lutetium-lu-177-dotatate and Neoplasm-Metastasis

To evaluate the efficacy of. All published clinical studies of NETs treated with. Fifteen studies were selected from 715 references. The pooled effect in the RECIST group (13 studies) was 27.58% (95% confidence interval (CI) 21.03-35.27%) for the DRR and 79.14% (95% CI 75.83-82.1%) for the DCR. In the SWOG criteria group (7 studies), the pooled effect was 20.59% (95% CI 10.89-35.51%) for the DRR and 78.28% (95% CI 74.39-81.72%) for the DCR. Therefore, the RECIST and SWOG groups showed similar DRRs and DCRs after. For patients with inoperable or metastatic NETs,

Topics: Humans; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Radiopharmaceuticals

The incidence of pancreatic Neuroendocrine Tumours (pNETs) has increased considerably in the last few decades. The characteristic features of this tumour and the development of new investigative and therapeutic methods had a great impact on its management.. The aim of this review is to investigate the outcome of Peptide Receptor Radionuclide Therapy (PRRT) in the treatment of pancreatic neuroendocrine tumours.. A comprehensive literature search strategy was used based on two databases (SCOPUS, and PubMed). We considered all studies published in English, evaluating the use of PRRT (177Luteciuim- DOTA-conjugated peptides and 90Yetrium- DOTA- conjugated peptides) in the treatment of pancreatic neuroendocrine tumours as a standalone entity or as a subgroup within the wider category of Gastroenteropancreatic Neuroendocrine Tumours (GEP NETs).. PRRT was found to be an effective treatment modality as a monotherapy or in combination with other therapies in the treatment of non-operable and metastatic pNETs where other options are limited. Complete response was reported to be between 2-6% while partial response was achieved in up to 60% of cases. Survival analysis was also impressive. Progression Free Survival (PFS) reached a mean of 34 months and Overall Survival (OS) of 53 months. PRRT also proved to improve patients' Quality of Life (QoL). Acute and sub-acute side effects like nephrotoxicity and haematotoxicity are usually mild and reversible.. PRRT is well tolerated and effective treatment option for non-operable and/or metastatic pNETs. Side effects are usually mild and reversible. Larger randomized controlled trails need to be done to compare PRRT with other treatment modalities and to provide more detailed guidelines regarding patient selections, the choice of PRRT, follow up and response assessment to maximum potential benefit.

Topics: Disease-Free Survival; Humans; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Peptides; Positron Emission Tomography Computed Tomography; Quality of Life; Radiation Oncology; Radiopharmaceuticals; Receptors, Peptide; Treatment Outcome

Neuroendocrine tumours (NETs) are a group of heterogeneous cancers that develop in cells in the diffuse neuroendocrine system.. To estimate the clinical effectiveness of three interventions [everolimus (Afinitor. The following databases were searched from inception to May 2016: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Daily, Epub Ahead of Print, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science.. We systematically reviewed the clinical effectiveness and cost-effectiveness literature on everolimus, 177Lu-DOTATATE and sunitinib for treating advanced, unresectable or metastatic progressive NETs. The following NET locations were considered separately: pancreas, gastrointestinal (GI) tract and lung, and GI tract (midgut only). We wrote a survival partition cohort-based economic evaluation in Microsoft Excel. Three randomised controlled trials (RCTs), RADIANT-3 [RAD001 in Advanced Neuroendocrine Tumors, Third Trial; pancreatic NETs (pNETs): everolimus vs. best supportive care (BSC)], A6181111 (pNETs: sunitinib vs. BSC) and RADIANT-4 (RAD001 in Advanced Neuroendocrine Tumors, Fourth Trial; GI and lung NETs: everolimus vs. BSC), met the inclusion criteria for the clinical effectiveness systematic review. The risk of bias was low. Although the NETTER-1 (Neuroendocrine Tumors Therapy) RCT, of 177Lu-DOTATATE plus 30 mg of octreotide (Sandostatin. A RCT with included comparators was not identified for 177Lu-DOTATATE. The indirect treatment comparison that our economic analysis was based on was of a simple Bucher type, unadjusted for any differences in the baseline characteristics across the two trials.. Given NICE's current stated range of £20,000-30,000 per QALY for the cost-effectiveness threshold, based on list prices, only sunitinib might be considered good value for money in England and Wales.. Further analysis of individual patient data from RADIANT-3 would allow assessment of the robustness of our findings. The data were not made available to us by the company sponsoring the trial.. This study is registered as PROSPERO CRD42016041303.. The National Institute for Health Research Health Technology Assessment programme.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cost-Benefit Analysis; Digestive System Neoplasms; Disease Progression; Everolimus; Humans; Lung Neoplasms; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Quality-Adjusted Life Years; Radioisotopes; Randomized Controlled Trials as Topic; Sunitinib

This report illustrates an excellent partial response of Merkel cell carcinoma with multiple bilobar hepatic metastases to a single cycle of peptide receptor radionuclide therapy (PRRT) with (177)Lu-DOTATATE. This response, coupled with minimal side effects, warrants consideration of this therapy early in the disease course (rather than at an advanced stage after failure of other therapies) if the metastatic lesions exhibit adequate tracer avidity on somatostatin receptor-based imaging. Our patient showed progression of systemic disease after having undergone a second surgery and adjuvant radiotherapy to the head and neck, as well as chemotherapy, and hence was considered a candidate for PRRT. In a pretreatment study, the metastatic lesions demonstrated avidity to both somatostatin receptors and (18)F-FDG. Three months after the first cycle of treatment, when the patient was being evaluated for a second cycle, both imaging parameters showed evidence of a partial response that included nearly complete resolution of the two previously seen lesions. In view of the relatively good tolerability, minimal side effects, and targeted nature of the treatment, PRRT may evolve to become the first-line therapy for metastatic Merkel cell carcinoma and should be examined further in a larger number of patients.

Topics: Carcinoma, Merkel Cell; Humans; Male; Middle Aged; Molecular Targeted Therapy; Neoplasm Metastasis; Octreotide; Organometallic Compounds; Positron-Emission Tomography; Receptors, Peptide; Skin Neoplasms; Treatment Outcome

Neuroendocrine tumours (NET) consist of a heterogeneous group of neoplasms with various organs of origin. At diagnosis 21% of the patients with a Grade 1 NET and 30% with a Grade 2 NET have distant metastases. Treatment with peptide receptor radionuclide therapy (PRRT) shows a high objective response rate and long median survival after treatment. However, complete remission is almost never achieved. The liver is the most commonly affected organ in metastatic disease and is the most incriminating factor for patient survival. Additional treatment of liver disease after PRRT may improve outcome in NET patients. Radioembolization is an established therapy for liver metastasis. To investigate this hypothesis, a phase 2 study was initiated to assess effectiveness and toxicity of holmium-166 radioembolization (. The HEPAR PLUS trial ("Holmium Embolization Particles for Arterial Radiotherapy Plus. This is the first prospective study to combine PRRT with. Clinicaltrials.gov NCT02067988 , 13 February 2014. Protocol version: 6, 30 november 2016.

Topics: Antineoplastic Agents; Biomarkers, Tumor; Combined Modality Therapy; Embolization, Therapeutic; Holmium; Humans; Liver Neoplasms; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Quality of Life; Radioisotopes; Radiopharmaceuticals; Remission Induction; Survival Analysis

The NETTER-1 trial demonstrated significantly improved progression-free survival (PFS) for peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors (NET) emphasizing the high demand for response prediction in appropriate candidates. In this multicenter study, