal clinical effect.

Topics: Bone Neoplasms; Bone Remodeling; Humans; Magnetic Resonance Imaging; Multimodal Imaging; Pain Management; Patient Selection; Positron-Emission Tomography; Radioisotopes; Samarium; Strontium Radioisotopes; Tomography, X-Ray Computed; Treatment Outcome

Strontium-89 (Sr-89) is a pure emitter with maximum beta energy of 1.46 MeV, average beta energy of 0.58 MeV, and a physical half-life of 50.5 days. It is rapidly taken up by bone and preferentially retained at the sites of osseous metastases. Its biological half-life is >50 days at the metastatic sites, but about 14 days only in the normal bone. The dose of its absorption in the tumor-bearing bone ranges from 21 +/- 4 to 231 +/- 56 cGy/MBq, 2-25 times higher than in the normal bone. Strontium-89 therapy is an effective palliative treatment of bone metastases from prostate cancer, with analgesic effectiveness in 80%.

Topics: Bone Neoplasms; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms; Strontium Radioisotopes

This review provides an update on the management of painful bone metastases, with an emphasis on radionuclide therapy, and introduces oligometastases and quantitative imaging evaluations for clinical trials.. The current use of radionuclides, alone and in combination with chemotherapy and radiation therapy for painful bone metastases, is discussed, including toxicity, cost and overall outcomes.. Radionuclide therapy is shown to be a useful and cost-effective means of alleviating bone pain in metastatic disease and may be more effective when combined with chemotherapy, bisphosphonates and radiation therapy. Early use of radionuclides in pain therapy may limit cancer progression by inhibiting oligometastases development. Thus, radionuclides can significantly decrease patient morbidity, prolong patient survival, and may decrease the occurrence of new bone metastases.. Palliative pain therapy is critical for effectively managing bone metastases, with treatment options including analgesics, external beam radiotherapy, chemotherapy and radionuclides. Radionuclide therapy is underutilized. Recent studies using radionuclides with chemotherapy and bisphosponates, or using newer radionuclides or combinations of radionuclides and treatment paradigms (e.g., higher activities, repetitive or cyclic administration, chemo sensitization, chemo supplementation), are encouraging. A comprehensive, inter-disciplinary clinical approach is needed. Clinical collaborations will optimize radionuclide therapy for pain palliation and increase awareness of its benefits.

Topics: Bone Neoplasms; Combined Modality Therapy; Humans; Neoplasm Metastasis; Pain; Palliative Care; Radioisotopes; Rhenium; Samarium; Strontium Radioisotopes

The aim of this article was to review the available literature regarding to the use of strontium-89 in the palliation of osteoblastic bone pain. The data of many researchers showed that approximately 80% of patients with pain from osteoblastic lesions resulting from prostate or breast cancer experience significant pain relief by administration of strontium-89, with only mild levels of hematotoxicity. The duration of pain relief in some cases exceeded 3-6 months. Indications for administration of strontium-89, effectiveness and duration of the treatment, side effects are reviewed in this article.

Topics: Adult; Bone Neoplasms; Breast Neoplasms; Contraindications; Female; Humans; Karnofsky Performance Status; Male; Osteoblasts; Pain, Intractable; Palliative Care; Pregnancy; Prostatic Neoplasms; Radiotherapy Dosage; Strontium Radioisotopes; Time Factors; Treatment Outcome

Pain management for painful bony metastases is the most important problem for symptom relief of terminally-ill cancer patients. Pathological fractures often decrease the activity of daily life (ADL) of patients, and cause deterioration of the quality of life (QOL) and prognosis. Basically pharmacological therapies of the World Health Organization (WHO) method are essential for symptom relief from cancer pain. This article provides the latest pain managements (palliative irradiation, bisphosphonate, orthopedic surgery, percutaneous vertebroplasty and radiopharmaceutical therapy) of bony metastases, and mentions the indications and the problems of these interventions. In consideration to prognosis, the QOL and patient's needs, medical staffs have to perform multidisciplinary approach for providing suitable palliative care.

Topics: Bone and Bones; Bone Neoplasms; Brachytherapy; Diphosphonates; Dose Fractionation, Radiation; Humans; Orthopedic Procedures; Pain; Pain Management; Palliative Care; Radiotherapy; Strontium Radioisotopes

Bone metastases are one of the most common conditions requiring radiation therapy today. Its main aim is relief of bone pain, prevention of pathological bone fractures as well as its healing, with anticipated effect upon improving mobility, function, and quality of life. For localized bone pain, external beam radiation therapy (EBRT) will be successful in reducing pain in some 80% of patients. However, optimal fraction dose and total doses of EBRT required for pain relief have been unknown. According to the recent reports, carbon ion radiotherapy seems to be a safe and effective modality in the management of metastatic bone tumor not eligible for conventional EBRT. For scattered painful metastases, the systemic administration of radioisotopes is thought to be effective.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Bone Neoplasms; Brachytherapy; Carbon Radioisotopes; Combined Modality Therapy; Dose Fractionation, Radiation; Humans; Iodine Radioisotopes; Pain; Palliative Care; Radiotherapy Dosage; Radiotherapy, High-Energy; Strontium Radioisotopes

Strontium-89 and samarium-153 are radioisotopes that are approved in the USA and Europe for the palliation of pain from metastatic bone cancer, whereas rhenium-186 and rhenium-188 are investigational. Radioisotopes are effective in providing pain relief with response rates of between 40% and 95%. Pain relief starts 1-4 weeks after the initiation of treatment, continues for up to 18 months, and is associated with a reduction in analgesic use in many patients. Thrombocytopenia and neutropenia are the most common toxic effects, but they are generally mild and reversible. Repeat doses are effective in providing pain relief in many patients. The effectiveness of radioisotopes can be greater when they are combined with chemotherapeutic agents such as cisplatin. Some studies with 89Sr and 153Sm indicate a reduction of hot spots on bone scans in up to 70% of patients, and suggest a possible tumoricidal action. Further studies are needed to address the questions of which isotope to use, what dose and schedule to use, and which patients will respond.

Topics: Bone Neoplasms; Humans; Neoplasm Metastasis; Pain, Intractable; Palliative Care; Radiography; Radioisotopes; Radiotherapy Dosage; Rhenium; Samarium; Strontium Radioisotopes

The purpose was to develop a systematic review that would address the following question: what is the role of radiopharmaceuticals in the palliation of metastatic bone pain in adults with uncomplicated, multifocal painful bone metastases whose pain is not controlled with conventional analgesic regimens? The outcomes of interest are pain response, analgesic consumption, overall survival, adverse effects and quality of life.. A systematic review of the English published literature was undertaken to provide evidence relevant to the above outcomes.. Six randomized phase III trials, two randomized phase II trials and one randomized crossover trial of strontium-89 were reviewed. A randomized phase III trial comparing strontium-89 plus cisplatin with strontium-89 plus placebo reported a significantly higher proportion of patients experiencing pain relief for a significantly longer duration with strontium-89 plus cisplatin. A randomized phase III trial comparing adjuvant strontium-89 with placebo following radiotherapy reported a higher proportion of pain-free patients with strontium-89. Patients who received strontium-89 also experienced fewer new sites of bone pain. A second, but underpowered study failed to confirm these results. In one randomized trial of strontium-89 versus radiotherapy (hemibody or local), patients treated with strontium-89 developed fewer new sites of pain. In a second trial comparing strontium-89 versus local radiotherapy, median overall survival was improved with radiotherapy, while pain response and time-to-progression were similar in the two groups. One randomized phase III trial reported no difference in pain relief between strontium-89 and placebo. Three randomized phase III trials and two randomized phase II trials investigating samarium-153 were reviewed. In a randomized phase III trial of three different doses of samarium-153, the pain responses were similar for all three doses. In a randomized phase III trial of two different doses of samarium-153 versus placebo, the complete pain response rate was significantly higher with the higher dose of samarium-153 compared with placebo. In a randomized phase III trial comparing samarium-153 with placebo, significant differences favouring samarium-153 were reported for pain and opiate use. In addition, one randomized phase III trial, two randomized phase II trials, one randomized crossover trial and 13 phase II or phase I trials of rhenium, one phase I trial of tin-117 m and one phase II trial of phosphorus-32 were reviewed. The majority of patients treated in trials of radiopharmaceuticals where histology was specified had metastatic breast cancer (approximately 5-10% of patients reported), metastatic hormone-refractory prostate cancer (80-90% of patients reported) or metastatic lung cancer (5-10% of patients reported). Information on histologic subtype was not available for a significant proportion of patients treated on trials (30-40% of patients reported).. Use of single-agent radiopharmaceuticals (strontium-89 and samarium-153) should be considered as a possible option for the palliation of multiple sites of bone pain from metastatic cancer where pain control with conventional analgesic regimens is unsatisfactory and where activity on a bone scan of the painful lesions is demonstrated. Ongoing clinical research should seek to establish the benefit of newer radiopharmaceuticals and radiopharmaceuticals in combination with other systemic therapies.

Topics: Bone Neoplasms; Humans; Palliative Care; Patient Selection; Radiopharmaceuticals; Randomized Controlled Trials as Topic; Rhenium; Strontium Radioisotopes

The paper presents the possibilities of therapy of painful bone metastases, which result from nuclear medicine development. Authors discuss fundamental problems connected with radionuclide therapy. The emphasis is put on the efficiency and safety of this treatment for patients and their environment.

Topics: Bone Neoplasms; Humans; Organometallic Compounds; Organophosphorus Compounds; Pain; Palliative Care; Radioisotopes; Radiopharmaceuticals; Samarium; Strontium; Strontium Radioisotopes

Topics: Analgesia; Bone Neoplasms; Contraindications; Drug Costs; Forecasting; Humans; Pain; Palliative Care; Radioisotopes; Radiopharmaceuticals; Rhenium; Samarium; Strontium Radioisotopes; Tin Radioisotopes; Treatment Outcome

Metabolic radiotherapy is a new therapy for management of bone pain in patients with bone metastatic prostate carcinoma. Strontium-89 and Samarium-153 concentrate in bone metastases and radiate them. A pain decrease is obtained in 60-70% of cases. Side effects are a significant hematological depression without great clinical consequences if good therapeutic indications are respected. Our multidisciplinary experience of these radionuclides in 54 performed treatments shows a rate of good responders of 66% with a rate of excellent results (total decrease of pain) in 47%. The therapeutic effectiveness is correlated with pain intensity measured by Visual Analogic Scale (VAS) and equivalent dose of morphine. Radionuclide therapy should be applied to patients as early as possible after establishment of bone metastases.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Analgesics, Opioid; Bone Neoplasms; Clinical Trials as Topic; Double-Blind Method; Forecasting; France; Hematologic Diseases; Humans; Male; Middle Aged; Organometallic Compounds; Organophosphorus Compounds; Pain; Palliative Care; Phosphorus Radioisotopes; Prospective Studies; Prostatic Neoplasms; Radioisotopes; Radiopharmaceuticals; Rhenium; Samarium; Strontium; Strontium Radioisotopes; Treatment Outcome

Topics: Androgens; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Clinical Trials as Topic; Clodronic Acid; Cyclophosphamide; Dexamethasone; Docetaxel; Estramustine; Humans; Male; Neoplasms, Hormone-Dependent; Paclitaxel; Prostatic Neoplasms; Strontium Radioisotopes; Taxoids; Tegafur; Treatment Outcome

Bone metastasis is a common sequella of solid malignant tumors such as prostate, breast, lung, and renal cancers, which can lead to various complications, including fractures, hypercalcemia, and bone pain, as well as reduced performance status and quality of life. A multidisciplinary approach is usually required not only to address the etiology of the pain and its complicating factors but also to treat the patient appropriately. Currently, the treatment of bone pain remains palliative at best with systemic therapy (analgesics, hormones, chemotherapy, steroids, and bisphosphonates) as well as local treatments (such as surgery, nerve blocks, and external beam radiation). However, many of these treatments are limited in their efficacy or duration and have significant side effects that seriously limit the cancer patient's quality of life. Various radiopharmaceuticals have shown good efficacy in relieving bone pain secondary to bone metastasis. This systemic form of metabolic radiotherapy is simple to administer and complements other treatment options. This has been associated with improved mobility in many patients, reduced dependence on narcotic and non-narcotic analgesics, improved performance status and quality of life, and, in some studies, improved survival. Additional radiopharmaceuticals are under investigation and appear promising. All of these agents, although comprising different physical and chemical characteristics, offer certain advantages in that they are simple to administer, are well tolerated by the patient if used appropriately, and can be used alone or in combination with the other forms of treatment.

Topics: Analgesics; Animals; Bone Neoplasms; Humans; Organometallic Compounds; Organophosphorus Compounds; Pain; Phosphates; Phosphorus Radioisotopes; Radioisotopes; Radiopharmaceuticals; Samarium; Strontium; Strontium Radioisotopes

Strontium-89 is a pure beta-emitting radioisotope, a chemical analogue of calcium, and it is therefore avidly concentrated by areas of high osteoblastic activity. Selective uptake and prolonged retention at sites of increased bone mineral turnover provide precise bone lesions targeting. 89Sr chloride (commercialised as Metastron) is typically administered in a single 150 MBq parenteral dose. Its radioactive emission poses very little radioprotection concerns. Overall, studies show pain relief in up to 80% of patients, of which 10 to 40% became effectively pain free. The mean duration of palliation was 3-4 months. The mechanism of pain relief is controversial ; it is probably, but not only, related to the absorbed dose in the tumour and bone. There is no clear dose-response relationship. The only reported toxicity is temporary myelosuppression. WBC and platelets should be monitored at least on a weekly basis until they return to baseline. It seems that only patients with a reasonably good general condition stand to benefit from this treatment. In conclusion, systemic radionuclide therapy using 89Sr represents a feasible, safe, effective, well tolerated and cost-effective palliative treatment in patients with refractory bone pain.

Topics: Bone Neoplasms; Dose-Response Relationship, Radiation; Female; Humans; Male; Pain, Intractable; Palliative Care; Strontium Radioisotopes

Strontium-89 is a pure Beta-emitting radioactive analogue of calcium that has been shown to be beneficial in the palliation of pain due to osseous metastases from adenocarcinoma of the prostate. The most significant reported toxicity is dose-related, reversible, myelosuppression characterized primarily by thrombocytopenia.. A report of two patients in whom acute myelogenous leukemia (AML) developed after treatment with strontium-89 and a review of the literature are presented.. The two patients described in the current study developed AML 17 months and 26 months, respectively, after exposure to strontium-89 for the treatment of prostate carcinoma. To the authors' knowledge these patients represent the first two reported cases of AML after strontium-89 therapy for prostate carcinoma.. The results of the current study suggest the leukemogenic potential of strontium-89 treatment in humans. To the authors' knowledge, the current study represents the first report of AML after therapeutic exposure to strontium-89. As this agent is used more frequently (and earlier in the disease course) in patients with prostate carcinoma, an increased incidence of secondary AML complicating the clinical management of patients with prostate carcinoma may be observed. [See editorial on pages 497-9, this issue.]

Topics: Adenocarcinoma; Aged; Beta Particles; Bone Neoplasms; Dose-Response Relationship, Radiation; Fatal Outcome; Follow-Up Studies; Humans; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Male; Neoplasms, Second Primary; Palliative Care; Prostatic Neoplasms; Radiopharmaceuticals; Strontium Radioisotopes; Thrombocytopenia

Most cases of advanced carcinoma of the prostate are hormonosensitive. The use of combined androgen blockade (CAB) seems to improve survival and quality of life, but only when combined with chemical castration by luteinizing-hormone-releasing hormone analog and without the use of steroidal antiandrogens. After CAB, further hormonal treatments remain efficacious, such as antiandrogen withdrawal followed by estrogens, aromatase inhibitors, and hormone-refractory prostate cancer multiple cytotoxic agents. For painful bone lesions, external beam radiotherapy, biphosphonates, and strontium 89 or samarium 153 provide pain relief. The use of new methods for the evaluation of response and quality of life will allow the rapid identification of effective treatments and permit powered phase III trials.

Topics: Androgen Antagonists; Bone Neoplasms; Brachytherapy; Combined Modality Therapy; Estrogens; Humans; Leuprolide; Male; Pain; Patient Care Planning; Prostatic Neoplasms; Quality of Life; Radiotherapy; Strontium Radioisotopes

Topics: Bone Neoplasms; Humans; Male; Prostatic Neoplasms; Radionuclide Imaging; Strontium Radioisotopes

Topics: Bone Neoplasms; Humans; Male; Pain; Palliative Care; Prostatic Neoplasms; Strontium Radioisotopes

Therapeutic use of radionuclides includes 131I for thyroid cancer and hyperthyroid Graves' disease, 89SrCl3 for metastatic bone tumors, 131I-MIBG for malignant pheochromocytoma and neuroblastoma, and radioimmunotherapies. 131I is concentrated in 60-70% of metastases from differentiated thyroid cancer following total thyroidectomy. Radioiodine uptake in metastatic lesions is greater in younger patients than in older ones. Hypothyroidism is often mild or even absent in patients with a large amount of tumor tissue, indicating that thyroid hormones produced by highly differentiated tumors compensate partially or even completely for hypothyroidism following total thyroidectomy. Adequate uptake of 131I has been reported to be associated with significant reduction in the size and number of metastases, and with lower recurrence and higher survival rates. Other favorable factors for longer survival are younger age, well-differentiated histological type, small disease extent, and early discovery of metastases. Older patients with extensive metastases and/or bulky tumor masses in the bone have a poor prognosis. Therefore, it is important to discover metastases as early as possible, when patients are still young. Long-term follow-up with periodic thyroglobulin measurements and imaging studies is strongly recommended. In Japan, 131I treatment for Graves' disease is performed only in selected patients in whom antithyroid drugs cannot be used because of side effects or not effective, considering the high prevalence of permanent hypothyroidism. 89SrCl3 is useful for reducing pain due to bone metastases of malignant tumors. 131I-MIBG therapy is effective for improvement of QOL in some patients with metastatic malignant pheochromocytoma. Radioimmuno-therapy using anti-CD20 has been used successfully in clinical application in patients with malignant B cell lymphoma.

Topics: 3-Iodobenzylguanidine; Antineoplastic Agents; Bone Neoplasms; Clinical Trials as Topic; Graves Disease; Humans; Iodine Radioisotopes; Prognosis; Radiopharmaceuticals; Strontium Radioisotopes; Thyroid Neoplasms

Many radiotherapeutic treatment options are available for the palliation of patients with metastatic prostate cancer. These include local field radiotherapy to symptomatic sites of metastasis and the use of radioisotope therapy either alone or in combination with local field radiotherapy. To date, the majority of patients treated with radioisotope therapy have been treated with 89Sr. Other agents, such as 153Sm-EDTMP are available now, also. Combined radioisotope therapy, cytotoxic chemotherapy, and biphosphonates hold great promise.

Topics: Bone Neoplasms; Humans; Male; Pain; Palliative Care; Prostatic Neoplasms; Strontium Radioisotopes

Four patients (men aged 75, 67, 65 and 69 years) with painful osseous metastases from prostate cancer were treated by intravenous radionuclide therapy using Strontium-89. All had secondary progression after initially successful hormonal treatment. Three of these four had good responses lasting from 5 to 9 months. One patient with rapidly progressive disease did not respond. Second and third injections were successful in two patients. Mild bone marrow suppression was observed in all, but was not clinically significant. The 70-80% chance of long-lasting pain alleviation through a single injection of Strontium-89 is a valuable addition in the treatment of painful bone metastases from prostate cancer, and probably also in such metastases from breast cancer.

Topics: Aged; Bone Marrow; Bone Neoplasms; Contraindications; Disease Progression; Humans; Injections, Intravenous; Male; Pain; Palliative Care; Prostatic Neoplasms; Radiotherapy; Recurrence; Strontium Radioisotopes; Treatment Outcome

Internal radiation therapy selectively targets beta- or alpha-emitting radionuclides to the area of the tumor tissue, and is therefore capable of treating disease regardless of the location and number of foci. The biological effect of internal radiation therapy is thought to be different from that of conventional external beam radiation. Thyroid cancer: The local recurrence and metastatic lesions from differentiated thyroid cancers can be controlled with 131I administration. Even though the patient does not have macroscopic disease, 131I is also utilized for thyroid remnant ablation in locally advanced cases. Recently, the maximum tolerable dose can be calculated based on the dosimetry of each patient, and safely administered. The therapeutic effect of this method is superior to the fixed dose method. 131I-MIBG: 131I-MIBG is taken up by sympathetic neurons as well as a group of tumors originating in the neural crest, especially phecromocytomas and neuroblastomas. The various symptoms caused by the hypersecretions of hormone-producing tumors can be improved. Pain palliation of bone metastases: Pain palliation using 89Sr is a very promising option in treating patients with painful bone metastases. The pain palliation mechanism of 89Sr is different from other drugs; therefore, complimentary usage is reasonable. The symptomatical improvement can last for several months, thus helping to maintain the quality of life of the patient.

Topics: 3-Iodobenzylguanidine; Bone Neoplasms; Humans; Iodine Radioisotopes; Neuroblastoma; Pain; Palliative Care; Strontium Radioisotopes; Thyroid Neoplasms; Thyroidectomy

Pain in patients with cancer metastatic to bone is a significant cause of morbidity and of referrals from general practice and specialist physicians. Management typically utilizes radiation therapy and the graduated use of opiate analgesics. Bone-seeking radiopharmaceuticals have provided a new option to these management strategies, which is effective and cost effective. Strontium 89 is now in routine clinical use, while rhenium 186 hydroxyethylidene diphosphonate (HEDP) and samarium 153 ethylenediaminetetramethylene phosphonate (EDTMP) are in Phase III trials and tin 117m (4+) diethylene triaminepentacetic acid (DTPA) is in Phase I trials. Evidence taken primarily from the Strontium 89 trial, shows unsealed source therapy with these bone-seeking radiopharmaceuticals to be effective in palliating pain, improving quality of life, reducing the rate at which new painful sites develop, reducing requirements for additional radiation therapy, and reducing lifetime management costs. Indications and contraindications to therapy have now been defined, and retreatment is an option with all radiopharmaceuticals.

Topics: Bone Neoplasms; Clinical Trials as Topic; Etidronic Acid; Female; Humans; Male; Organometallic Compounds; Organophosphorus Compounds; Pain; Pain Management; Palliative Care; Pentetic Acid; Phosphorus Radioisotopes; Radioisotopes; Rhenium; Safety; Strontium Radioisotopes; Syndrome

Strontium-89 systemic radiotherapy can play a significant role in the palliation of symptomatic osseous metastases from prostate cancer. Given as a single injection, strontium's affinity for osteoblastic activity draws it to all sites of osseous involvement simultaneously. The metastases are bathed with beta-particles whose short range in tissues spares the surrounding normal structures. This article will review the rationale, physiology, and patient selection criteria for its use. Approximately 80% of patients will respond to treatment as documented by the authors experience and by a review of the literature.

Topics: Adult; Aged; Bone Neoplasms; Controlled Clinical Trials as Topic; Humans; Male; Middle Aged; Multicenter Studies as Topic; Palliative Care; Patient Selection; Prognosis; Prostatic Neoplasms; Strontium Radioisotopes; Survival Rate

Pain management often is difficult in patients with bone metastases. Metastatic disease represents >40% of oncologic practice, and >70% of patients with metastatic disease have uncontrolled cancer-related pain. Significant morbidity caused by pathologic fracture and spinal cord compression can result from untreated bone metastases. Representing both a manifestation of systemic disease as well as causing localized symptoms, bone metastases require a multidisciplinary therapeutic approach. Radiation therapy provides both localized and systemic treatment options in addition to chemohormonal therapies and surgery. External beam irradiation provides palliation in >70% of patients through tumor regression of a localized lesion. Systemic radiopharmaceuticals treat multifocal disease either alone or as an adjuvant to external beam irradiation. Efficient and comprehensive management of bone metastases is imperative because of the associated symptoms, prior therapies, complex underlying medical problems, and clinical presentations that often require emergent interventions. Intensification of pain may be observed with hormonal therapy and systemic radiopharmaceuticals. Symptomatic relief from antineoplastic therapies generally requires 4-12 weeks and may be related to reossification. Symptoms, occurring due to the disease and/or while awaiting response to therapy, must be aggressively managed. Persistent or recurrent pain after therapy may be due to bony instability or fracture before reossification occurs. An Interdisciplinary Bone Metastases Clinic, with representatives from Diagnostic Radiology, Medical Oncology, Nuclear Medicine, Orthopedic Surgery, Pain and Symptom Management, Physical Medicine and Rehabilitation, and Radiation Oncology, was developed that allows coordinated evaluation, treatment, and symptom management of these complex clinical presentations.

Topics: Bone Diseases; Bone Neoplasms; Dose Fractionation, Radiation; Dose-Response Relationship, Radiation; Fractures, Spontaneous; Hemibody Irradiation; Humans; Pain; Palliative Care; Prognosis; Prospective Studies; Radiography; Radiopharmaceuticals; Spinal Cord Compression; Strontium Radioisotopes

Topics: Bone Neoplasms; Controlled Clinical Trials as Topic; Humans; Male; New Jersey; Pain, Intractable; Palliative Care; Prognosis; Prostatic Neoplasms; Strontium Radioisotopes

To review the current use of strontium-89 (89Sr) to treat pain related to bony metastasis secondary to prostate cancer.. Published articles.. Prostate cancer is the most commonly diagnosed cancer in the United States. The disease's most common site of metastasis is the bones. Bone metastasis leads to unrelenting pain. If healthcare providers are able to manage a patient's pain successfully, the patient's quality of life improves.. When conventional therapies fail, 89Sr can be used as an alternative or an adjunct to pain management of bony metastasis in prostate cancer.. Nursing intervention primarily involves assessing pain, monitoring analgesics until 89Sr can begin to take effect, educating patients on using other medications with 89Sr, and assessing fatigue resulting from 89Sr-induced myelosuppression. As pain decreases, nurses also should monitor patients' activity levels, since they are at risk for pathologic fractures.

Topics: Bone Neoplasms; Humans; Male; Nursing Assessment; Pain; Pain Measurement; Palliative Care; Prostatic Neoplasms; Radiotherapy Dosage; Strontium Radioisotopes; Treatment Outcome

Metastatic bone disease from hormone-refractory prostate cancer can lead to significant morbidity such as pain, nerve compression and fractures which diminishes the quality of life of these patients substantially. Pain from osteoblastic metastases can significantly be improved by both external radiotherapy and Strontium-89 (89Sr), whereas lytic metastases are only responsive to external irradiation. Pain relief is obtained in approximately 80% of patients. Toxicity is mild and retreatment is usually possible. External beam radiotherapy is indicated when spinal cord or nerve root compression is demonstrated, or when osteolytic metastases with danger of fracture are visualized. External radiotherapy and Strontium-89 are important treatments to palliate patients suffering from metastatic prostate cancer. Because of their mild toxicity and highly effective analgesic effect, implementation of irradiation and 89Sr should be start of early in the disease process of these patients in order to keep them ambulatory and pain-free as long as possible.

Topics: Bone Neoplasms; Humans; Male; Pain; Palliative Care; Prostatic Neoplasms; Radioisotope Teletherapy; Strontium Radioisotopes

Topics: Bone Neoplasms; Combined Modality Therapy; Female; Fractures, Spontaneous; Hemibody Irradiation; Humans; Male; Pain Management; Palliative Care; Radioisotopes; Radiotherapy Dosage; Spinal Cord Compression; Strontium Radioisotopes; Treatment Outcome

Topics: Bone Neoplasms; Humans; Male; Palliative Care; Prostatic Neoplasms; Strontium Radioisotopes

To present the current state of systemic radiopharmaceutical therapy for the palliation of pain in individuals with metastatic cancer and to evaluate the palliative effect and degree of hemotoxicity of strontium chloride 89 (89Sr) in patients with painful osteoblastic metastases primarily from prostate and breast cancer.. A MEDLINE search through December 1994 was performed to identify English-language studies that met the following criteria. All eligible studies reported treatment of patients with painful osteoblastic bony metastases primarily from prostate or breast cancer treated with intravenous 89Sr. For study eligibility, evaluation of clinical response as assessed by the Karnofsky index, need for pain medication, or changes in mobility or sleep patterns was required. Hemotoxicity data were a requirement. A minimum of 10 prostate cancer cases was necessary for study inclusion. Only those studies assessing clinical response following one injection of 89Sr were included. Preliminary reports of cooperative studies were not included. Doses of 89Sr ranged from 0.6 MBq/kg (16 microCi/kg) to 400 MBq (10.8 mCi) per patient. Evaluation of patients for at least 3 months following 89Sr treatment was required. In addition, two studies examining issues of cost with regard to 89Sr treatment were identified.. Baseline pain assessment and periodic pain estimates as measured by the Karnofsky index, medication diaries, changes in mobility, sleep patterns, and/or ability to work were the basis for assessment of response. Baseline and periodic complete blood cell counts were the basis for hemotoxicity evaluation.. Palliation and hemotoxicity data were analyzed separately for each study. Some improvement occurred in as many as approximately 80% of patients. Several studies demonstrated complete relief of pain in at least 10% of patients The nadir of platelet and white blood cell counts appears at approximately 4 to 8 weeks following injection, with a partial return to baseline by 12 weeks. As many as 10 injections spaced 3 months apart have been given to some patients with repeated palliative effect and without serious hemotoxicity. Reinjection may be limited by a platelet count below 60 x 10(9)/L, a white blood cell count below 2.4 x 10(9)/L, or the absence of osteoblastic skeletal metastasis as seen on bone scan. Studies examining treatment costs suggest that 89Sr may decrease costs associated with palliation of pain due to metastatic disease.. As many as 80% of selected patients with painful osteoblastic bony metastases from prostate or breast cancer may experience some pain relief following 89Sr administration. In addition, as many as 10% or more may become pain free. Duration of clinical response may average 3 to 6 months in some cases. Hemotoxicity is mild. A decrease in treatment costs with administration of 89Sr to patients with painful osteoblastic bony metastases from prostate cancer may occur. These observations reflect the preliminary nature of knowledge in this field and point to the need for larger clinical trials of the use of 89Sr palliation.

Topics: Bone Neoplasms; Breast Neoplasms; Cost-Benefit Analysis; Drugs, Investigational; Etidronic Acid; Female; Hematologic Tests; Humans; Male; Organometallic Compounds; Organophosphorus Compounds; Pain; Pain Measurement; Palliative Care; Patient Selection; Prostatic Neoplasms; Radioisotopes; Radiotherapy Dosage; Strontium; Strontium Radioisotopes

Bony metastasis is the most common cause of cancer pain. Strontium-89 (Sr-89), or Metastron, therapy has been shown to be effective for the palliation of pain due to skeletal metastases. By reducing opioid analgesics intake and restoring mobility, Sr-89 improves the patient's quality of life. Sr-89 is given conveniently as an outpatient procedure, and when necessary it can be repeated at 3-month intervals. Sr-89 is useful as an adjunct to local external beam radiation (EBR) because Sr-89 will target all skeletal metastases, including those not included in the EBR field. Because Sr-89 is a beta-emitting radionuclide with a long physical half-life (50.5 days), precautions should be taken by the caretaker(s) against Sr-89 contamination from the patient's blood or excretions, particularly if the patient is incontinent.

Topics: Bone Neoplasms; Clinical Trials as Topic; Humans; Palliative Care; Radiotherapy, Adjuvant; Strontium; Strontium Radioisotopes

Topics: Bone Neoplasms; Clinical Trials as Topic; Humans; Palliative Care; Radioisotopes; Radiotherapy Dosage; Strontium Radioisotopes

The role of strontium chloride Sr 89 in the palliative treatment of pain associated with metastatic bone disease is reviewed. Conventional therapies to relieve metastatic bone pain include nonopioid and opioid analgesics, hormonal therapy, external-beam irradiation, and chemotherapy. Limitations in the long-term safety and effectiveness of these treatments have increased interest in using systemic radioactive isotopes for palliation of pain. Strontium chloride Sr 89 is a relatively new bone-seeking radiopharmaceutical that has FDA-approved labeling for use in relieving pain associated with skeletal metastases. An analogue of calcium, strontium chloride Sr 89 is rapidly cleared from the blood after i.v. injection. The agent selectively irradiates metastatic sites while generally sparing normal soft-bone tissue. In clinical studies, a majority of patients with prostate or breast cancer obtained substantial relief from bone pain after receiving strontium chloride Sr 89 alone or in combination with external-beam irradiation. Adverse effects tend to be mild, but patients should be monitored for possible hematologic toxicity. Patients should discontinue any calcium-containing products before receiving the agent. The typical dose is 4 mCi (148 MBq) administered by slow i.v. push over one to two minutes; doses can be repeated at three-month intervals. Pain relief usually begins in 10-20 days and lasts up to six months. Radiation safety measures are necessary in handling strontium chloride Sr 89 and the wastes of patients. Strontium chloride Sr 89 is costly, but preliminary analysis indicates that it may reduce management expenditures overall.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Bone Neoplasms; Clinical Trials as Topic; Combined Modality Therapy; Humans; Pain; Palliative Care; Strontium; Strontium Radioisotopes

Topics: Aged; Bone Neoplasms; Clinical Trials as Topic; Combined Modality Therapy; Dose-Response Relationship, Drug; Follow-Up Studies; Hormones; Humans; Male; Middle Aged; Orchiectomy; Pain, Intractable; Palliative Care; Prostatic Neoplasms; Strontium Radioisotopes; Treatment Failure

The Council on Scientific Affairs of the California Medical Association presents the following epitomes of progress in nuclear medicine. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and clinical importance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, and scholars to stay abreast of progress in medicine, whether in their own field of special interest or another. The epitomes included here were selected by the Advisory Panel to the Section on Nuclear Medicine of the California Medical Association, and the summaries were prepared under the direction of Dr Lyons and the panel.

Topics: Bone Neoplasms; Humans; Palliative Care; Strontium Radioisotopes

Bone metastases that develop in patients with advanced prostate cancer often cause deep, unremitting pain. Palliative options for the control of this pain include analgesic support, cytotoxic chemotherapy and external-beam radiotherapy. In addition to external irradiation, interest in intravenously injected radioisotopes that are preferentially localized to bone has been mounting. Metastron (an isotope of strontium) imitates the biodistribution of calcium in vivo and is avidly taken up into bony metastases where it has a biological half-life of just over 50 days. The biological half-life in undiseased bone is far shorter, approximately 14 days. Various studies have been conducted to evaluate the role of Metastron in metastatic prostate cancer. An optimum dose has yet to be finalized, but it is clear that the change of haematological toxicity becomes more significant at much larger doses. In the large, randomized Trans Canada study in which Metastron or placebo was given to patients as an adjunct to local field irradiation, those patients treated with Metastron had a significantly reduced intake of analgesics. Furthermore, progression of pain, as measured either by sites of new pain or by the requirement for further palliative radiotherapy, demonstrated statistically significant differences in favour of Metastron. There is thus increasing evidence of a useful role for Metastron in the treatment of prostate cancer metastatic to bone.

Topics: Antineoplastic Agents; Bone Neoplasms; Humans; Male; Palliative Care; Prostatic Neoplasms; Strontium; Strontium Radioisotopes

New advances in systemic radionuclide therapy have increased the number of treatment options available for patients with painful osseous metastases. This form of therapy has three major appeals: 1) it addresses all sites of involvement; 2) selective absorption into bone limits irradiation of normal tissues; and 3) as a result, toxicity may be reduced and the therapeutic ratio improved. The clinical experience with radioactive phosphorus, strontium, samarium, and rhenium are reviewed. To date, the best studied and the only Food and Drug Administration approved agent is strontium-89. About 60% to 90% of patients treated with strontium-89 respond with complete or partial relief of pain for a median duration of 6 months. Large, prospectively randomized clinical trials have established the efficacy of strontium-89 as a first-line therapy and as an adjuvant to external-beam radiotherapy. Particularly advantageous is its usefulness in situations in which external-beam radiotherapy options have been exhausted and normal tissue tolerance has been reached. Newer radiopharmaceuticals are still under investigation.

Topics: Bone Neoplasms; Humans; Phosphorus Radioisotopes; Radioisotopes; Rhenium; Samarium; Strontium Radioisotopes

Topics: 3-Iodobenzylguanidine; Antibodies, Monoclonal; Bone Neoplasms; Brachytherapy; Humans; Iodine Radioisotopes; Iodobenzenes; Neoplasms; Phosphorus Radioisotopes; Radioisotopes; Radiotherapy Dosage; Rhenium; Samarium; Strontium Radioisotopes; Thyroid Neoplasms

Recent advances in targeted radiotherapy offer a new approach for the management of metastatic bone pain. This paper will review the scientific basis for radionuclide therapy and will examine the evidence for clinical efficacy. The therapeutic potential of targeted radiotherapy can only be appreciated by comparison with established treatments. Alternative treatment options will, therefore, be discussed, to bring the potential advantages and hazards of targeted radiotherapy into perspective and to define its place in routine management.

Topics: Analgesics; Bone Neoplasms; Combined Modality Therapy; Etidronic Acid; Humans; Organometallic Compounds; Organophosphorus Compounds; Pain, Intractable; Palliative Care; Radioisotopes; Radiotherapy; Rhenium; Samarium; Strontium Radioisotopes

Strontium-89 chloride is a radiopharmaceutical that localizes to actively forming new bone, such as metastatic bone lesions from prostate and breast cancer. It provides effective systemic endo-osseous local radiation therapy to these painful lesions. Strontium-89 will soon be available to physicians in the United States for use in the palliative management of metastatic bone pain.

Topics: Bone Neoplasms; Breast Neoplasms; Clinical Trials, Phase III as Topic; Female; Humans; Male; Palliative Care; Prostatic Neoplasms; Strontium Radioisotopes

Several radiopharmaceuticals with a propensity to concentrate in painful metastatic bone cancer lesions are under development as a systemic radiation alternative to 32P. All are reactor produced and, when injected, have in all but 117mSn-DTPA decreased or eliminated the pain in more than three quarters of the patients, and all have caused transient myelotoxicity. Three of the four are under clinical evaluation and the generated data will be used for new drug applications for routine human use.

Topics: Animals; Bone Neoplasms; Clinical Trials as Topic; Humans; Palliative Care; Phosphorus Radioisotopes; Radioisotopes; Rhenium; Samarium; Strontium Radioisotopes; Tin Radioisotopes

Strontium-89 is preferentially taken up at sites of increased bone mineral turnover, its uptake adjacent to malignant metastases being up to five times greater than for normal bone. Strontium-89 is also selectively retained in bone adjacent to metastatic sites. The initial therapeutic ratio is therefore good and increases with time. The pharmacokinetics of strontium-89 thus favor the objective of achieving a clinically effective beta radiation dose to tumor deposits while minimizing radiation exposure to healthy tissue. Clinical studies show that 150 MBq [corrected] strontium-89 can relieve bone pain in up to 80% of patients with prostatic metastases. Greater activities do not appear to increase this level of response. Once a response has been achieved, strontium-89 therapy can be repeated when pain recurs. Although hematologic toxicity at this dosage is low, strontium-89 should not be given to patients with evidence of significant bone marrow depression. With this precaution, no serious toxicity has been encountered when the agent is administered at the recommended doses.

Topics: Bone Neoplasms; Humans; Palliative Care; Strontium Radioisotopes

Reports published in the English literature of clinical trials utilizing intravenous strontium 89 (89Sr) in the treatment of patients with prostatic adenocarcinoma metastatic to bone were reviewed. Correlation coefficients were calculated for increasing dose of 89Sr and complete pain relief and complete and partial pain relief. Statistically significant positive correlations were obtained for complete relief of pain. Positive correlations were also found between those patients who had at least partial pain relief (defined as at least a 50% reduction in analgesia requirement), but these did not reach significance. This analysis suggests that a dose response relationship may exist between the dosage of 89Sr administered, and complete relief of pain due to skeletal metastases. The optimal dosage of 89Sr in this clinical situation has not been established, and prospective, carefully executed and analyzed randomized trials will be required to test whether and to what extent dose intensity of 89Sr determines outcome independently of other factors.

Topics: Adenocarcinoma; Bone Neoplasms; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Infusions, Intravenous; Male; Pain; Palliative Care; Prostatic Neoplasms; Research Design; Strontium Radioisotopes

Strontium-89 is a radioactive calcium analog that provides an energetic beta particle for radiation therapy of osteoblastic disease. Strontium-89 is used as palliative therapy with the primary goal being pain relief. More than 500 patients with painful blastic metastatic disease were treated at University of Kansas Medical Center since the initiation of the first clinical trial there 15 years ago. Most patients have had metastatic prostate cancer to bone or breast cancer, as these tumors are commonly associated with bone pain as their primary clinical management problem. Improvement (decrease in pain, increase in physical activity level) was noted in 80% of patients with prostate carcinoma and 81% of patients with metastatic breast cancer to bone. Marrow toxicity levels were acceptable. The therapy can be repeated at 3-month intervals. Strontium-89 is a safe and effective systemic therapy for painful blastic metastatic disease. There is no longer any reason why the vast majority of persons with painful blastic metastatic disease should continue to hurt.

Topics: Bone Neoplasms; Humans; Osteoblasts; Pain; Strontium Radioisotopes

Topics: Adult; Bone Neoplasms; Humans; Male; Pain; Strontium Radioisotopes

Bone metastases are a major problem in the clinical management of patients with breast or prostate cancer. Severe bone pain can be a particularly debilitating effect of metastatic disease, resulting in a growing dependency on opioid analgesics and a reduced quality of life in patients who have a short time to survive. The radiopharmaceutical strontium-89 has been demonstrated to be generally well tolerated as well as effective in reducing metastatic bone pain in breast or prostate cancer patients. Unlike other radioisotopes or external radiation treatments, it represents systemic, targeted therapy that is simple and fast to administer in an outpatient setting. Data accumulated over the last 15 years demonstrates that 89Sr provides pain relief in up to 80% of patients with bony metastases arising from breast or prostatic malignancies. Pain palliation is maintained for several months, along with improvements in functional status and quality of life. As many as one fifth of 89Sr-treated patients become pain free and require no further pain medication. The adverse effects of intravenous 89Sr are minimal. Bone marrow toxicity is observed in many patients, resulting in some reduction of platelet and white blood cell counts. Despite reductions of 20% to 30%, these hematologic effects are generally reversible and the majority of patients maintain platelet counts that are within normal limits. Strontium-89 is effective systemic radioisotopic therapy for the palliation of painful bony metastases from breast and prostate carcinoma.

Topics: Bone Neoplasms; Breast Neoplasms; Humans; Male; Prostatic Neoplasms; Strontium Radioisotopes

This contribution on the biology and management of bone metastases from prostatic cancer is divided into three parts. The first details a study conducted at Stanford University on the prevention of bone metastases in the lumbar spine, in patients in whom the lumbar spine has been irradiated coincidental to the radiation treatment of the paraaortic lymph nodes. The incidence of metastases was significantly reduced in 71 patients in whom the apparently normal lumbar spine was irradiated, as compared to the incidence of metastases in 65 patients who received no lumbar irradiation. The implications of these observations on developing strategies for early, or preemptive, irradiation for bone metastases are discussed. In the second part, the optimum radiation dose and fractionation scheme for the palliation of overt bone metastases is addressed. Drawing largely from the work of Arcangeli et al., a total dose of 40-50 Gy*, fractionated at 2 Gy per day, seems to be the regimen of choice for enduring pain relief for most patients with prostatic metastases to bone. Finally, the recent utilization of strontium-89 in the palliation of advanced bone metastases is addressed. *The Gy is the current international unit of radiation. 1Gy = 100 Rad; 1cGy (centigray) = 1 Rad.

Topics: Bone and Bones; Bone Neoplasms; Humans; Incidence; Life Tables; Lumbar Vertebrae; Lymphatic Metastasis; Male; Pain; Palliative Care; Pelvis; Prostatic Neoplasms; Radioisotope Teletherapy; Radiotherapy Dosage; Retrospective Studies; Spinal Neoplasms; Strontium Radioisotopes

The palliation of bone pain is a common clinical problem once metastatic prostate cancer has escaped from hormonal control. This retrospective study compares the results of treatment using hemibody irradiation (HBI) at the Royal Marsden Hospital (27 cases) with isotope therapy using the bone-seeking isotope strontium-89 (89Sr) at Southampton General Hospital (51 cases). Prior to analysis patients were matched for potential prognostic factors (performance status, bone scan extent of disease, age, histology and duration of hormone response) to minimize the effect of treatment selection bias. Pain control assessed at 3 months was similar for HBI and matched 89Sr cases, with 63% and 52% respectively showing some benefit. Median survival was similar for these groups at 20 and 21 weeks respectively. The unmatched 89Sr group, which had more favourable prognostic factors, had a better outcome with 96% showing improvement in pain and with a median survival of 59 weeks. Subsequent univariate analysis demonstrated that performance status and extent of disease on bone scan were of overriding importance in determining outcome. Transfusion requirements were higher for the HBI group than for the matched 89Sr group (50% and 25% respectively) but other bone marrow toxicity was similar. Despite routine anti-emetic therapy 37% of patients treated with HBI had some nausea or vomiting. Although expensive, 89Sr appears as effective a treatment option as HBI. Response is most likely with either approach when patients have a good performance status and a limited extent of disease.

Topics: Actuarial Analysis; Blood Cells; Bone Neoplasms; Cobalt Radioisotopes; Humans; Male; Palliative Care; Particle Accelerators; Prognosis; Prostatic Neoplasms; Radiotherapy; Radiotherapy Dosage; Remission Induction; Retrospective Studies; Strontium Radioisotopes; Time Factors

The radiation oncologist is an important member of the multidisciplinary team involved in the management of patients with metastatic bone disease. Radiation therapy provides local tumor control of the metastatic deposit and effective pain relief in the majority of patients. If there is a risk of fracture, prophylactic fixation is done before radiation therapy.

Topics: Analgesia; Bone Neoplasms; Humans; Palliative Care; Phosphorus Radioisotopes; Radiotherapy Dosage; Strontium Radioisotopes

Tumor-induced hypercalcemia and tumor-induced osteolysis are essentially due to a marked increase in osteoclast-mediated bone resorption, although the kidneys play an important contributory role in the genesis of tumor-induced hypercalcemia. Parathyroid hormone-like protein plays an essential role in tumor-induced hypercalcemia, and maybe in tumor-induced osteolysis, but other factors could also be responsible for the osteoclast activation secondary to the neoplastic infiltration of the skeleton. Treatment of tumor-induced hypercalcemia essentially consists of volume repletion and administration of potent anti-osteolytic drugs. The bisphosphonate pamidronate is particularly useful for that matter and a dose of 1.0 to 1.5 mg/kg can normalize serum calcium in about 90% of hypercalcemic cancer patients. The apparently low response rate of bone metastases to systemic antineoplastic therapy seems to essentially reflect the relative insensitivity of our current methods for assessing response in tumor-induced osteolysis. Newly developed biochemical markers of bone turnover could be particularly useful for that matter. Bisphosphonates are the most potent of the available inhibitors of osteoclast activity. Prolonged administration of oral pamidronate could reduce by almost one half the complications of tumor-induced osteolysis, and repeated bisphosphonate infusions could induce a dramatic relief of bone pain in one third and a sclerosis of lytic lesions in one fourth of the cases. These data must, however, be confirmed in randomized, blinded trials and many questions remain unanswered concerning the optimal therapeutic schemes. Medical therapy of tumor-induced osteolysis by noncytotoxic means has nevertheless become a reality.

Topics: Antineoplastic Agents; Bone Neoplasms; Bone Resorption; Calcitonin; Combined Modality Therapy; Diphosphonates; Etidronic Acid; Humans; Hypercalcemia; Hypocalcemia; Osteoclasts; Osteolysis; Pain; Pamidronate; Strontium Radioisotopes

Management of bone pain in patients with multiple osseous metastases is a significant clinical problem. Phosphorus-32 has been used as systemic radioisotope therapy for the management of bone pain for over 40 years. However, significant hematological depression usually results and its use is limited. More recently, the bone-seeking radiopharmaceuticals strontium-89, samarium-153-ethylenediaminetetramethylene phosphonic acid, and rhenium-186-hydroxyethylidene diphosphonate have all been used as palliative treatment for patients with clinically significant bone pain. Excellent clinical responses with acceptable hematological toxicity have been observed. The clinical results rival those of external beam radiation therapy, with fewer systemic and hematological side effects. Systemic radionuclide therapy is indicated in the management of patients with painful metastatic prostate cancer in bone as soon as they escape primary hormonal management. This therapy also should play a role in the management of many patients with advanced breast cancer metastatic to bone. The role of radionuclidic therapy in osseous metastases from other malignancies is still being investigated. These compounds also hold promise as primary therapy for tumors of osseous origin. Systemic radionuclide therapy of painful bony metastases will become common in nuclear medicine practice in the next decade.

Topics: Bone Neoplasms; Humans; Pain, Intractable; Radioisotopes; Strontium Radioisotopes

Topics: Bone Neoplasms; Humans; Infusions, Intravenous; Pain; Palliative Care; Platelet Count; Strontium Radioisotopes; Time Factors

Radiation is an effective modality for palliation of osseous metastases. In patients with a limited number of lesions, local external beam irradiation is the most expedient method of delivering radiation therapy. Complete or partial relief of pain will occur in 80-90% of patients. When metastases are widespread or when new sites continue to appear, localized external irradiation becomes logistically difficult. In such cases, hemibody irradiation has been effective with an overall response rate of 85%. However, nausea, vomiting, diarrhea, and bone marrow and pulmonary toxicity may complicate therapy. In these cases, an effective alternative is systemic phosphorus-32 (32P) or strontium-89 (89Sr). Relief of pain in the range of 60-90% has been reported. Toxicity of 32P is largely that of bone marrow suppression, while 89Sr appears to be relatively marrow-sparing. In this review, we consider systemic 32P or 89Sr as viable options to external beam or hemibody irradiation in the presence of numerous bone metastases.

Topics: Bone Neoplasms; Humans; Palliative Care; Phosphorus Radioisotopes; Radiotherapy; Radiotherapy Dosage; Strontium Radioisotopes; Whole-Body Irradiation

Topics: Animals; Blood Cell Count; Bone Neoplasms; Cerium Radioisotopes; Dogs; Electrons; Gamma Rays; Humans; Iodine Radioisotopes; Liver; Micronesia; Neoplasms, Radiation-Induced; Rabbits; Radiation Injuries; Radiation Injuries, Experimental; Radioactive Fallout; Radioisotopes; Rats; Strontium Radioisotopes; Thyroid Gland

Bone scanning is a sensitive test for the detection of metastatic breast cancer, but not all abnormal findings on bone scan are diagnostic of skeletal metastasis. Recent studies have found a relatively low rate (less than or equal to 5%) of abnormal scans in patients with Stage I and II breast cancers, and only half of those with positive scans subsequently had documented bony metastasis. The overwhelming clinical experiences summarized here question the value of including bone scanning as part of the routine work-up of patients with early breast cancers.

Topics: Bone and Bones; Bone Neoplasms; Breast Neoplasms; Diphosphates; False Negative Reactions; False Positive Reactions; Female; Fluorine; Humans; Neoplasm Staging; Prognosis; Radioisotopes; Radionuclide Imaging; Strontium Radioisotopes; Technetium; Technetium Tc 99m Pyrophosphate

The observation by Subramanian and his co-workers that a 99mTc-labeled polyphosphate had excellent affinity for bone has led to widespread use of 99mTc-labeled phosphates as bone scanning agents. Initially, only polyphosphate was employed, but because of somewhat inconstant results and difficulty in preparation of this product, other phosphate compounds were sought. We soon discovered that an inorganic compound, pyrophosphate, appeared to have certain advantages over polyphosphate. Other workers formulated diphosphonates (organic phosphates) which also demonstrated advantages over polyphosphates. Comparison studies in rabbits utilizing 85Sr, 87mSr, 18F, and several phosphates (inorganic and organic) proved the 99mTc-labeled phosphates to be clearly superior in delineating normal skeletal anatomy. Studies in humans confirmed that excellent visualization of bone was obtained with 99mTc-labeled phosphates using either a gamma camera or a rectilinear scanner. What was not known, however, was just how reliable this class of agents would prove to be in detecting bone disease when compared to bone-seeking radiopharmaceuticals such as 85Sr, 87mSr, and 18F. Further comparative analyses have clearly demonstrated that both inorganic and organic 99mTc phosphate complexes are extremely sensitive in revealing more bone disease than the older bone scanning agents.

Topics: Adult; Aged; Animals; Bone Neoplasms; Breast Neoplasms; Carcinoma, Squamous Cell; Colonic Neoplasms; Diphosphates; Female; Fluorine; Hodgkin Disease; Humans; Kidney Neoplasms; Lung Neoplasms; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Metastasis; Phosphates; Prostatic Neoplasms; Rabbits; Radioisotopes; Radionuclide Imaging; Strontium Radioisotopes; Technetium

Bone scanning is most useful in the detection of bone metastases. The recent introduction of new radiopharmaceuticals and instrumentation has reduced the time needed to perform the study and its relative cost, while increasing the usefulness of the study in detecting roentgenographically occult diseases. Metastatic disease is used as the pathophysiologic model for understanding the principles of bone scanning. When a tumor invades bone, in addition to causing bone destruction, it also causes reactive bone formation or repair. It is here that radioisotopes are of considerable value, since some radionuclides are incorporated into the hydroxyapatite crystals of reactive bone. Bone repair is described as occurring in three phases. In Phase I, the roentgenogram shows no change in bone density, but the scan is abnormal. In Phase II, both scintigraphic and roentgenographic abnormalities increase, and in Phase III, when the osteoid has calcified completely, the roentgenogram shows radiodensities and the scan appears almost normal. Fewer than 5 per cent of patients have a normal scan in the presence of an abnormal roentgenogram. Presently, most bone scans are performed with phosphate compounds labeled with -99m-Tc. In the past, 85-Sr, 87M-Sr, and 18-F were more broadly used. Scanning may be performed on either a rectilinear scanner or a scintophoto (gamma) camera. Areas which are abnormal on bone scan should be interpreted with current roentgenograms in the light of clinical findings.

Topics: Autopsy; Biopsy; Bone Diseases; Bone Neoplasms; Female; Fluorine; Half-Life; Humans; Lumbar Vertebrae; Male; Middle Aged; Neoplasm Metastasis; Radiography; Radioisotopes; Radionuclide Imaging; Strontium Isotopes; Strontium Radioisotopes; Technetium

Bony metastatic castration-refractory prostate cancer is associated with a poor prognosis and high morbidity. TRAPEZE was a two-by-two factorial randomised controlled trial of zoledronic acid (ZA) and strontium-89 (Sr-89), each combined with docetaxel. All have palliative benefits, are used to control bone symptoms and are used with docetaxel to prolong survival. ZA, approved on the basis of reducing skeletal-related events (SREs), is commonly combined with docetaxel in practice, although evidence of efficacy and cost-effectiveness is lacking. Sr-89, approved for controlling metastatic pain and reducing need for subsequent bone treatments, is generally palliatively used in patients unfit for chemotherapy. Phase II analysis confirmed the safety and feasibility of combining these agents. TRAPEZE aimed to determine the clinical effectiveness and cost-effectiveness of each agent.. Patients were randomised to receive six cycles of docetaxel plus prednisolone: alone, with ZA, with a single Sr-89 dose after cycle 6, or with both. Primary outcomes were clinical progression-free survival (CPFS: time to pain progression, SRE or death) and cost-effectiveness. Secondary outcomes were SRE-free interval (SREFI), total SREs, overall survival (OS) and quality of life (QoL). Log-rank test and Cox regression modelling were used to determine clinical effectiveness. Cost-effectiveness was assessed from the NHS perspective and expressed as cost per additional quality-adjusted life-year (QALY). An additional analysis was carried out for ZA to reflect the availability of generic ZA.. 757 randomised (median age 68.7 years; Eastern Cooperative Oncology Group scale score 0, 40%; 1, 52%; 2, 8%; prior radiotherapy, 45%); median prostate-specific antigen 143.78 ng/ml (interquartile range 50.8-353.9 ng/ml). Stratified log-rank analysis of CPFS was statistically non-significant for either agent (Sr-89, p = 0.11; ZA, p = 0.45). Cox regression analysis adjusted for stratification variables showed CPFS benefit for Sr-89 [hazard ratio (HR) 0.845, 95% confidence interval (CI) 0.72 to 0.99; p = 0.036] and confirmed no effect of ZA (p = 0.46). ZA showed a significant SREFI effect (HR 0.76; 95% CI 0.63 to 0.93; p = 0.008). Neither agent affected OS (Sr-89, p = 0.74; ZA, p = 0.91), but both increased total cost (vs. no ZA and no Sr-89, respectively); decreased post-trial therapies partly offset costs [net difference: Sr-89 £1341; proprietary ZA (Zometa(®), East Hanover, NJ, USA) £1319; generic ZA £251]. QoL was maintained in all trial arms; Sr-89 (0.08 additional QALYs) and ZA (0.03 additional QALYs) showed slight improvements. The resulting incremental cost-effectiveness ratio (ICER) for Sr-89 was £16,590, with £42,047 per QALY for Zometa and £8005 per QALY for generic ZA.. Strontium-89 improved CPFS, but not OS. ZA did not improve CPFS or OS but significantly improved SREFI, mostly post progression, suggesting a role as post-chemotherapy maintenance therapy. QoL was well maintained in all treatment arms, with differing patterns of care resulting from the effects of Sr-89 on time to progression and ZA on SREFI and total SREs. The addition of Sr-89 resulted in additional cost and a small positive increase in QALYs, with an ICER below the £20,000 ceiling per QALY. The additional costs and small positive QALY changes in favour of ZA resulted in ICERs of £42,047 (Zometa) and £8005 for the generic alternative; thus, generic ZA represents a cost-effective option. Additional analyses on the basis of data from the Hospital Episode Statistics data set would allow corroborating the findings of this study. Further research into the use of ZA (and other bone-targeting therapies) with newer prostate cancer therapies would be desirable.. Current Controlled Trials ISRCTN12808747.. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 53. See the NIHR Journals Library website for further project information.

Topics: Aged; Antineoplastic Agents; Bone Density Conservation Agents; Bone Neoplasms; Cost-Benefit Analysis; Diphosphonates; Disease-Free Survival; Docetaxel; Humans; Imidazoles; Male; Middle Aged; Prednisolone; Prostatic Neoplasms, Castration-Resistant; Quality of Life; Quality-Adjusted Life Years; Strontium Radioisotopes; Taxoids; Zoledronic Acid

Radiopharmaceutical use may improve the survival time of patients with castrate-resistant prostate cancer and bone metastases. Whether androgen-deprivation therapy (ADT) combined with bone-targeted therapy provides a clinical benefit to patients with advanced castrate-sensitive prostate cancer has not been investigated.. Eighty male patients were enrolled, and 79 were randomized: 40 to the control arm and 39 to the strontium-89 (Sr-89) arm. After randomization, patients in both study arms received ADT, doxorubicin, and zoledronic acid. Kaplan-Meier methodology was used to evaluate the progression-free survival (PFS) time. Multivariate Cox proportional hazards regression was used to evaluate the effects of Sr-89 after controlling for the number of bone metastases.. The median follow-up time for the 29 patients alive at the last follow-up was 76.9 months (range, 0.07-103.4 months). The median PFS time was 18.5 months (95% confidence interval, 9.7-49.4 months) for the control arm and 12.9 months (95% confidence interval, 8.9-72.5 months) for the Sr-89 arm (P = .86). No patient developed myelodysplastic syndrome or a hematologic malignancy. An unplanned subgroup analysis suggested increased efficacy of bone-targeted therapy with a greater extent of bone involvement (ie, >6 bone metastases vs ≤6 bone metastases on the bone scan).. The data showed that bone-targeted therapy using 1 dose of Sr-89 combined with chemohormonal ablation therapy did not favorably affect the PFS of patients with castrate-sensitive prostate cancer. The combined therapy was feasible and safe. Whether such bone-targeted therapy provides a favorable outcome for those patients with a greater tumor burden in the bone warrants further investigation.

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Combined Modality Therapy; Diphosphonates; Doxorubicin; Humans; Imidazoles; Male; Prostatic Neoplasms; Strontium Radioisotopes; Survival Analysis; Treatment Outcome; Zoledronic Acid

To evaluate the efficacy of radionuclide palliative therapy (RPT) in women suffering from painful metastatic bone disease (MBD) due to breast cancer (BrCa), and to investigate the possible relationship between the RPT efficacy and cytokines levels.. Sixty-three BrCa women patients with MBD enrolled in a prospective, nonrandomized study. Thirty were treated with Rhenium-186-hydroxyethylidenediphosphonic acid ((186)Re-HEDP), 21 with Strontium-89-Chloride ((89)Sr-Cl2), and 12 with Samarium-153-thylenediaminetetramethylenephosphonic acid ((153)Sm-EDTMP). Blood samples were collected pre- and post-therapy to assess the interleukin (IL)-2, IL-6 and tumor necrosis factor (TNF)-a titers. The palliative effect of the treatment was evaluated using a modified Wisconsin test.. All three radiopharmaceuticals were equally effective in pain relief. Pain palliation was complete in 52% of patients, partial in 31%, and absent in 16%. Responders to therapy had higher IL-2 and lower IL-6/TNF-a concentrations, compared with nonresponders, even though statistically significant difference in cytokines levels between responders and nonresponders before treatment was noted only for IL-6.. All used radiopharmaceuticals had the same therapeutic effect. Pretherapy low titers of IL-6 levels seems to have a favorable prognostic value for the therapeutic outcome, while IL-2 and TNF-a alterations pre- and post-therapy can only serve as markers of a better RPT response.

Topics: Aged; Bone Neoplasms; Breast Neoplasms; Cytokines; Female; Humans; Interleukin-6; Middle Aged; Organometallic Compounds; Organophosphorus Compounds; Pain, Intractable; Palliative Care; Prognosis; Prospective Studies; Radiopharmaceuticals; Rhenium; Strontium Radioisotopes

Approximately 80% of patients with prostate cancer will develop bone metastases, which often lead to bone pain and skeletal-related events. Sr-89 is an established alternative for the palliation of bone pain in prostate cancer. We aimed to assess the effect of Sr-89 radionuclide therapy on quality of life (QOL) in prostate cancer patients with painful bone metastases.. Thirteen patients received a single intravenous injection of Sr-89 at a dose of 2.0 MBq/kg. All patients underwent QOL evaluation prior to Sr-89 treatment and 1, 2, and 3 months afterward using the Japanese version of the EORTC QLQ-BM22, EORTC QLQ-C30, a VAS, and face scale. We also evaluated PSA and ALP response and toxicity of the Sr-89 therapy.. The pain characteristics subscale of the EORTC QLQ-BM22 was significantly reduced from 1 month onward compared with the baseline. The functional interference and psychosocial aspects subscales were significantly higher than baseline from 2 months onward. At 2 months, VAS indicated a significant reduction in pain as compared to the baseline. Sr-89 therapy caused a nonsignificant reduction in PSA and ALP levels. No patients had leukocyte toxicity, and one patient had grade 3 platelet toxicity.. Sr-89 radionuclide therapy can provide not only reduced pain characteristics but also better psychosocial aspects and functional interference in patients with painful bone metastases of prostate cancer.

Topics: Alkaline Phosphatase; Bone Neoplasms; Humans; Male; Pain; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Strontium Radioisotopes

The study was designed to compare the effectivnes of 89Sr-chlorid injections by 50 Mbk fractions with standard 150 Mbk injection in patients with bone metastases. Fifty patients with bone metastases were included in the study, 25 of them received 89Sr-chloride by fractional and 25 (control group) by single injection. The pain intensity, white blood cells and thrombocytes concentration values were evaluated in both groups before and after treatment. The study proved the possibility of using systemic 89Sr-chloride fractional radiotherapy in patients with bone metastases and concurrent stage 2-3 myelosupression. The method of fractial 89Sr-chloride injection is effective in symptomatic treatment of patients with bone metastases.

Topics: Aged; Aged, 80 and over; Bone Neoplasms; Dose Fractionation, Radiation; Female; Humans; Injections; Leukocyte Count; Middle Aged; Pain; Pain Measurement; Platelet Count; Strontium; Strontium Radioisotopes; Treatment Outcome

In this study, we investigated the clinical and laboratory factors that may enhance (89)Sr uptake to strengthen its tumoricidal effect.. We enrolled 21 patients with multiple bone metastases (n = 23) from breast cancer and classified them into 2 groups according to their zoledronic acid (ZOL) treatment history. (89)Sr imaging with bremsstrahlung was performed 2 to 6 weeks after administration and (89)Sr index was measured using combined imaging with bone scintigraphy. We compared the Sr index with the levels of alkaline phosphatase, bone-specific alkaline phosphatase, serum cross-linked N-telopeptides, carboxy-terminal telopeptide of type 1 collagen, C-reactive protein, calcium, and hemoglobin on administration and evaluated the differences among the groups.. The (89)Sr index ranged from 0.01 to 2.0 and was significantly correlated with C-reactive protein and alkaline phosphatase and moderately correlated with carboxy-terminal telopeptide of type 1 collagen, serum cross-linked N-telopeptides, and bone-specific alkaline phosphatase. The (89)Sr index was not significantly correlated with calcium or hemoglobin. The group with less than 1 year of ZOL treatment demonstrated a mean (SD) (89)Sr index of 1.11 (0.59), and the group with 1 or more years of ZOL treatment showed a mean (89)Sr index of 0.36 (0.26). The Wilcoxon signed-rank test demonstrated a significant difference between the 2 groups (P < 0.001).. (89)Sr accumulation seemed to be associated with bone turnover, in particular bone resorption, and vascularization due to inflammation or tumor growth. Long-term ZOL treatment may reduce bone resorption and vascularization. To enhance the tumoricidal effect and palliation of bone pain by (89)Sr, combined therapy must be established.

Topics: Adult; Aged; Biomarkers, Tumor; Bone Neoplasms; Breast Neoplasms; Diphosphonates; Electromagnetic Radiation; Female; Humans; Imidazoles; Middle Aged; Pain Management; Radionuclide Imaging; Strontium Radioisotopes; Zoledronic Acid

Bone-targeted therapy that combines strontium-89 (Sr-89) with alternating weekly chemohormonal therapy may improve clinical outcomes in patients with metastatic hormone-refractory prostate cancer. This phase II study investigated the addition of Sr-89 to an alternating weekly regimen of doxorubicin and ketoconazole with paclitaxel and estramustine in patients with progressive prostate cancer and bone involvement.. Twenty-nine patients with progressive adenocarcinoma of the prostate and osteoblastic bone metastases who failed conventional hormonal therapy were registered for the study. Of those, 27 were treated with Sr-89 on day 1 of week 1. On weeks 1, 3, and 5, patients received doxorubicin (20 mg/m on day 1) and oral ketoconazole (400 mg 3 times a day for 7 days). On weeks 2, 4, and 6, patients received paclitaxel (100 mg/m(2)) and oral estramustine (280 mg 3 times a day for 7 days). No treatment was given during weeks 7 and 8. Cycles were repeated every 8 weeks.. A > or =50% reduction in prostate-specific antigen level was maintained for at least 8 weeks in 77.7% of the patients (21 patients) at 16 weeks and in 66.6% (18 patients) at 32 weeks. The median progression-free survival was 11.27 months (range, 1.83-29.53), and the median overall survival was 22.67 months (1.83-57.73+). Two patients died during study because of disease progression. Overall, the chemotherapy combined with Sr-89 was well tolerated.. Our results demonstrate that the combination of alternating weekly chemohormonal therapies with Sr-89 demonstrates a prolonged progression-free and overall survival with acceptable toxicity. Further investigation of combination therapies with Sr-89 is warranted.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Combined Modality Therapy; Doxorubicin; Estramustine; Humans; Ketoconazole; Male; Middle Aged; Paclitaxel; Prostate-Specific Antigen; Prostatic Neoplasms; Strontium Radioisotopes; Survival Rate; Treatment Outcome

Painful bone metastases are most frequent in patients with advanced prostate or breast carcinoma. The aim of this study was to compare the analgesic effect of radionuclide therapy using Sr and Sm-EDTMP in patients with painful bone metastases of these tumours.. One hundred patients treated with radionuclide bone palliation therapy were analysed. The study population consisted of 60 male patients with advanced prostate carcinoma and 40 female patients with advanced breast carcinoma. Fifty patients (30 men and 20 women) were treated with Sr (150 MBq). The other 50 patients were treated with Sm-EDTMP (37 MBq x kg). The treatment efficacy was evaluated by a visual analogue scale (VAS), Karnofsky performance scale, and dosage of analgesic drugs used.. Complete pain relief was found in 40% of women and 40% of men treated using Sm-EDTMP and in 25% of women and 33% of men treated with Sr. No analgesic effect occurred in 20% of patients. A better analgesic effect was found in cases of osteoblastic metastases compared to mixed metastases. Statistically significant reduction of pain intensity, use of analgesic drugs and improvement of performance in Karnofsky scale was found in cases of both radionuclides.. The analgesic effects of Sr and Sm-EDTMP was similar in both prostate and breast carcinoma. However, the effect was dependent on the type of metastases; better response was observed in cases of osteoblastic metastases than in patients with mixed metastases. Severe adverse reactions after this therapy were rare.

Topics: Aged; Bone Neoplasms; Breast Neoplasms; Carcinoma; Female; Humans; Male; Middle Aged; Organometallic Compounds; Organophosphorus Compounds; Pain; Pain Measurement; Palliative Care; Prostatic Neoplasms; Radiopharmaceuticals; Strontium Radioisotopes; Treatment Outcome

We have used 89SrCl2 for the palliative treatment of painful bone metastases from various malignant diseases. We studied the correlation between serum interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) levels and the response to 89SrCl2 therapy.. Forty-two patients (24 men and 18 women) were treated intravenously with 89SrCl2 at a dose of 148 MBq (4 mCi).. The response rate was 33 of 42 (79%). In the control subjects, serum IL-2 concentrations were higher but TNF-alpha concentrations lower (P < 0.05) than in the patients with bone metastases. After treatment with 89SrCl2, IL-2 levels increased and TNF-alpha levels decreased, with maximal changes at the fourth month after therapy. After comparing the serum levels of IL-2 and TNF-alpha between responders and nonresponders, we found that these variables did not differ before 89SrCl2 therapy but differed significantly (P < 0.05) after therapy. Responders had higher IL-2 and lower TNF-alpha concentrations than nonresponders. A good correlation was found between IL-2 and TNF-alpha levels and the number of metastases and pain score.. 89SrCl2 is effective for palliation of bone pain in patients with disseminated bone metastases. In addition to managing pain, 89SrCl2 can improve immunity and the quality of life for most patients. Further studies are needed to elucidate the roles of IL-2 and TNF-alpha in the response to 89SrCl2 therapy and to evaluate their usefulness as indicators of 89SrCl2 efficacy.

Topics: Biomarkers, Tumor; Bone Neoplasms; Female; Humans; Interleukin-2; Male; Middle Aged; Neoplasm Proteins; Pain; Statistics as Topic; Strontium; Strontium Radioisotopes; Treatment Outcome; Tumor Necrosis Factor-alpha

To evaluate the therapeutic effects of Guliu capsule (GLC) combined with 89Sr in treating metastatic bone tumors.. On the basis of random sampling and grouping, 50 patients with metastatic bone tumors were selected to receive combined treatment with GLC and (89)Sr with another 50 patients recruited for (89)Sr treatment alone. The therapeutic effect of the therapies were evaluated according to the relief of ostalgia and quality-of life (QOF), local bone metabolism and hematopoietic function of the bone marrow.. The efficacy rate of GLC+89Sr and (89)Sr in relieving ostalgia was 94.0% and 76.0%, and the rate of QOF improvement and stabilization was 94.0% and 74.0%, respectively, both showing significant difference between the two groups (P<0.05). The effect of the two treatment protocols on local bone metabolism and their hemotoxicity were also significantly different (P<0.05, P<0.01, respectively).. Combined treatment with GLC and (89)Sr is effective for metastatic bone tumor and improves the patient's QOF with enhanced ostalgia relief rate and decreased hemotoxicity.

Topics: Adolescent; Adult; Aged; Bone Neoplasms; Capsules; Combined Modality Therapy; Drugs, Chinese Herbal; Female; Humans; Male; Middle Aged; Strontium Radioisotopes

To compare the clinical curative effects between 89Sr and its combination with the Guliu recipe (GLR, a Chinese herbal medicine) in treating multiple bone metastatic tumor of mammary cancer (MBM-MC).. By adopting the random sampling and grouping method, 89Sr alone (Sr) and 89Sr combined with CHM (Sr-GLR) were used in treating 86 and 40 patients with MBM-MC respectively. The efficacy of therapy were appraised according to the degree of ostalgia relieving and quality of life (QOF) in patients, and the effect of treatment on focal bone metabolism and bone marrow hematopoietic function were compared.. The effective rate of Sr and Sr-GLR in relieving ostalgia was 83.72% and 95.00%, respectively (P > 0.05), the QOF improving and stabilizing rate of them 80.23% and 95.00% (P < 0.05), the effective rate on focal bone metabolism 59.30% and 52.50% (P > 0.05) and their hemo-toxicity 28.00% and 30.00% (P > 0.05).. Sr-GLR is a combination therapy in treating MBM-MC with good effect, it could raise the patient's QOF, enhance the ostalgia relieving effect without increasing the hemo-toxicity of treatment.

Topics: Adult; Aged; Bone Neoplasms; Breast Neoplasms; Carcinoma, Ductal, Breast; Combined Modality Therapy; Drugs, Chinese Herbal; Female; Humans; Middle Aged; Phytotherapy; Quality of Life; Strontium Radioisotopes

The objectives of the current study were to determine the maximum tolerated dose and to evaluate the efficacy of gemcitabine given in combination with strontium-89 to patients with androgen independent prostate carcinoma.. Patients with androgen-independent prostate carcinoma and painful osteoblastic bone metastases were eligible. On a 12-week course, patients received gemcitabine (600 mg/m(2) or 800 mg/m(2)) on Days 1, 8, 15, 43, 50, and 57. A single dose of strontium-89 (55 microCi/kg) was administered on Day 8.. Fifteen patients were registered, and all were assessable for response and toxicity. Four patients were treated at Dose Level 1 (gemcitabine 600 mg/m(2)) without dose-limiting toxicity. Eleven patients received a total of 13 courses at Dose Level 2 (gemcitabine 800 mg/m(2)). Platelet nadirs of 25000-50000 platelets per microL were common at Dose Level 2, and 1 patient had Grade 4 thrombocytopenia that was dose-limiting. Granulocyte nadirs up to < 500 granulocytes per microL occurred in 4 patients at Dose Level 2 and were reversible. There were no responses, as measured by prostate specific antigen concentration, although 6 patients (40%) had stable disease.. The authors concluded that 800 mg/m(2) gemcitabine was the maximum tolerated dose for the combination. The study was terminated on the basis that an overall response rate > than 10% was unlikely. Further study at this dose level and schedule is not warranted. .

Topics: Aged; Bone Neoplasms; Carcinoma; Combined Modality Therapy; Deoxycytidine; Drug Administration Schedule; Gemcitabine; Humans; Injections, Intravenous; Male; Maximum Tolerated Dose; Middle Aged; Neoplasms, Hormone-Dependent; Prostate-Specific Antigen; Prostatic Neoplasms; Radiation-Sensitizing Agents; Strontium; Strontium Radioisotopes; Testosterone

To explore the efficacy of adjuvant (89)Sr applied with external beam radiotherapy (EBRT) to treat bone metastases.. Ninety-five patients were randomized to (89)Sr (Arm A) or saline (Arm B) on Day 1 of EBRT to demonstrate a reduction in 3-month physician-assessed subjective progression from 70% to 45%.. At 3 and 6 months, no difference between treatment arms was observed in the progression rate. At 3 months, the physician-assessed response rate for all patients was 25%, with 46% of the patients progressing. The pretreatment use of opiates was independently associated with short progression-free survival. On the basis of the quality-of-life assessments, pain relief occurred in 50% of patients and 32% experienced improvement in global quality of life, without impact from (89)Sr. Differences were observed between the physician evaluation of radiotherapy efficacy and the patient assessment. In Arm A, serum alkaline phosphatase, but not serum prostate-specific antigen, decreased during the first 3 months after treatment.. (89)Sr, adjuvant to ERBT, does not seem to reduce the number of patients with subjective progression at 3 months. Patients should be referred for palliative RT before their bone pain requires high doses of opiates. In radiotherapy trials, the evaluation of pain and pain relief remains problematic because of the confounding use of analgesics.

Topics: Aged; Aged, 80 and over; Bone Neoplasms; Double-Blind Method; Female; Humans; Male; Middle Aged; Palliative Care; Quality of Life; Strontium Radioisotopes

To compare toxicity, subjective response rate, time to subjective progression and overall survival in patients with painful bone metastases of hormone-resistant prostate cancer (HRPC) treated with a single intravenous injection of 150MBq (4mCi) Strontium(89) Chloride (S) or palliative local field radiotherapy (R) with the usual radiotherapy regimen used at each centre. The costs of both treatments were also assessed.. 101 patients were randomized to S and 102 to R. Time to event endpoints were compared with the Logrank test and Kaplan-Meier curves, in the intent-to-treat population (2-sided alpha=0.05).. Baseline characteristics of both groups were comparable. There was a borderline statistically significant difference in overall survival in favour of the local field radiotherapy (R: 11 months; S: 7.2 months; p=0.0457). There was no difference in progression-free survival or time to progression. Subjective response was seen in 34.7% in the S-arm and in 33.3% in the R-arm. A biochemical response was observed in 10% and 13% of the R- and S-groups, respectively. There was no difference in treatment toxicity between the two groups.. In symptomatic HRPC, pain treatment with local field radiotherapy is associated with a better overall survival compared to Strontium(89). The lower costs of local field radiotherapy also favour the use of this treatment in patients with HRPC. The reason for the apparent survival benefit of localised radiation treatment is not clear.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Bone Neoplasms; Chi-Square Distribution; Disease Progression; Humans; Injections, Intravenous; Male; Middle Aged; Pain Measurement; Prostatic Neoplasms; Statistics, Nonparametric; Strontium Radioisotopes; Survival Rate; Treatment Outcome

This study evaluated the effects of low-dose cisplatin plus 89Sr versus 89Sr alone in the treatment of painful bone metastases from prostate cancer, addressing both pain palliation and cytostatic effects.. Seventy patients with metastatic hormone-refractory prostate cancer were randomized into 2 groups: One group (arm A) received 148 MBq 89Sr plus 50 mg/m(2) cisplatin, and the other group (arm B) received 148 MBq 89Sr plus placebo. After treatment, the patients were followed up until death to evaluate the outcome variables: grade and duration of pain palliation, onset of new painful sites, changes in bone disease, global survival, serum prostate-specific antigen and alkaline phosphatase changes, and hematologic toxicity.. Overall pain relief occurred in 91% of patients in arm A and 63% of patients in arm B (P < 0.01), with a median duration of 120 d in arm A and 60 d in arm B (P = 0.002). New painful sites on previously asymptomatic bone metastases appeared in 14% of patients in arm A and in 30% of patients in arm B (P = 0.18). The median survival without new painful sites was 4 mo in arm A and 2 mo in arm B (P = 0.04). Bone disease progression was observed in 27% of patients in arm A and in 64% of patients in arm B (P = 0.01). Median global survival after therapy was 9 mo in arm A and 6 mo in arm B (P = 0.30). Transient and moderate hematologic toxicity, as determined by World Health Organization criteria, was apparent in both arms without significant differences.. The addition of a low dose of cisplatin enhances the effect of a standard dose of 89Sr without significant side effects, producing a significant improvement in pain palliation and a cytostatic effect on bone disease.

Topics: Aged; Antineoplastic Agents; Bone Neoplasms; Cisplatin; Combined Modality Therapy; Humans; Male; Palliative Care; Prospective Studies; Prostatic Neoplasms; Strontium Radioisotopes; Survival Rate

93 patients with hormone refractory metastatic prostate cancer were entered on a prospective study to measure reduction in pain and changes in quality of life (QoL) after the administration of 150 MegaBequerel (MBq) Strontium-89 (Sr-89). QoL was assessed using a validated instrument, the Functional Living Index - Cancer (FLIC) questionnaire. Pain response was measured using the Radiation Therapy Oncology Group scoring system. Overall there was limited QoL improvement over 3 months following Sr-89. However, in the 53 patients (63%) achieving pain responses, QoL did significantly improve within 6 weeks of receiving Sr-89 compared to patients with stable or worsening bone pain, and this was independent of other parameters that might influence QoL outcomes, such as performance status, baseline PSA and extent of skeletal disease (P = 0.004). PSA 'response' occurred in 30 patients (37%) over 4 months after Sr-89. This did not appear to correlate with clinical improvement. This study supports the presumption that improvement in pain following Sr-89 is accompanied by better QoL. The lack of correlation of PSA response and clinical parameters indicates that in the palliative setting, PSA may not provide a useful surrogate for treatment outcome.

Topics: Bone Neoplasms; Diarrhea; Follow-Up Studies; Hematologic Diseases; Humans; Male; Nausea; Neoplasm Metastasis; Pain; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Spinal Cord Compression; Strontium; Strontium Radioisotopes; Surveys and Questionnaires; Treatment Outcome; Vomiting

Prostate carcinoma is linked to osteoblastic metastasis. We therefore investigated the value of bone-targeted consolidation therapy in selected patients with advanced androgen-independent carcinoma of the prostate.. 103 patients received induction chemotherapy, consisting of ketoconazole and doxorubicin alternating with estramustine and vinblastine. After two or three cycles of induction chemotherapy, we randomly assigned 72 patients who were clinically stable or responders to receive doxorubicin with or without strontium-89 (Sr-89) every week for 6 weeks.. Overall 62 of the 103 (60%, 95% CI 50-70) patients had a 50% or greater reduction in serum prostate-specific antigen concentration that was maintained for at least 8 weeks, and 43 (42%, 32-52) had an 80% or greater reduction. 49 (52%) patients with bone pain at registration had complete resolution of pain. After follow-up of 67 patients until death, the estimated median survival for all 103 patients was 17.5 months (range 0.5-37.7). For the 36 patients randomly assigned to receive Sr-89 and doxorubicin, the median survival time was 27.7 months (4.9-37.7), and for the 36 who received doxorubicin alone it was 16.8 months (4.4-34.2) (p=0.0014). The hazard ratio was 2.76 (95% CI 1.44-5.29).. Bone-targeted consolidation therapy consisting of one dose of Sr-89 plus doxorubicin once a week for 6 weeks, when given to patients with stable or responding advanced androgen-independent carcinoma of the prostate after induction chemotherapy, improved overall survival.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Bone Neoplasms; Carcinoma; Doxorubicin; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Strontium Radioisotopes; Survival Analysis; Texas

The study evaluates the therapeutic efficacy of Strontium-89-chloride (89Sr) and 186Re-1,1-hydroxyethylidene diphosphonate (186Re-HEDP) in the palliation of painful bone metastases from breast cancer.. Fifty patients with painful multifocal bone metastases from breast cancer entered the study and were randomized into two groups according to the radiopharmaceutical used: 148 MBq 89Sr i.v. (Group A: 25 patients) and 1406 MBq 186Re-HEDP i.v. (Group B: 25 patients). Pain palliation was evaluated on the basis of the Wisconsin pain test improvement at two months and response was graded as complete, partial, minimal or absent. Hematological toxicity and side effects were reported according to WHO guidelines.. The global response rate was 84% (21/25) for 89Sr and 92% (23/25) for 186Re-HEDP, respectively. The onset of pain palliation appeared significantly earlier in Group B (p < 0.0001). The duration of pain relief ranged from two months to 14 months (mean of 125 days with a median value of 120 days) in Group A and from one month to 12 months (mean of 107 days with a median value of 60 days) in Group B (p = 0.39). A moderate hematological toxicity was apparent in both groups. Platelet and white blood cell counts returned to baseline levels within 12 weeks after 89Sr administration and 6 weeks after 186Re-HEDP administration (p < 0.01).. Both 89Sr and 186Re-HEDP are effective and safe in bone pain palliation in breast cancer with the latter showing a significantly faster onset of pain relief.

Topics: Adult; Aged; Bone Neoplasms; Breast Neoplasms; Disease-Free Survival; Etidronic Acid; Female; Humans; Infusions, Intravenous; Karnofsky Performance Status; Middle Aged; Organometallic Compounds; Pain Measurement; Pain, Intractable; Palliative Care; Radionuclide Imaging; Radiopharmaceuticals; Rhenium; Strontium Radioisotopes; Treatment Outcome

It has been affirmed that observational studies give analogous results to randomised controlled ones.. A multicentre observational trial was conducted between 1996-1998 in order to evaluate the efficacy of palliative radionuclide therapy for bone metastases in a large number of patients. An evaluation was made on 510 patients with prostate cancer and painful bone metastases, treated with a single iv. dose of 89Sr-chloride (527 treatments) or 186Re-HEDP (83 treatments), in 29 Italian Nuclear Medicine Departments. Eighty-one patients received up to five injections, totalling 100 retreatments. Patients were followed up for a period of 3 months-2 years. Results were expressed at four levels of response: excellent, good, mild, and nil.. Responses were excellent in 26.4%, good in 33.3%, mild in 21.3% and nil in 19% of all treatments, while good and excellent responses were obtained in 48% of retreatments. No statistically significant correlations were found between response and age of patients, skeletal extension of tumour, pretherapeutic PSA levels, evidence of non-bony metastases, previous chemotherapy and/or external-beam radiotherapy; osteolytic lesions responded worse than osteoblastic or mixed ones. Hematological toxicity (mild to moderate), mainly affecting platelets, was observed in 25.5% of all treatments and in 38.9% of retreatments. No clear differences were found between the two radiopharmaceuticals employed.. Bearing in mind that observational studies can provide just as accurate results as randomised controlled trials, this study confirms the main findings of various limited monocentre trials.

Topics: Bone Neoplasms; Etidronic Acid; Humans; Male; Organometallic Compounds; Pain, Intractable; Palliative Care; Prostatic Neoplasms; Radiopharmaceuticals; Rhenium; Strontium; Strontium Radioisotopes; Tin Radioisotopes

Most studies of prostate cancer have shown that strontium-89 chloride (89Sr) is effective in the palliation of metastatic bone pain, refractory to conventional analgesia. The aim of this study was to evaluate the usefulness of 89Sr for bone pain palliation in breast cancer patients. Forty women were treated with 148 MBq of 89Sr. Six patients were retreated, receiving two or more doses. The Karnofsky performance status was assessed and pain and analgesia were scored on scales of 9 and 5 points, respectively. The efficacy of 89Sr was evaluated at 3 months of treatment. The response was good in 60% of the patients and partial in 32%; there was no response in the remaining 8% (pre-treatment Karnofsky < or = 60). The duration of the response was 120+/-143 days. In the patients retreated, the response was good in 83% and partial in 17%, without significant differences compared with the first dose, but the pre-treatment Karnofsky and the duration of the efficacy were lower (P < 0.05). A transient and slight decrease of leukocyte and platelet counts after the first month of treatment with 59Sr was observed. In conclusion, breast cancer patients with metastatic bone pain can benefit from therapy with 89Sr. If necessary, the treatment may be repeated safely and with the same efficacy as is achieved after the first dose. A low functional performance status could be a cause of the lower effectiveness of 89Sr.

Topics: Aged; Bone Neoplasms; Breast Neoplasms; Female; Humans; Leukocyte Count; Middle Aged; Pain Measurement; Pain, Intractable; Strontium Radioisotopes

Several radiopharmaceuticals were compared previously with regard to the efficiency in pain palliation of bone metastases. Furthermore, first results were reported on the suitability for such kind of therapy of the generator produced radionuclide rhenium-188.. Influence of Rhenium-188-HEDP (Re-188), Rhenium-186-HEDP (Re-186) and Strontium-89 (Sr-89) on pain symptoms and bone marrow function were obtained in 44 patients (pts). These were 16 pts. with Re-188 (2943 +/- 609 MBq), 13 pts. with Re-186 (1341 +/- 161 MBq) and 15 pts. with Sr-89 (152 +/- 18 MBq) (6 woman with breast cancer and 38 men with prostata cancer).. 81 of pts. after Re-188, 77% after Re-186 and 80% after Sr-89 reported relief of pain. The Karnofsky-Index established by pts. increased from 74 +/- 9% to 85 +/- 11% after Re-188, from 70 +/- 11% to 76 +/- 11% after Re-186 and from 62 +/- 10% to 69 +/- 10% after Sr-89. However, the difference between the pre- and the post-therapeutic value is only statistically significant in the case of Re-188 therapy (p = 0.001). A decrease of platelets of 30 +/- 14% after 2.8 +/- 0.7 for pts. treated with Re-188, of 39 +/- 20% after 3.7 +/- 1.0 weeks for pts. treated with Re-186 and of 34 +/- 26% after 4.4 +/- 1.0 weeks for pts. treated with Sr-89 compared to the value before therapy was observed. The difference was not significant between the 3 groups of pts. (p = 0.125 to 0.862).. All tried radiopharmaceuticals were effective in pain palliation. The various radionuclides had no significant difference in the pain relief or the bone marrow impairment. If only the Karnofsky-Index after Re-188 HEDP seems to be a little more increase.

Topics: Bone Neoplasms; Breast Neoplasms; Etidronic Acid; Female; Humans; Leukocyte Count; Male; Middle Aged; Organometallic Compounds; Pain; Palliative Care; Platelet Count; Prostatic Neoplasms; Radioisotopes; Rhenium; Strontium Radioisotopes; Tomography, X-Ray Computed

A review was performed of all patients who received strontium-89 chloride or samarium-153 ethylenediamine-tetramethylenephosphonate for prostate cancer metastatic to bone at the Royal Brisbane Hospital between 1992 and 1997. There were 57 patients, 38 treated with strontium-89 and 19 with samarium-153. Forty patients had radionuclide therapy alone, and 28/40 (or 70%) responded in terms of experiencing a beneficial effect on pain. In the other 17 patients, the effect of the radionuclide on pain could not be assessed because they received external beam radiotherapy concomitant with a therapeutic radionuclide. There was no difference in response rates between the samarium and strontium groups as measured by the effect on pain or in the time to progression. The median time to progression for all patients was 2-3 months. The present study confirms that following administration of a therapeutic radionuclide, a high proportion of patients experienced improvement of pain, but the time to progression is not long, so that the overall degree of benefit is modest.

Topics: Aged; Aged, 80 and over; Bone Neoplasms; Humans; Male; Middle Aged; Prostatic Neoplasms; Radioisotopes; Retrospective Studies; Samarium; Strontium; Strontium Radioisotopes

One hundred and eighteen patients with painful skeletal metastases of malignant diseases (predominantly prostate, breast and lung cancer) were treated with 150 MBq of strontium-89 chloride (Metastron, Amersham, UK) intravenously. The results were evaluated according to a score considering pain relief, mobility, analgesic intake and general feeling. In only five patients (4.2%) was no improvement observed; mild improvement was noted in 48 (40.7%), and substantial or complete improvement in 56 (47.5%) and 9 (7.6%), respectively. The mean painless period after a single 89SrCl dose was 3.3 +/- 2.28 months (in patients with prostate, lung, breast and other types of cancer it was 3.65 +/- 2.11, 3.29 +/- 1.27, 3.08 +/- 0.48 and 3.44 +/- 1.36 months, respectively). During a 3-year study, 89SrCl treatment was successively repeated up to 5 times in some patients (total number of Metastron applications was 256) who benefited from the first Metastron administration and did not show signs of myelosuppression. Even after repeated treatment, relief was consistent and the duration of the period without pain increased (in particular in patients with breast cancer, in whom the period of relief was prolonged from 3.08 +/- 0.48 months after the first dose to 5.33 +/- 2.36 months after the fifth 89SrCl administration). The increased painless period was not observed after repeated treatment in the patient group comprising miscellaneous types of cancer, and the degree of improvement was less apparent. During the course of successive 89SrCl treatments, transient signs of myelosuppression indicated by a decrease in white cell and thrombocyte counts of at least 25% were observed 10 times after Metastron administration (twice in two patients), i.e. in 3.9% of all 89SrCl administrations; these transient haematological changes of moderate grade were closely connected with Metastron administration. Palliative treatment of metastatic skeletal pain with 89SrCl improves the quality of life in most patients suffering from prostate, lung and breast cancer and may be safely repeated with the same benefit and without significant myelosuppression. The beneficial effect of 89SrCl treatment seems to be less pronounced in other types of cancer with painful skeletal metastases.

Topics: Adult; Aged; Aged, 80 and over; Bone Neoplasms; Female; Humans; Leukocyte Count; Male; Middle Aged; Pain, Intractable; Palliative Care; Platelet Count; Strontium Radioisotopes; Treatment Outcome

The clinical management of skeletal metastatic disease is problematic because of the difficulty in treating and accurately monitoring therapy impact and disease progression. This investigation measured serum procollagen type I C-terminal peptide (PICP) concentrations as a semi-quantitative index of bone turnover in patients with metastatic prostatic adenocarcinoma before and following palliative 89Sr chloride therapy. 10 patients with early stage (stage A2, B1 and B2) biopsy-confirmed prostatic adenocarcinoma were investigated (n = 10). Two groups of 10 patients each (n = 10 per group) with advanced (stage D) metastatic prostatic adenocarcinoma who had previously undergone hormonal manipulation were also investigated. One group of patients with scintigraphically documented metastatic bone disease received additional irradiation for new symptomatic bone metastases, whereas the other group received 89Sr chloride therapy. A radioimmunoassay for PICP was used to measure serum concentrations of patients in each of these groups as well as positive and negative controls. The concentration of serum PICP rose from 649 +/- 279 before treatment with external beam radiotherapy to 927 +/- 157 ng ml-1 4 months after therapy (p < 0.05). However, the results demonstrated a four-fold decrease (p < 0.001) in serum PICP in clinical responders to 89Sr chloride therapy versus baseline 4 months after the completion of treatment. The clinical non-responders demonstrated no significant change in PICP concentrations during that interval. This may be due to an increase in untreated bony metastases in the non-89Sr treated group. Although a relatively small representative group of patients was studied, these data demonstrate that serum PICP concentration correlates with clinical response to 89Sr chloride therapy. This objective laboratory technique may be useful for monitoring and predicting the need for 89Sr chloride therapy and optimizing palliative care. It may also be extremely useful in predicting a therapeutic response to such intervention.

Topics: Adenocarcinoma; Aged; Analgesics, Opioid; Biomarkers, Tumor; Bone Neoplasms; Drug Administration Schedule; Humans; Male; Middle Aged; Morphine; Palliative Care; Peptide Fragments; Procollagen; Prostatic Neoplasms; Strontium Radioisotopes; Treatment Outcome

In a prospective randomized Canadian trial, addition of radionuclide strontium (89Sr) to external radiotherapy (ER) was found to prolong the time to further ER by 15 weeks (35 versus 20, P = 0.006) compared to ER alone in patients with hormone-refractory metastatic prostate cancer (HRMPC). The total direct lifetime costs within the Swedish health care system for the following two treatment strategies was estimated as follows: (a) ER initially and in the event of relapse and (b) ER + 89Sr initially and ER in the event of relapse.. Calculation of lifetime costs was based on the initial total treatment cost and the probability of future treatment costs. In a retrospective analysis, the average cost of a relapse treated with ER alone was calculated from the actual care consumption of 79 consecutive patients from the south of Sweden who received ER because of skeletal pain due to HRMPC. The costs related to ER included skeletal scintigraphy, ER, outpatient visits, inpatients days, and travel to the treatment center. When 89Sr was added, the cost also included the radionuclide and its administration. Costs in Swedish currency (SEK) were based on the regional tariff for 1993 (U.S. $1 = SEK 8.30).. The initial cost for one relapse treated with ER alone was estimated to be SEK 31,011 (U.S. $3736) per patient resident within county (close to hospital) and SEK 48,585 (U.S. $5854) per patient resident out of county (far from hospital). The corresponding figure for initial addition of 89Sr to ER was SEK 43,426 (U.S. $5232) and 61,000 (U.S. $7349), respectively. However, comparison between estimated lifetime cost for the two treatment strategies indicated potential cost savings with initial addition of 89Sr to 3% SEK 2720 (U.S. $328) and 7% SEK 11,290 (U.S. $1360), respectively.. Strontium-89 as initial supplement to ER for palliation of pain in HRMPC is beneficial both from the patient and lifetime health service costs perspectives.

Topics: Bone Neoplasms; Cost of Illness; Costs and Cost Analysis; Humans; Male; Neoplasm Recurrence, Local; Pain; Prostatic Neoplasms; Strontium Radioisotopes

Strontium-89 (89Sr) is currently used for the treatment of painful bone metastases. This study reports the use of low-dose carboplatin as a radiosensitizer in 89Sr radioisotope therapy. The study design comprised two groups: 15 patients treated with 89Sr (148 MBq) followed by carboplatin (100 mg m-2 at 7 and 21 days) and 15 patients treated with 89Sr alone. Their pain response was assessed 8 weeks post-injection. Follow-up was continued for up to 1 year in the survivors. Twenty-seven patients were evaluable. A pain response was observed in 20 of 27 (74%) patients. The pain response in the patients treated with 89Sr and carboplatin was clearly superior to that seen in the patients treated with 89Sr alone (P = 0.025), whereas survival was only marginally better in the combined treatment group (8.1 vs 5.7 months, P = 0.19). No clinically significant adverse effects or myelosuppression by carboplatin were observed. Low-dose carboplatin enhances the effects of 89Sr radioisotope therapy on pain from bone metastases.

Topics: Adult; Aged; Bone Neoplasms; Breast Neoplasms; Carboplatin; Combined Modality Therapy; Female; Humans; Male; Middle Aged; Pain; Palliative Care; Prostatic Neoplasms; Radiation-Sensitizing Agents; Strontium Radioisotopes

From 1988 to 1991, 284 patients with prostatic cancer and painful bone metastases were treated with either radiotherapy or strontium-89 (200 MBq). Patients were first stratified according to suitability for local or hemibody radiotherapy, then randomly allocated that form of treatment or strontium-89 (i.v. injection). After 4, 8 and 12 weeks pain sites were mapped, toxicity monitored, and all additional palliative treatments recorded. There was no significant difference in median survival (after > 80% had died); 33 weeks following strontium-89 and 28 weeks following radiotherapy (p = 0.1). All treatments provided effective pain relief; improvement was sustained to 3 months in 63.6% after hemibody radiotherapy compared with 66.1% after strontium-89, and in 61% after local radiotherapy compared with 65.9% in the comparable strontium-89 group. Fewer patients reported new pain sites after strontium-89 than after local or hemibody radiotherapy (p < 0.05). Radiotherapy to a new site was required by 12 patients in the local radiotherapy group compared with 2 after strontium-89 (p < 0.01), although there was no significant difference between hemibody radiotherapy (6 patients) and strontium-89 (9 patients) in this respect. Platelets and leukocytes fell by an average 30-40% after strontium-89 but sequelae were uncommon, and other symptoms rare.

Topics: Aged; Bone Neoplasms; Humans; Male; Palliative Care; Prostatic Neoplasms; Radiotherapy; Radiotherapy Dosage; Strontium Radioisotopes; Survival Analysis; Time Factors

A retrospective study was performed on the cost-effectiveness of treatment for advanced prostate cancer metastatic to bone. Patients (n = 29) recruited into the trans Canada trial at the Cross Cancer Institute, Edmonton and randomized to treatment with Metastron (strontium-89 chloride) (n = 14) or placebo (n = 15) after local field irradiation therapy for pain palliation were studied over their entire survival time. Estimates were made of the direct costs of treatment, i.e. drugs (analgesics and hormonal agents) and external radiotherapy, and the indirect costs (investigations, outpatient visits and inpatient days, either total or for tertiary care) based on records from the referring hospital, the cancer clinic and any hospitals to which the patients may subsequently have been referred. Meaningful differences were apparent between the two groups in direct costs with the group receiving Metastron showing a reduction over the entire survival time of Can$ 1,720/person compared with placebo; it should be noted that in this analysis neither the costs of the Metastron, nor of the initial radiotherapy, have been included. The Metastron group also showed a reduction in costs of hospitalization for tertiary care of Can$ 5,696/person, though the total cost of hospitalization was similar in the two groups. These results suggest that treatment with Metastron can bring about reductions in management costs for patients with advanced prostate cancer and, coupled with the findings of the Trans Canada trial on the improvement in quality of life for patients given Metastron, they add financial support to the clinical rationale for the use of Metastron for the palliative treatment of patients with bone metastases resulting from prostate cancer.

Topics: Aged; Antineoplastic Agents; Bone Neoplasms; Cost-Benefit Analysis; Hospital Costs; Humans; Male; Palliative Care; Prostatic Neoplasms; Retrospective Studies; Strontium; Strontium Radioisotopes

Radiation therapy plays a major role in the management of patients with either locally recurrent or metastatic carcinoma of the prostate.. In 23 patients with isolated postprostatectomy local recurrences treated with doses of 60-65 Gy, 17 (74%) had tumor control, and 45% survived relapse-free for 5 years after treatment of the recurrence. Pelvic irradiation has been used to treat patients with elevated prostate-specific antigen (PSA) levels after radical prostatectomy. This was tried, and 17 of 24 patients (70%) showed a significant decrease in PSA levels after irradiation, in five without subsequent elevation. Two of the seven patients with elevated PSA levels later had distant metastases. Local irradiation has been reported to yield excellent relief of symptoms in 100% of patients with hematuria, 80% with urinary outflow obstruction, and 50-70% with ureteral obstruction or pelvic pain secondary to locally advanced prostatic carcinoma. Reirradiation, particularly with brachytherapy (in preliminary studies combined with hyperthermia) has been used in the management of postirradiation prostatic recurrences with satisfactory tumor regression in approximately 75% of patients. The Radiation Therapy Oncology Group (RTOG) reported on the palliative effects of external irradiation on patients with bony metastasis. Approximately 54% of such patients had complete relief, and 29% had partial relief of bone pain. However, the retreatment rate of the bony metastasis was lower in the patients receiving higher doses. In a RTOG protocol in which all patients received local irradiation for osseous metastases, 77 were randomized to receive elective hemibody irradiation and 69, local treatment only. The frequency of additional treatment at 1 year was lower in the hemibody irradiation group (54% versus 78%). Occasionally, brain, mediastinal, or liver metastasis can be treated with irradiation. Radioactive phosphorus-32 or strontium-89 has been administered for disseminated bony metastasis with improvement of bone pain in approximately 70-80% of treated patients.. The role of irradiation in the treatment of spinal cord compression is discussed. Significant improvement of neurologic function has been reported in 36-60% of the patients, depending on severity of deficit and promptness in instituting emergency treatment.

Topics: Bone Neoplasms; Brachytherapy; Brain Neoplasms; Humans; Liver Neoplasms; Male; Neoplasm Recurrence, Local; Phosphorus Radioisotopes; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radioisotopes; Radiotherapy Dosage; Rhenium; Spinal Cord Compression; Strontium Radioisotopes

Topics: Bone Neoplasms; Humans; Male; Palliative Care; Prostatic Neoplasms; Radiotherapy; Strontium Radioisotopes; Survival Analysis

In a multicenter, randomized controlled trial involving 126 patients with endocrine-resistant advanced prostate cancer, all of whom received external beam radiotherapy, additional treatment with a single injected dose of 400 MBq strontium-89 (Metastron) significantly improved overall pain control. Adjuvant therapy with strontium-89 also significantly reduced analgesia requirements compared with placebo and delayed disease progression, as indicated by the requirement for further external beam radiotherapy. On certain measures, patients receiving strontium-89 also showed enhanced quality of life. Accompanying these changes, levels of prostate tumor markers were significantly reduced by strontium-89 treatment. The benefits resulting from adjuvant strontium therapy were associated with tolerable hematologic toxicity. The addition of strontium-89 to external beam radiation had no effect on survival. However, it has clear implications for improved palliation in advanced prostate cancer and may also impact positively on treatment costs.

Topics: Aged; Bone Neoplasms; Humans; Male; Palliative Care; Prostatic Neoplasms; Radiotherapy; Strontium Radioisotopes; Survival Analysis

A large proportion of the practice of radiotherapy in the management of metastatic adenocarcinoma of the prostate is associated with palliation of pain from osseous metastases and improving quality of life. Radiation therapy is well known to be effective in treating painful sites and may also be effective in reducing the propensity for adjuvantly treated disease to become symptomatic. Strontium-89 is a systemic radionuclide that has clinical efficacy in the palliation of pain from bony metastases.. The study was a Phase-III randomized placebo control trial performed in eight Canadian Cancer Centers to evaluate the effectiveness of strontium-89 as an adjunct to local field radiotherapy. Patients with endocrine refractory metastatic prostate cancer received local field radiotherapy and either strontium-89 as a single injection of 10.8 mCi or placebo.. One hundred twenty-six patients were recruited. No significant differences in survival or in relief of pain at the index site where noted. Intake of analgesics over time demonstrated a significant reduction in the arm treated with strontium-89. Progression of pain as measured by sites of new pain or the requirement for radiotherapy showed statistically significant differences between the arms in favor of strontium-89. Tumor makers including prostate specific antigen, acid phosphatase, and alkaline phosphatase were also reduced in patients receiving strontium-89. A Quality-of-Life analysis was performed as a multivariate data set and demonstrated an overall superiority of strontium-89 with alleviation of pain and improvement in physical activity being statistically significant. Toxicity was evaluated and demonstrated increased hematological toxicity in the group receiving strontium-89.. It is concluded that the addition of strontium-89 is an effective adjuvant therapy to local field radiotherapy reducing progression of disease as evidenced by new sites of pain and the requirement of further radiotherapy and improving quality-of-life and need for analgesic support in this group of patients.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Bone Neoplasms; Humans; Male; Middle Aged; Prostatic Neoplasms; Quality of Life; Strontium Radioisotopes; Survival Rate

Bone metastases are a major problem in the clinical management of patients with breast or prostate cancer. Severe bone pain can be a particularly debilitating effect of metastatic disease, resulting in a growing dependency on opioid analgesics and a reduced quality of life in patients who have a short time to survive. The radiopharmaceutical strontium-89 has been demonstrated to be generally well tolerated as well as effective in reducing metastatic bone pain in breast or prostate cancer patients. Unlike other radioisotopes or external radiation treatments, it represents systemic, targeted therapy that is simple and fast to administer in an outpatient setting. Data accumulated over the last 15 years demonstrates that 89Sr provides pain relief in up to 80% of patients with bony metastases arising from breast or prostatic malignancies. Pain palliation is maintained for several months, along with improvements in functional status and quality of life. As many as one fifth of 89Sr-treated patients become pain free and require no further pain medication. The adverse effects of intravenous 89Sr are minimal. Bone marrow toxicity is observed in many patients, resulting in some reduction of platelet and white blood cell counts. Despite reductions of 20% to 30%, these hematologic effects are generally reversible and the majority of patients maintain platelet counts that are within normal limits. Strontium-89 is effective systemic radioisotopic therapy for the palliation of painful bony metastases from breast and prostate carcinoma.

Topics: Bone Neoplasms; Breast Neoplasms; Humans; Male; Prostatic Neoplasms; Strontium Radioisotopes

Since 1976 200 patients with multiple skeletal metastases from prostatic cancer were treated with 89Sr. In the present study the results were evaluated in order to confirm the efficacy of this therapy. Following the application of 3 injections each of 0 (n = 21), 37 (n = 65), 75 (n = 72), 100 (n = 25) or 150 (n = 17) MBq 89Sr subjective pain relief, scintigraphic follow-up observations, survival times and haematological complications were recorded. In comparison to the results of placebo administration the effects of 89Sr on pain were: in the placebo group deterioration 11%, no change 55%, improvement 17% and full pain relief 17% whereas in the Sr groups combined the corresponding figures were 3, 38, 26 and 33%. Pain relief correlated with the activity administered. A dose relationship to scintigraphic regression is probable, the latter correlating with pain relief. Due to a decrease of early deaths the survival rate increased during the first months after start of treatment but later on returned to the level observed in untreated patients. Pain relief and regressive scintigraphic findings were combined with increased marrow involvement which, however, did not by itself influence survival rates. 89Sr therapy is an effective additional treatment of patients with multiple skeletal metastases from prostatic cancer.

Topics: Berlin; Bone Neoplasms; Humans; Male; Palliative Care; Prostatic Neoplasms; Retrospective Studies; Strontium Radioisotopes; Survival Rate

The palliative efficacy of strontium-89 chloride has been evaluated in a prospective double-blind crossover study comparing it with stable strontium as placebo in 32 patients with prostate cancer metastatic to bone. Response was assessed 5 weeks after each treatment. 26 patients were evaluable. Complete pain relief was only reported following strontium-89 injection. Statistical comparison between placebo and strontium-89 showed clear evidence of a therapeutic response to strontium-89 compared with only a limited placebo effect (P less than 0.01).

Topics: Aged; Bone Neoplasms; Double-Blind Method; Humans; Male; Middle Aged; Pain; Palliative Care; Platelet Count; Prospective Studies; Prostatic Neoplasms; Strontium Radioisotopes

In a multi-centre study strontium-89 was shown to be effective in relieving bone pain from prostatic carcinoma in patients who had failed conventional therapies. Of 83 patients assessed at 3 months, following the administration of a dose of at least 1.5 MBq/kg, 75% derived benefit and 22% became pain free. Symptomatic improvement usually occurred within 6 weeks and continued for between 4 and 15 months (mean 6 months). Based on the dose estimation part of this study the recommended dose of strontium-89 is 150 MBq. Toxicity was low, provided platelet levels were above 100 x 10(9) l-1 at the time of treatment. Repeat treatments with strontium-89 may be given at intervals of not less than 3 months. Strontium-89 is administered intravenously on an out-patient basis with no special radiological protection precautions.

Topics: Bone Neoplasms; Humans; Male; Palliative Care; Platelet Count; Prostatic Neoplasms; Radiotherapy Dosage; Strontium; Strontium Radioisotopes

Forty-nine patients were treated with either 3 x 75 MBq 89Sr or saline as placebo. Analysis of results 1 to 3 years after therapy revealed the ineffectiveness of 89Sr to relieve pain from metastases. Unexpectedly, a higher survival rate was found after Sr application (46% vs 4% after 2 years). Covariate analysis underlines the effect of 89Sr therapy on life expectation.

Topics: Aged; Bone Neoplasms; Clinical Trials as Topic; Double-Blind Method; Humans; Male; Middle Aged; Palliative Care; Prognosis; Prostatic Neoplasms; Random Allocation; Strontium Radioisotopes

A Phase I and II study has been conducted of the safety and efficacy of 89Sr (injected i.v. as the chloride) to alleviate bone pain due to osseous metastatic disease. Potential attendant hematologic toxicity was also examined. Strontium-90 impurities were always less than 1.5%, employing a new quality control technique which detects the 90Y "daughter". Thirty-eight patients with pain due to osseous metastases requiring regular narcotic more than twice a day, documented by an abnormal bone scan and radiography, received 45 doses (1-4.5 mCi, 16-70 microCi/kg) of 89Sr after informed consent. The performance status (Karnofsky scale) ranged from 20-80%. One patient had complete pain relief while 22 other doses yielded at least a 25% reduction in narcotic requirement lasting at least 1 mo and/or 20% improvement in Karnofsky scale rating. Two patients had marked to complete relief in tumor sites which were not fractured, with no change in fracture pain. Twenty-two did not respond. Response was independent of narcotic requirements, tumor type, or Karnofsky status. No hematologic toxicity occurred. Strontium-89 may be useful as adjuvant therapy for diffuse bone pain, but a double-blind study comparing it to other nonnarcotic modalities is required.

Topics: Bone Neoplasms; Clinical Trials as Topic; Dose-Response Relationship, Radiation; Etidronic Acid; Female; Humans; Male; Organotechnetium Compounds; Pain, Intractable; Strontium; Strontium Radioisotopes; Technetium; Time Factors; Yttrium Radioisotopes

Topics: Bone Neoplasms; Breast Neoplasms; Female; Hand; Humans; Strontium Radioisotopes

Topics: Bone Neoplasms; Breast Neoplasms; Female; Hand; Humans; Strontium Radioisotopes

Extravasation of various imaging tracers during administration was not a rare complication during nuclear medicine practice. However, the occurrence of extravasation of therapeutic radiopharmaceutical was rarely reported. Here we reported a 60-year-old woman with breast cancer and diffuse painful bone metastases who received strontium chloride (SrCl2) therapy to palliate her bone pain. Accidental subcutaneous extravasation in the injection site occurred. The extravasated Sr was absorbed rapidly by arm elevation, squeezing a stress ball, local warming, and gently massaging. Follow-up results showed the patient's bone pain significantly relieved and her right arm remained normal.

Topics: Bone Neoplasms; Breast Neoplasms; Female; Humans; Injections; Male; Middle Aged; Palliative Care; Radionuclide Imaging; Strontium; Strontium Radioisotopes

To utilize single-photon emission computed tomography/computed tomography (SPECT/CT) scanning to investigate the usefulness of nerve root compression (NRC) and radioactive cold zone lesions (RCZLs) for predicting poor therapeutic efficacy of strontium-89 chloride (Sr-89) in patients with bone metastasis. Patients with bone metastatic neoplasms who had undergone baseline bone SPECT/CT scanning before Sr-89 therapy (148 MBq Sr-89 chloride by an intravenous injection for each patient) between July 2011 and July 2018 were included. Bone SPECT/CT images were assessed by two readers independently. Associations between imaging features and therapeutic efficacy were obtained via multivariate logistic regression analysis. Of 231 patients analyzed, 50 (21.6%) had NRC at baseline. Of 31 patients who experienced poor therapeutic efficacy, 29 (93.5%) had NRC. In multivariate logistic regression analysis baseline NRC independently predicted poor therapeutic efficacy. The sensitivity of NRC for predicting poor therapeutic efficacy was 93.5%, specificity was 89.5%, positive predictive value was 58.0%, and negative predictive value was 98.9%. RCZLs were detected in17 patients (7.4%), of whom 14 experienced poor Sr-89 therapeutic efficacy. The sensitivity of the presence of RCZLs for predicting poor therapeutic efficacy was 45.2%, specificity was 98.5%, positive predictive value was 82.4%, and negative predictive value was 92.1%. After adjusting for age, bone metabolism and lesion type, the significant independent predictors of poor Sr-89 therapeutic efficacy were presence of NRC (p < 0.001) and RCZL (p = 0.001). NRC and RCZL on baseline bone SPECT/CT are reliable independent predictors of poor Sr-89 therapeutic efficacy in patients with bone metastasis. These associations may facilitate the administration of more effective therapeutic interventions.

Topics: Adult; Aged; Aged, 80 and over; Bone Neoplasms; Female; Humans; Male; Middle Aged; Multimodal Imaging; Radiopharmaceuticals; Strontium Radioisotopes; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Treatment Outcome

The patient was a 47-year-old female with stage IV breast cancer and multiple bone metastases. She received various systemic therapies (hormone therapy and chemotherapy) and underwent mastectomy between 2013 and 2018; in the beginning of 2018, she started experiencing bone metastatic pain in the right hip joint and neural pain on the dorsal side of the left thigh. These symptoms worsened gradually, and nonsteroidal anti-inflammatory analgesics or narcotic analgesics were not effective for treating this pain. Strontium-89 (

Topics: Bone Neoplasms; Breast Neoplasms; Fatal Outcome; Female; Humans; Middle Aged; Neuralgia; Pain Management; Quality of Life; Strontium Radioisotopes; Treatment Outcome

We experienced 2 cases in which strontium chloride was used for pain associated with gastric cancer bone metastasis. Case 1 was of a 69-year-old woman. In 2015, she underwent surgery for advanced gastric cancer followed by adjuvant chemotherapy with S-1 for 1 year. Multiple bone metastases were confirmed 2 years and 3 months after surgery. Obvious pain relief was obtained after 89Sr was administered, and SOX therapy was started. Case 2 was of a 62-year-old man. In 2016, he underwent curative surgery for stomach cancer. Chemotherapy with S-1 was performed for approximately 6 months, but 9 months after surgery multiple LN metastases, liver metastasis, and multiple bone metastases were observed . In case 2, 89Sr was administered, but good pain control was not obtained. The use of 89Sr for pain relief against multiple bone metastases should be based on the previous literature.

Topics: Aged; Bone Neoplasms; Female; Humans; Male; Middle Aged; Pain; Pain Management; Palliative Care; Stomach Neoplasms; Strontium Radioisotopes

The skeleton is the most common metastatic site in patients with advanced cancer. Pain is a major healthcare problem in patients with bone metastases. Bone-seeking radionuclides that selectively accumulate in the bone are used to treat cancer-induced bone pain and to prolong survival in selected groups of cancer patients. The goals of these guidelines are to assist nuclear medicine practitioners in: (a) evaluating patients who might be candidates for radionuclide treatment of bone metastases using beta-emitting radionuclides such as strontium-89 (

Topics: Bone Neoplasms; Humans; Male; Organometallic Compounds; Organophosphorus Compounds; Prostatic Neoplasms; Quality of Life; Radioisotopes; Samarium; Strontium Radioisotopes

With an objective to develop a cost-effective radiochemical formulation for palliation of pain due to skeletal metastases, we have demonstrated a viable method for large-scale production of (45)Ca (t½=163 days, Eβmax=0.3MeV) using moderate flux research reactor, its purification from radionuclidic impurities adopting electrochemical approach and preclinical evaluation of (45)CaCl2.. Irradiation parameters were optimized by theoretical calculations for production of (45)Ca with highest possible specific activity along with minimum radionuclidic impurity burden. Based on this, the radioisotope was produced in reactor by irradiation of isotopically enriched (98% in (44)Ca) CaO target at a thermal neutron flux of ~1 × 10(14) n.cm(-2).s(-1) for 4 months. Scandium-46 impurity co-produced along with (45)Ca was efficiently removed adopting an electrochemical separation approach. The bone specificity of (45)CaCl2 was established by in vitro studies involving its uptake in hydroxyapatite (HA) particles and also evaluating its biodistribution pattern over a period of 2 weeks after in vivo administration in Wistar rats.. Thermal neutron irradiation of 100mg of enriched (98% in (44)Ca) CaO target followed by radiochemical processing and electrochemical purification procedure yielded ~37 GBq of (45)Ca with a specific activity of ~370 MBq/mg and radionuclidic purity>99.99%. The reliability and reproducibility of this approach were amply demonstrated by process demonstration in several batches. In vitro studies indicated significant uptake of (45)CaCl2 (up to 65%) in HA particles. In vivo biodistribution studies in Wistar rats showed specific skeletal accumulation (40-46%ID) with good retention over a period of 2 weeks.. To the best of our knowledge, this is the first study on utilization of (45)CaCl2 in the context of nuclear medicine. The results obtained in this study hold promise and warrant further investigations for future translation of (45)CaCl2 to the clinics, thereby potentially enabling a cost-effective approach for metastatic bone pain palliation especially in developing countries.

Topics: Animals; Bone Neoplasms; Calcium Chloride; Calcium Radioisotopes; Durapatite; Hydrogen-Ion Concentration; Neutrons; Pain; Pain Management; Palliative Care; Radiochemistry; Rats; Rats, Wistar; Strontium Radioisotopes

In addition to its direct cytotoxic effects, radiation therapy renders tumor cells more susceptible to T cell-mediated cytotoxicity by modulating cell surface molecules involved in antigen presentation. The purpose of the present study was to determine the benefit of combined 89Sr radiation and dendritic cell (DC) vaccine therapy in bone metastasis patients.. Patients were treated with intravenous 89Sr at a dose of 40 μCi/kg of body weight on the first day after the peripheral blood mononuclear cell collection. Seven days later, patients received DCs once a week for 6 weeks. The first three vaccines were administered by intravenous infusion, and the last three vaccines were administered by 24-point intradermal injection. Clinical response was evaluated by the number of bone metastatic foci demonstrated on bone scintigraphy; cell-mediated cytotoxicity response was evaluated by delayed-type hypersensitivity (DTH) reaction. All treatment-related toxicities including vaccine-induced fever and 89Sr-associated hematological toxicity were carefully monitored.. Twenty-six patients with histologically diagnosed with primary cancers and multiple bone metastases demonstrated on bone scintigraphy were studied. The overall survival rate was 58.3%. The total positive DTH rate was 50%. The efficiency rate for pain relief was 60% (6/10), for quantity of life was 80%, and for clinic responses was 90%. Out of 10 cases, the Grade 1 or 2 of hematological depression in 4, erythema in 1, and fever in 7 were observed.. The study has important implications for that combined 89Sr radiation, and DC vaccine therapy can benefit cancer patients with bone metastasis.

Topics: Aged; Bone Neoplasms; Cancer Vaccines; Combined Modality Therapy; Dendritic Cells; Female; Humans; Hypersensitivity, Delayed; Male; Middle Aged; Pain Management; Quality of Life; Strontium; Strontium Radioisotopes; Survival Rate; Treatment Outcome

To relieve pain associated with multiple bone metastases radiopharmaceutical method of treatment is of great importance--the use of beta-emission isotope of strontium chloride-89 (metastron). Passing through the human skeletal system, strontium-89 accumulates in areas of high mineral density, which is it typical for osteoblastic metastases. In our institution in the frames of a randomized trial in 90 patients with metastatic hormone-resistant prostate cancer it was carried out systemic radiotherapy with strontium-89 chloride as a stage of complex treatment. Stabilization of pain syndrome during treatment was 72,7% and its progression was noted in 27,3% cases. Radiopharmaceutical therapy is well tolerated and can be used as a stage in complex treatment of patients with hormone-resistant prostate cancer.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Bone Neoplasms; Drug Resistance, Neoplasm; Humans; Male; Middle Aged; Pain; Prostatic Neoplasms; Radionuclide Imaging; Radiopharmaceuticals; Strontium; Strontium Radioisotopes; Treatment Outcome

The aim of the present study was to consider the safety and efficacy of concurrent use of strontium-89 (Sr-89) with external beam radiotherapy (EBRT) for multiple bone metastases, including lesions that require urgent therapy.. A retrospective review was performed of a consecutive series of patients who received Sr-89 for multiple bone metastases. Forty-five patients with multiple bone metastases received Sr-89 injection. Since 17 of the 45 patients had osteolytic bone lesions requiring emergent EBRT, they underwent concurrent use of Sr-89 with EBRT (concurrent group). The remaining 28 patients, none of whom had osteolytic lesions requiring urgent EBRT, were given Sr-89 injection only (singularity group). The injection of Sr-89 was to be given during EBRT, or on the day before the first day of EBRT. The dose of EBRT was 30 Gy in 10 fractions or 40 Gy in 20 fractions. Adverse events were evaluated according to hematological toxicity as measured by the Common Terminology Criteria for Adverse Events (V4.0). To assess efficacy, we checked changes in the pain scale and analgesic drug dosages, and the presence or absence of serious complications from bone metastases.. Fifteen of 17 patients (88.2%) in the concurrent group and 17 of 28 patients (60.7%) in the singularity group reported bone pain relief. A statistically significant difference was found between the two groups, and severe complications (spinal cord compression and pathological fracture) from bone metastases could be prevented in all patients in the concurrent group. Severe hematological toxicity (grade 3 or higher) was not observed in the two groups. There was no statistical difference between the two groups. No one required additional intervention. The adverse events were tolerable.. The results of our study suggest that concurrent use of Sr-89 with EBRT for multiple bone metastases can be performed safely if it is carried out with care, and that it may be an effective therapy in cases requiring emergency treatment.

Topics: Adult; Aged; Aged, 80 and over; Bone Neoplasms; Female; Humans; Male; Middle Aged; Pain; Radiotherapy, Computer-Assisted; Retrospective Studies; Safety; Strontium Radioisotopes

89Sr is useful for the palliation of painful bone metastasis, but its antitumor activity as a monotherapy has not been shown by 18F-FDG PET. Here, we report a case of a 75-year-old woman with multiple bone metastases of breast cancer in which 18F-FDG PET demonstrated a significant reduction in uptake of 18F-FDG after administration of 89Sr.

Topics: Aged; Bone Neoplasms; Breast Neoplasms; Female; Fluorodeoxyglucose F18; Humans; Multimodal Imaging; Positron-Emission Tomography; Strontium Radioisotopes; Tomography, X-Ray Computed

Strontium-89 (Sr-89) has been considered to have a tumoricidal effect with minimal adverse events. However, few reports have investigated these effects in detail. In this study, we examined the tumoricidal and pain-relief effects of Sr-89 on prostate cancer with bone metastasis as well as survival.. A retrospective study was performed involving 31 prostate cancer patients with bone metastasis treated with Sr-89. Using PSA as an evaluation criterion of cancer control, patients were divided into PSA responder and non-responder groups, and the survival rates of these groups were compared. In addition, using the total amount of painkillers administered as an evaluation criterion of pain relief, patients were divided into pain responder and non-responder groups, and the survival rates of these groups were also compared. As secondary investigation items, age, PSA (ng/ml), pain site, extent of the disease, the presence or absence of castration-resistant prostatic cancer (CRPC), the presence or absence of a past medical history of treatment with docetaxel in CRPC cases, Gleason Score, hemoglobin (g/dl), platelet (Plt) (/μl), serum carboxyterminal telopeptide of type I collagen (ng/ml), and bone-alkaline phosphatase (BAP) (U/l) were investigated.. Longer survival was expected for the PSA responder group than for the PSA non-responder group, and whether the spine was the pain site and the presence or absence of CRPC were useful as predictors of this. Plt was suggested to be a useful indicator. Furthermore, the survival time was significantly longer in the pain responder group than in the pain non-responder group, and whether the pain site was present in the spine was considered to be a predictor; however, no significant difference was noted in any of the items assumed to be biomarkers.. Sr-89 has the potential to control PSA and prolong survival. A large-scale prospective study of the therapeutic effect of Sr-89 is expected.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Bone Neoplasms; Humans; Male; Middle Aged; Pain Management; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Strontium Radioisotopes; Survival Rate; Treatment Outcome

Strontium-89 chloride ((89)Sr) bremsstrahlung single photon emission computed tomography (SPECT) imaging was evaluated for detecting more detailed whole body (89)Sr distribution.. (89)Sr bremsstrahlung whole body planar and merged SPECT images were acquired using two-detector SPECT system. Energy window A (100 keV ± 50 %) for planar imaging and energy window A plus adjacent energy window B (300 keV ± 50 %) for SPECT imaging were set on the continuous spectrum. Thirteen patients with multiple bone metastases were evaluated. Bone metastases can be detected with (99m)Tc-HMDP whole body planar and merged SPECT images and compared with (89)Sr bremsstrahlung whole body planar and merged SPECT images. Based on the location of metastatic lesions seen as hot spots on (99m)Tc-HMDP images as a reference, the hot spots on (89)Sr bremsstrahlung images were divided into the same bone parts as (99m)Tc-HMDP images (a total of 35 parts in the whole body), and the number of hot spots were counted. We also evaluated the incidence of extra-osseous uptakes in the intestine on (89)Sr bremsstrahlung whole body planar images.. A total of 195 bone metastatic lesions were detected in both (99m)Tc-HMDP whole body planar and merged SPECT images. Detection of hot spot lesions in (89)Sr merged SPECT images (127 of 195; 66 %) was more frequent than in (89)Sr whole body planar images (108 of 195; 56 %), based on metastatic bone lesions in (99m)Tc-HMDP whole body planar and merged SPECT images. A large intestinal (89)Sr accumulation was detected in 5 of the 13 patients (38 %).. (89)Sr bremsstrahlung-merged SPECT imaging could be more useful for detailed detection of whole body (89)Sr distribution than planar imaging. Intestinal (89)Sr accumulation due to (89)Sr physiologic excretion was detected in feces for 4 days after tracer injection.

Topics: Adult; Aged; Aged, 80 and over; Bone and Bones; Bone Neoplasms; Female; Gamma Cameras; Humans; Intestines; Male; Middle Aged; Radiopharmaceuticals; Strontium; Strontium Radioisotopes; Technetium Tc 99m Medronate; Tomography, Emission-Computed, Single-Photon

A 50-year-old woman complaining of right flank pain visited our hospital. Computed tomography revealed adrenal gland tumor measuring 10 cm in diameter, and multiple bone and liver metastases. It was diagnosed as a malignant pheochromocytoma by means of endocrinological examination and metaiodobenzylguanidine scintigraphy. Although 8 courses of cyclophosphamide, vincristine and dacarbazine therapy were performed, the tumor grew larger gradually, and the bony pain progressed and became uncontrollable with oxycodone hydrochloride. After zoredronic acid and strontium-89 were administered, the bony pain reduced, and the opioid usage could be reduced. In accordance with disease progression, the bony pain progressed again, but the readministration of strontium-89 could diminish the pain again. To our knowledge, this is the first case of malignant pheochromocytoma which strontium-89 was administered, and was effective.

Topics: Adrenal Gland Neoplasms; Bone Neoplasms; Female; Humans; Middle Aged; Pain; Pheochromocytoma; Strontium Radioisotopes

Throughout the years, the palliative treatment of bone metastases using bone seeking radiotracers has been part of the therapeutic resources used in oncology, but the choice of which bone seeking agent to use is not consensual across sites and limited data are available comparing the characteristics of each radioisotope. Computational simulation is a simple and practical method to study and to compare a variety of radioisotopes for different medical applications, including the palliative treatment of bone metastases. This study aims to evaluate and compare 11 different radioisotopes currently in use or under research for the palliative treatment of bone metastases using computational methods.. Computational models were used to estimate the percentage of deoxyribonucleic acid (DNA) damage (fast Monte Carlo damage algorithm), the probability of correct DNA repair (Monte Carlo excision repair algorithm), and the radiation-induced cellular effects (virtual cell radiobiology algorithm) post-irradiation with selected particles emitted by phosphorus-32 ((32)P), strontium-89 ((89)Sr), yttrium-90 ((90)Y ), tin-117 ((117m)Sn), samarium-153 ((153)Sm), holmium-166 ((166)Ho), thulium-170 ((170)Tm), lutetium-177 ((177)Lu), rhenium-186 ((186)Re), rhenium-188 ((188)Re), and radium-223 ((223)Ra).. (223)Ra alpha particles, (177)Lu beta minus particles, and (170)Tm beta minus particles induced the highest cell death of all investigated particles and radioisotopes. The cell survival fraction measured post-irradiation with beta minus particles emitted by (89)Sr and (153)Sm, two of the most frequently used radionuclides in the palliative treatment of bone metastases in clinical routine practice, was higher than (177)Lu beta minus particles and (223)Ra alpha particles.. (223)Ra and (177)Lu hold the highest potential for palliative treatment of bone metastases of all radioisotopes compared in this study. Data reported here may prompt future in vitro and in vivo experiments comparing different radionuclides for palliative treatment of bone metastases, raise the need for the careful rethinking of the current widespread clinical use of (89)Sr and (153)Sm, and perhaps strengthen the use of (223)Ra and (177)Lu in the palliative treatment of bone metastases.

Topics: Algorithms; Beta Particles; Bone Neoplasms; Computer Simulation; DNA; DNA Damage; DNA Repair; Humans; Lutetium; Monte Carlo Method; Neoplasm Metastasis; Palliative Care; Radioisotopes; Radiopharmaceuticals; Radium; Rhenium; Samarium; Strontium Radioisotopes

Topics: Adult; Bone Neoplasms; Female; Humans; Male; Middle Aged; Radionuclide Imaging; Strontium Radioisotopes

A 77-year-old man was diagnosed as having cholangiocellular carcinoma. The patient underwent partial right hepatectomy in June 2008, and multiple bone metastases occurred approximately 9 months after surgery. He refused salvage chemotherapy and radiation therapy. Although he had been treated with opiate analgesics, he was unable to sit up owing to severe pain in the left ilium. He was hospitalized because of buttock pain and left leg numbness. Even a combination of fentanyl patch, gabapentin, and subarachnoid block was ineffective in controlling pain. Strontium-89 (89Sr) therapy was successful in eliminating the intractable pain, and there were no serious side effects during therapy. The patient was discharged from the hospital, and he received palliative care at home for a short period.

Topics: Aged; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Bone Neoplasms; Cholangiocarcinoma; Humans; Male; Pain, Intractable; Palliative Care; Strontium Radioisotopes

Topics: Bone Neoplasms; Humans; Manuals as Topic; Strontium Radioisotopes

Randomized clinical trials of palliative radiation therapy and radiopharmaceuticals are emphasized, and new concepts in targeted alpha-emitter therapy are introduced.. Radiation therapy has a proven palliative role in the treatment of patients with advanced prostate cancer. Findings from 223radium clinical trials emphasize the importance of alpha particles as a new therapeutic modality in patients with bone metastatic castrate-resistant prostate cancer. We introduce the concept of alpha-emitting particles from both a basic and clinical perspective in the realm of bone-targeted radiopharmaceuticals and discuss how these agents compare and contrast with conventional beta-emitting radioisotopes. The physics, radiobiology, and survival data with 223radium are unique compared with previously used radiopharmaceuticals.. Targeted alpha-emitting therapies such as 223radium have the capacity to change the way we treat patients with bone-metastatic prostate cancer.

Topics: Alpha Particles; Bone Neoplasms; Dose Fractionation, Radiation; Evidence-Based Medicine; Humans; Male; Organometallic Compounds; Organophosphorus Compounds; Palliative Care; Prostatic Neoplasms; Radiopharmaceuticals; Radium; Randomized Controlled Trials as Topic; Strontium Radioisotopes; Treatment Outcome

This report describes the case of a 57-year-old woman with liver and bone metastases from malignant insulinoma, who was afflicted with severe hypoglycemia. Treatment of the liver metastases using octreotide, diazoxide and transarterial embolization failed to raise her blood glucose level and she required constant glucose infusion (about 1000 kcal/day) and oral feeding (about 2200 kcal/day) to avoid a hypoglycemic attack. Subsequently, 110 MBq (2.0 MBq/kg) of strontium-89 were administered by intravenous injection. Three weeks after the strontium-89 injection, we could reduce the dose of constant glucose infusion while maintaining a euglycemic status. Six weeks after the injection, the constant glucose infusion was discontinued. Although strontium-89 therapy is indicated for patients with multiple painful bone metastases, it was also useful as a means of inhibiting tumor activity and controlling hypoglycemia in this case. To our knowledge, this is the first report to provide evidence that strontium-89 can be useful in controlling intractable hypoglycemia in patients with malignant insulinoma with bone metastases.

Topics: Blood Glucose; Bone Neoplasms; Female; Humans; Hypoglycemia; Injections, Intravenous; Insulinoma; Liver Neoplasms; Middle Aged; Pancreatic Neoplasms; Radionuclide Imaging; Strontium Radioisotopes; Tomography, X-Ray Computed

Topics: Analgesics, Non-Narcotic; Bone Neoplasms; Humans; Iodine Radioisotopes; Lymphoma; Organometallic Compounds; Organophosphorus Compounds; Palliative Care; Radiotherapy; Radium; Strontium Radioisotopes; Synovial Membrane

Topics: Aged; Bone Neoplasms; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Male; Strontium Radioisotopes

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Blood Banks; Blood Preservation; Bone Neoplasms; Bone Remodeling; Denosumab; Disasters; Earthquakes; Humans; Japan; Nuclear Power Plants; Occupational Exposure; Peripheral Blood Stem Cell Transplantation; Radiation Injuries; Radioactive Hazard Release; RANK Ligand; Strontium Radioisotopes

To study the influence of 89SrCl2 on CD4+ CD25+ regulatory T cells and its Foxp3 mRNA expression in cancer patients with bone metastases.. Peripheral blood samples were collected from 57 patients with bone metastases cancer and 25 healthy controls, the amount of CD4+ CD25+ regulatory T cells in peripheral blood was determined by flow cytometry, the expression level of Foxp3 mRNA in these regulatory T cells was detected by RT-PCR.. The percentage of CD4+ CD25+ regulatory T cells in CD4+ cells was (11.3 +/- 5.5) % in the patients with bone metastases, which was significantly more than that (5.6 +/- 1.5)% in healthy control (P < 0.01). After the treatment of 89SrCl2, it was decreased to (10.4 +/- 5.2)%, and the decrease was statistically significant (P < 0.05). The expression level of Foxp3 mRNA was decreased significantly from 0.348 +/- 0.028 to 0.296 +/- 0.029 by the treatment of 89SrCl2 (P < 0.05). In addition, the amount of CD4+ CD25+ T cells in the patients obtaining 89SrCl2 therapeutic effects was (9.3 +/- 4.2) %, which was lower than that in those patients without effects (12.9 +/- 5.3)% (P < 0.01). The relative expression level of Foxp3 mRNA was 0.254 +/- 0.025 in the patients obtaining therapeutic effects, which was also significantly less than that (0.397 +/- 0.029) in those patients without any effects (P < 0.01).. Foxp3 gene play a pivotal role in the regulation of CD4+ CD25+ T cells. The treatment of 89SrCl2 could decrease the amount of CD4+ CD25+ T cells and down-regulate Foxp3 mRNA expression of these cells in bone metastases cancer patients.

Topics: Adult; Aged; Bone Neoplasms; Female; Forkhead Transcription Factors; Humans; Male; Middle Aged; RNA, Messenger; Strontium; Strontium Radioisotopes; T-Lymphocytes, Regulatory; Young Adult

We report a case of a 39-year-old man with intractable multifocal pain caused by metastatic urachal carcinoma to the bone. The patient underwent a partial cystectomy in May 2008, and lung metastasis occurred 9 months after the surgery. He then received salvage chemotherapy, but developed metastasis to the liver, brain, and bone. He was hospitalized due to a shoulder pain, a lower back pain, buttocks pain, numbness in both legs, and drop foot in right leg. MRI revealed metastases to the spine, and lumbar spinal canal stenosis with cauda equina compression. Even a combination of fentanyl-patch, oral acetaminophen, gabapentin and paroxetine was not effective for pain control. Strontium-89 therapy and subarachnoid phenol block successfully eliminated intractable pain. The patient could be discharged from hospital and received a palliative care at home for a short period of time.

Topics: Adult; Bone Neoplasms; Humans; Magnetic Resonance Imaging; Male; Pain, Intractable; Phenol; Strontium Radioisotopes; Subarachnoid Space; Urinary Bladder Neoplasms

Topics: Bone Neoplasms; Humans; Male; Palliative Care; Prostatic Neoplasms; Strontium Radioisotopes

Bone metastases are observed in 30-70% of patients with cancer. Painful bone metastases require regular control and treatment. Systemic palliative radiotherapy using beta-emitting radionuclides is an alternative method to analgesics and external beam radiotherapy. The aim of the study was to establish the efficacy and risk of side effects of radionuclide therapy in patients with bone metastases.. Strontium-89 (Sr-89) therapy was performed in 49 patients, 14 women and 35 men, aged 42-82 (mean 62) years with bone metastases confirmed by MDP-Tc99m whole body scan. The primary tumour was prostate cancer in 28 patients, breast cancer in 14, bladder cancer in 2, lung cancer in 2, gastric cancer in 2, and renal cancer in 1 patient. Intravenous injection of 150 MBq of Sr-89 was given and patients were observed for at least 3 months. Blood count, intensity of pain, drugs intake, life activity, and duration of effect were assigned 0-3 points. The overall response index was very good when the points totalled 10-12, good - 7-9, satisfactory - 4-6, poor - 2-3 and no response 0-1 points. Haemotoxicity was evaluated according to the Common Toxicity Criteria of the World Health Organisation (WHO).. We found a very good response in 10 (20%) patients, good in 20 (41%), satisfactory in 8 (16%), poor in 2 (4%), and no response in 9 (19%) patients. Transient haemotoxicity of the Sr-89 therapy was observed in 39 (80%) patients. The mean decrease in platelets and leukocytes was 33-35%, but the haemoglobin concentration was reduced by only 15% in comparison to baseline values. The majority of patients did not require any treatment for haematologic side effects. Hospitalization was necessary in only 2 patients with grade 4 CTC WHO.. Palliative radionuclide treatment of painful bone metastases with Strontium-89 in various primary tumours is in most cases an effective therapy with limited haemotoxicity.

Topics: Adult; Aged; Aged, 80 and over; Bone Neoplasms; Female; Hematologic Diseases; Humans; Male; Middle Aged; Pain Measurement; Palliative Care; Strontium Radioisotopes

Palliative therapy using radioactive strontium (89Sr) was performed on 60 patients suffering from cancer. Seventy-one percent of the patients had stopped or reduced their opiates and/or analgesics. Pain relief continued for up to three months. Patients with breast and prostatic cancer showed the best pain reduction. However, pain reduction was limited for lung cancer patients. Repeated usage of 89Sr with/without opiate and analgesics served to maintain the reduced level of pain. Side effects of repeated usage of 89Sr were decrease of hemoglobin, WBC, and platelets. The decreased level was limited within Level 1. The indication of 89Sr therapy is important. DIC cases and renal failure cases will have increased side effect risk. Image diagnosis is also important. A bone scan is a minimum requirement. Poor accumulation of 99mTc-MDP cases are not indication. Rapidly progressive disease cases, radiculopathy cases, and soft tissue invasion cases should not be given 89Sr therapy. At present, the uses of 89Sr are limited to end-stage patients. The use of 89Sr should change from end stage to early stage in combination with chemotherapy.

Topics: Bone Neoplasms; Humans; Pain; Pain Measurement; Palliative Care; Radiography; Strontium Radioisotopes

Bone metastases are a major problem in the clinical management of patients with prostate cancer. Despite the use of analgesic for the relief of such pain, the outcomes are not often satisfactory. Strontium-89 (89Sr) is a pure beta-emitting radioisotope to be avidly concentrated in the areas of high osteoblastic activity. The aim of this study was to evaluate the efficacy of 89Sr in the therapy for bone metastases of prostate carcinoma. 116 patients received intravenous injection of 89Sr at the dose of 3mCi (111MBq). All patients underwent physical examination and Karnofsky's Performance Score (KPS) evaluation before and after administration; the analgesic effects were evaluated by scores of pain. The complete response (CR) was defined as scores of pain > 75%; no response (NR) was defined as scores of pain < 25% the remaining was partial response (PR). The changes of bone metastases were screened by CT, MRI and 99mTc-MDP bone scintigraphy according to the standards of WHO. After the treatment with 89Sr, the total response rate was 80.2%. In the 116 cases, 21 cases (18.1%) displayed complete response and 72 cases (62.1%) displayed partial response, but 23 cases (19.2%) showed no response. The mean score on Karnfsky's performance status (KPS) was 20.0% higher. About 1/3 cases exhibited an obvious decrease in the number of metastases, and some foci disappeared. Thirteen cases (12%) showed a greater decrease in prostate-specific antigen (PSA) value. 89Sr chloride is an effective and safe therapy of the bone metastases from prostate cancer.

Topics: Adult; Aged; Aged, 80 and over; Bone Neoplasms; Humans; Male; Middle Aged; Prostatic Neoplasms; Strontium Radioisotopes

Metastatic bone disease is often associated with severe pain in cancer patients, and has become an increasingly important quality-of-life issue. Radionuclides, such as strontium-89 (Sr-89), have provided effective palliation of metastatic bone pain. Although strontium follows the biochemical pathways of calcium in the body, changes in calcium homeostasis related to Sr-89 therapy have rarely been reported. We present a case of a 32-year-old male with poorly differentiated neuroendocrine carcinoma and extensive skeleton metastases who developed profound hypocalcemia after Sr-89 administration.

Topics: Adult; Bone Neoplasms; Humans; Hypercalcemia; Male; Neuroendocrine Tumors; Radiation Injuries; Radiopharmaceuticals; Strontium Radioisotopes

The radiation exposure to bystanders from 89SrCl2, 186Re-HEDP and 153Sm-EDTMP, is generally thought to be caused by "bremsstrahlung" and gamma-radiation, with negligible contribution from beta-radiation. The latter assumption may be erroneous. The aim of this prospective study was the investigation of radiation safety after treatment with these radiopharmaceuticals. The radiation field around treated patients was characterized and the magnitude estimated.. 33 patients (30 prostate carcinoma, 3 breast carcinoma) were treated with 150 MBq 89SrCl2 (9 patients), 1295 MBq 186Re-HEDP (12 patients) or 37 MBq/kg 153Sm-EDTMP (12 patients). External exposure rates at 30 cm from the patient were measured at times 0 to 72 h post-injection. To evaluate the respective contribution of Bremsstrahlung, beta- and gamma-radiation, a calibrated survey meter was used, equipped with a shutter. For each patient, the measured exposure rate-versus-time data were fit to a curve and the curve integrated (area under the curve) to estimate the total exposure.. For 29/33 patients the total ambient equivalent doses (mean+/-1 standard deviation [SD]) based on the integral of the fitted curve were 2.1+/-1.2 mSv for 89SrCl2, 3.3+/-0.6 mSv for 186Re-HEDP and 2.8+/-0.6 mSv for 153Sm-EDTMP. Beta-radiation contributes significantly to these doses (>99% for 89SrCl2, 87% for 186Re-HEDP and 27% for 153Sm-EDTMP). The effective doses (at 30 cm) are <0.1 mSv for 89SrCl2, 0.3 mSv for 186Re-HEDP and 1.6 mSv for 153Sm-EDTMP.. Patients treated with 89SrCl2, 186Re-HEDP or 153Sm-EDTMP emit a spectrum of radiation, including non-negligible beta-radiation. With specific instructions effective doses to bystanders are acceptable.

Topics: Adult; Aged; Bone and Bones; Bone Neoplasms; Breast Neoplasms; Etidronic Acid; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Organometallic Compounds; Organophosphorus Compounds; Prostatic Neoplasms; Radiation Injuries; Radioisotopes; Rhenium; Safety; Samarium; Strontium; Strontium Radioisotopes

Topics: Antibodies, Monoclonal; Antigens, CD20; Bone Neoplasms; Brachytherapy; Contraindications; Humans; Lymphoma, B-Cell; Pain; Strontium Radioisotopes; Thyroid Neoplasms; Yttrium Radioisotopes

These retrospective study is aimed to evaluate the efficacy of therapy with Stronthium-chloride 89 (89SrCl) and Samarium 153 conjugated with ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP) in the palliation of bone pain due to metastatic malignancy.. The study refers to a presentation sample of 27 patients with bone metastases caused by different cancers (16 prostate, 5 breast, 6 lung) who were enrolled and followed-up for 11.5 +/- 6.3 months. 89SrCl (150MBq) was administered in 17 pts, 153Sm-EDTMP (37 MBq/Kg) in 10 pts. All patients showed multiple metastatic sites of 99Tc-HDP uptake documented by a standard bone scintigraphy. Effectiveness of treatment was evaluated by questionnaires about pain and quality of life, Karnofsky index, specific cancer markers, a post-treatment bone scintigraphy. Presence of flare reaction and haematological toxicity were evaluated too.. Questionnaire scores decreased both in patients treated with 89SrCl and in those given 153Sm-EDTM, without significant difference. Karnofsky index significantly increased only in patients with prostate cancer. After therapy, there were no significant changes of tumor marker levels, neither in bone scintigraphic pattern. Flare reaction occurred in 44% of the cases within 2 weeks from the therapy. Remarkable variations of platelets and leukocytes occurred in 33.3% and 18.5% of patients, respectively, independently of the radiopharmaceutical used, but reversed within 6 weeks after therapy.. Radionuclide therapy with bone-seeker agents 89Sr and 153Sm in the palliation of painful bone metastases allows a partial/total relief of pain with an improvement of quality of life. No tumoricid effect was found. Haematological toxicity was limited and reversible. Patients with prostate cancer seem to have a higher response rate.

Topics: Adult; Aged; Aged, 80 and over; Analgesics; Analgesics, Non-Narcotic; Bone Neoplasms; Combined Modality Therapy; Drug Resistance; Female; Humans; Male; Middle Aged; Organometallic Compounds; Organophosphorus Compounds; Pain; Pain Management; Palliative Care; Retrospective Studies; Strontium; Strontium Radioisotopes

To evaluate the efficacy of strontium-89 (89Sr) in the treatment of painful bone metastases of prostate cancer.. A total of 116 patients with painful bone metastases of prostate cancer received bilateral orchiectomy and incretion, followed by intravenous injection of 89Sr at the dose of 1.48-2.22 MBq (40-60 microCi)/kg. The clinical effects were evaluated by follow-up analysis.. After the 89Sr treatment, appetite and sleep were evidently improved in 33.6% and 56.0% of the patients respectively, the applied dose of anodyne reduced in 61.2%, pain alleviated in 83.6%, with an absolute palliation rate of 24.1%. Pain relief started at 3-21 (10.2 +/- 6.5) days and lasted 3-12 (5.3 +/- 2.2) months. Flare ache occurred in 31.9% of the patients. Compared with pre-treatment, the mean score on Karnofsky's performance status (KPS) was 20.0% higher, and the WBC count decreased to 3.0-3.9 x 10(6)/L in 18.1% of the patients. Whole body bone scintigraphy of 53 followed-up patients showed that 39 (73.6%) of them exhibited an obvious decrease in the number of metastases, 10 (18.9% remained in a stabilized state and only 4 (7.5% deteriorated.. 89Sr, capable of inhibiting bone metastasis, palliating pain and improving the quality of life with few adverse effects, can be used as a desirable therapeutic for painful bone metastases of prostate cancer.

Topics: Aged; Aged, 80 and over; Bone Neoplasms; Follow-Up Studies; Humans; Male; Middle Aged; Pain, Intractable; Prostatic Neoplasms; Strontium Radioisotopes; Treatment Outcome

The objective of the present work is to apply the plasma clearance parameters to strontium, previously determined in our laboratory, to improve the biokinetic and dosimetric models of strontium-90 ((90)Sr) used in radiological protection; and also to apply this data for the estimation of the radiation doses from strontium-89 ((89)Sr) after administration to patients for the treatment of the painful bone metastases. Plasma clearance and urinary excretion of stable strontium tracers of strontium-84 ((84)Sr) and strontium-86 ((86)Sr) were measured in GSF-National Research Center for Environment and Health (GSF) in 13 healthy German adult subjects after intravenous injection and oral administration. The biological half-life of strontium in plasma was evaluated from 49 plasma concentration data sets following intravenous injections. This value was used to determine the transfer rates from plasma to other organs and tissues. At the same time, the long-term retention of strontium in soft tissue and whole body was constrained to be consistent with measured values available. A physiological urinary path was integrated into the biokinetic model of strontium. Parameters were estimated using our own measured urinary excretion values. Retention and excretion of strontium were modeled using compartmental transfer rates published by the International Commission on Radiological Protection (ICRP), the SENES Oak Ridge Inc. (SENES), and the Urals Research Center for Radiation Medicine (TBM). The results were compared with values calculated by applying our GSF parameters (GSF). For the dose estimation of (89)Sr, a bone metastases model (GSF-M) was developed by adding a compartment, representing the metastases, into the strontium biokinetic model. The related parameters were evaluated based on measured data available in the literature. A set of biokinetic parameters was optimized to represent not only the early plasma kinetics of strontium but also the long-term retention measured in soft tissue and whole body. The ingestion dose coefficients of (90)Sr were computed and compared with different biokinetic model parameters. The ingestion dose coefficients were calculated as 2.8 x 10(-8), 2.1 x 10(-8), 2.5 x 10(-8) and 3.8 x 10(-8) Sv Bq(-1) for ICRP, SENES, TBM and GSF model parameters, respectively. Moreover, organ absorbed dose for the radiopharmaceutical of (89)Sr in bone metastases therapy was estimated based on the GSF and ICRP biokinetic model parameters. The effective do

Topics: Administration, Oral; Body Burden; Bone Neoplasms; Eating; Kinetics; Metabolic Clearance Rate; Organ Specificity; Radiation Dosage; Relative Biological Effectiveness; Strontium Radioisotopes; Tissue Distribution

Theoretical data of external Bremsstrahlung (EB) radiation cross section of bone is estimated using tabulated results of EB cross section given for various elements at various photon and electron energies. This data may be useful in the analysis of Bremsstrahlung imaging which is the technique applied in medical therapy.

Topics: Beta Particles; Bone and Bones; Bone Neoplasms; Humans; Models, Theoretical; Radiation Monitoring; Radiometry; Strontium; Strontium Radioisotopes

To evaluate the safety and efficacy of strontium-89-chloride for management of bone metastases in patients without bone pain.. Fifty-four patients without painful bone metastases were given a single intravenous dose (1.48-2.22 MBq/kg) of strontium-89-chloride, which was repeated once or twice at the interval between 3 and 6 months.. The total response rate was 74.0% in these, and the response rate was significantly lower in patients with focal size>2 cm than in those with focal size

Topics: Adult; Aged; Aged, 80 and over; Bone Neoplasms; Female; Humans; Lung Neoplasms; Male; Middle Aged; Pain; Prostatic Neoplasms; Strontium Radioisotopes; Treatment Outcome

The aim of this study was to evaluate changes in the peripheral blood CD(4)(+) and CD(8)(+) T-lymphocyte populations following strontium-89 chloride ((89)SrCl(2)) therapy for painful bone metastases and to relate these changes to a therapeutic response. Forty-two (42) patients with painful bone metastases were treated with 148 MBq (4 mCi) of (89)SrCl(2). Blood samples were drawn before and monthly for 6 months after the treatment. CD(4)(+) and CD(8)(+) T-lymphocyte levels were measured using flow cytometry. The number of bone metastases and the pain score were used to assess the effect of therapy. Before the administration of (89)SrCl(2), the ratio of CD(4)(+) to CD(8)(+) T-lymphocytes was lower in patients with bone metastases than in the control subjects (p < 0.01); after therapy, the ratio increased up to the fourth month and then gradually declined to pretreatment levels. Responders had higher post-therapeutic ratios of CD(4)(+) to CD(8)(+) than nonresponders. There was a good correlation between the ratio of CD(4)(+) to CD(8)(+) and both the number of bone metastases and the pain score. The ratio of CD(4)(+) to CD(8)(+) T-lymphocytes correlated strongly with the response of bone metastases to (89)SrCl(2), and therefore, may be used as an indicator of (89)SrCl(2) efficacy.

Topics: Bone Neoplasms; Breast Neoplasms; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Female; Humans; Lymphocyte Count; Male; Middle Aged; Pain; Radiography; Radiotherapy Dosage; Reference Values; Strontium Radioisotopes; Treatment Outcome; Whole-Body Irradiation

We evaluated the pain response and daily discomfort in patients with painful bone metastases treated by merging 89Sr-chloride and zoledronic acid. The results were compared with those of patients who received 89Sr-chloride or zoledronic acid separately.. 25 patients (12 women; mean age 65+/-13 years) chronically treated with zoledronic acid underwent bone pain palliation with 150 MBq of 89Sr-chloride at least 6 months later that bisphoshonate therapy started (group A). 13 patients (6 women; mean age 70+/-12 years) received 89Sr-chloride alone (group B) and 11 patients (5 women; mean age 69+/-12 years) were chronically treated and continued to receive only zoledronic acid therapy (group C), both constituted the control groups. Patients kept a daily pain diary assessing both their discomfort and the pain of specific sites by using a visual analog scale (VAS), rating from 0 (no d iscomfort-no pain) to 10 (worst discomfort-pain). These diaries were reviewed weekly for 2 months and three different physicians rated the pain response on a scale of -2 (considerable deterioration) to +2 (considerable improvement).. Baseline characteristics were similar in the three groups. The reduction of total discomfort and of bone pain in the group A was significantly greater as compared to group B (P<0.01) and group C (P<0.01). During the monitored period, a significant improvement of clinical conditions was observed in the group A, varying the rate from -1 to 1 as compared to both groups B and C in which the rate changed from -1 to 0.. Our findings indicate that combined therapy of 89Sr-chloride and zoledronic acid in patients with painful bone metastases is more effective in treating pain and improving clinical conditions than 89Sr-chloride or zoledronic acid used separately.

Topics: Aged; Aged, 80 and over; Bone Neoplasms; Breast Neoplasms; Combined Modality Therapy; Diphosphonates; Female; Follow-Up Studies; Humans; Imidazoles; Male; Middle Aged; Neoplasm Metastasis; Pain; Palliative Care; Prostatic Neoplasms; Strontium Radioisotopes; Time Factors; Treatment Outcome; Zoledronic Acid

Topics: Antibodies, Monoclonal; Ascites; Bone Neoplasms; Chromium Compounds; Humans; Hyperthyroidism; Iodine Radioisotopes; Lymphoma, Non-Hodgkin; Organometallic Compounds; Organophosphorus Compounds; Pain; Patient Isolation; Phosphates; Pleural Effusion, Malignant; Polycythemia Vera; Radiation Protection; Radiopharmaceuticals; Sodium Iodide; Strontium Radioisotopes; Thrombocytopenia; Thyroid Neoplasms; Yttrium Radioisotopes

Retrospective comparative analysis of strontium-89 chloride (Sr89) and rhenium-186-hydroxyethylidene diphosphonate (Re186-HEDP) radionuclide treatment to find predictors of response in patients with painful metastases from hormone refractory prostate cancer.. Clinical data from 60 hormone refractory PCA patients (i.e. rising PSA at castrate testosterone serum levels) was obtained. Twenty-nine were treated with Sr89, 31 were treated with Re186-HEDP for painful osseous metastasis. Response was defined as a patient-reported decrease in pain and/or reduction in pain medication with stable pain level. Hematological parameters and serum levels of PSA, alkaline phosphatase, and lactate dehydrogenase were assessed prior to and at 4-week intervals after treatment.. Median survival of all patients was 7 months (95% CI: 6-9 months). Overall, 33/60 (55%) patients reported a decrease in pain after the first radionuclide treatment. This percentage was similar for patients treated with Re168-HEDP and Sr89. Mean duration of reported pain response was 75 days (+/- 68 days) for Sr89 and 61 days (+/- 56 days) for Re186-HEDP, which was not significantly different. A lower blood hemoglobin concentration was associated with a lower pain response rate. In a multivariate Cox regression analysis, pain response to radionuclide treatment predicted longer survival after treatment.. Pain response was present in 55% of patients. Serum hemoglobin concentration prior to radionuclide treatment predicted pain response for both Re186-HEDP and Sr89. A reduction in pain upon radionuclide treatment was associated with a longer survival after treatment.

Topics: Aged; Bone Neoplasms; Etidronic Acid; Hemoglobins; Humans; Male; Organometallic Compounds; Pain; Predictive Value of Tests; Prostatic Neoplasms; Radioisotopes; Retrospective Studies; Strontium Radioisotopes

Strontium-89 (Sr-89) alone or with concurrent chemotherapy has a role in the treatment of patients with prostate cancer (PCP). The schedules for repeated doses of Sr-89 or for concurrent chemotherapy is undetermined. The objective of this study was to measure the effective half-life (Te) of Sr-89 using a detector available in a nuclear research facility. Blood and urine samples obtained from PCP treated with Sr-89 (Metastron, Amersham, U.K.) were measured for radioactivity with a High Pure Germanium (HPGe) detector in a gamma spectrometry system (Eurisys, France). Twenty-five urine and 22 blood samples were obtained from 8 patients during a period of 160 days after Metastron injection. Sr-89 radioactivity levels in blood and urine were quite low (<8.2 x 10(-3) microCi/mL) in all patients after 21 days, whereas Sr-85 (available in 0.5% of Metastron) urine and, to a lesser extent, blood radioactivity levels were moderately high and could be detected up to 160 days. Based on Sr-85 urine levels, the calculated Sr-89 Te ranged from 9.6 to 20.7 days. Sr-89 Te can be routinely calculated in PCP based on HPGe detection of Sr-85 radioactivity levels in urine. This measurement can establish schedules for either repeated doses of Sr-89 or concurrent chemotherapy.

Topics: Aged; Aged, 80 and over; Bone Neoplasms; Drug Administration Schedule; Half-Life; Humans; Male; Middle Aged; Palliative Care; Prostatic Neoplasms; Radiopharmaceuticals; Strontium Radioisotopes

To evaluate the clinical value of (89)SrCl(2) (Ke xing Inc, Shanghai) as a palliative therapy modality for cancer patients with bone metastasis.. In 504 cancer patients with painful limitation of movement due to bony metastasis, a dose of 1.48-2.22 MBq/kg (40-60 uCi/kg) iv infusion of (89)SrCl(2) was given.. In 97 patients (19.2%) there was no improvement in pain and life quality, 298 patients (59.1%) showed mild to moderate improvement (moderately effective), 109 patients (21.6%) became free of pain and were subsequently fully ambulatory (markedly effective). The pain relief appeared from D1-D46 after (89)SrCl(2) administration, most frequently from D5-D14. The palliative effect could last for about 56 days to 13 months. Repeated bone scans of some patients showed that the metastatic foci in the bone became smaller or even disappeared gradually after the administration of (89)SrCl(2). Approximately 55% of patients experienced grade I approximately III bone marrow depression attributable to (89)SrCl(2), which would return to the pre-treatment level within 3 approximately 9 months.. (89)SrCl(2) is effective and safe for the relief of bone pain and improvement of quality of life in cancer patients with painful bony metastasis.

Topics: Adult; Aged; Aged, 80 and over; Bone Neoplasms; Breast Neoplasms; Female; Humans; Lung Neoplasms; Male; Middle Aged; Pain Measurement; Pain, Intractable; Quality of Life; Strontium Radioisotopes

Clinicians may have reservations about using strontium-89 for the treatment of bone metastases because of concerns that it may limit future use of chemotherapy. We assessed the rate of bone marrow failure in patients with prostate cancer who had received a dose of strontium-89.. This subgroup analysis involved 34 patients with androgen-independent prostate cancer who had been given a dose of strontium-89 and six weekly doses of doxorubicin after response to induction chemotherapy. We assessed subsequent hematotoxicity in terms of bone marrow failure and the ability to tolerate additional treatments during a median of 25 months (range, 7 to 76 months) after the strontium-89 was administered.. No patients developed bone marrow failure within 6 months of receiving strontium-89. Five (15%) of 34 patients developed bone marrow failure at a median 23 months (range, 6 to 53 months) after the strontium-89 treatment. Bone marrow biopsy performed in two of these five patients showed complete replacement of the marrow by tumor. Thirty-one patients (91%) received subsequent cytotoxic treatments at a median 11 months (range, 1 to 33 months) after the strontium-89 treatment.. This analysis demonstrated that a single dose of strontium-89 combined with chemotherapy did not affect the delivery of subsequent courses of chemotherapy in a select group of patients. However, a majority of these therapies were given off protocol and were administered at a dose schedule that might be considered inappropriate or inadequate. The clinical role and safety profile of radiopharmaceuticals combined with chemotherapy in prostate cancer therapy deserve further exploration.

Topics: Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Bone Marrow; Bone Neoplasms; Combined Modality Therapy; Doxorubicin; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasms, Hormone-Dependent; Palliative Care; Prostatic Neoplasms; Strontium Radioisotopes; Survival Rate; Treatment Outcome

To investigate the influence of (89)SrCl(2) (strontium-89 chloride) on immune functions in patients with simple bone metastases.. Twenty-five patients diagnosed as simple bone metastases with un-detectable primary tumors were treated with (89)SrCl(2). The CD4(+), CD8(+), CD4(+)/CD8(+) lymphocyte subsets were assessed before and after (89)SrCl(2) treatment. Twenty normal individuals served as controls.. The CD4(+), CD8(+) and CD4(+)/CD8(+) in the control group were (38.83 +/- 8.95)%, (32.19 +/- 8.51)% and 1.29 +/- 0.47, respectively. In patients, they were (31.12 +/- 8.12)%, (41.75 +/- 10.91)% and 0.84 +/- 0.22 before treatment, and (36.21 +/- 8.71)%, (35.08 +/- 10.14)% and 1.19 +/- 0.27 after treatment, respectively (P < 0.05). The patients were divided into treatment effective and non-effective groups by pain score. Before treatment, the immunologic parameters in the two groups had no significant differences (P > 0.05). After treatment, the frequencies of CD4(+) and CD8(+) subsets, CD4(+) to CD8(+) ratios and the number of metastatic foci in the effective group were (37.81 +/- 5.18)%, (33.17 +/- 6.38)%, 1.33 +/- 0.31 and 6.64 +/- 3.11, respectively, while in the treatment non-effective group, they were (32.09 +/- 5.72)%, (39.99 +/- 5.38)%, 0.82 +/- 0.22 and 9.87 +/- 3.46, respectively (P < 0.05).. The immune functions in patients with simple bone metastases are inhibited. Treatment with (89)SrCl(2) may improve their immunity to certain extent. The degree of recovery in the treatment effective patients was better than that in the treatment non-effective cases.

Topics: Adult; Aged; Bone Neoplasms; CD4-CD8 Ratio; Female; Humans; Male; Middle Aged; Neoplasms, Unknown Primary; Strontium; Strontium Radioisotopes; T-Lymphocyte Subsets

We report our experience in the use of radionuclides in the treatment of bone metastases in patients with various primary cancers: breast cancer, prostate cancer, lung cancer, etc.. Eighty-seven patients (53 women, 34 men) with bone metastases were treated for pain relief with either 32-P (71 patients) or 89-Sr (16 patients). Fifty-three of the patients had breast cancer, 27--rostate cancer, 6--lung cancer and 1--kidney cancer. The patients were examined for side effects when 32-P was administered perorally and 89-Sr injected intravenously. We also studied the changes in the levels of hemoglobin, white blood cells (WBCs) count and platelets count.. We found a significant decrease in the WBC and platelet count in the patients treated with 32-P (U = 2.20, P < 0.05 and U = 4.57, P < 0.001) one month after the therapy. These parameters showed no significant decrease in the group treated with 89-Sr. The pain, which was the rationale to use the radioactive isotopes, was relieved and the patients restored their previous mobility.. The fact that 32-P alleviated the grave symptom of pain at the relatively weak radiation dose used (2 mCi) is a strong indication that this radiopharmaceutical can be used successfully for such a purpose, although some authors argue against its use in view of the myelosuppresion it causes. This myelosuppression, however, is mild and transient even without treatment and patients could benefit from this adjuvant treatment to manage the pain syndrome. 89-Sr administered intravenously in a dose of 4mCi also relieves pain efficiently but its use is limited by the cost of the quantity needed for 1 patient and for a single dose. The National Health Insurance Fund currently reimburses for a very limited quantity of this substance which makes the cost of the procedure 15 times as expensive as that using radioactive phosphorus.. Using the radiopharmaceuticals 32-P and 89-Sr provides an additional, easy and efficacious means for palliation of cancer patients with bone metastases, especially those who are refractory to percutaneous irradiation.

Topics: Bone Neoplasms; Breast Neoplasms; Female; Humans; Leukocyte Count; Lung Neoplasms; Male; Pain; Pain Measurement; Phosphorus Radioisotopes; Platelet Count; Prostatic Neoplasms; Strontium Radioisotopes; Treatment Outcome

Examination of 127 patients with generalized prostate cancer established a low prophylactic effect of systematic treatment with strontium-39 chloride: it failed to alleviate pain in metastatic cancer, nor was it followed by longer mean survival. Repeat systematic radiotherapy is not indicated when palliative measures such as hormonal therapy, local radiotherapy and chemotherapy are still effective.

Topics: Aged; Bone Neoplasms; Humans; Male; Middle Aged; Neoplasm Staging; Pain; Palliative Care; Prostatic Neoplasms; Quality of Life; Retreatment; Strontium; Strontium Radioisotopes; Treatment Failure; Whole-Body Irradiation

To investigate the therapeutic effects of strontium-89 against osseous metastases of lung cancer.. A total of 126 patients with osseous metastases of lung cancer received strontium-89 treatment ((89)SrCl(2)) at the dose of 148 MBq given through a single intravenous injection. The analgesic effect was evaluated by the changes in the degree, frequency and scores of the pain, and the therapeutic effect assessed by observing the changes in the number and volume of osseous lesions after therapy and compared between different pathological types of lung cancer by Ka-square test.. Within 6 months after the injection, the total pain relief rate was 70.6% (89/126), including 25 (19.8%) cases with pain vanished, suggesting significant alleviation of the pain intensity by the treatment (u=5.361, P<0.01). The frequency of pain was reduced in 78.6% (99/126) of the cases (u=4.589, P<0.01), and the average score of pain decreased significantly from 7.54+/-3.29 to 4.19+/-4.38 (t=6.865, P<0.001). The number and size of lesions decreased by more than 25% in 57 cases, showing a total efficacy rate of 45.2% (57/126). No significant difference was noted in the therapeutic effects among the 4 pathological types of lung cancer (P>0.05).. Strontium-89 is effective for pain relief and tumor focus confinement in osseous metastases of lung cancer. No significant difference has been found in its effect between 4 different pathological types of lung cancer.

Topics: Adenocarcinoma; Adult; Aged; Bone Neoplasms; Carcinoma, Squamous Cell; Female; Humans; Lung Neoplasms; Male; Middle Aged; Pain, Intractable; Strontium Radioisotopes

We studied the correlation between the efficacy of local external beam radiotherapy and the efficacy of strontium-89 in the palliation of osteoblastic metastatic bone pain in 43 patients with cancer. All 43 had been treated with hormonal or chemotherapy according to the primary malignancies and analgetic pharmacotherapy as needed, 36 received local external beam radiotherapy as a palliative before strontium-89 injection, and all 43 were ultimately treated with strontium-89 as salvage therapy. Responses to the first strontium treatment, and to the first radiation treatment if given, were taken from patient files. Pain was evaluated by Karnofsky performance status, analgesic dosage, and duration of response to treatment translated into numeric scores on a pain duration scale and an integrated response scale. The efficacy of limited field external radiation in metastatic bone pain palliation was 80.6% versus 58.1% for strontium-89. Patients treated with both external radiation and strontium had a positive correlation of 0.4 with a probability of P = 0.0158 between the responses to the 2 treatments, indicating that response to external radiotherapy could be viewed as an indicator of strontium-89 efficacy in metastatic osteoblastic bone pain palliation in the same patient. No significant correlation was found between strontium efficacy and gender, location of metastases to weight-bearing bones, duration of hormonal therapy or chemotherapy, or type of primary neoplasm.

Topics: Bone Neoplasms; Female; Humans; Male; Pain Measurement; Pain, Intractable; Palliative Care; Radiopharmaceuticals; Retrospective Studies; Salvage Therapy; Strontium Radioisotopes

A clinical test of strontium-89 chloride effect was carried out in 150 patients with bone metastases and bone pain from different patterns of tumor. Different types of bone lesions were considered. Pain-relieving effect was reported in 77%, irrespective of lesion gravity. There was no response to strontium-89 chloride in 150 patients with bone metastases. It mostly occurred in cases of lysis. Strontium-89 chloride therapy contributed to partial bone tissue repair. It is indicated as a component of complex treatment for bone metastases.

Topics: Analgesics; Antineoplastic Agents; Bone Neoplasms; Breast Neoplasms; Female; Humans; Male; Pain; Prostatic Neoplasms; Radionuclide Imaging; Strontium; Strontium Radioisotopes

Topics: Bone Neoplasms; Child, Preschool; Female; Humans; Osteosarcoma; Pain; Palliative Care; Strontium Radioisotopes

Topics: Anthracyclines; Bone Neoplasms; Disease Progression; Humans; Male; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Strontium Radioisotopes; Survival Analysis

The goals of this investigation are to determine whether commercially available dose calibrators can be used to measure the activity of beta-emitting radionuclides used in pain palliation and to establish whether manufacturer-supplied calibration factors are appropriate for this purpose.. Six types of commercially available dose calibrators were studied. Dose calibrator response was controlled for 5 gamma-emitters used for calibration or typically encountered in routine use. For the 4 most commonly used beta-emitters ((32)P, (90)Sr, (90)Y, and (169)Er) dose calibrator efficiency was determined in the syringe geometry used for clinical applications. Efficiency of the calibrators was also measured for (153)Sm and (186)Re, 2 beta-emitters with significant gamma-contributions. Source activities were traceable to national standards.. All calibrators measured gamma-emitters with a precision of +/-10%, in compliance with Swiss regulatory requirements. For beta-emitters, dose calibrator intrinsic efficiency depends strongly on the maximal energy of the beta-spectrum and is notably low for (169)Er. Manufacturer-supplied calibration factors give accurate results for beta-emitters with maximal beta-energy in the middle-energy range (1 MeV) but are not appropriate for use with low-energy ((169)Er) or high-energy ((90)Y) beta-emitters. beta-emitters with significant gamma-contributions behave like gamma-emitters.. Commercially available dose calibrators have an intrinsic efficiency that is sufficient for the measurement of beta-emitters, including beta-emitters with a low maximum beta-energy. Manufacturer-supplied calibration factors are reliable for gamma-emitters and beta-emitters in the middle-energy range. For low- and high-energy beta-emitters, the use of manufacturer-supplied calibration factors introduces significant measurement inaccuracy.

Topics: Beta Particles; Bone Neoplasms; Erbium; Humans; Palliative Care; Phosphorus Radioisotopes; Radiation Monitoring; Radioisotopes; Radiometry; Radiotherapy; Strontium Radioisotopes; Yttrium Radioisotopes

Topics: Bone Neoplasms; Cost-Benefit Analysis; Health Care Costs; Humans; Pain; Quality of Life; Strontium Radioisotopes

More than two-thirds of the patients with osseous metastases experience debilitating bone pain, requiring some form of pain relief. Analgesics are limited in their efficacy. Palliative application of hemi-body external beam radiation therapy in the treatment of multiple osseous metastases also is limited due to toxicity associated with large treatment ports. Intravenous injections of bone seeking radioisotopes are effective in the palliation of pain with fewer side effects. Forty-one patients with multiple osseous metastases due to prostate and breast cancer were treated with strontium chloride 89 (89Sr) at the department of radiation oncology, in a university hospital. A retrospective analysis of these patients indicated that all subjects had severe pain that diminished their quality of life. Most of these patients had multiple co-morbid factors. Many were on opioids leading to adverse effects such as nausea, constipation, and drowsiness that required additional medication. Objective findings and evaluation of the responses were not always available for all patients. Following treatmentwith 89Sr, over two-thirds of the patients responded favorably and required lower doses of opioids.

Topics: Black or African American; Bone Neoplasms; Breast Neoplasms; Female; Hospitals, University; Humans; Male; Pain; Palliative Care; Prostatic Neoplasms; Retrospective Studies; Strontium; Strontium Radioisotopes

To investigate the influence of 89Sr on the cell immune function in patients with multiple bone metastases.. Patients with multiple bone metastases were treated with in vivo radiation of 89Sr. The T cell subsets, NK cell activities, and lymphocyte transformation rate (LTR) of multiple bone metastases before and after the 89Sr treatment were measured.. With the palliation of the pain of the patients after the 89Sr treatment, the T cell subset level, NK cell activities, and LTR increased. There was no significant change in the patients with the pain.. Treating multiple bone metastases with 89Sr can improve the cell immune function of the patients to a certain extent.

Topics: Adult; Aged; Bone Neoplasms; Breast Neoplasms; Female; Humans; Immunity, Cellular; Killer Cells, Natural; Male; Middle Aged; Prostatic Neoplasms; Strontium Radioisotopes; T-Lymphocyte Subsets

The biological effect of a radiopharmaceutical depends heavily on the heterogeneity of the uptake in the various tissues. A comparative study of two radiopharmaceuticals should therefore include a comparison of the uptake patterns in different tissues. To eliminate the problems caused by variation in kinetics and tumour characteristics between individuals, such a comparison should be based on measured distributions of the radiopharmaceuticals in the same tissue sample. The excellent linearity between activity and counts in images obtained with a digital silicon strip detector allows such distributions to be derived from two autoradiographs acquired at different time points. This method was applied in a comparison of the uptake patterns of 153Sm-EDTMP and 89SrCl2 in sections obtained from a dog with spontaneous osteosarcoma, containing both tumour and normal bone tissues. As the areas of the section were larger than the detector area, the section had to be cut into smaller parts. Images of these were later merged by means of image processing techniques. There were significant differences in the uptake patterns of the two nuclides. In the primary tumour, the uptake of 153Sm was highly heterogeneous, while 89Sr was more uniformly distributed. In trabecular bone, the accumulation of 153Sm was higher than that of 89Sr. In solid cortical bone, 89Sr had the highest uptake.

Topics: Animals; Autoradiography; Bone Neoplasms; Dog Diseases; Dogs; Organometallic Compounds; Organophosphorus Compounds; Osteosarcoma; Radioisotopes; Radionuclide Imaging; Radiopharmaceuticals; Samarium; Strontium; Strontium Radioisotopes

The radiation absorbed dose in the rabbit bone delivered by 153Sm-EDTMP (samarium ethylenediaminetetra methylene diphosphonic acid) and 89SRCl2 (strontium chloride) was measured by means of electron spin resonance (ESR). These radioisotopes are used in systemic radiotherapy for palliation of painful bone metastases. The knowledge of the dose is important in order to avoid side effects to the bone marrow. The ESR radiation dose signal was calibrated by the additive dose method using cobalt-60 gamma rays. For 153Sm-EDTMP, the bone doses in three rabbits were (4 +/- 2), (5 +/- 1) and (5 +/- 2) cGy kg/MBq. For 89SrCl2, a dose of (2 +/- 1) cGy kg/MBq was found in one rabbit.

Topics: Animals; Bone and Bones; Bone Marrow; Bone Neoplasms; Electron Spin Resonance Spectroscopy; Humans; Organometallic Compounds; Organophosphorus Compounds; Palliative Care; Rabbits; Radioisotopes; Radiometry; Radiopharmaceuticals; Radiotherapy Dosage; Samarium; Strontium; Strontium Radioisotopes

Topics: Aged; Bone and Bones; Bone Neoplasms; Humans; Male; Pain, Intractable; Palliative Care; Prostatic Neoplasms; Radionuclide Imaging; Radiopharmaceuticals; Strontium Radioisotopes; Technetium Tc 99m Medronate

Topics: Antineoplastic Agents; Bone Neoplasms; Doxorubicin; Humans; Male; Prostatic Neoplasms; Strontium Radioisotopes; Survival Rate

A review of 50 patients treated with strontium-89 for prostate cancer bone metastases from January 1993-1997 at the Wellington Cancer Centre was undertaken to determine if there was any correlation between changes in prostate-specific antigen (PSA) following treatment and subsequent survival. Thirty cases were evaluable for PSA response. Of these, 14 had a fall in PSA following strontium-89 treatment, and their mean survival was 641 days. The remaining 16 patients did not demonstrate a post-treatment fall in PSA and their mean survival was 275 days. A difference between these two groups in the time to development of new bone symptoms following treatment was also observed. No significant correlation between pretreatment PSA and PSA response was observed. In conclusion, a PSA response following strontium-89 treatment appears to predict for improved survival in patients with bone metastases from carcinoma of the prostate. Further prospective studies are indicated.

Topics: Aged; Bone Neoplasms; Humans; Male; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Strontium Radioisotopes; Survival Analysis; Treatment Outcome

The purpose of the present work was to investigate how haematopoietic stem cell survival is affected by the differences in the dose distribution that arise from different radionuclides contained in bone-seeking radiopharmaceuticals. This was carried out in three steps: (a) calculations of representative dose distributions in individual bone marrow cavities that are irradiated by sources of 89Sr, 186Re, 117mSn or 153Sm, uniformly distributed on the bone surfaces; (b) assessment of the corresponding haematopoietic stem cell survival and (c) a comparison of these results with results obtained using the assumption of a uniform dose distribution. Two different idealized models of the geometry of trabecular bone were formulated, each consisting of an infinite array of identical elements. Monte Carlo simulations were used to generate dose-volume histograms that were used to assess haematopoietic stem cell survival with two different assumptions about spatial cell distributions. Compared with a homogeneous dose distribution, the estimated cell survival was markedly higher for 117mSn and 153Sm, and only slightly different for 89Sr and 186Re. The quantitative results differed between the two geometric models and the assumptions about spatial cell distribution, but the trends were the same. The results imply that it is necessary to include dose distributions for individual bone marrow cavities in considerations concerning bone marrow toxicity.

Topics: Age Factors; Bone Neoplasms; Cell Survival; Dose-Response Relationship, Radiation; Hematopoietic Stem Cells; Humans; Isotopes; Models, Theoretical; Monte Carlo Method; Radioisotopes; Radiotherapy Planning, Computer-Assisted; Rhenium; Samarium; Strontium Radioisotopes; Tin

A multicentre observational study was conducted by the Italian Association of Nuclear Medicine between 1996 and 1998. Twenty-nine Nuclear Medicine Departments participated. The aims of the study were to systematically evaluate the efficacy, toxicity and repeatability of radionuclide therapy of painful bone metastases (RTBM) in a large number of patients and to assess its incidence in patients with prostate cancer. Out of 818 treatments performed with a single i.v. dose of 148 MBq of strontium-89 chloride or 1,295 MBq of rhenium-186 hydroxyethylidene diphosphonate (HEDP), 610 could be evaluated (527 with 89Sr and 83 with 186Re-HEDP). Eighty-one patients received multiple (up to five) RTBM. The total number of retreatments was 100. Patients were followed up for a period of 3-24 months. Results, assessed according to pain relief and consumption of analgesic drugs, were expressed at four levels: 1, no response; 2, mild response; 3, good response; 4, excellent response. Responses were: level 1 in 19%, level 2 in 21.3%, level 3 in 33.3% and level 4 in 26.4% of cases. Retreatments showed significantly (P<0.01) worse responses (48% levels 3+4), in comparison to first RTBM. Duration of palliation was 5.0+/-3.5 months, and was longer in cases of excellent response, in first RTBM, in patients with limited metastases and when 89Sr was used. Better responses were found in cases of limited skeletal disease, under good clinical conditions, when life expectancy exceeded 3 months, and in radiologically osteoblastic or mixed bone lesions. The only statistically significant predictive factor was life expectancy (P<0.001). Flare phenomenon (14.1% of cases) did not correlate with the response. Haematological toxicity (mild to moderate in most cases) mainly affected platelets, and was observed in 25.5% of cases overall and in 38.9% of retreatments. RTBM did not seem to prolong life, though in some cases scintigraphic regression of bone metastases was observed. The two radiopharmaceuticals did not show any statistically significant differences in palliative efficacy and toxicity, either in first RTBM or in retreatments.

Topics: Aged; Aged, 80 and over; Bone Neoplasms; Etidronic Acid; Humans; Injections, Intravenous; Male; Middle Aged; Organometallic Compounds; Pain; Pain Measurement; Palliative Care; Prostatic Neoplasms; Radionuclide Imaging; Radiopharmaceuticals; Rhenium; Strontium; Strontium Radioisotopes

This work was done to evaluate the indication, effectiveness, and side effects of internal radiotherapy with radioactive nuclide strontium-89 (89Sr) in patients with malignant metastasis in the bone.. Fifty-six patients with skeletal metastasis received this internal radiotherapy. The patients were observed and followed up with respect to pain control, lesion improvement and side effects.. The overall effective rate of pain control was 76.8% with the effective rate of prostatic cancer and breast cancer higher than 80%. The lesions in 81.8% patients as assessed by SPECT imaging, were improved. The mild lowering of white cells, platelets and red cells was the main side effect.. Internal radiotherapy with 89Sr is very useful for patients with malignant cancer metastasis in the bone.

Topics: Adult; Aged; Bone and Bones; Bone Neoplasms; Breast Neoplasms; Female; Humans; Lung Neoplasms; Male; Middle Aged; Pain; Prostatic Neoplasms; Strontium; Strontium Radioisotopes; Treatment Outcome

89SrCl2 is currently used as a palliative treatment for painful osseous metastases associated with an osteoblastic reaction in bone. However, the underlying biologic mechanism by which 89SrCl2 accumulates at these lesions and mediates palliation remains unclear. The aim of this study was therefore to elucidate this mechanism.. An in vitro cell biologic model, incorporating the MC3T3-E1 murine osteoblast cell line, was established to replicate the process of collagen production and mineralization. Experiments were performed to investigate the cellular association of 89SrCl2 and 45CaCl2 with both MC3T3-E1 cells and the PC-3 human prostate adenocarcinoma cell line.. No evidence of intracellular localization of 89SrCl2 or 45CaCl2 was found for either cell line. Localization of radiolabel was seen to be associated with MC3T3-E1 cells but only in cultures that had undergone both differentiation and mineralization. The association of 89SrCl2 was inhibited by the alkaline phosphatase inhibitor levamisole, and extracellular localization of 89SrCl2 was confirmed by microautoradiography.. 89SrCl2 acts as a calcium mimic and, as such, becomes associated with the collagen matrix produced by the MC3T3-E1 cells during collagen mineralization.

Topics: Animals; Bone and Bones; Bone Neoplasms; Calcification, Physiologic; Calcium Chloride; Calcium Radioisotopes; Cell Line; Collagen; Humans; Male; Mice; Palliative Care; Prostatic Neoplasms; Strontium; Strontium Radioisotopes; Time Factors; Tumor Cells, Cultured

Topics: Analgesics, Non-Narcotic; Animals; Bone Neoplasms; Humans; Organometallic Compounds; Organophosphorus Compounds; Pain, Intractable; Palliative Care; Phosphorus Radioisotopes; Radioisotopes; Samarium; Strontium; Strontium Radioisotopes

Palliative systemic radionuclide therapy with 89Sr-chloride is a useful intervention for patients with bone pain from metastatic prostatic cancer. Although this radionuclide is highly effective, its mechanism of action remains unresolved. This investigation sought to determine whether systemic radionuclide therapy decreases the production of cell adhesion molecules (E-selectins) that participate in the metastatic process.. Sera were collected from 25 men with metastatic (stage IV) prostate carcinoma who received 89Sr-chloride palliative therapy and from 10 age-matched healthy volunteers. The serum concentration of E-selectin was quantified by an enzyme-linked immunosorbent assay. Sera from 5 patients who received 2 courses of radionuclide therapy were also included in the analysis.. A 2.8-fold decrease in serum E-selectin concentration occurred within 2 mo of radionuclide therapy (P < 0.0001). At 10 mo, however, the concentration increased to a mean (+/- SD) of 151.2 +/- 51.3 ng/mL, surpassing the baseline concentration. This pattern coincided with symptomatic improvement and subsequent health status deterioration. For patients who received 2 courses of radionuclide therapy, a second fall in serum E-selectin concentration followed the second radionuclide treatment.. A significant decrease in serum E-selectin concentration was observed after systemic radionuclide therapy. This finding suggests that expression of cell adhesion molecules, an important determinant of metastatic progression, may be inhibited by 89Sr-chloride.

Topics: Adenocarcinoma; Aged; Bone Neoplasms; E-Selectin; Enzyme-Linked Immunosorbent Assay; Humans; Male; Pain; Pain Management; Pain Measurement; Palliative Care; Prostate-Specific Antigen; Prostatic Neoplasms; Strontium; Strontium Radioisotopes

Strontium-89 chloride (89Sr) is a new radiopharmaceutical that provides effective pain relief for metastatic bone lesions, and is expected to be available soon in the palliative management for metastatic bone pain in Japan. Because of relatively long physical half life (50.5 days), 89Sr may affect to the radioactive draining-water system by exceeding the limits of activity concentration for radioactive drain. In this article, the influence of 89Sr use on the radioactive drainage system was simulated.. The standard tank capacity of drainage and draining frequency was determined from the results of questionnaire carried out for the nationwide medical and research institutes where radioisotope treatment are performed. On the assumption that 89Sr of 148 MBq for one therapy was used twice a week and several common radionuclides were used as the same activity as used at Chiba Cancer Center, the influence of 89Sr was estimated. The calculation was performed using the activity contamination ration into the draining-water system of each radionuclide of 0.01, which was legally determined.. The simulation revealed that the sum of the contamination ratios of individual radionuclides exceeded a legal value of 1.0 in standard drainage with the capacity of 5 m3 and 10 m3 and draining frequency of 7 times per year. The actual contamination ratios of common radiopharmaceuticals measured at Chiba Cancer Center ranged from 1/100 to 1/1000 of the legal values.. It is necessary that the legal value of activity contamination ratios into the draining-water system should be reassessed before starting 89Sr therapy.

Topics: Bone Neoplasms; Half-Life; Humans; Medical Waste Disposal; Radioactive Waste; Radiopharmaceuticals; Sanitary Engineering; Strontium Radioisotopes; Time Factors; Waste Disposal, Fluid; Water Pollution, Radioactive

Investigation of a possible increase in sensitivity to occurrence of radionuclide-induced skeletal malignancy with increasing body size was analyzed among 358 beagles injected as young adults with either 226Ra or monomeric 239Pu and maintained for their lifespans. Corresponding analyses were performed for about 240 other beagles injected as young adults with 90Sr, 228Ra, or 228Th. Body masses at the time of injection ranged between about 5.6 and 16 kg. Logistic regression analysis using body mass and cumulative skeletal radiation dose as the independent variables indicated that there could not be established a dependency of tumor occurrence upon body mass, although skeletal dose was found to be significantly correlated with occurrence of bone cancer. Regression analysis indicated that for any dosage group there could not be established a correlation between body mass and skeletal dose. Each dosage group having similar injected kBq kg(-1) for each nuclide was divided into 2 subgroups of equal size, one containing the less massive dogs and the other containing the more massive dogs. These subgroups within a roughly uniform value of skeletal dose-rate were compared by Fisher's Exact Test, and the less massive subgroups were combined within each nuclide for an additional, separate analysis against the combined more massive subgroups using the same method. In only one instance (the dosage group given 3607 kBq 90Sr kg(-1)) was there indicated a substantially greater tumor occurrence among dogs in the more massive subgroup (p = 0.061). However, for the group given 0.382 kBq 239Pu kg(-1) there was indicated a significant difference between subgroups, but the effect was exactly opposite to that found for the highest level 90Sr dogs in that the less massive subgroup had a higher relative tumor occurrence than the most massive (p = 0.042). For all groups with a p-value < 0.10, a possible correlation was investigated between survival and body mass at injection (since bone tumor occurrence might be a function of longevity), but a significant relationship could not be determined. No significant differences could be established between the combined more massive and the combined less massive subgroups for any radionuclide. We conclude that, for the conditions in our experiment, relative size within a species does not contribute importantly to the sensitivity (lifetime occurrence) for induction of skeletal malignancy.

Topics: Animals; Body Constitution; Bone Neoplasms; Dogs; Dose-Response Relationship, Radiation; Neoplasms, Radiation-Induced; Plutonium; Radiation Dosage; Radioisotopes; Radium; Regression Analysis; Sensitivity and Specificity; Strontium Radioisotopes; Thorium; Time

This retrospective study evaluated the toxicity and efficacy of strontium-89 chloride (Metastron, Amersham) in 94 patients with painful bone metastases of prostate cancer (117 injections of 150 MBq) and compared the efficacy of treatment in patients with moderate and extensive bone involvement. The predictive value of flare response with regard to analgesic response was also studied. High-grade leukothrombopenias were observed after only 5% of injections. An improvement in quality of life was obtained in 65% of cases, a decrease in pain in 78% (31% complete response) and a reduction of analgesics in 60%. Efficacy was significantly better for pain decrease (P=0.005) and reduction of analgesics (P=0.018), and response was significantly longer (P<0.0035) in patients with moderate than in patients with extensive bone involvement. The flare response observed in 23% of cases was not predictive of pain response (P=0.919) or reduction of analgesics (P=0.353). A second dose prolonged analgesia in three-quarters of cases without any apparent increase in toxicity. These results confirm the benefit of 89Sr chloride for the treatment of metastatic bone pain and suggest that internal radiotherapy should be started earlier. A bone scan could be proposed at the time of hormonal escape resulting in bone pain, and internal radiotherapy could be initiated when several metastatic foci exist, even if only one is painful. In this way, pain-free follow-up could be prolonged, and the transition to other therapeutic approaches, particularly opioids, delayed.

Topics: Aged; Aged, 80 and over; Analgesia; Analgesics; Bone Neoplasms; Humans; Injections, Intravenous; Male; Middle Aged; Pain; Pain Management; Palliative Care; Prostatic Neoplasms; Quality of Life; Radiopharmaceuticals; Retrospective Studies; Strontium; Strontium Radioisotopes

Our analysis of data from the beagle project completed at the University of Utah has provided some comparisons that appear to be useful in testing the model proposed by Raabe of effective thresholds for induction of skeletal malignancy by bone-seeking radionuclides in beagles. Raabe's model predicted that cumulative skeletal doses of less than about 0.9 to 1.4 Gy from alpha emitters or 28 to 70 Gy from beta emitters deposited in the skeleton require a long enough time for bone cancer expression that the dog's natural lifespan would be exceeded before the tumor appeared. Results from the Utah beagle project seem to confirm these projections for 226Ra, 228Ra and, perhaps, for 90Sr. The lowest doses at which malignant bone tumors were observed in animals injected with these radium isotopes were about 0.9 Gy (226Ra) and 3 Gy (228Ra). For the beta emitter, 90Sr, the lowest doses at which bone tumors were seen were about 18, 50, and 70 Gy with an expectation for naturally occurring tumor of about one. Twenty-six of the two hundred and thirty-three Utah beagles given monomeric 239Pu that developed skeletal malignancies had doses between 0.02 and 0.51 Gy (80 of these dogs had skeletal doses of less than 0.9 Gy). Three dogs of 54 given 241Am with doses lower than 0.9 Gy had bone tumors at 0.23, 0.56, and 0.88 Gy with the expectation of about one naturally occurring case. For 25 animals injected with 228Th at skeletal doses below 0.9 Gy, one bone tumor dog had a dose of about 0.4 Gy, and the expectation of a dog with natural tumor among the group was only about 0.38. Five beagles of 74 given 224Ra with resulting doses of less than 0.9 Gy died with skeletal malignancy at 0.32 Gy or less with an expectation for non 224Ra induced tumor of about one. It appears that Raabe's proposal might be confirmed for some but not all of the radionuclides used in the Utah studies. Models presented in earlier papers by Raabe provide results that are somewhat different from his recent abstract and compare more favorably with those cited herein for Utah dogs. Re-examination of our data for these analyses has suggested a novel concept for calculation of carcinogenic dose to endosteal bone surfaces.

Topics: Americium; Animals; Bone Neoplasms; Dogs; Neoplasms, Radiation-Induced; Plutonium; Radium; Strontium Radioisotopes; Thorium

32p and 89Sr have been shown to produce significant pain relief in patients with skeletal metastases from advanced cancer. Clinically significant pancytopenia has not been reported in doses up to 12 mCi (444 MBq) of either radionuclide. To date, no reports comparing the relative efficacy and toxicity of the two radionuclides in comparable patient populations have been available. Although a cure has not been reported, both treatments have achieved substantial pain relief. However, several studies have used semiquantitative measures such as "slight," "fair," "partial" and "dramatic" responses, which lend themselves to subjective bias. This report examines the responses to treatment with 32P or 89Sr by attempting a quantification of pain relief and quality of life using the patients as their own controls and compares toxicity in terms of hematological parameters.. Thirty-one patients with skeletal metastases were treated for pain relief with either 32P (16 patients) or 89Sr (15 patients). Inclusion criteria were pain from bone scan-positive sites above a subjective score of 5 of 10 despite analgesic therapy with narcotic or non-narcotic medication, limitation of movement related to the performance of routine daily activity and a predicted life expectancy of at least 4 mo. The patients had not had chemotherapy or radiotherapy during the previous 6 wk and had normal serum creatinine, white cell and platelet counts. 32P was given orally as a 12 mCi dose, and 89Sr was given intravenously as a 4 mCi (148 MBq) dose. The patients were monitored for 4 mo.. Complete absence of pain was seen in 7 of 16 patients who were given 32P and in 7 of 15 patients who were given 89Sr. Pain scores fell by at least 50% of the pretreatment score in 14 of 16 patients who were given 32P and 14 of 15 patients who were given 89Sr. Mean duration of pain relief was 9.6 wk with 32P and 10 wk with 89Sr. Analgesic scores fell along with the drop in pain scores. A fall in total white cell, absolute granulocyte and platelet counts occurred in all patients. Subnormal values of white cells and platelets were seen in 5 and 7 patients, respectively, with 32P, and in 0 and 4 patients, respectively, after 89Sr therapy. The decrease in platelet count (but not absolute granulocyte count) was statistically significant when 32P patients were compared with 89Sr patients. However, in no instance did the fall in blood counts require treatment. Absolute granulocyte counts did not fall below 1000 in any patient. There was no significant difference between the two treatments in terms of either efficacy or toxicity.. No justification has been found in this study for the recommendation of 89Sr over the considerably less expensive oral 32P for the palliation of skeletal pain from metastases of advanced cancer.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Analgesia; Blood Cell Count; Bone Neoplasms; Humans; Infusions, Intravenous; Male; Middle Aged; Pain; Pain Management; Pain Measurement; Palliative Care; Phosphorus Radioisotopes; Quality of Life; Strontium Radioisotopes

Topics: Bone Neoplasms; Breast Neoplasms; Female; Follow-Up Studies; Humans; Male; Palliative Care; Strontium Radioisotopes; Tomography, Emission-Computed

There are fundamental problems with the calculation of radiation doses to the skeleton from internal emitters deposited in bone. Some of these include dose inhomogeneities, identity of cells at risk and their dynamics, changing deposition patterns of bone-seeking radionuclides with time after exposure, seemingly unique responses of the skeleton to each deposited radionuclide, the role of radioactive progeny produced by deposited emitters and their individual dynamics and effects, different responses of mammals of different ages at exposure to identical dosages, different responses to different chemical forms of a given radionuclide, and different responses to an identical dose from a given radionuclide at different dose-rates. This situation makes it necessary to choose some common dose parameter that will allow the overall effects of different radionuclides to be compared directly so that projected effects of each of them in humans can be estimated. For radiation protection purposes, it appears premature to abandon the concept of average skeletal dose (which appears to be a practical compromise for use) until an undelusive, non-artificial and uncontrived method of calculating absorbed dose to the appropriate cells in bone is developed that fulfills the requirement of equal cancer response for equal skeletal dose for all circumstances.

Topics: Age Factors; Animals; Bone and Bones; Bone Neoplasms; Dogs; Dose-Response Relationship, Radiation; Humans; Mice; Microspheres; Models, Biological; Plutonium; Radioisotopes; Radiometry; Radium; Strontium Radioisotopes; Yttrium Radioisotopes

The aim of this retrospective study was to evaluate the efficacy of 85Sr in the palliation of metastatic bone pain. 85Sr decays by electron capture with a gamma emission of 514 keV and associated x-ray emissions of 10-15 keV; physical half-life is 64 d.. Between 1977 and 1992, 119 doses of 85Sr chloride (mean activity 335 MBq [9 mCi]) were intravenously administered to 108 patients with hyperalgic generalized bone metastases from prostatic carcinoma (52 patients), breast carcinoma (41) or other cancers (15). Pain, performance status, blood and urinary excretion values were investigated during follow-up, and survival time was recorded. Strontium bone scans were obtained up to 8 wk after injection to document isotope biodistribution and to estimate absorbed doses.. At 12 wk, 72.2% of patients showed significant benefit from treatment, i.e., enhanced quality of life and pain relief; 49.1% became free of pain. These beneficial effects lasted from 1 to 36 mo (mean 4.3 mo). The best symptomatic improvement was seen in patients treated at an early stage of metastatic skeletal disease and in prostate cancer patients. No evidence of a significant dose-response relationship was found in the data analysis. The mean absorbed dose ratio of metastases to marrow was estimated at 8.2. We found no evidence that hematological toxicity was a major problem; however, all patients experienced a reduction in blood counts, especially in platelets.. Systemic radionuclide therapy using 85Sr is a feasible, effective and well-tolerated palliative treatment in patients with refractory bone pain. We attained at least the same response rate as that reported with bone-seeking beta-emitting radionuclides such as 89Sr. The patients who benefited the most from 85Sr treatment were in an early stage of metastatic disease or had prostate cancer. Our clinical findings could not be linked to either the total injected activity of 85Sr or the estimated absorbed dose delivered to metastases.

Topics: Bone Neoplasms; Breast Neoplasms; Dose-Response Relationship, Radiation; Female; Humans; Male; Middle Aged; Pain, Intractable; Palliative Care; Prostatic Neoplasms; Retrospective Studies; Strontium; Strontium Radioisotopes

The objective of this study was to determine whether there is consistency of opinion regarding the management of metastatic bone disease pain among medical oncologists who are given the option of using systemic radionuclide therapy (89Sr, 153Sm).. One hundred board-certified medical oncologists were given a brief clinical summary of three patients with metastatic cancer. Management options included oral, parenteral and transdermal delivery forms of opioid analgesics; external beam irradiation; and systemic radionuclide therapy. The oncologists rated, in whole numbers from 1 (most appropriate) to 10 (least appropriate), their opinions on the appropriateness of each proposed intervention for each patient.. Systemic radionuclide therapy was perceived consistently as having low appropriateness for palliation of metastatic bony pain compared with opioid analgesics. A slight increase in appropriateness for systemic therapy was indicated for the patient with widespread metastatic disease, who, on the basis of literature reports, was unlikely to benefit from such therapy. The oncologists rated the appropriateness of systemic therapy as low in the patient with limited early disease, in which the literature indicates the greatest benefit will be derived from such intervention.. Referring oncologists perceive the appropriateness of systemic radionuclide therapy as low. Their perception of its appropriateness increases with extent of disease. As a result, this palliative option is underutilized or used in less-than-optimal disease settings.

Topics: Aged; Analgesics, Opioid; Attitude of Health Personnel; Bone Neoplasms; Data Collection; Female; Humans; Male; Medical Oncology; Middle Aged; Pain; Palliative Care; Radioisotopes; Samarium; Strontium Radioisotopes

Strontium-89 is effective in the palliation of bone pain caused by skeletal metastases. Its primary side effect is mild thrombocytopenia that typically recovers in 3 or 4 months. Subclinical disseminated intravascular coagulation is reported to be present in approximately 10% to 20% of patients with advanced prostate cancer. These patients may be at increased risk for severe marrow depression after radionuclide therapy for bone pain palliation. This report describes a patient with painful bony metastases resulting from prostate carcinoma. He had a normal platelet count and no clinical evidence of a coagulation disorder at the time of strontium-89 therapy, and a severe disseminated intravascular coagulation developed and lead to death after treatment. A normal platelet count before strontium-89 therapy does not preclude subsequent disseminated intravascular coagulation, and we support the Society of Nuclear Medicine's bone pain treatment procedure guideline that patients referred for bone palliation should be screened for disseminated intravascular coagulation before therapy.

Topics: Adenocarcinoma; Aged; Bone Neoplasms; Disseminated Intravascular Coagulation; Humans; Male; Pain, Intractable; Palliative Care; Prostatic Neoplasms; Strontium Radioisotopes

Topics: Bone Neoplasms; Child; Humans; Male; Neuroblastoma; Pain; Palliative Care; Strontium Radioisotopes

89Sr is a beta emitter used for palliation of pain in patients with metastatic bone cancer. After each intravenous administration, up to 80% of the isotope is eliminated in the urine. A simple chemical process is described, which permits the recovery and purification of the 89Sr from the urine.

Topics: Bone Neoplasms; Humans; Pain; Palliative Care; Strontium; Strontium Radioisotopes

What is the role of strontium-89 in effective palliative care of patients with stage D endocrine-refractory prostate cancer and multiple sites of painful bone metastases?. To make recommendations about the routine use of 89Sr in this clinical setting.. Effective palliation is the primary outcome of interest. Patient survival and toxic effects of treatment are also considered.. Evidence was selected and reviewed by 3 members of the Genitourinary Cancer Disease Site Group (Genitourinary Cancer DSG) of the Cancer Care Ontario Practice Guidelines Initiative. Earlier drafts of the guideline were circulated and reviewed by members of the DSG. The Genitourinary Cancer DSG comprises medical oncologists, radiation oncologists, urologists, a pathologist and a community representative. Guideline approval requires input from community representatives.. Three randomized controlled trials (RCTs) were available for evaluation. Two compared 89Sr with placebo, and one RCT compared 89Sr with conventional radiation (either hemibody or involved-field radiotherapy, as determined before randomization).. One of the 2 studies comparing 89Sr with placebo demonstrated the palliative efficacy of the intervention (p < 0.01); the other showed no benefit. The third study, comparing 89Sr with conventional radiation, concluded that all treatments provided equally effective pain relief and that improvement was sustained for at least 3 months in similar proportions of patients. The difference in the median duration of patient survival between groups in this study was neither clinically nor statistically significant.. The use of 89Sr may cause bone marrow suppression, but clinically significant sequelae are uncommon. The use of 89Sr may preclude further systemic chemotherapy or eligibility for clinical trials of systemic therapy. Symptoms other than those due to bone marrow suppression are rare.. 89Sr is recommended for use in patients with endocrine-refractory prostate cancer who have multiple uncontrolled painful sites of bone metastases on both sides of the diaphragm not adequately controlled with conventional analgesic therapy, and in whom the use of multiple single fields of external beam radiation is not possible. 89Sr has proven to be efficacious in the palliation of hormone-refractory painful bone metastases from prostate cancer. It has not been shown to lengthen the average duration of patient survival. There is limited evidence on the relative efficacy of 89Sr compared with wide-field radiotherapy. 89Sr is the treatment of choice given all the following specific indications: Established diagnosis of prostate cancer metastatic to bone. Metastatic disease refractory to hormone therapy. Progressive sites of pain poorly controlled with conventional narcotics. Painful sites of disease on both sides of the diaphragm (otherwise, hemibody radiotherapy is equally efficacious). Patient or tumour factors (number of involved sites, location of involved sites or level of pain control) that are relative contraindications to the use of multiple single fields of radiation as an alternative. No evidence of impending spinal cord compression. Adequate bone marrow reserve. Evidence from a diagnostic bone scan of radionuclide concentration in painful bone lesions. PRACTICE GUIDELINE DATE: Nov. 23, 1997. Part 2.. What is the role of 89Sr in effective palliative care of patients with stage D hormone-refractory prostate cancer receiving involved-field radiotherapy for isolated painful bone metastases?. As described in preceding abstract (Part 1).. One RCT was available for evaluati

Topics: Bone Marrow; Bone Neoplasms; Humans; Male; Palliative Care; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Strontium Radioisotopes

The authors report the cases of two patients in whom strontium-89 (89Sr) was used to relieve diffuse metastatic bone pain. The type of cancer involved, thymic carcinoid tumor, is itself rare and the risk of its metastasizing to the bone is very low. Both patients showed a measure of response to treatment, suggesting that this analgesic method has value for some patients. The marked benefit of one patient for a total of 9 months was attributable to two 89Sr injections, whereas the other patient improved for only 5 weeks after one injection.

Topics: Adult; Analgesics; Bone Neoplasms; Carcinoid Tumor; Humans; Injections, Intravenous; Male; Middle Aged; Pain, Intractable; Radiopharmaceuticals; Strontium Radioisotopes; Thymus Neoplasms

Strontium-89 is routinely used for pain control in advanced skeletal metastatic disease. A common side effect of Sr-89 therapy is a mild to moderate bone marrow suppression. To avoid complications from marrow suppression, a pretreatment platelet count of > 60,000/mm3 and a WBC count of > 2,400/mm3 are suggested. The authors present two patients who, despite satisfying these criteria, developed profound and prolonged bone marrow suppression after therapy. The severity of this response was most likely caused by pre-existing extensive bone marrow replacement with tumor. The contribution of local radiation therapy to bone marrow suppression is presumed to be minimal. The authors recommend that pretreatment criteria for determination of eligibility for Sr-89 therapy in selected patients be expanded to include steadily decreasing blood counts, and evaluation of extent of marrow involvement by biopsy or MR imaging.

Topics: Bone Marrow; Bone Marrow Neoplasms; Bone Neoplasms; Humans; Male; Middle Aged; Pain; Radiotherapy; Strontium Radioisotopes; Thrombocytopenia

An autopsy was performed on a patient who died after receiving 89Sr-chloride for treatment of bone pain from metastatic prostate carcinoma. Coordination between nuclear medicine physicians, radiation safety division personnel and pathologists resulted in minimal radiation exposure and the acquisition of dosimetry data.

Topics: Aged; Aged, 80 and over; Autopsy; Bone Neoplasms; Environmental Monitoring; Fatal Outcome; Humans; Male; Occupational Exposure; Prostatic Neoplasms; Protective Clothing; Strontium; Strontium Radioisotopes; Whole-Body Counting

Systemic radionuclide therapy with strontium chloride Sr 89 is a rediscovered alternative to relieve pain from bony metastases. Although numerous advances have been made in the diagnosis and treatment of cancer, pain remains a serious and debilitating disease complication. An increasing number of clinical trials are reporting satisfactory results with 89Sr-chloride therapy, now available for widespread clinical use. We have treated 11 patients with this radionuclide; of these patients, 8 had excellent to dramatic pain relief and 3 had mild to moderate improvement. Clinical response was based on subjective pain relief, increased mobility, decreased analgesic uptake, and/or improvement in daily activities, including work habits.

Topics: Activities of Daily Living; Bone Neoplasms; Breast Neoplasms; Humans; Male; Pain; Prostatic Neoplasms; Radiopharmaceuticals; Strontium Radioisotopes; Treatment Outcome

The urinary production of pyridinium collagen cross-links, pyridinoline (PYD) and deoxypyridinoline (DPD), has been correlated to increased bone resorption in patients with neoplasms. This study investigated the production of these compounds in patients with metastatic prostate carcinoma who received palliative treatment that did and did not include 89Sr-chloride therapy.. Urinary production of PYD and DPD was measured by high-performance liquid chromatography and natural flucrescence detection methods. The urine from several age-matched groups of patients was examined for these compounds including healthy controls (n = 20), patients with early-stage (Stage A-B) prostate carcinoma (n = 8), patients with metastatic prostate carcinoma treated with conventional analgesic and radiotherapeutic palliation (n = 20), patients with metastatic disease who underwent 89Sr-chloride therapy (n = 20) and patients with mild Paget's disease (n = 5). Patients were also monitored for urinary PYD and DPD production for a 6-mo interval after a palliative intervention.. Elevated PYD and DPD (p < 0.05) concentrations were measured in patients with metastatic and nonmetastatic prostate cancer and Paget's disease. The urinary production of these compounds remained unchanged for 6 mo after 89Sr-chloride therapy for symptomatic osseous metastases. However, the patients who did not undergo 89Sr-chloride therapy exhibited a two-fold increase in PYD and a four-fold increase in DPD above controls during the interval.. PYD and DPD are sensitive and specific bone resorption markers which demonstrate a slowing of bone resorption after palliative 89Sr-chloride therapy in patients with bone metastases.

Topics: Aged; Amino Acids; Bone Neoplasms; Bone Resorption; Case-Control Studies; Humans; Male; Osteitis Deformans; Palliative Care; Prostatic Neoplasms; Strontium; Strontium Radioisotopes; Time Factors

The bone-seeking radiopharmaceutical Sr-89 has been used as a palliative treatment for patients with bone pain caused by bone metastases. The authors report the results of nine patients (three with prostate cancer, four with breast cancer, one with thyroid cancer, and one with lung cancer) who underwent therapy with Sr-89 chloride for painful bone metastases, and evaluate Sr-89 imaging with bremsstrahlung. Two levels of dosage (1.5 and 2.2 MBq/kg) were used. Sr-89 imaging was performed in seven patients 1 week after injection. Abnormal uptake was seen in all and was consistent with the results of Tc-99m HMDP imaging. Six patients were assessed at 3 months and three patients toward the time they were terminal; 78% (seven of nine) derived some benefit. Two patients had a favorable clinical response and showed improvement on Tc-99m HMDP imaging.

Topics: Adult; Aged; Bone and Bones; Bone Neoplasms; Breast Neoplasms; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Pain; Palliative Care; Prostatic Neoplasms; Radionuclide Imaging; Radiopharmaceuticals; Radiotherapy Dosage; Remission Induction; Strontium Radioisotopes; Technetium Tc 99m Medronate; Terminal Care; Thyroid Neoplasms

We have used strontium-89 chloride (89Sr) for the palliative treatment of metastatic bone pain. Seventy-six patients (50 males with prostate carcinoma and 26 females with breast cancer) were treated with 148 MBq of 89Sr. Sixteen patients were retreated, receiving two or three doses; the total number of injected doses was consequently 95. The Karnofsky performance status was assessed and pain and analgesia were scored on scales of 9 and 5 points, respectively. The efficacy of 89Sr was evaluated at 3 months of treatment. Three levels of response were considered: good - when there was an increase in the Karnofsky status and a decrease in the pain score (equal to or higher than 4) or analgesic score (equal to or higher than 1); partial - when there was an increase in the Karnofsky status and a decrease in the pain score (2 or 3 points) without significant changes in the analgesic score; no response - if no variation or deterioration in these parameters was observed. In prostate cancer patients, the response was good in 64% of cases and partial in 25%, and there was no response in the remaining 11%. In breast cancer patients, the response was good in 62% of cases and partial in 31%, and there was no response in the remaining 8%. Duration of the response ranged from 3 to 12 months (mean 6 months). In the patients who were retreated the effectiveness was as good as after the first dose of 89Sr. A decrease in the initial leucocyte and platelet counts was observed after the 1st month of treatment, with a gradual partial to complete recovery within 6 months. It is concluded that 89Sr is an effective agent in palliative therapy for metastatic bone pain in patients with prostate or breast carcinoma. If required, retreatment can be administered safely and with the same efficacy as is achieved by the first dose.

Topics: Aged; Bone Neoplasms; Breast Neoplasms; Female; Humans; Karnofsky Performance Status; Male; Middle Aged; Pain, Intractable; Palliative Care; Prostatic Neoplasms; Radiotherapy Dosage; Strontium; Strontium Radioisotopes

The aim of this study was to optimise the parameters affecting the Bremsstrahlung scintigraphy of patients injected with strontium-89 chloride. The parameters considered were : (1) instrumental detection efficiency, and (2) tissue attenuation factor for 89Sr calibrated sources, which permit quantitative evaluation of the activity in a given bone lesion. Some typical examples of in vivo 89Sr imaging are presented to illustrate the clinical utility of the imaging procedure developed by us, which is implemented in our department for all patients treated with 89Sr chloride.

Topics: Bone Neoplasms; Breast Neoplasms; Calibration; Gamma Cameras; Humans; Lung Neoplasms; Male; Prostatic Neoplasms; Radionuclide Imaging; Radiopharmaceuticals; Strontium Radioisotopes; Technetium Tc 99m Medronate

Topics: Analgesics, Non-Narcotic; Bone Neoplasms; Female; Humans; Iodine Radioisotopes; Isotopes; Male; Organometallic Compounds; Organophosphorus Compounds; Palliative Care; Pentetic Acid; Radioisotopes; Recombinant Proteins; Samarium; Strontium; Strontium Radioisotopes; Thyroid Neoplasms; Thyrotropin; Tin

A model of strontium biodistribution similar to the one created by the International Commission on Radiological Protection (ICRP) was applied for activity and absorbed dose calculations in a patient with bone metastases treated with Sr-89 strontium chloride. Metastases are represented just like all other organs and tissues collecting strontium. Data from the ICRP's standard Reference Man were used.. Results include calculated time-activity data for all model compartments and for relevant target organs. Absorbed doses per unit administered activity were calculated for blood (0.036 cGy/MBq), soft tissues (0.046 cGy/MBq), bone marrow (1.15 cGy/MBq), bone surface (1.45 cGy/MBq), upper large intestine (ULI) (0.13 cGy/MBq), lower large intestine (LLI) (0.38 cGy/MBq), bladder (0.12 cGy/MBq), and metastases (37.5 cGy/MBq).. Results of the absorbed dose calculations are comparable with results presented in references for specific clinical cases. Discrepancies in dose values may be effected by the size of metastases and the patient's condition.

Topics: Bone Neoplasms; Humans; Radiotherapy Dosage; Strontium Radioisotopes

Strontium-89 chloride (Metastron) is an FDA-approved treatment for palliation of cancer pain. We evaluated blood count changes and pain relief in 28 patients with widespread painful bony metastasis treated with strontium-89 at the University of Minnesota Hospital and Clinics. Eighteen patients had prostate cancer (all hormone-refractory cancer), seven patients had breast cancer, and three patients had lung cancer, all previously treated with either radiation, chemotherapy, or a combination of the two. Serial blood counts were performed weekly up to 8 weeks and at 12 weeks after administering Metastron. Pain scale and blood values were monitored simultaneously. The mean baselines of hemoglobin (Hgb), white blood count (WBC), and platelets (Plts) were 11.4, 5900, and 258,000, respectively. The mean dose of Metastron was 3 mCi (range 2.2-4.4). The median time (range) to nadir was about 6 weeks. The percentage reductions relative to baseline were 32% (range 0-72%) for WBC; 14% (range 0-50%) for Hgb; 15% (range 0-47%) for the red blood cell (RBC) count; and 40% (range 0-85%)for Plts. We did not find a close relationship among the baseline blood count, reduction of subsequent blood counts, or previously irradiated active bone marrow volume. The median time of survival was 23 weeks (range 2-66 weeks). At 12 weeks, 29% of patients had moderate to dramatic improvement of pain, 32% had some relief of pain, and 50% had no improvement in pain. Thirty-two percent of the treated patients required additional palliative external beam radiation to their bony lesions within the study period. Our results show that Metastron for palliation for bony metastases should be used with caution because of moderate to severe bone marrow toxicity, especially in platelets, associated with its use. Careful evaluation of patients given Metastron is needed to assess accurately its full benefit.

Topics: Adult; Aged; Aged, 80 and over; Bone Marrow; Bone Neoplasms; Breast Neoplasms; Erythrocytes; Female; Follow-Up Studies; Hemoglobins; Humans; Leukocyte Count; Lung Neoplasms; Male; Middle Aged; Minnesota; Pain; Palliative Care; Platelet Count; Prostatic Neoplasms; Radiotherapy Dosage; Strontium; Strontium Radioisotopes; Survival Rate

We report two cases of children with metastatic bone disease who received strontium-89 intravenously. An 11-year-old boy with stage IV neuroblastoma received 50 microCi/kg of strontium-89. He had a good response, and his pain abated to the point that he could be taken off IV Dilaudid and was discharged from the hospital. A 7-year-old girl with the diagnosis of squamous cell carcinoma of the lung disclosed minimal increased uptake on a bone scan. Following the strontium-89 therapy, she did not have any significant improvement in pain, probably due to the minimal osteoblastic activity evidenced by the minimal abnormalities on the bone scan. Until this report there has been no reported case of using strontium-89 in the treatment of children with metastatic disease.

Topics: Analgesics, Opioid; Bone Neoplasms; Carcinoma, Squamous Cell; Child; Cranial Irradiation; Fatal Outcome; Female; Humans; Hydromorphone; Injections, Intravenous; Lung Neoplasms; Male; Neoplasm Staging; Neuroblastoma; Osteoblasts; Pain; Palliative Care; Patient Discharge; Remission Induction; Spinal Cord; Strontium Radioisotopes

Topics: Bone Neoplasms; Disseminated Intravascular Coagulation; Humans; Male; Palliative Care; Prostatic Neoplasms; Strontium Radioisotopes

Topics: Animals; Antineoplastic Agents; Bone Neoplasms; Diphosphonates; Humans; Methotrexate; Pain Management; Strontium Radioisotopes

In our institution, 4 mCi doses of the radiopharmaceutical strontium-89 (Sr89) have been given to 101 prostate cancer patients suffering from symptomatic bone metastases. Patients were prospectively analyzed for pain response, treatment-related hematologic toxicity, and survival. Pre-treatment clinical factors were correlated with outcome. Karnofsky Performance Scores (KPS) predicted for survival and pain response. Myelosuppression from the Sr89 treatment was minimal. Twenty-eight of the treated patients had a KPS of 60 or less. This group of patients had a median actuarial survival of 17.5 weeks, and collectively, met Hospice admission survival criteria. In a subset analysis of this group, patients with a KPS of 50 or less demonstrated a low pain response (40%) and average survival (12.5 weeks), both of which did not appear to justify the significant cost and risk of toxicity associated with Sr89 treatment. In these patients, opioids appeared to offer more cost-effective pain control. Patients with a pre-treatment KPS score of 60 had a mean survival of 20.5 weeks following Sr89 therapy, with 42 percent of patients experiencing a reduction in pain. We conclude that patients with a pretreatment KPS of 50 or less should not be treated with Sr89 and patients with a pretreatment KPS of 60 should be evaluated on a case-by-case basis to determine whether or not Sr89 represents the most reasonable treatment option for palliation of their bone pain.

Topics: Bone Neoplasms; Cost-Benefit Analysis; Hospice Care; Humans; Male; Pain Measurement; Palliative Care; Prospective Studies; Prostatic Neoplasms; Strontium Radioisotopes; Survival Analysis

Topics: Bone Neoplasms; Female; Humans; Male; Nuclear Medicine; Pain, Intractable; Palliative Care; Societies, Medical; Strontium Radioisotopes

Strontium-89 chloride is widely available in the U.S. and Europe for patients afflicted by bone metastasis associated with pain. 89Sr is a pure beta-emitter and it is thought to be difficult to estimate its distribution externally. We tried to image the distribution of 89Sr uptake with bremsstrahlung from beta-minus decay of 89Sr by using Nal scintillation camera. Pronounced 89Sr depositions in the bone metastatic sites were imaged in the energy windows from 50 keV to 150 keV bremsstrahlung. The distribution of these depositions corresponded to 99mTc-HMDP image may be suspected to the effectiveness of this therapy. The identification of 89Sr distribution might be useful in evaluating the bone marrow radiation dose too.

Topics: Aged; Bone and Bones; Bone Neoplasms; Female; Gamma Cameras; Humans; Male; Middle Aged; Pain, Intractable; Radionuclide Imaging; Radiotherapy, High-Energy; Scattering, Radiation; Scintillation Counting; Strontium Radioisotopes; Technetium Tc 99m Medronate

Radioactive strontium chloride (89Sr) was administered for pain relief in 6 patients with bone metastases (4 prostate cancer and 2 breast cancer patients). Out of 6 patients, 2 showed apparent relief of bone pain and improvement of QOL, and 3 showed slight relief of the pain with or without improvement of QOL; that is, 83% was effective. Side effects were seen in 2 patients; transient deterioration of bone pain in one patient and bone marrow suppression in the other patient. The patient who showed bone marrow suppression had rather more lesions of bone metastasis (diffuse metastasis) and least urinary excretion of the radioactivity. Urinary excretion for 2 days varied 5 to 40% of the administered dose and was less in the patients with more metastatic lesions.

Topics: Bone Marrow; Bone Neoplasms; Breast Neoplasms; Female; Humans; Male; Pain, Intractable; Prostatic Neoplasms; Radiotherapy, High-Energy; Strontium; Strontium Radioisotopes

Topics: Analgesics; Bone Neoplasms; Humans; Insurance, Health, Reimbursement; Pain; Strontium; Strontium Radioisotopes; United States

Topics: Bone Neoplasms; Humans; Male; Pain; Palliative Care; Prostatic Neoplasms; Strontium Radioisotopes

The systemic administration of 89Sr has proven effective in the palliation of painful osseous metastases. Biodistribution studies with the gamma-emitter 85Sr suggest that both its uptake and retention are increased in bone metastases, where increased mineral turnover takes place. To study the pattern and nature of this process further, bones containing metastatic deposits were obtained from three patients who had previously been treated with 148 MBq of 89Sr. The bones were cut into 0.5-1.0 cm sections. The cut surfaces which faced together were marked with India ink, and adjacent sections were submitted for histology and autoradiography. Strontium deposition and retention were observed in regions which exhibited significant osteoblastic activity, mostly in areas adjacent to metastatic deposits, but also in subchondral and endosteal locations, as well as in an area corresponding to a pathological fracture with callus formation. With these exceptions, strontium deposition was not observed in histologically normal bone or within the marrow. Our findings demonstrate directly the selective nature of accumulation and retention of 89Sr and confirm previous clinical impressions.

Topics: Adenocarcinoma; Biopsy; Bone Neoplasms; Breast Neoplasms; Female; Humans; Male; Pain; Palliative Care; Prostatic Neoplasms; Strontium Radioisotopes; Tissue Distribution

The total absorbed dose after systemic administration of 89Sr has been determined by measuring directly its activity in bone metastases. Autoradiography was performed on sections of bones obtained from patients treated with 89Sr to study the pattern of deposition. Discs of 5 and 8 mm diameter were cut from metastatic sites and normal bone. The beta-ray activity was determined with a scintillation counter, which was calibrated using similar bovine cancellous bone discs, onto which a known activity of 89Sr was transferred by pipette. From the activity measured, the initial activity (at the time of 89Sr administration) was calculated. The absorbed dose was estimated using the methodology described in NCRP Report No. 58. The estimated initial activity of 89Sr in the bone metastases varied from 2.3 to 240 MBq kg-1, with a mean value of 31 +/- 27 MBq kg-1. The total absorbed dose ranged from 1.3 to 64 Gy, with a mean of 18 +/- 16 Gy. The average total dose to normal bone sites was 1.1 +/- 0.4 Gy. The metastases to normal bone dose ratio in individual samples varied from 8 +/- 4 to 40 +/- 25. These estimates are in agreement with those obtained previously by indirect methods.

Topics: Autoradiography; Bone Neoplasms; Breast Neoplasms; Humans; Lung Neoplasms; Models, Theoretical; Radionuclide Imaging; Strontium Radioisotopes

Topics: Aged; Bone Neoplasms; Fatal Outcome; Humans; Male; Occupational Exposure; Prostatic Neoplasms; Strontium Radioisotopes

Topics: Bone Neoplasms; Humans; Pain; Patient Education as Topic; Strontium Radioisotopes

Topics: Bone Neoplasms; Humans; Male; Prostatic Neoplasms; Strontium Radioisotopes

Topics: Antineoplastic Agents; Bone Neoplasms; Government Agencies; Humans; Injections; Pain; Radiometry; Strontium; Strontium Radioisotopes; United States

Fifteen patients with breast cancer and skeletal metastases who had bone pain refractory to opioid analgesics and who were not eligible for or had not responded to local field radiotherapy, were treated with strontium-89. All patients had received previous treatment with chemotherapy and radiotherapy for bone metastases. Severity of bone pain, sleeping pattern, mobility and dependency on analgesics were evaluated before and 4, 8 and 12 weeks after 89Sr administration. Patients received 2 MBq/kg (118-148 MBq) of 89Sr by i.v. injection. Pain relief and a reduction in analgesic requirements were observed in 7 of the 15 (47%) patients, with a reduction in the severity score from 34% to 71%. Duration of the response varied from 3 to 7 months. A decrease in peripheral blood cell count was observed in 11 patients: a 15%-66% reduction in white cell count and a 14%-75% reduction in platelet count were detected at 12 weeks after treatment in these patients. We conclude that 89Sr is effective (47% response rate) for bone pain palliation in patients with bone metastases from breast cancer. Dependency on opioid analgesics may be reduced in patients with refractory bone pain.

Topics: Aged; Aged, 80 and over; Analgesics, Opioid; Bone Neoplasms; Breast Neoplasms; Female; Humans; Middle Aged; Pain, Intractable; Palliative Care; Prospective Studies; Strontium Radioisotopes

In several bone disorders, including those with metastatic involvement, changes in procollagen type I C-terminal and type III N-terminal peptides are detected, as indications of altered bone metabolism. Assessment of bone turnover could play a role in the evaluation of response to Strontium-89 used as palliative treatment in symptomatic bone metastases from various primary tumors. A correlation between bone formation rate markers procollagen I and III and efficacy of ionic Strontium-89 was shown in a group of 13 patients who underwent treatment with 4 mCi of Strontium-89 for painful bone metastases: 5 from breast, 7 from prostate, and 1 from lung carcinoid cancer. Assessed as a modification of analgesic intake, pain, and ambulation, there were 6 complete remissions, 3 partial remissions, and 4 nonresponders. The duration of the response was from 2 to 11 months. Procollagen I and III levels were found to be highly abnormal in those with no benefit from Strontium-89 administration but were in the normal range or only slightly elevated in those achieving complete or partial pain control, thus correlating with the clinical response.

Topics: Adult; Aged; Aged, 80 and over; Bone Density; Bone Neoplasms; Female; Humans; Male; Middle Aged; Palliative Care; Strontium Radioisotopes

Topics: Bone Neoplasms; Female; Georgia; Humans; Male; Pain, Intractable; Palliative Care; Physicians; Strontium Radioisotopes; Surveys and Questionnaires

Topics: Bone Neoplasms; Humans; Osteoblasts; Pain, Intractable; Palliative Care; Strontium Radioisotopes

A patient with metastatic prostate cancer was found to have low-grade disseminated intravascular coagulation (DIC). He had significant bone pain despite external-beam radiotherapy and was given 89Sr with subsequent thrombocytopenia and epistaxis. The patient died from generalized hemorrhage 36 days postinjection. Although it is not possible to establish a causal relationship between the 89Sr and DIC, practitioners should be alert to complications associated with the primary disorder which might occur at a time to raise concern about the intervention.

Topics: Adenocarcinoma; Aged; Bone Neoplasms; Disseminated Intravascular Coagulation; Epistaxis; Fatal Outcome; Humans; Male; Prostatic Neoplasms; Strontium Radioisotopes; Thrombocytopenia

Strontium-89 is an effective agent for palliation of pain due to bony metastases from breast and prostate carcinoma. As a functional analog of calcium, 89Sr is taken up by bone in areas of osteoblastic activity. Since patients with multiple myeloma frequently have osteolytic metastases, 89Sr might not be considered to be a therapeutic option. However, metastases which appear osteolytic by radiographs may demonstrate osteoblastic activity on bone scans. Consequently, the bone scan may be used to identify a subset of patients with osteolytic metastases who may benefit from 89Sr treatment. This report describes a patient with severe rib pain due to multiple myeloma whose chest radiograph showed multiple lucent lesions throughout the bones of the chest wall but whose bone scan showed marked osteoblastic activity. The patient was treated with 89Sr and received substantial pain relief. Bone scans may be useful in selecting myeloma patients or other cancer patients with osteolytic radiographic lesions who may benefit from 89Sr therapy.

Topics: Bone and Bones; Bone Neoplasms; Female; Follow-Up Studies; Humans; Middle Aged; Multiple Myeloma; Radionuclide Imaging; Strontium Radioisotopes; Technetium Tc 99m Medronate

Bone metastases can have a devastating effect on a patient's quality of life due to pain and pathologic fractures. Local external beam radiotherapy is very effective for patients with only a few involved areas. Systemic therapy consisting of chemotherapy and hormonal therapy is extremely useful until the patient becomes refractory to treatment. Systemic radionuclide therapy using Strontium-89 has been shown to be very valuable, specifically in patients with bone metastases from hormonally-resistant prostate cancer. Studies have shown a significant improvement in analgesic requirement, time to further radiotherapy, and a reduction in tumor markers with this treatment. The use of Strontium-89 in the treatment of other bone neoplasms and the use of other radionuclides, such as Rhenium-186 HEDP and Samarium-153 EDT-MP, are still investigational.

Topics: Bone Neoplasms; Combined Modality Therapy; Humans; Male; Prostatic Neoplasms; Strontium Radioisotopes

Prostate cancer is one of the most common tumors in men. At presentation, 50% of patients have advanced disease and 25% have bone metastases. Hormonal palliation is the treatment of choice for metastatic bone pain, with a pain-free response rate of 75% for a period of 16-18 months. Second-line treatment with chemotherapy has a moderate and short-term effect. Once endocrine therapy and chemotherapy cease to be effective, radiotherapy is a good option for recurrent painful bone metastases. Diffuse painful metastases can be treated with half-body irradiation with a response rate of up to 70%, but there is considerable toxicity. Strontium-89 (Metastron) is a calcium analog radionuclide that is selectively absorbed at bone locations with increased osteoblastic activity. It is a pure beta-emitter with bone penetration of 0.8 cm, and it has been used in multiple trials with response rates of up to 80%. Results are reported with Metastron in 28 patients with diffuse painful bone metastases, in whom a response rate of 82% was seen.

Topics: Aged; Aged, 80 and over; Bone Neoplasms; Humans; Male; Middle Aged; Prostatic Neoplasms; Strontium Radioisotopes

Topics: Bone Neoplasms; Drug Approval; Humans; Pain; Palliative Care; Strontium; Strontium Radioisotopes; United States; United States Food and Drug Administration

Topics: Bone Neoplasms; Etidronic Acid; Humans; Organometallic Compounds; Organophosphorus Compounds; Pain, Intractable; Palliative Care; Radioisotopes; Rhenium; Samarium; Strontium Radioisotopes

Measurement of radioactivity levels in the urine of patients undergoing strontium-89 therapy can be used to evaluate the efficacy of therapy or for patient's management (radiation protection rules and waste disposal). The complex beta counting procedures require extensive sample manipulation during preparation of the liquid scintillation cocktail. The high activity levels that may be found permit one to measure 89Sr activity sample by counting the low yield gamma emission (909 keV) of the radionuclide. However, the contamination of 85Sr due to the reaction for producing 89Sr, if measured with sufficient precision, could be used to evaluate 89Sr activity in urine samples. In other words, the contaminant 85Sr can be used as a tracer of 89Sr. This method was tested in four patients and the accuracy was found to be sufficient to obtain the individual time-activity curves of the urinary excretion.

Topics: Bone Neoplasms; Breast Neoplasms; Female; Humans; Monitoring, Physiologic; Neoplasms, Unknown Primary; Palliative Care; Strontium Radioisotopes

Topics: Bone Neoplasms; Humans; Palliative Care; Strontium Radioisotopes

A total of 66 primary bone sarcomas were diagnosed in 47 beagles; 43 of these dogs were part of the 403 beagles fed 90Sr and 4 were part of the 162 controls. Multiple primary bone sarcomas were found in 15 of the 47 beagles (32%). The incidence of multiple primary bone sarcoma was restricted to the two highest dose groups, except for a single control dog which developed two bone sarcomas. A threshold-like radiation dose response was observed; no sarcomas were observed in the lowest three dose groups, but the number of primary bone sarcomas increased rapidly in the higher dose groups. Of the 66 primary sarcomas, 49 were osteosarcomas (74%). As the dose increased, the proportion of osteosarcomas increased sharply, 4/10 (40%), 26/29 (90%), and 16/18 (89%), in the three highest dose groups. Thirteen of the bone sarcomas of other types occurred in males, and 4 in females, whereas 21 osteosarcomas occurred in males, and 28 in females. The ratio of bone sarcomas of the appendicular skeleton to those in the axial skeleton was 40:26, with osteosarcomas occurring more often in the appendicular than the axial skeleton (32:17), whereas nonosteogenic tumors showed no predilection (8:9). A statistical study of the distribution of bone sarcomas among 16 separate bone groups showed a correlation only with the distribution of cancellous bone volume-to-surface ratio and not with either skeletal mass distribution or dose distribution. The highest occurrence of sarcomas was in the humeri, femora, and mandible, and no occurrence in the coccygeal vertebrae, paws, or sternum. It is postulated that the distribution of bone sarcomas reflects a critical combination of the osteosarcoma precursor cell population, their cell division rate, and the radiation dose absorbed by these cells.

Topics: Animals; Bone Neoplasms; Dogs; Dose-Response Relationship, Radiation; Female; Male; Neoplasms, Radiation-Induced; Neoplasms, Second Primary; Sarcoma, Experimental; Strontium Radioisotopes

Until now, patients with a progressive prostatic cancer, in whom all therapies failed and the disease spread locally and distally, was considered "a lost patient"; because it did not exist an effective therapy easily to be used. The skeletal pain control is a serious problem and it is a great responsibility also for the Urologists especially if the patient has not a short survival time and the quality of life is very poor. Physicians feel the need for a systemic, well tolerated and effective therapy also for a long time, uniform and repeatable, able to be efficient for these patients. Strontium 89 chloride seems to offer all these possibilities and to be the best procedure for Urologist, Radiotherapists and Nuclear Specialists in order to satisfy the patients requirements. International research has shown Sr-849 Chloride is a powerful new therapy. Sr-89 Chloride is a radiopharmaceutical product for the treatment of painful metastases from prostatic cancer. It is a new treatment but its effectiveness is well documented and results are reported in the most important international literature. In our Department a clinical research has started and our purpose is to produce more data for a clinical and biological evaluation of the results, hoping that a similar research will extend as a multicenter study.

Topics: Bone Neoplasms; Carcinoma; Humans; Male; Pain; Prostatic Neoplasms; Radiation Protection; Radiotherapy Dosage; Remission Induction; Strontium; Strontium Radioisotopes

Topics: Acute Disease; Adolescent; Adult; Age Factors; Bone Neoplasms; Child; Child, Preschool; Cohort Studies; Environmental Exposure; Humans; Incidence; Infant; Leukemia, Myeloid; Leukemia, Radiation-Induced; Lymphoma, Non-Hodgkin; Neoplasms; Nuclear Energy; Risk Factors; Scotland; Strontium Radioisotopes

Bone tumours from beagles exposed by inhalation to 90SrCl2 at the Inhalation Toxicology Research Institute (ITRI), by chronic ingestion of 90Sr at the Laboratory of Energy-Related Health Research (LEHR), and by injection of 90Sr citrate at the University of Utah were analysed to determine if the bone tumour characteristics differed among the three studies. The range of average skeletal doses at which the bone tumours occurred was similar in all three studies, but differences in the skeletal distribution, histological phenotype, and time to death were observed. The differences observed were attributed to the difference in dose-rate pattern obtained in the chronic ingestion study, in contrast to the inhalation and injection studies. In general, however, the differences noted in bone tumour characteristics were subtle, and would be unlikely to make an impact on models developed to assess the risk of human exposure to 90Sr.

Topics: Administration, Inhalation; Administration, Oral; Animals; Bone Neoplasms; Dogs; Hemangiosarcoma; Injections, Intravenous; Neoplasms, Radiation-Induced; Osteosarcoma; Strontium Radioisotopes

Hematological and biochemical parameters were evaluated in 31 patients receiving 150 MBq 89Strontium (89Sr) intravenously due to painful skeletal metastases from hormone resistant prostate cancer. Two and 3 months after the injection prostate specific antigen (PSA) had increased by a median of 36% and 100%, respectively, as compared to the pretreatment value whereas alkaline phosphatase (APHOS) had decreased by about 20% (median). The leucocyte and platelet counts were reduced by about 20-35%, without reaching grade greater than or equal to 2 toxicity. Pain relief was reported in 14 of 29 evaluable patients at 2 months and in 11 of 23 patients at 3 months. It is concluded that 89Sr represents a worthwhile therapeutic modality in the palliation treatment of patients with hormone resistant prostate cancer, though the biological significance of frequently increasing PSA and decreasing APHOS is not yet completely understood.

Topics: Aged; Alkaline Phosphatase; Analgesics; Biomarkers, Tumor; Bone Neoplasms; Humans; Injections, Intravenous; Male; Pain Management; Palliative Care; Prostatic Neoplasms; Radionuclide Imaging; Strontium Radioisotopes; Technetium

Topics: Bone Neoplasms; Humans; Pain; Strontium Radioisotopes

Clonal origin of skin and bone tumors produced by repeated beta-irradiation was determined by using mice with cellular mosaicism created by random X-chromosome inactivation, on the basis of phosphoglycerate kinase-1 (PGK). The backs of female C3H/He (Pgk-1a/Pgk-1b) mice were exposed to beta rays from 90Sr-90Y at a dose of 3 Gy per exposure 3 times weekly until tumors appeared. The cumulative tumor incidence reached 100% 500 days after the beginning of irradiation, as determined by the Kaplan-Meier method. All 8 tumors examined were of a single PGK phenotype: 5 squamous cell carcinomas and 2 osteosarcomas of A-type, and 1 squamous cell carcinoma of B-type. The absence of double PGK phenotype (AB-type) tumors indicated the monoclonal origin of the tumors produced by repeated irradiation.

Topics: Animals; Beta Particles; Bone Neoplasms; Carcinoma, Squamous Cell; Dosage Compensation, Genetic; Female; Mice; Mice, Inbred C3H; Mosaicism; Neoplasms, Radiation-Induced; Osteosarcoma; Phosphoglycerate Kinase; Skin Neoplasms; Strontium Radioisotopes; Yttrium Radioisotopes

Until now, patients with a progressive prostatic cancer, in whom all therapies failed and the disease spread locally and distally, was considered "a lost patient"; because it did not exist an effective therapy easily to be used. The skeletal pain control is a serious problem and it is a great responsibility also for the Urologists especially if the patient has not a short survival time and the quality of life very poor. Physicians feel the need for a systemic, well tolerated and effective therapy also for a long time, uniform and repeatable, able to be efficient for these patients. Strontium 89 chloride seems to offer all those possibilities and to be the best procedure for Urologist, Radiotherapists and Nuclear Specialists in order to satisfy the patients requirements. International research has shown Sr-89 Chloride is a powerful new therapy. Sr-90 Chloride is a radiopharmaceutical product for the treatment of painful metastases from prostatic cancer. It is a new treatment but its effectiveness is well documented and results are reported in the most important international literature. In our Department a clinical research has started and our purpose is to produce more data for a clinical and biological evaluation of the results hoping that a similar research will extend as a multicenter study.

Topics: Bone Neoplasms; Evaluation Studies as Topic; Humans; Male; Prostatic Neoplasms; Radionuclide Imaging; Strontium Radioisotopes

Strontium-89 radiotherapy is becoming an important treatment in the palliation of bone pain from osteoblastic metastases. The absorbed dose delivered to bone metastases during 89Sr radiotherapy has been estimated in four patients with metastatic prostatic carcinoma. Patients were injected with a tracer dose of 85Sr-chloride. Blood and urine samples were obtained during the week following injection. Strontium-85 scintigrams of metastases and normal bone were obtained up to 8 wk postinjection. Half of the patients showed elevated whole-body retention; plasma-strontium concentrations were decreased from normal values. Uptake of strontium in metastases was 2-25 times that in normal bone but rates of washout of strontium from metastases were similar to those from normal bone. Absorbed doses delivered in infinite time to the metastases by 89Sr ranged from 21 +/- 4 to 231 +/- 56 cGy/MBq with a median value of 68 cGy/MBq. Doses to red marrow were less by a factor of 2 to 50. These absorbed doses are sufficiently large to be expected to produce a therapeutic benefit.

Topics: Bone Neoplasms; Humans; Male; Prostatic Neoplasms; Radiotherapy Dosage; Strontium Radioisotopes

A series of experiments was conducted to examine the effect of glucan on the reticuloendothelial system (RES) and on the development of 90Sr-induced osteosarcomas and malignant lymphomas in CBA/S mice. Glucan demonstrated a strong RES-stimulating effect, as evidenced by a dose-related increase in lysozyme levels in the plasma and an enlargement of the liver and spleen. Weekly injections of glucan between 150 and 250 days after exposure to 90Sr suppressed the actuarial appearance of the fibroblastic type of osteosarcomas and stimulated the emergence of malignant lymphomas. Glucan itself had no tumorigenic effect in mice not exposed to 90Sr.

Topics: Animals; Bone Neoplasms; Drug Administration Schedule; Female; Glucans; Lymphoma; Macrophages; Male; Mice; Mice, Inbred CBA; Mononuclear Phagocyte System; Muramidase; Neoplasms, Radiation-Induced; Organ Size; Osteosarcoma; Spleen; Strontium Radioisotopes

Strontium-89 has been used for the treatment of painful bony metastases in patients suffering from disseminated adenocarcinoma of the prostate, with a variable proportion of patients obtaining clinically significant reductions in analgesic requirements. Based on data revealing enhancement of continuous low-dose rate irradiation by low-dose cisplatin in murine models, a protocol using 148 MBq (4 mCi) of 89Sr and 35 mg/m2 of cisplatin infused over 2 days, 1 and 4 wk after administration of the radioisotope was undertaken. Preliminary data suggest good pain relief with 55% of 18 patients entered thus far obtaining at least a 50% reduction in analgesic requirements. Improvements in total alkaline phosphatase and serum lactate dehydrogenase have consistently been seen, with some patients exhibiting improvements in hemoglobin, tumor markers and bone scans. Toxicity appears to be mild, with no life-threatening complications. In particular, myelosuppression after one course of treatment was modest, but retreatments in two patients has resulted in grade 3 hematologic toxicity. Two patients developed a "pain flare" after administration of cisplatin. Further accrual to this study will allow more accurate determination of pain response rate, and improved evaluation of parameters of objective response.

Topics: Adenocarcinoma; Aged; Bone Neoplasms; Cisplatin; Combined Modality Therapy; Drug Evaluation; Humans; Male; Middle Aged; Pain; Prostatic Neoplasms; Strontium Radioisotopes

Topics: Bone Neoplasms; Humans; Pain; Palliative Care; Radiotherapy Dosage; Strontium Radioisotopes

The backs of female ICR mice were irradiated with beta rays from 90Sr-90Y three times a week throughout life. Previously we observed 100% tumor incidence at five different dose levels ranging from 1.5 to 11.8 Gy per exposure, but no tumor on repeated irradiation with 1.35 Gy for 300 days (Radiat. Res. 115, 488, 1988). In the present study, delay of tumor development was again seen at a dose of 1.5 Gy per exposure, with further delay at 1.0 Gy. The final tumor incidence was 100% with these two doses. At 0.75 Gy per exposure, no tumor appeared within 790 days after the start of irradiation, but one osteosarcoma and one squamous cell carcinoma did finally appear. These findings indicate a threshold-like response of tumor induction in this repeated irradiation system and further suggest that the apparent threshold may be somewhat less than 0.75 Gy per exposure.

Topics: Animals; Beta Particles; Bone Neoplasms; Female; Mice; Neoplasms, Radiation-Induced; Radiation Dosage; Skin Neoplasms; Strontium Radioisotopes; Yttrium Radioisotopes

Two hundred and two patients with bone pain from metastatic cancer were treated with 40 microCi/kg of Sr-89. Patients were followed with pain diaries, records of medication taken, sleep patterns, serial bone scans and a Karnofsky Index. One hundred and thirty-seven patients with adequate followup survived at least 3 months, including 100 with prostate and 28 with breast carcinoma. Eighty of the 100 patients with prostate cancer responded, and 25 of the 28 breast cancer patients improved. Ten patients with prostate cancer and five with breast cancer became pain free. Little hematologic depression was noted. Sr-89 kinetic studies showed that strontium taken up in osteoblastic areas remained for 100 days. The tumor-to-marrow absorbed dose ratio was 10:1.

Topics: Bone Neoplasms; Breast Neoplasms; Female; Humans; Male; Pain, Intractable; Palliative Care; Prostatic Neoplasms; Radionuclide Imaging; Strontium Radioisotopes; Technetium Tc 99m Medronate

Strontium plasma clearance is an important factor determining the absorbed dose to metastases and bone marrow in patients receiving 89Sr radionuclide therapy for metastatic bone disease. Amongst male patients with disseminated prostatic carcinoma, the renal component of strontium clearance is frequently greatly reduced compared with values reported for healthy middle aged men. We report a study of renal and gut strontium plasma clearance, renal function, calcium urinary excretion, parathyroid function and extent of skeletal osteoblastic metastatic disease in patients referred for radiostrontium therapy for metastasised prostatic malignancy. The wide variation in net strontium clearance was principally due to variation in the renal component. Low values of strontium renal clearance were found to correlate with the elevation of serum PTH and nephrogenous cyclic AMP, which in turn correlated with extent of skeletal metastatic disease. This suggests that the osteosclerotic metastases characteristic of prostatic carcinoma induce secondary hyperparathyroidism due to the high avidity of the skeleton for calcium. The resulting reduction in strontium excretion may be beneficial to the objectives of radiostrontium therapy.

Topics: Bone Neoplasms; Calcium; Cyclic AMP; Humans; Kidney; Male; Parathyroid Hormone; Prostatic Neoplasms; Strontium Radioisotopes

Ionizing irradiation by incorporated strontium-90 exerts two major effects: it induces tumours (mainly osteosarcomas and lymphoreticular tumours) and depresses the immune system. The interrelation between these functions, i.e. the significance of decreased immunological responsiveness in the oncogenic process, remains unclear. The influence of the 90Sr dose and the role of immune modulation on the tumour yield, were investigated in young adult CBA mice. The animals were exposed to different single doses of 90Sr and, in addition, some groups were subjected to long-term unspecific immune suppression by adult thymectomy (ATx) and/or prolonged antilymphocyteglobulin (ALG) treatment. The present paper (part I) reports on the effects of the treatments on bone tumour responses as reflected by incidence, multiplicity, latency time, histologic characteristics and growth behaviour. The histogenesis of osteosarcomas, as evidenced morphologically by preneoplastic and early neoplastic growth, is illustrated and discussed. The results demonstrate a positive dose-response relationship for osteosarcomas, in which the relative incidences of the various osteosarcoma subtypes were differentially affected. Thus, well-differentiated tumours were gradually replaced by less differentiated types as the dose decreased. A correlation was also observed between the incidence of osteosarcomas and that of assumed preneoplastic lesions in the same bones and sites. Immune suppression by ATx and/or ALG did not distinctly alter the neoplastic or preneoplastic responses at any dose-level of 90Sr.

Topics: Animals; Antilymphocyte Serum; Bone Marrow; Bone Neoplasms; Male; Mice; Mice, Inbred CBA; Neoplasms, Radiation-Induced; Osteosarcoma; Precancerous Conditions; Strontium Radioisotopes; Thymectomy

The efficacy of strontium-89 in relieving pain caused by disseminated bone metastases was studied in 11 patients with prostatic carcinoma. The therapy consisted either of 3 i.v. injections of 100 MBq strontium-89 chloride in intervals of 4 weeks in 8 patients or 200 MBq i.v. administered on one occasion in 3 patients. The study suggests that 1-3 i.v. injections of 100 MBq strontium-89 may be a worthwhile and fairly atoxic treatment for palliation of bone pain from metastatic prostatic carcinoma.

Topics: Bone Neoplasms; Humans; Male; Palliative Care; Prostatic Neoplasms; Strontium Radioisotopes

Eight hundred and twenty male CBA-mice, 75 +/- 3 days of age were divided into four main series. Three of these; A, B and C were further divided into three subgroups. To these 90Sr was given at three different dose levels alone (A) or in combination with either oestrogen (B) or prednisolone (C). In one series (D) all animals were given only oestrogen. The development of intramedullary oestrogen induced bone formation and the early events of bone tumour induction are reported. The 90Sr activities were selected in such a way that the lowest one would be below, the intermediate beyond and the highest well above the limit of bone tumour induction. Comparing the 90Sr injected animals with those given also oestrogen revealed that oestrogen had no promoting effect at the lowest and intermediate dose levels but increased the tumour incidence with a factor 4 at the highest dose level whereas prednisolone had an inhibitory effect. From the results obtained it was proposed that oestrogen may act only as a preparatory promoter and not assist in the initiating events. As has been reported elsewhere, the frequency of osteoblastic and osteoclastic osteosarcomas was higher in animals given oestrogen and 90Sr than 90Sr only. Mice given only oestrogen did not develop bone tumours.

Topics: Animals; Bone Neoplasms; Cell Division; Estrogens; Male; Mice; Mice, Inbred CBA; Neoplasms, Radiation-Induced; Osteogenesis; Osteosarcoma; Prednisolone; Strontium Radioisotopes

Late-occurring biologic effects were studied in beagle dogs that were given graded levels of 90SrCl2 via single brief inhalation exposures and were subsequently observed for their life-span. Due to the soluble chemical form of the aerosol, 90Sr was rapidly translocated from lung and deposited in bone where it was subsequently retained for a long period of time. Radiation-induced lesions were confined to the bone, bone marrow, and adjacent soft tissue. Forty-five primary bone tumors occurred in 31 of 66 exposed dogs. Metastasis occurred from 21 tumors, with the lung being the most frequent site of metastasis (76%). Twenty-seven tumors were classified as different subtypes of osteosarcoma, 14 as hemangiosarcomas, 3 as fibrosarcomas, and 1 as a myxosarcoma. Four carcinomas arising from soft tissues adjacent to bone were also considered to be 90Sr induced. In contrast to bone tumors arising in beagles chronically exposed to 90Sr through ingestion, histologic lesions of radiation osteodystrophy were minimal in this study, indicating that these lesions are not a necessary precursor of osteosarcoma development. The incidences of hemangiosarcomas (31%) and telangiectatic osteosarcomas (11%) in addition to osteosarcomas suggest that the cell of origin for all of these neoplasms is a multipotent mesenchymal cell with the potential for various morphologic expressions dependent on local environmental factors.

Topics: Aerosols; Animals; Body Burden; Bone Neoplasms; Dogs; Female; Lung Neoplasms; Male; Neoplasms, Radiation-Induced; Physical Examination; Strontium; Strontium Radioisotopes; Whole-Body Counting

Amongst patients referred for 89Sr palliation of disseminated prostatic carcinoma, we have found wide variations in extent of skeletal metastatic disease and in strontium renal plasma clearance. A numerical technique using impulse response function analysis is reviewed which enables the effect of such variations on the total body, plasma and metastatic strontium retention functions to be calculated. The prediction of the model are compared with kinetic data from patients presenting for radiostrontium therapy, and correlations that have important implications for 89Sr dosimetric studies are confirmed. The simplest kinetic data required to allow for these effects in studies of dose-response and haematological toxicity following radio-strontium treatment are discussed and attention is drawn to a small group of patients who may form a significant exception to the general model.

Topics: Bone Neoplasms; Humans; Lumbar Vertebrae; Male; Metabolic Clearance Rate; Prostatic Neoplasms; Radiation Dosage; Spinal Neoplasms; Strontium Radioisotopes

We report a study of strontium kinetics in two patients who received 89Sr therapy for disseminated osteogenic sarcoma, together with estimates of absorbed dose to the principal metastases and to bone marrow. In neither patient did tumour uptake of strontium have a significant effect on whole-body retention. In one patient, whole-body strontium kinetics agreed closely with the ICRP standard model, while in the second, retention was extremely prolonged, probably due to hypertrophic osteoarthropathy. Strontium-85 scintigraphy, surface counting and high-resolution whole-body profiles agreed in showing that in both patients tumour turnover of strontium was very rapid, with a biological half-life of only a few days. Absorbed dose to tumour was found to be comparable in magnitude to the mean bone-marrow dose. We have no reason to believe that 89Sr therapy was of clinical benefit to either patient.

Topics: Adolescent; Adult; Bone Marrow; Bone Neoplasms; Humans; Kinetics; Neoplasm Metastasis; Osteosarcoma; Radiation Dosage; Soft Tissue Neoplasms; Strontium Radioisotopes

Ten patients with disseminated bone metastases, nine from prostatic and one from renal cell carcinoma, were treated with intravenous strontium-89. Half the patients experienced significant improvement in pain control and increased general well-being for an average of 14 weeks. Sequential radiophosphate bone scanning showed decreased activity in lesions present at the time of therapy, with subsequent remineralization of the metastases on radiographs. Some patients showed simultaneous reduction in alkaline and acid phosphatase levels. These objective findings prove a physiologic basis for the clinical improvement. Treatments, however, did not prevent progression at initially uninvolved sites, particularly in the extremities.

Topics: Aged; Aged, 80 and over; Bone Neoplasms; Carcinoma; Follow-Up Studies; Humans; Male; Middle Aged; Prostatic Neoplasms; Radiography; Radionuclide Imaging; Strontium Radioisotopes

Radiation-induced bone tumors in beagle dogs exposed to 90Sr have been evaluated in terms of their incidence, time of appearance, occurrence as multiple tumors, anatomic distribution, and the influence of sex on their development. Among dogs fed 90Sr during skeletal development, the incidence of bone tumors was dose dependent. Tumors thus appeared in 10 of 19 dogs receiving average skeletal doses of 130 Gy, 15 of 60 receiving 97 Gy, 5 of 61 receiving 61 Gy, 2 of 65 receiving 26 Gy, and 1 of 40 receiving 1.3 Gy. No tumors appeared among 66 dogs who received 8 Gy, 78 who received 0.3 Gy, and 80 non-irradiated controls, all of which have been observed for life. Among dogs given a single intravenous injection of 90Sr in early adulthood, tumor production was somewhat higher than among 90Sr-fed dogs at the same radiation dose: bone tumors were present in 6 of 25 dogs who received 62 Gy and 1 of 20 dogs who received 7.5 Gy. Bone tumors appeared sooner and were more often multiple in animals receiving the higher doses. Long bones were the sites of most of the tumors appearing after the highest dose level. Bones of the head, particularly the mandible, were the predominant site of tumors in the next highest dose level group.

Topics: Animals; Bone Neoplasms; Dogs; Dose-Response Relationship, Radiation; Female; Male; Neoplasms, Radiation-Induced; Pregnancy; Prenatal Exposure Delayed Effects; Sex Factors; Strontium Radioisotopes

In a series of patients receiving 89Sr palliation for metastasised prostatic carcinoma, strontium renal plasma clearance was found to vary from 0.14 to 11.81 day-1, and the extent of skeletal metastatic disease seen on 99Tcm-MDP images varied from a few small metastases to a superscan. Using a numerical technique based on impulse response function (IRF) analysis, we have investigated the effect of such variation between patients on 89Sr dosimetry. The whole-body IRF, HWB(t), is defined by the deconvolution of the whole-body strontium retention function, RWB(t), with the plasma retention function, P(t). For patients with minimal metastatic bone disease we assumed HWB(t) = HO(t), where HO is the IRF derived from the International Commission on Radiological Protection model for normal strontium metabolism. The strontium plasma clearance, k, was allowed to vary, and the resulting variation of RWB(t), P(t) and absorbed dose to bone marrow calculated. By convoluting P(t,k) with the IRF measured for a discrete metastasis, the effect of varying k on tumour dose was investigated. Tumour and bone marrow dose were shown to change by a factor of three as k varied over the range observed in patients. For patients with extensive metastatic bone disease we assumed HWB(t) = (1-beta)HO(t) + beta HS(t), where HS was the IRF measured for a superscan patient and beta was a parameter reflecting the extent of skeletal metastatic disease. The effect of varying beta on tumour and bone marrow dose was investigated, and dose shown to decrease by a factor of five as beta increased from zero to unity. Impulse response function analysis was found to be a powerful and useful aid in clarifying the relationship between strontium kinetics and 89Sr dosimetry.

Topics: Bone Marrow; Bone Neoplasms; Humans; Kinetics; Male; Prostatic Neoplasms; Radiotherapy Dosage; Strontium Radioisotopes; Time Factors

We have utilized 89Sr as palliative treatment for bone pain secondary to metastatic cancer in the skeleton of over 200 patients. The best results have been in patients with carcinoma of the prostate (80% response rate) and breast (89%). Results in a small number of patients with a variety of other cell types were not nearly as encouraging. Strontium-89 provides excellent palliation in the management of bone pain secondary to prostate and breast carcinoma.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bone Neoplasms; Breast Neoplasms; Female; Humans; Male; Middle Aged; Pain; Prostatic Neoplasms; Strontium Radioisotopes

At the University of Kansas Medical Center, systemic use of strontium 89 ((89)Sr), a betaemitting radioisotope, was evaluated in the treatment of metastatic carcinoma to bone for relief of bone pain. Eighty-five patients were treated with systemic (89)Sr in the dosage of 30 to 40 μCi/kg. All patients had multiple bone metastases, the majority with primary breast or prostatic cancer. The response to treatment was evaluated by daily diary entries, changes in the amount of pain medication, periodic bone scans, and other laboratory values.In the patients who survived (47) and who were observed for three or more months, overall results showed 15 percent becoming pain free; 23 percent showed marked improvement with decreased consumption of pain medication; 53 percent showed mild but significant improvement in pain relief and decrease in pain medication requirement; and 9 percent showed no improvement. No patients noted a worsening of bone pain after the treatment. There was a combined favorable response in 91 percent (43/47) of patients with some meaningful palliation after (89)Sr therapy. This study, using (89)Sr systemic therapy, suggests that this isotope may be a valuable adjuvant therapy for palliation of pain from metastatic bone lesions.

Topics: Aged; Bone Neoplasms; Female; Humans; Male; Middle Aged; Palliative Care; Strontium Radioisotopes

Initial clinical trials using strontium-89 (Sr-89) chloride for the treatment of painful skeletal metastases have observed minimal or no hematological depression secondary to the radiostrontium. A patient with marked bone marrow depression temporally related to the administration of the Sr-89 is reported, and the need for close hematological monitoring is emphasized. Bone marrow tumor replacement may predispose patients to marrow depression from radiostrontium, and such patients should be treated with caution.

Topics: Aged; Bone Marrow; Bone Neoplasms; Humans; Male; Palliative Care; Prostatic Neoplasms; Strontium; Strontium Radioisotopes

Topics: Bone Neoplasms; Diphosphates; Humans; Radionuclide Imaging; Strontium Radioisotopes; Technetium; Technetium Tc 99m Pyrophosphate

Strontium kinetics were investigated in a group of 14 patients receiving 89Sr palliation for metastatic bone disease secondary to prostatic carcinoma. Using 85Sr as a tracer, total body strontium retention R(t) was monitored for a 3 month period following 89Sr administration, and at 90 days was found to vary from 11% to 88% and to correlate closely with the fraction of the skeleton showing scintigraphic evidence of osteoblastic metastatic involvement. Strontium renal plasma clearance varied from 1.6 l/day to 11.6 l/day, and in nine patients was significantly reduced compared with values found in healthy adult men, probably due to increased renal tubular reabsorption associated with the disturbance of calcium homoeostasis. Renal clearance rate was the principal factor determining R(t) for t less than 6 days, and was an important secondary factor at later times. Over the interval 30 days less than t less than 90 days, R(t) was closely fitted by the power law function R(t) = R30 (t/30)-b, with R30 and b showing the close correlation expected from the effect of R(t) on strontium recycling. The correction of the data for this effect to determine the true skeletal release rate is described. Measurement of localized strontium turnover in individual metastatic deposits from whole body profiles and scintigraphic images gave retention curves that typically rose to a plateau by 10 days after therapy, and then decreased very slowly. In contrast, retention curves for adjacent normal trabecular bone showed more rapid turnover, peaking at 1 day and subsequently decreasing following a t-0.2 power law function.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Bone and Bones; Bone Neoplasms; Humans; Male; Metabolic Clearance Rate; Prostatic Neoplasms; Radionuclide Imaging; Strontium Radioisotopes; Whole-Body Counting

Experimental chemotherapy using high-dose methotrexate (MTX) with citrovorum factor (CF) was performed on ddN strain mice bearing 89Sr-induced osteosarcoma and the antitumor efficacy was analyzed through autoradiography ([3H]thymidine). The administration was done using sustained infusion via the tail vein using our own device to maintain certain elevated blood levels of the drugs. As the first experiment, MTX was administered to 4 different groups of mice with dose levels of 250, 500, 1,000, 2,000 mg/kg for 6 hours followed by CF 200 mg/kg for 24 hours. It was found that the blood levels of MTX were maintained at 10(-4) M by the dosage of 500 mg/kg, but no higher levels were achieved by increasing dosage. Tissue such as the small intestine and the bone marrow recovered from the toxicity of MTX in about 1 week after the dosage of 500 mg/kg. In tumors, on the other hand, the tissue showed a gradual recovery with time, but the uptake of [3H]thymidine by the tissue was not restored to the pretreatment level. When the antitumor efficacy of a single dosage of 1,000 mg/kg and 2 dosages of 500 mg/kg each with 1 week interval were compared, the latter was definitely more effective. It was, therefore, concluded that the administration of the drugs should be done repeatedly with optimum doses of MTX and CF rather than with ultrahigh doses of MTX and CF all at once.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Injections, Intraperitoneal; Injections, Intravenous; Leucovorin; Male; Methotrexate; Mice; Mice, Inbred Strains; Neoplasms, Radiation-Induced; Osteosarcoma; Strontium Radioisotopes

The molecular structure of murine retroviruses expressed in spontaneous and radiation-induced bone tumours was studied. These viruses induce osteomas, lymphomas and osteopetrosis in mice of the NMRI strain. RNase T1 fingerprint analysis indicates the presence of mixed virus populations in the tumours, with major components showing close relationship to Akv MuLV. Cloned viruses, closely related to Akv MuLV, have the same oncogenic properties as the original mixtures. In its nucleotide sequence of the repeat segments of the transcriptional enhancer in the LTR, one cloned virus analysed was distinct from Akv MuLV, but closely related to a spontaneous bone tumour virus isolate, FBJ MuLV.

Topics: Animals; Base Sequence; Bone Neoplasms; Gene Expression Regulation; Mice; Neoplasms, Radiation-Induced; Oligoribonucleotides; Osteoma; Retroviridae; RNA, Neoplasm; RNA, Viral; Strontium Radioisotopes

Topics: Adolescent; Angiography; Bone Neoplasms; Diphosphates; Female; Humans; Radionuclide Imaging; Strontium Radioisotopes; Technetium; Technetium Tc 99m Pyrophosphate

Topics: Bone and Bones; Bone Neoplasms; Humans; Male; Prostatic Neoplasms; Radionuclide Imaging; Strontium Radioisotopes

Topics: Adolescent; Adult; Aged; Bone Neoplasms; Diphosphates; Female; Humans; Male; Middle Aged; Osteolysis; Radiography; Radionuclide Imaging; Ribs; Strontium Radioisotopes; Technetium; Technetium Tc 99m Pyrophosphate; Time Factors

The induction of skeletal tumours, which can be classified as osteosarcomas of many different types, is considered to be the primary carcinogenic effect of radiostrontium. In the present report the cell surface morphology in vivo of 90Sr-induced osteosarcoma cells was investigated, since a variety of tumour cells--and especially those investigated in vitro--have been shown to possess morphologic changes compared with their normal counterparts. Using scanning electron microscopy, variations in cell surface morphology were observed in 2 tumour series, which were serially transplanted in mice for 45 and 60 transfer generations, respectively. The slow-growing osteosarcoma cells of the early transfer generations, of osteoblastic as well as fibroblastic type, seemed to have more cytopodia than the fast-growing osteosarcoma cells from later generations. This may be due to the fact that slowly growing cell populations have a large proportion of cells in G1, in which stage there is a higher frequency of cellular cytopodia.

Topics: Animals; Bone Neoplasms; Cell Membrane; Female; Male; Mice; Mice, Inbred CBA; Microscopy, Electron, Scanning; Neoplasm Transplantation; Neoplasms, Radiation-Induced; Osteosarcoma; Strontium Radioisotopes

In a large series of experiments, fractionated injections of short-lived bone-seekers have been shown in many cases to cause a remarkable increase of the osteosarcoma incidence compared with a single administration of the same total skeletal dose. This effect has been observed with both alpha- and beta-emitters. In addition the latency period was shortened by protracting the dose. The total skeletal doses investigated ranged between 0.9 and 20 Gy for alpha-emitters (224Ra and 227Th) and between 28 and 112 Gy for the beta-emitter (177Lu). In all cases the protracted dose had higher or at least equal effects when compared with a single application. Reference experiments with long-lived alpha- and beta-emitting bone-seeking nuclides (226Ra and 90Sr) showed that the incidence of osteosarcomas per Gy was sometimes lower than that observed when the same skeletal dose was applied by protraction of short-lived radionuclides. The dependence of osteosarcoma incidence on dose-time distribution, duration of internal irradiation, and radiation quality is discussed. In this context the possibility that the critical initial dose rate may be related to the initiating event within the multi-stage hypothesis of carcinogenesis is considered.

Topics: Animals; Bone Neoplasms; Lutetium; Male; Mice; Mice, Inbred Strains; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Radioisotopes; Radium; Relative Biological Effectiveness; Strontium Radioisotopes; Thorium; Time Factors

The osteotropic radionuclides 89Sr and 32P are now mainly used in the treatment of bone metastases. This therapy is palliative and is mainly directed at alleviating pain. The indications, procedure, treatment result and side effects are described as discussed. Bone metastases of iodinophilous thyroid carcinomas represent a special case. These can be treated selectively with 131I. However, complete regression of the tumour by means of radioactive iodine is only rarely achieved in bone metastases. Nevertheless, the complaints and symptoms are definitely alleviated even with relatively small radiation doses, similar to the therapy employing strontium.

Topics: Adenocarcinoma; Bone Neoplasms; Female; Humans; Iodine Radioisotopes; Male; Prostatic Neoplasms; Rectal Neoplasms; Strontium Radioisotopes; Thyroid Neoplasms

Susceptibility to cancer implies being easily affected by carcinogen, as well as having an overt spontaneous incidence of cancer. The susceptibility of a population to the development of fatal cancer of a given organ can be represented by a frequency distribution. This distribution depends both upon the genetic susceptibility of the population and upon all environmental carcinogens that have impinged on that population. The method for construction of such a susceptibility distribution has been simplified and applied to experimental data on bone tumor induction with 90Sr in mice, and to bone tumor mortality and prostate cancer mortality in man. The relative susceptibilities of different human organs to the development of fatal tumors can be defined in terms of the spontaneous tumor mortalities.

Topics: Adult; Aged; Animals; Bone Neoplasms; Computers; Disease Susceptibility; Female; Humans; Male; Mice; Mice, Inbred BALB C; Middle Aged; Neoplasms; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Strontium Radioisotopes

The life-time tumor dose-response relationships observed in beagles injected with 226Ra or fed 90Sr at the University of California, Davis, provide a basis for understanding the induction of bone cancer for these bone-seeking radionuclides and for scaling to people. In these studies 385 dogs were exposed to graded dosage levels of 90Sr and 243 dogs were exposed to graded dosage levels of 226Ra with a total of 159 unexposed controls. The results show different dose-response relationships for bone cancer for the two radionuclides based upon the gravimetric average dose rates and cumulative doses to bone. These relationships were found to be well represented by three-dimensional log-normal dose-response surfaces that yield risk as a function of average dose-rate and time after beginning of exposure. All dose-rates suggested a 100% risk at some later time post-exposure but the time required to reach a given level of risk was long for low dose rates so that there exists a practical threshold in that at lower dose rates individuals may die spontaneously from causes associated with natural aging prior to the expected appearance of radiogenic cancer. The risks to people at various 226Ra body burdens (average skeletal dose rates) are estimated based on the model.

Topics: Animals; Body Burden; Bone Neoplasms; Dogs; Dose-Response Relationship, Radiation; Humans; Life Expectancy; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Radium; Relative Biological Effectiveness; Risk; Strontium Radioisotopes

Because of the polymorphism of osteogenic sarcomas, examination of a biopsy specimen, which is necessarily small, cannot give an accurate evaluation of the differentiation of the whole tumor. Therefore, a test which provides an overall assessment of the functional capacity of the tumor is needed. For the last ten years, we have been using 85 strontium, which has a metabolism similar to that of calcium and radioactive characteristics that allow external measurements. With this isotope, classification of osteogenic sarcomas is more accurate, ensuring better therapeutic trials.

Topics: Adult; Bone Neoplasms; Child; Humans; Kinetics; Osteosarcoma; Prognosis; Radionuclide Imaging; Strontium Radioisotopes

421 C57BL/6J female mice were subdivided into 11 groups. Five of these groups were given 300 rad total body irradiation from a 137Cs source at an age of 65 days. One day later, these irradiated mice were treated intraperitoneally with varying amounts of 90Sr (0, 0.032, 0.10, 0.32, and 1.0 mu Ci/g of body weight). Five groups of mice that had not been irradiated were treated on the same day with the same doses of 90Sr as given the five irradiated groups, and a sixth unirradiated group was treated with 2 mu Ci/g body weight. Each mouse treated with 90Sr and still alive was monitored between 249 and 303 days later in a total body well scintillation detector; mice with counts that differed by more than approximately 50% from the mean for their group were eliminated. A total of 402 mice were accepted for the experiment; these mice were followed to the end of their life span and then autopsied. Mice treated with the highest doses of 90Sr (1.0 and 2.0 mu Ci/g) experienced significantly elevated number of deaths from infections relative to the control group; these deaths occurred relatively early after 90Sr injection, and were particularly severe in the group of mice that had received 300 rad of external irradiation in addition to 1.0 mu Ci90Sr/g. There was no evidence of synergism between 90Sr injection and 300 rad external irradiation for production of bone tumors. Tumors of the type that occur spontaneously in C57BL/6J mice appeared to be more frequent in 90Sr-treated mice and in externally irradiated mice than in controls, but the numbers of excess tumors in these groups were not statistically significant (P less than 0.09).

Topics: Animals; Bone Neoplasms; Cesium Radioisotopes; Female; Infections; Injections, Intraperitoneal; Leukemia, Radiation-Induced; Lung Neoplasms; Mice; Mice, Inbred C57BL; Neoplasms, Radiation-Induced; Radiation Injuries, Experimental; Strontium Radioisotopes; Whole-Body Irradiation

In the urological department of the Wilhelminenspital altogether 22 patients with incurable bone pains in metastasizing carcinoma were treated with radioisotopes between 1976 and 1980. 32P and 89Sr were used in a dosage of 3 times 3 mCi and once 1 mCi. A reaction to the therapy could be proved in 46%, in 23% the success could be estimated as very good. Clinic and therapy were discussed with the help of own cases and literature.

Topics: Adenocarcinoma; Aged; Bone Neoplasms; Carcinoma; Female; Humans; Kidney Neoplasms; Male; Neoplasm Staging; Palliative Care; Phosphorus Radioisotopes; Prostatic Neoplasms; Strontium Radioisotopes

Topics: Animals; Body Burden; Bone Marrow Diseases; Bone Neoplasms; Dogs; Dose-Response Relationship, Radiation; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Radiation Injuries, Experimental; Radium; Soft Tissue Neoplasms; Strontium Radioisotopes; Time Factors; Toxicology

Topics: Animals; Bone Neoplasms; Diet; Dogs; Dose-Response Relationship, Radiation; Female; Humans; Injections, Intravenous; Mice; Neoplasms, Radiation-Induced; Radium; Strontium Radioisotopes

Topics: Bone Neoplasms; Breast Neoplasms; Female; Humans; Radionuclide Imaging; Strontium Radioisotopes

From 90Sr-induced primary tumours, three transfer series were established by serial in vivo transplantation. Chromosome counts were obtained from 2 of the primary tumours and 284 transplanted tumours. The recording of abnormalities was limited to numerical chromosome deviations and the occurrence of metacentric configurations. By means of the serial tumour transplantation the numerical chromosome progression was also analysed. Though appearing at different stages of the tumour evolution, similarities in chromosome pattern were observed.

Topics: Animals; Bone Neoplasms; Chromosome Aberrations; Female; Metaphase; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Strontium Radioisotopes

Topics: Animals; Bone and Bones; Bone Neoplasms; Diphosphates; Diphosphonates; Dogs; Fluorine; Humans; Krypton; Neoplasm Transplantation; Neoplasms, Experimental; Rabbits; Radioisotopes; Radionuclide Imaging; Spinal Neoplasms; Strontium Radioisotopes; Technetium

Topics: Bone Neoplasms; Chondroblastoma; Chondroma; Diphosphates; Evaluation Studies as Topic; Giant Cell Tumors; Humans; Multiple Myeloma; Osteoma, Osteoid; Radionuclide Imaging; Sarcoma; Strontium Radioisotopes; Technetium; Technetium Tc 99m Pyrophosphate

Topics: Bone Neoplasms; Humans; Iodine Radioisotopes; Lung Neoplasms; Phosphorus Radioisotopes; Radionuclide Imaging; Strontium Radioisotopes; Technetium; Thyroid Neoplasms

The analgesic properties of 89Sr were investigated in 17 patients with multiple painful bone metastases. 89Sr is a radioisotope, the metabolism of which in the body is comparable to that of calcium. It is a pure beta emitter and its half-life is 51 days. When injected intravenously it is captured by bone, especially at locations where the turnover is increased. Each patient received 1--2 mCi of 89Sr. Bone scans and hematological investigations were performed before, and 2 months after, treatment. No significant changes were found. Shealy's method was used to assess pain, initially twice a week and then at more prolonged intervals. One patient suffering from multiple myeloma showed a spectacular improvement and 6 others responded favourably. Improvement generally occurred within 3--7 days, but was sometimes delayed for up to 3 weeks. Relief lasted for up to several months. Five patients had an increase of pain during the 24 hours immediately after treatment. An average of 28% of the administered radioactive dose was found in the urine collections during the first 48 hours. Although the treatment was not successful in every case, the use of 89Sr as a long acting analgesic in multiple bone metastases should be considered more frequently, especially as there are no side effects.

Topics: Aged; Bone Neoplasms; Female; Humans; Injections, Intravenous; Male; Middle Aged; Pain; Strontium Radioisotopes

The short range tissue destruction of beta-emitting radioisotopes can be utilized in painful metastatic disease of the skeleton by employing a radionuclide that is specifically metabolized in or adjacent to these lesions. Sodium phosphate P 32 has been used for this purpose for the past 25 yr. It uptake in skeletal tumor and in osteoblastic new bone adjacent to tumor can be markedly increased by pharmacologic stimulation using androgenic steroids, or during rebound deposition after a course of parathyroid hormone. Although efficacy in terms of subjective pain relief is high, more objective signs of success are often lacking, and survival, while more confortable, is not prolonged. Marrow depression is the most significant side effect. A beta-emitting, bone-seeking isotope, 89Sr, may have a better therapeutic/toxic ratio, and should receive further trial. Radiation-induced necrosis has also been applied, though more hesitantly, to the proliferative, destructive, but nonmalignant synovium in rheumatoid disease. Here, a number of colloidal preparations, most commonly 198Au, have been employed. Again, relief of symptoms, particularly recurrent joint effusions, is quite high, although the basic disease process is not reversed. The major hazard here appears to be leakage of material to regional lymph nodes, resulting in irradiation of circulating lymphocytes. Although chromosomal damage can be detected when such cells are then cultured, the actual consequences of this, if any, are not presently known. Both shorter-lived (165Dy) and longer-lived (32P) larger-size colloids are being evaluated, which may prove safer in this regard than 198Au.

Topics: Bone Marrow; Bone Neoplasms; Gold Radioisotopes; Humans; Joint Diseases; Neoplasm Metastasis; Pain, Intractable; Palliative Care; Phosphorus Radioisotopes; Radiation Dosage; Radioisotopes; Strontium Radioisotopes; Synovial Membrane

Topics: Age Factors; Animals; Bone Neoplasms; Diet; Dogs; Dose-Response Relationship, Radiation; Female; Injections, Intravenous; Male; Myeloproliferative Disorders; Neoplasms, Radiation-Induced; Osteosarcoma; Radium; Respiration; Strontium Radioisotopes; Yttrium Radioisotopes

Topics: Adolescent; Adult; Arthritis, Infectious; Bone Diseases; Bone Neoplasms; Bone Transplantation; Epiphyses, Slipped; Femoral Fractures; Femur Head; Follow-Up Studies; Fractures, Bone; Hip Joint; Humans; Joint Diseases; Osteochondritis; Osteomyelitis; Pseudarthrosis; Radionuclide Imaging; Strontium Radioisotopes; Transplantation, Homologous

Topics: Animals; Bone and Bones; Bone Diseases; Bone Neoplasms; Fluorine; Gallium Radioisotopes; History, 20th Century; Humans; Nuclear Medicine; Phosphorus Radioisotopes; Radioisotopes; Radionuclide Imaging; Strontium Radioisotopes; Technetium

Following a firm diagnostic and therapeutic schedule for patients with prostatic carcinoma. 89Strontium therapy was introduced for multiple metastases. Positive skeletal scintigraphy with 99mTc-EHDP induced check for affinity to Sr using 85Sr scintigraphy. Of 80 patients, multiple metastases were found in 26. Therapy with 1 mCi of 89Sr-chloride was started in 20 cases. In 8 patients, relief from severe pain appeared shortly afterward, and a further 8 it was possible to prevent the development of pain. Moderate success in 3 cases and a failure to provide relief in 1 were observed.

Topics: Bone Neoplasms; Diphosphonates; Humans; Male; Neoplasm Metastasis; Pain, Intractable; Prostatic Neoplasms; Radionuclide Imaging; Radiotherapy Dosage; Strontium Radioisotopes; Technetium

Topics: Autoradiography; Biopsy; Bone Neoplasms; Humans; Radionuclide Imaging; Strontium Radioisotopes; Time Factors; Tissue Distribution

Topics: Bone Neoplasms; Humans; Male; Prostatic Neoplasms; Strontium Radioisotopes; Time Factors

Topics: Bone Neoplasms; Cartilage Diseases; Chondroblastoma; Chondroma; Chondrosarcoma; Diagnosis, Differential; Humans; Radionuclide Imaging; Strontium Radioisotopes; Time Factors

Topics: Adult; Bone Neoplasms; Cesium Radioisotopes; Child; Humans; Indonesia; Iodine Radioisotopes; Leukemia, Radiation-Induced; Maximum Allowable Concentration; Neoplasms, Radiation-Induced; Radioactive Fallout; Strontium Radioisotopes

In order to allay pains or make them cease, fifteen patients with extended tumors and generalized formation of skeleton metastases were submitted in 1976 to an internal palliative radiotherapy. They received between 0.8 and 2.7 mCi of Sr-89, five patients were treated again after four to five months because the pains had reappeared. The results were relatively good. Two patients showed a prompt effect and were completely free of pains within 48 hours, three patients did not present any demonstrable effect. The analgetic effect remained from four days to four months. Due to the utilization of the pure beta emitter Sr-89, the radiation doses measured in the patients after the application are relatively small: after the application they amount at most to 0.5 mR/h in a distance of 1 m.

Topics: Adult; Aged; Bone Neoplasms; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Palliative Care; Radiotherapy Dosage; Strontium Radioisotopes; Time Factors

The intravenous application of 89-strontium for the relief of pain in 43 patients with breast cancer, bronchogenic cancer, carcinoma of the prostate, hypernephroma and lymphoma with generalized bone metastases is reported. A remarkable clinical improvement was achieved in 33 (76.7%) patients. In four patients a transient analgesic effect was observed. In six cases no response could be achieved. The therapeutic effect usually was long-lasting. At the same time, an increase of alkaline phosphatase was observed, which was interpreted as an indication for the stimulation of osteoblasts and osteoid peripheral zones owing to beta-emission of the radioisotope in the affected areas. There was a significant correlation between the concentration of 85Sr in the bone scan and the therapeutic result of 89Sr-therapy. The indication for such therapy and possible late adverse effects of bone-seeking isotopes are discussed.

Topics: Bone and Bones; Bone Neoplasms; Half-Life; Humans; Liver Neoplasms; Neoplasm Metastasis; Pain, Intractable; Radionuclide Imaging; Strontium Radioisotopes

Topics: Antigens; BCG Vaccine; Bone Neoplasms; Neoplasms, Experimental; Osteosarcoma; Strontium Radioisotopes

Topics: Adolescent; Adult; Bone Neoplasms; Chondrosarcoma; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Radiography; Radionuclide Imaging; Strontium Radioisotopes; Tibia

Topics: Bone Neoplasms; Female; Humans; Male; Neoplasm Metastasis; Pain; Palliative Care; Radiotherapy Dosage; Strontium Radioisotopes

The dynamics of uptake of osteotropic radionucleides in normal and abnormal bone were studied by means of sequential and functional scans. Various phosphate and phosphonate complexes were compared in vivo and in vitro. Only phosphonates were considered as suitable for bone scanning. In normal bones in beagles, radioactivity after HEDP fell to 65% after two hours, but was 105% with 18F. In relation to healing fractures, the curves differ quantitatively and qualitatively. In this situation, functional curves derived from dynamic scans provide a better parallel with histological findings than does static scintigraphy with an uptake quotient. Sequential and functional scanning are able to document the therapeutic effect of irradiation of bone metastases.

Topics: Animals; Bone and Bones; Bone Diseases; Bone Neoplasms; Breast Neoplasms; Diphosphonates; Dogs; Female; Fluorine; Humans; Male; Neoplasm Metastasis; Phosphates; Prostatic Neoplasms; Pseudarthrosis; Radioisotopes; Radionuclide Imaging; Strontium; Strontium Radioisotopes; Technetium

Experiments with phantoms have shown that there is a higher probability of showing areas of increased uptake when using a camera than with a scanner. In 49 patients with suspected bone metastases, scans were performed during their pre-operative work-up, under identical conditions, using a whole body scintigraphic scanner with a 5-inch double head and a scintillation camera with total body facility. The scintillation camera showed a significantly higher sensitivity to bone metastases, but there was no difference in the pick-up rate of distant metastases. Despite the possibly more frequent use of the camera, its cost is no higher than that of the scanner. Both on diagnostic and economic grounds, we consider the scintillation camera, with a total body facility, to be the instrument of choice for total skeleton scintigraphy.

Topics: Bone Neoplasms; Breast Neoplasms; Cost-Benefit Analysis; Diagnostic Errors; Evaluation Studies as Topic; Female; Humans; Male; Methods; Neoplasm Metastasis; Prostatic Neoplasms; Radionuclide Imaging; Strontium Radioisotopes; Technetium; Whole-Body Counting

Topics: Animals; Bone Neoplasms; Iodine Radioisotopes; Male; Neoplasms, Radiation-Induced; Osteosarcoma; Parathyroid Glands; Rats; Strontium Radioisotopes; Thyroid Gland; Thyroidectomy

Topics: Adolescent; Adult; Aged; Angiography; Bone Neoplasms; Chondrosarcoma; Chordoma; Humans; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Osteomyelitis; Osteosarcoma; Sarcoma, Ewing; Strontium Radioisotopes

To control the state of transplanted bone in different terms following the plastic procedure a radioisotope study by strontium-85 was performed in 29 patients. The results of scannography (in 31 cases) and radiometry (in 42 cases) were analysed. The determination of the character of strontium-85 distribution and the intensity of its accumulation in the operated extremity makes it possible to assess the graft condition and the intensity of osteogenesis a greater precision and earlier than does roentgenography. Radioisotope investigation conducted dynamically enable the prognostication of the course of the graft healing process.

Topics: Bone Neoplasms; Bone Regeneration; Bone Transplantation; Bony Callus; Chondroblastoma; Giant Cell Tumors; Graft Survival; Humans; Male; Osteoma, Osteoid; Periosteum; Radioisotopes; Radionuclide Imaging; Strontium Radioisotopes; Time Factors

Topics: Bone Neoplasms; Castration; Cortisone; Cryosurgery; Estrogens; Humans; Hypophysectomy; Male; Neoplasm Metastasis; Prostatic Neoplasms; Radiotherapy, High-Energy; Strontium Radioisotopes

The commonest skeletal tumour occurring in male CBA and C3H mice injected with 7--13 muCi 90Sr (per mouse) at Harwell was diagnosed with the light microscope as haemangiosarcoma. On the other hand, Nilsson, using male CBA mice injected with similar amounts of 90Sr, recorded the predominant tumour as fibroblastic osteosarcoma. To resolve the apparent discrepancy, samples of non-osteogenic tumours induced by 90Sr at Harwell were examined with the electron microscope and their ultrastructure compared with that described for fibroblastic osteosarcoma by Nilsson. The tumours diagnosed as haemangiosarcoma at Harwell showed ultrastructural features not observed in the fibroblastic osteosarcomas. Vasoformation was marked, the vascular channels varying in shape, size and in the character of their lining cells. Some vascular channels were lined by cuboidal cells, crowded together, and surrounded by a basement membrane. Others were lined by an attenuated endothelium and often formed networks. The tumour cells showed great variation in shape, size and ultrastructure and were sometimes enclosed by a basement membrane. Thus the ultrastructure of the tumours described in this report supports the diagnosis of haemangiosarcoma, rather than fibroblastic osteosarcoma. The question of whether these haemangiosarcomas truly originate from vascular endothelium, or are mimics, is discussed.

Topics: Animals; Bone Neoplasms; Hemangiosarcoma; Mice; Mice, Inbred C3H; Mice, Inbred CBA; Microscopy, Electron; Neoplasms, Radiation-Induced; Sarcoma, Experimental; Strontium Radioisotopes

Topics: Adolescent; Adult; Bone Neoplasms; Diagnostic Errors; Humans; Middle Aged; Radionuclide Imaging; Strontium Radioisotopes

The radiopharmacons produced in Hungary and suitable for the demonstration of reactive bone alterations are discussed by the authors. These pharmacons are the following: 85ScCl2=Strontiumchloride, 153Sm-EDTA=Samarium ethylendiamintetraacetate, 169Yb-citrate=Ytterbium-citrate, 99mTc-HEDSPA=Technetium-hydroxy-ethylene-diphosphonate, 99mTc-pyrophosphate. The scintigraphic pictures obtained by the use of these radiopharmacons are presented. On the basis of their experimental examinations the numerous advantages of the use of 99mTc-HEDSPA are pointed out and the possibilities are outlines, which are to be obtained in the detection of occult bone alterations, in the examination of juvenile patients and perhaps in the case of osteotransplantation.

Topics: Bone and Bones; Bone Diseases; Bone Neoplasms; Diagnosis, Differential; Humans; Radiation Dosage; Radioisotopes; Radionuclide Imaging; Samarium; Strontium Radioisotopes; Technetium; Ytterbium

No statistically significant difference in alkaline phosphatase levels was demonstrated in animals injected with the FBJ virus. However, there was a significant increase associated with the development of osteosarcomas in response to the iv injection of 1.0 uCi 90 Sr/g body weight into 11-18-mo-old Anl:CFl females. It was proposed that alkaline phosphatase determinations can be used as well as roentenographic analysis to detect 90Sr-induced tumors in mice.

Topics: Alkaline Phosphatase; Animals; Bone Neoplasms; Female; Gammaretrovirus; Mice; Neoplasms, Radiation-Induced; Osteosarcoma; Radiography; Rodent Diseases; Sarcoma, Experimental; Strontium Radioisotopes

Under observation were 23 patients, aged from 9 to 57 years, with chondromyxoid fibroma of bones. All patients were treated surgically. In 5 cases the involved bone was resected, in 6--edge resection with homoplasty and in 7--segmental resection with automoplasty were employed, in 4--amputation, in 1--exarticulation in the coxa. 20 patients are being kept under observation for 1-7 years without any recurrence and metastases, one patients is still being treated. Two patients died as a result of lung metastases.

Topics: Adolescent; Adult; Bone and Bones; Bone Neoplasms; Child; Chondroma; Female; Humans; Male; Methods; Middle Aged; Radiography; Radioisotope Dilution Technique; Strontium Radioisotopes; Technetium

In primary bone tumors the possibilities of bone scans are discussed. Exact differentiation between malignant and benign disease by this method is impossible. However, scanning provides important information about extent of the disease, metastases, multiplicity of benign lesions and influence of adjoining diseases to the bone. A special indication exists in cases of cerebral meningiomas and an absolute indication for searching osteoplastic metastases, e.g. in carcinomas of the breast and the prostate gland.

Topics: Bone Diseases; Bone Neoplasms; Child; Fluorine; Granuloma; Hemangiosarcoma; Humans; Male; Meningioma; Neoplasm Metastasis; Osteitis Deformans; Osteoma; Radioisotopes; Radionuclide Imaging; Sarcoma, Ewing; Strontium; Strontium Isotopes; Strontium Radioisotopes; Technetium

The therapeutic application of 89strontium for the relief of pain in 11 cases of carcinoma of the prostate with skeletal metastases is reported. A significant clinical improvement could be observed in 8 of the 11 patients with generalized osseous metastases of prostatic carcinoma after the application of 30 muCi. 89strontium per kg. The effect was long lasting. At the same time an increase of alkaline phosphatase was observed, which was interpreted as an indication of the reactivation of osteoblasts and osteoid peripheral zones owing to beta-emission of the radioisotope in the affected areas. The indications for such therapy are discussed.

Topics: Alkaline Phosphatase; Bone Neoplasms; Humans; Male; Neoplasm Metastasis; Pain, Intractable; Prostatic Neoplasms; Radiography; Radionuclide Imaging; Strontium Radioisotopes; Time Factors

Topics: Bone Neoplasms; Humans; Neoplasm Metastasis; Radionuclide Imaging; Strontium Radioisotopes

The natural radiographic appearance of the various bones of the skeleton are described for several strains of laboratory mice. The Harwell substrains of CBA, A and 101 are generally similar and become osteoporotic on ageing. Harwell C57BL have similar, but more delicately chiseled, bones. Harwell C3H mice have bones with stouter cortices and may show osteosclerosis on ageing. CF1 females (donated by Dr M. Finkel) showed osteosclerosis and osteophytic outgrowths when aged. NMRI mice (donated by Dr A. Luz) appeared larger than the pure-strain Harwell mice. In general, mouse bones are simple tubular structures with an ivory cortex and a marrow cavity. Cancellous trabecular bone is scanty, even in vertebrae, flat bones and the metaphyses of long bones. Bone-seeking radionuclides administered to mice lead to skeletal tumours: (a) osteosarcomata, which are commonly radio-opaque to a variable degree owing to calcified tumour bone, but which may be osteolytic, (b) primitive mesenchymal (angio-) sarcomata which are non-osteogenic and osteolytic, (c) fibrosarcomata--which also are osteolytic--and to local or general lymphomata from irradiation of parental cells in bone marrow, but no special radiological features have been found associated with these last-named tumours.

Topics: Aging; Animals; Bone and Bones; Bone Neoplasms; Fibrosarcoma; Hemangiosarcoma; Lymphoma; Mice; Mice, Inbred A; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Inbred Strains; Neoplasms, Radiation-Induced; Osteosarcoma; Plutonium; Radiography; Radium; Species Specificity; Strontium Radioisotopes

Groups of female CBA-mice were given 90Sr (14.8 kBq/g-0.4muCi/g--bodyweight) alone or in combination with polyestrodiolphosphate, methylprednisolone or nortestosterone, respectively. When 90Sr was given in the first combination, the frequency of osteosarcomas was significantly increased whereas the tumour latency time was decreased compared to mice given 90Sr alone. In combination with nortestosterone such effects were not found, whereas the combination 90Sr + methylprednisolone resulted in a strong reduction of the osteosarcoma incidence and a prolonged tumour latency time. The latter experiment was repeated in a larger experiment whereby the results were confirmed.

Topics: Animals; Bone Neoplasms; Cocarcinogenesis; Estradiol; Female; Methylprednisolone; Mice; Mice, Inbred CBA; Nandrolone; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Strontium Radioisotopes; Time Factors

In a series of experiments, mainly CBA/H, but also C2H/H, mice aged 3 months were injected intraperitoneally with solutions of 90Sr Cl2, the dose per mouse varying from 7 to 20 muCi, and compared with similar mice treated with 226Ra or 239Pu, discussed elsewhere. In male mice, the commonest tumour resulting at each dose of 90Sr was non-osteogenic (angio) sarcoma, a tumour not seen after 226Ra. In females, this tumour occurred far less frequently than osteosarcoma. In CBA mice of both sexes converted to radiation chimaeras (which are sterile) and similarly treated with 90Sr, the only skeletal tumours were osteosarcomas. When only half the body of CBA mice was X-irradiated with 1000 rad and the mice given 90Sr, non-osteogenic sarcoma occurred predominantly in those mice X-irradiated in the cephalic half. The results suggest that intact testes may provide co-factors for this type of neoplasm, whereas others have shown that oestrogens facilitate murine osteosarcoma. The non-osteogenic osteosarcomas arise from damaged stromal elements in bone-marrow of selected bones. The risk to this component of bone-marrow, as well as to haematopoietic tissue, should be considered in radiation protection.

Topics: Animals; Bone Marrow; Bone Neoplasms; Female; Hemangiosarcoma; Male; Mice; Mice, Inbred C3H; Mice, Inbred CBA; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Radiography; Strontium Radioisotopes

Bone imaging techniques are a sensitive and accurate method for the detection of primary and secondary neoplastic disease of the skeleton. Such procedures have been demonstrated to be superior to evaluation via blood chemistry levels or routine skeletal radiographic surveys. These techniques are also helpful in establishing sites for biopsy and for objective evaluation of therapeutic modalities. They suffer the disadvantage of being nonspecific, and as a result, all positive areas identified by scanning techniques should be correlated with radiographic changes.

Topics: Bone Neoplasms; Fluorine; Humans; Neoplasm Metastasis; Radiography; Radionuclide Imaging; Strontium Radioisotopes; Technetium

A total of 146 patients were investigated for the presence of osseous metastases with 99mTc polyphosphate or 99mTc pyrophosphate bone scans. Results of bone imaging were retrospectively compared to roentgenographic results surveying similar anatomic areas in 128 patients. This comparison revealed that roentgenographic interpretations were in error in 19% of the cases. Thirty-three patients had bone scans and roentgenograms that were in agreement and considered abnormal, but in more than one third of these cases the patients had multiple abnormalities that were shown by the bone scan but were not recognized roentgenographically. In consideration of the low toxicity, ready availability, economy, shortened procedure time, and low radiation dose associated with the use of these new bone-seeking agents, it is concluded that they are superior to roentgenograms and previously utilized radionuclides for early detection of osseous metastases.

Topics: Bone Neoplasms; Carcinoma; Diphosphates; Fluorine; Humans; Lung Neoplasms; Male; Neoplasm Metastasis; Phosphates; Prostatic Neoplasms; Radioisotopes; Radionuclide Imaging; Scintillation Counting; Strontium Radioisotopes; Urinary Bladder Neoplasms

Topics: Bone and Bones; Bone Neoplasms; Diphosphates; Drug Evaluation; Humans; Neoplasm Metastasis; Radionuclide Imaging; Strontium Radioisotopes; Technetium

Topics: Americium; Arthritis, Rheumatoid; Bone and Bones; Bone Diseases; Bone Neoplasms; Calcium Radioisotopes; Fluorine; Humans; Iodine Radioisotopes; Osteitis Deformans; Osteomalacia; Osteoporosis; Radioisotopes; Radionuclide Imaging; Spondylitis, Ankylosing; Strontium Radioisotopes; Technetium

Topics: Bone Diseases; Bone Neoplasms; Diagnosis, Differential; Humans; Neoplasm Metastasis; Radionuclide Imaging; Strontium Radioisotopes; Technetium

Scanning is based on the uptake of a nuclide by the crystal lattice of bone and is related to bone blood flow. Cancer cells do not take up the tracer. Normally, the scan visualizes the highly vascular bones. Scans are useful and are indicated in metastatic bone disease, primary bone tumors, hematologic malignancies and some non-neoplastic diseases. The scan is more sensitive than x-ray in the detection of malignant diseases of the skeleton.

Topics: Adult; Bone Diseases; Bone Neoplasms; Child; Diagnosis, Differential; Evaluation Studies as Topic; Femoral Fractures; Fluorine; Humans; Lymphoma; Multiple Myeloma; Neoplasm Metastasis; Osteitis Deformans; Osteosarcoma; Pelvic Bones; Phosphates; Radiography; Radioisotopes; Radionuclide Imaging; Skull Neoplasms; Strontium Isotopes; Strontium Radioisotopes; Technetium

Comparative studies between radiological (equals R; x-ray, thermography, angiography) and nuclear medical examinations (equals NM; scanner-, scintillation camera-sequential scintigraphy) in 339 patients with different bone diseases led to the following results: Thermography proved to be inferior to scanning in detecting of bone diseases. Angiography was the procedure of choice in detecting malignant bone tumors. Sequential scintigraphy performed by means of the Anger-HP-scintillation camera and Intertechnique-Cine-System allowed to establish the kinetic behaviour of tumors: an early increased TcPoP accumulation was observed in tumors with high perfusion (sarcoma), a late accumulation in those with low perfusion (osteoid osteoma).

Topics: Angiography; Bone Diseases; Bone Neoplasms; Diagnosis, Differential; Diagnostic Errors; Femoral Neoplasms; Humans; Kinetics; Neoplasm Metastasis; Osteoma, Osteoid; Osteosarcoma; Phosphates; Radiography; Radionuclide Imaging; Strontium Radioisotopes; Technetium; Thermography; Tibia

Topics: Bone Neoplasms; Humans; Osteosarcoma; Radionuclide Imaging; Strontium Radioisotopes

Topics: Animals; Bone Neoplasms; Gallium Radioisotopes; Rabbits; Radionuclide Imaging; Strontium Radioisotopes; Technetium

Strontium 87m bone scanning was used in the assessment of 162 patients with breast cancer. Seventy-two patients had abnormal bone scans and in 63 (87 percent) these findings were subsequently confirmed. More metastases were detected by scanning and radiology than by radiology alone. There was a false positive rate of 7 percent. Of the 90 negative scans 23 showed evidence of metastasis either radiologically or at autopsy. This represented a false negative rate of 26 percent. The reasons for the false results are discussed particularly in relation to the problems of imaging the dorsal spine.

Topics: Bone Neoplasms; Breast Neoplasms; Diagnostic Errors; Female; Humans; Neoplasm Metastasis; Radiography; Radionuclide Imaging; Spinal Neoplasms; Strontium Radioisotopes

The value of bone scanning with 99mTc-polyphosphate was assessed in 186 patients with various types of tumors. The sensitivity of this technique was greater than that of metastatic roentgenographic series and the reported results of 85-Sr-bone scans, in the detection of osseous involvement by tumors. Three cases with normal bone scans and abnormal roentgenographic studies illustrated the necessity and complementary value of comparing bone scan findings with radiographic studies. Patients with carcinoma of the breast, lung, or prostate displayed characteristic patterns of bone involvement by their tumors. The importance of clinical information, including bone symptoms, antecedent bone disease, and serum calcium and alkaline phosphatase, was stressed in the detection and interpretation of bone scan abnormalities.

Topics: Alkaline Phosphatase; Bone Neoplasms; Breast Neoplasms; Evaluation Studies as Topic; Female; Humans; Hypercalcemia; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Pelvic Neoplasms; Prostatic Neoplasms; Radionuclide Imaging; Ribs; Skull Neoplasms; Spinal Neoplasms; Strontium Radioisotopes; Technetium

In a group of 30 patients with neoplastic processes, 13 were found to have a significantly increased serum alkaline phosphatase activity. This finding correlated with the results of investigation with 85Sr in 7 patients, but owing to a concomitant hepatal symptomatology, it proved of differential diagnostic value in only one of them. On the other hand, the activity of bone isoenzyme of alkaline phosphatase was significantly altered in 15 patients. In 14 of them the increase in bone isoenzyme activity corresponded to an X-ray and a radionuclear finding of a tumor process in the bones. This activity was within the normal range of values in only one patient with a positive result of the 85Sr investigation. An agreement between the results of determination of bone isoenzyme activity of alkaline phosphatase and those of radionuclear investigations was found in 27 patients. In addition, a correlation was established between the increased activity of bone isoenzyme and that of intestinal isoenzyme of alkaline phosphatase. Enzyme investigation can be suitably utilized, alongside radionuclear examination, for early detection of a bone process.

Topics: Adult; Aged; Alkaline Phosphatase; Bone and Bones; Bone Neoplasms; Female; Humans; Isoenzymes; Male; Middle Aged; Strontium Radioisotopes

In a series of related experiments to evaluate the relative toxicity of inhaled radionuclides, beagles were exposed to aerosols containing relatively soluble (chloride) or relatively insoluble (fused clay) forms of 144-Ce and 90Sr. With the solubled 144-CeCl3, significant radiation doses were delivered to the lungs, liver, and skeleton whereas, after 90-SrCl2 exposure, the radiation dose was delivered predominantly to the skeleton. In dogs exposed to 144-Ce and 90-Sr in fused clay particles, radiation doses were delivered mostly to the lungs and tracheobronchial lymph nodes. In most dogs dying within 2 years after exposure, deaths were attributable to nonneoplastic radiation-induced lesions in the target organ systems. At later times after exposure, neoplasms were the major cause of death, again occurring mostly in target organs or the adjacent tissues. Lung liver, and bone-related neoplasms, including five hepatic hemangiosarcomas, developed after 144-CeCl3 exposure. Among the bone-related sarcomas seen in dogs exposed to 144-CeC3 or 90-SrC2, the incidence of hemangiosarcomas was over 40%. Among the 20 dogs dying with pulmonary neoplasms after exposure to 144-Ce or 90Sr in fused clay particles, all had hemangiosarcomas and several also had other neoplasms. This high after exposure and differs from results in other laboratories where beagles have been exposed to both alpha and beta-emitting radionuclides.

Topics: Aerosols; Animals; Bone and Bones; Bone Neoplasms; Cesium Radioisotopes; Dogs; Hemangiosarcoma; Humans; Infant, Newborn; Liver; Liver Neoplasms; Lung; Lung Neoplasms; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Radiation Dosage; Radioisotopes; Strontium Radioisotopes; Time Factors

Strontium nitrate Sr 87m bone scans were made preoperatively in a group of women with suspected breast cancer, 35 of whom subsequently underwent radical mastectomy. In 3 of the 35 (9%), the scans were abnormal despite the absence of clinical or roentgenographic evidence of metastatic disease. All three patients has extensive axillary lymph node involvement by tumor, and went on to have additional bone metastases, from which one died. Roentgenograms failed to detect the metastases in all three. Occult bone metastases account in part for the failure of radical mastectomy to cure some patients with breast cancer. It is recommended that all candidates for radical mastectomy have a preoperative bone scan.

Topics: Adult; Aged; Bone Neoplasms; Breast Neoplasms; Female; Follow-Up Studies; Humans; Lymphatic Metastasis; Mammography; Mastectomy; Middle Aged; Neoplasm Metastasis; Nitrates; Preoperative Care; Radionuclide Imaging; Strontium Radioisotopes; Thermography; Time Factors

Topics: Adolescent; Adult; Bone Neoplasms; Child; Diagnosis, Differential; Female; Giant Cell Tumors; Humans; Male; Osteoma, Osteoid; Osteomyelitis; Radionuclide Imaging; Strontium Radioisotopes

Topics: Adolescent; Bone Diseases; Bone Neoplasms; Child, Preschool; Exostoses; Female; Fibroma; Fractures, Bone; Humans; Male; Maxillary Sinus; Middle Aged; Osteoma, Osteoid; Paranasal Sinus Neoplasms; Radiography; Radionuclide Imaging; Strontium Radioisotopes

Topics: Bone Neoplasms; Gallium Radioisotopes; Humans; Indium; Iodine Radioisotopes; Radioisotopes; Radionuclide Imaging; Selenium; Soft Tissue Neoplasms; Strontium Radioisotopes; Technetium

Malignant disease very often spreads to the skeleton. This is particularly true for carcinomas of the breast, the lungs, the prostate, and the thyroid. Knowledge of the state of the skeleton in these disorders is therefore desirable since patient management will largely depend on the early detection of bony deposits. Primary bone disease often spreads to soft tissue (lungs), and the early detection of this may alter significantly the therapeutic approach to the primary lesion. Traditionally, X-ray skeletal surveys and serum enzyme measurements provide indices which can be used in the staging of these disorders. Complementary techniques such as mammography, xeroradiography, thermography, and radionuclide imaging have been used to provide further relevant information. A number of benign bone diseases need early assessment in order to institute the best form of treatment. It is of importance to assess the circulation in localized areas of bone and to predict the appearance of avascular necrosis, to understand the healing mechanisms involved in fractures, and to predict the outcome of bone grafting. In this paper the clinical role of bone scanning is reviewed, particular attention being given to the recent advances brought about by the introduction of the 99mTc compounds. It is important that the non-specialist should be aware of the great improvement in the results obtained and in the help they can give him in deciding on the best management of each patient as an individual.

Topics: Bone and Bones; Bone Diseases; Bone Neoplasms; Fluorine; Humans; Kidney Diseases; Neoplasm Metastasis; Osteolysis; Phosphates; Radioisotopes; Radionuclide Imaging; Strontium Isotopes; Strontium Radioisotopes; Technetium

Topics: Bone Neoplasms; Humans; Radionuclide Imaging; Strontium Radioisotopes

Topics: Adolescent; Adult; Aged; Bone Neoplasms; Breast Neoplasms; Calcium Radioisotopes; Female; Fluorine; Hodgkin Disease; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Radioisotopes; Radionuclide Imaging; Strontium Radioisotopes; Technetium

Topics: Animals; Bleomycin; Bone Neoplasms; Diphosphates; Gallium; Neoplasm Transplantation; Neoplasms, Experimental; Rabbits; Radionuclide Imaging; Strontium Radioisotopes; Technetium

Topics: Angiography; Bone Diseases; Bone Neoplasms; Diagnosis, Differential; Fluorides; Follow-Up Studies; Humans; Methods; Neoplasm Metastasis; Radioisotopes; Radionuclide Imaging; Strontium Radioisotopes; Technetium; Thermography

Topics: Adolescent; Adult; Aged; Biopsy; Bone and Bones; Bone Diseases; Bone Neoplasms; Calcium; Female; Fluorides; Fractures, Bone; Hodgkin Disease; Humans; Hydroxyapatites; Ion Exchange; Male; Middle Aged; Paraganglioma, Extra-Adrenal; Radiation Dosage; Radiography; Radioisotopes; Radionuclide Imaging; Strontium Radioisotopes; Technetium

Topics: Bone and Bones; Bone Diseases; Bone Neoplasms; Calcium; Diphosphates; Fluorine; Humans; Methods; Phosphates; Radioisotopes; Radionuclide Imaging; Strontium Radioisotopes; Technetium

Topics: Administration, Oral; Aged; Bone Neoplasms; Diethylstilbestrol; Humans; Hydroxyproline; Injections, Intravenous; Male; Methods; Middle Aged; Neoplasm Metastasis; Neoplasm Regression, Spontaneous; Phosphoric Monoester Hydrolases; Prostatic Neoplasms; Radiography; Strontium Radioisotopes; Time Factors

Topics: Bone Marrow; Bone Neoplasms; Densitometry; Diphosphates; Humans; Male; Neoplasm Metastasis; Phosphates; Prostatic Neoplasms; Radiation Dosage; Radionuclide Imaging; Strontium Radioisotopes; Technetium

Topics: Adult; Bone Neoplasms; Chondrosarcoma; Humans; Male; Radioisotopes; Radionuclide Imaging; Strontium Isotopes; Strontium Radioisotopes; Technetium

Topics: Adenocarcinoma; Adult; Aged; Arthritis; Bone Diseases; Bone Neoplasms; Breast Neoplasms; Colonic Neoplasms; Female; Fluorine; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neoplasm Metastasis; Osteitis Deformans; Prostatic Neoplasms; Radiation Dosage; Radiation Monitoring; Radiography; Radioisotopes; Radionuclide Imaging; Ribs; Shoulder; Skull Neoplasms; Strontium Radioisotopes; Technetium; Thoracic Neoplasms

Topics: Adrenalectomy; Adult; Anabolic Agents; Androgens; Antineoplastic Agents; Bone Neoplasms; Breast Neoplasms; Castration; Cyclophosphamide; Estrogens; Ethinyl Estradiol; Female; Humans; Hypophysectomy; Methods; Middle Aged; Neoplasm Metastasis; Strontium Radioisotopes

Topics: Adolescent; Adult; Bone and Bones; Bone Diseases; Bone Neoplasms; Breast Neoplasms; Chondroma; Female; Fractures, Bone; Hodgkin Disease; Humans; Male; Middle Aged; Neoplasm Metastasis; Radionuclide Imaging; Sarcoma, Ewing; Spinal Neoplasms; Strontium Radioisotopes; Time Factors

Topics: Alkaline Phosphatase; Bone and Bones; Bone Marrow Examination; Bone Neoplasms; Breast Neoplasms; Female; Humans; Middle Aged; Neoplasm Metastasis; Radiography; Strontium Radioisotopes; Technetium

Topics: Bone Neoplasms; Humans; Neoplasm Metastasis; Radionuclide Imaging; Strontium Radioisotopes; Thermography

Topics: Adult; Bone Neoplasms; Femoral Neoplasms; Half-Life; Humans; Male; Middle Aged; Phosphates; Radiography; Radioisotopes; Radionuclide Imaging; Spinal Neoplasms; Spine; Strontium Radioisotopes; Technetium

Topics: Adult; Air Pollution, Radioactive; Animals; Bone Marrow; Bone Marrow Cells; Bone Neoplasms; Dogs; Dose-Response Relationship, Drug; Energy Transfer; Humans; Infant; Male; Maximum Allowable Concentration; Neoplasms, Radiation-Induced; Radiation Dosage; Radiation Effects; Radiation Protection; Radiobiology; Radionuclide Imaging; Radiotherapy Dosage; Radium; Strontium Radioisotopes

Topics: Bone Neoplasms; Breast Neoplasms; Feces; Female; Hodgkin Disease; Humans; Injections, Intravenous; Kinetics; Male; Neoplasm Metastasis; Osteolysis; Osteoporosis; Prostatic Neoplasms; Radionuclide Imaging; Spinal Neoplasms; Strontium; Strontium Radioisotopes; Time Factors

Topics: Bone Neoplasms; Female; Giant Cell Tumors; Humans; Male; Neoplasm Metastasis; Osteoma, Osteoid; Radiography; Radionuclide Imaging; Scintillation Counting; Strontium Radioisotopes

Topics: Acetabulum; Bone Neoplasms; Breast Neoplasms; Diagnosis, Differential; False Negative Reactions; Femoral Neoplasms; Half-Life; Humans; Lung Neoplasms; Neoplasm Metastasis; Osteoporosis; Pelvic Neoplasms; Posture; Pubic Bone; Radiography; Radionuclide Imaging; Ribs; Spinal Neoplasms; Strontium Radioisotopes

Topics: Adult; Bone Neoplasms; Female; Humans; Middle Aged; Neoplasm Metastasis; Radionuclide Imaging; Strontium Radioisotopes; Thermography

Topics: Bone Neoplasms; Elementary Particles; Fluorine; Humans; Radiation Dosage; Radioisotopes; Radionuclide Imaging; Scattering, Radiation; Strontium Radioisotopes; Technetium

Topics: Bone Neoplasms; Humans; Neoplasm Metastasis; Radionuclide Imaging; Strontium Radioisotopes

Topics: Adolescent; Adult; Bone Neoplasms; Chondroma; Female; Fibrous Dysplasia of Bone; Giant Cell Tumors; Humans; Male; Middle Aged; Multiple Myeloma; Radionuclide Imaging; Strontium Radioisotopes

Topics: Autopsy; Bone and Bones; Bone Diseases; Bone Neoplasms; False Negative Reactions; Fluorine; Half-Life; Humans; Neoplasm Metastasis; Radiography; Radionuclide Imaging; Strontium Isotopes; Strontium Radioisotopes; Technetium

Topics: Adolescent; Adult; Aged; Bone Neoplasms; Brain Neoplasms; Breast Neoplasms; Child; Diagnosis, Differential; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Neoplasm Metastasis; Radiography; Radioisotopes; Radionuclide Imaging; Selenium; Strontium Radioisotopes; Technetium; Thoracic Neoplasms

Topics: Bone Neoplasms; Humans; Methods; Neoplasm Metastasis; Radionuclide Imaging; Strontium Radioisotopes

Topics: Bone Neoplasms; Chondrosarcoma; Fibrosarcoma; Humans; Lymphoma, Large B-Cell, Diffuse; Osteosarcoma; Radiography; Radionuclide Imaging; Sarcoma; Sarcoma, Ewing; Strontium Isotopes; Strontium Radioisotopes; Technetium

Topics: Acid Phosphatase; Aged; Biopsy, Needle; Bone and Bones; Bone Marrow; Bone Neoplasms; Castration; Humans; Ilium; Male; Middle Aged; Neoplasm Metastasis; Prostatectomy; Prostatic Neoplasms; Radionuclide Imaging; Strontium Radioisotopes

Topics: Bone Neoplasms; Fluorine; Humans; Phosphates; Radioisotopes; Radionuclide Imaging; Strontium Radioisotopes; Technetium

Topics: Animals; Bone Diseases; Bone Neoplasms; Bony Callus; Diagnosis, Differential; Female; Fractures, Bone; Half-Life; Humans; Injections, Intravenous; Male; Neoplasm Metastasis; Rabbits; Spinal Neoplasms; Strontium Radioisotopes

Topics: Alkaline Phosphatase; Bone Neoplasms; Breast Neoplasms; Female; Hematopoiesis; Humans; Male; Neoplasm Metastasis; Pain, Intractable; Prostatic Neoplasms; Radiation Effects; Strontium Radioisotopes; Time Factors

Topics: Bone Neoplasms; Female; Humans; Male; Neoplasm Metastasis; Radionuclide Imaging; Strontium Radioisotopes

Topics: Age Factors; Bone and Bones; Bone Diseases; Bone Neoplasms; Calcification, Physiologic; Fluorine; Fractures, Bone; Humans; Infections; Necrosis; Neoplasm Metastasis; Osteitis; Radioisotopes; Radionuclide Imaging; Regional Blood Flow; Sclerosis; Strontium Radioisotopes; Technetium; Time Factors; Whole-Body Counting

Topics: Acute Disease; Bone and Bones; Bone Diseases; Bone Neoplasms; Breast Neoplasms; Chronic Disease; Citrates; Female; Femur Head Necrosis; Humans; Neoplasm Metastasis; Osteomyelitis; Phosphates; Radionuclide Imaging; Strontium Radioisotopes; Technetium; Whole-Body Counting

Topics: Bone Diseases; Bone Neoplasms; Humans; Neoplasm Metastasis; Radiography; Radionuclide Imaging; Strontium Radioisotopes; Technetium

Topics: Bone Neoplasms; Diphosphates; Humans; Neoplasm Metastasis; Radionuclide Imaging; Remission, Spontaneous; Strontium Radioisotopes; Technetium; Tomography, X-Ray

Topics: Animals; Bone Development; Bone Neoplasms; Cell Division; Delayed-Action Preparations; Estradiol; Female; Male; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Organophosphorus Compounds; Osteoblasts; Osteoclasts; Osteosarcoma; Polymers; Radiation Effects; Rats; Strontium Radioisotopes; Time Factors

Topics: Adolescent; Adult; Aged; Bone Neoplasms; Child; Female; Fluorine; Humans; Male; Middle Aged; Radioisotopes; Radionuclide Imaging; Strontium Isotopes; Strontium Radioisotopes

Topics: Adolescent; Biopsy; Bone Diseases; Bone Neoplasms; Child; Child, Preschool; Female; Humans; Infant; Male; Radiography; Radionuclide Imaging; Retrospective Studies; Strontium Radioisotopes

Topics: Adult; Bone Neoplasms; Female; Humans; Hydronephrosis; Middle Aged; Neoplasm Metastasis; Pelvic Neoplasms; Radionuclide Imaging; Strontium Isotopes; Strontium Radioisotopes; Ureteral Obstruction

Topics: Alkaline Phosphatase; Bone Neoplasms; Clinical Enzyme Tests; Evaluation Studies as Topic; Humans; Neoplasm Metastasis; Radionuclide Imaging; Strontium Radioisotopes; Technetium

Topics: Adult; Bone Diseases; Bone Neoplasms; Female; Humans; Male; Methods; Middle Aged; Neoplasm Metastasis; Radionuclide Imaging; Strontium Radioisotopes

Topics: Adult; Bone Diseases; Bone Neoplasms; Female; Humans; Male; Methods; Middle Aged; Strontium Radioisotopes

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Bone Neoplasms; Bone Resorption; Breast Neoplasms; Female; Hematologic Diseases; Humans; Injections, Intravenous; Male; Middle Aged; Movement; Multiple Myeloma; Neoplasm Metastasis; Pain, Intractable; Radionuclide Imaging; Remission, Spontaneous; Strontium Radioisotopes; Urinary Bladder Neoplasms; Uterine Neoplasms

Topics: Adult; Aged; Bone and Bones; Bone Diseases; Bone Neoplasms; Female; Fractures, Bone; Humans; Hydroxyproline; Male; Middle Aged; Radiography; Radionuclide Imaging; Strontium Radioisotopes

Topics: Adenocarcinoma; Bone Neoplasms; Breast Neoplasms; Carcinoma; Female; Humans; Male; Neoplasm Metastasis; Phosphates; Prostatic Neoplasms; Radionuclide Imaging; Strontium Radioisotopes; Technetium

Topics: Adolescent; Adult; Bone Neoplasms; Hodgkin Disease; Humans; Lymphatic Metastasis; Middle Aged; Radionuclide Imaging; Strontium Radioisotopes

Topics: Bone Neoplasms; Humans; Pelvic Bones; Radionuclide Imaging; Strontium Radioisotopes

Topics: Barium; Bone Diseases; Bone Neoplasms; Fluorine; Humans; Radiation Dosage; Radioisotopes; Radionuclide Imaging; Strontium Radioisotopes; Technetium

Topics: Adolescent; Adult; Bone Neoplasms; Female; Gallium; Humans; Male; Middle Aged; Neoplasm Metastasis; Pelvic Neoplasms; Radioisotopes; Radionuclide Imaging; Spinal Neoplasms; Strontium Radioisotopes

Topics: Bone Neoplasms; Evaluation Studies as Topic; Humans; Pelvic Neoplasms; Radionuclide Imaging; Strontium Radioisotopes

Topics: Bone Neoplasms; Breast Neoplasms; Female; Humans; Radionuclide Imaging; Strontium Radioisotopes; Technetium

Topics: Autoradiography; Bone Neoplasms; Neoplasms; Osteosarcoma; Sarcoma; Strontium; Strontium Radioisotopes

Topics: Bone Neoplasms; Calcium; Calcium Radioisotopes; Humans; Radioisotopes; Radiometry; Strontium; Strontium Radioisotopes

Topics: Animals; Bone Neoplasms; Incidence; Mice; Mice, Inbred CBA; Neoplasms; Osteosarcoma; Sarcoma; Strontium; Strontium Radioisotopes

Topics: Bone Neoplasms; Breast Neoplasms; Humans; Neoplasms; Spinal Cord Neoplasms; Spine; Strontium; Strontium Radioisotopes

Topics: Bone and Bones; Bone Neoplasms; Cartilage Diseases; Humans; Neoplasms; Radiometry; Strontium; Strontium Radioisotopes

Topics: Bone and Bones; Bone Neoplasms; Calcium; Calcium Radioisotopes; Calcium, Dietary; Neoplasms; Radiation Injuries; Radioisotopes; Strontium; Strontium Radioisotopes

Topics: Animals; Bone and Bones; Bone Neoplasms; Citrates; Citric Acid; Mice; Neoplasms; Osteosarcoma; Strontium; Strontium Radioisotopes; Zirconium

Topics: Bone and Bones; Bone Neoplasms; Morphogenesis; Neoplasms; Radiation, Ionizing; Strontium; Strontium Radioisotopes

Topics: Animals; Bone and Bones; Bone Neoplasms; Neoplasms; Osteosarcoma; Rats; Sarcoma, Experimental; Strontium; Strontium Radioisotopes

Topics: Bone Neoplasms; Neoplasms; Osteosarcoma; Sarcoma; Strontium; Strontium Radioisotopes

Topics: Animals; Bone Neoplasms; Morphogenesis; Neoplasms; Neoplasms, Experimental; Osteosarcoma; Sarcoma; Strontium; Strontium Radioisotopes

Topics: Animals; Bone Neoplasms; Dogs; Neoplasms, Experimental; Osteosarcoma; Strontium; Strontium Radioisotopes

Topics: Bone Neoplasms; Humans; Male; Strontium; Strontium Radioisotopes

Topics: Animals; Bone and Bones; Bone Neoplasms; Humans; Neoplasms; Neoplasms, Experimental; Strontium; Strontium Radioisotopes

Topics: Bombs; Bone and Bones; Bone Neoplasms; Humans; Neoplasms; Radioactivity; Strontium; Strontium Radioisotopes

Topics: Animals; Arvicolinae; Bone Neoplasms; Fibula; Humans; Neoplasms; Osteosarcoma; Sarcoma; Strontium; Strontium Radioisotopes; Tibia

Topics: Bone Neoplasms; Humans; Neoplasms; Strontium; Strontium Radioisotopes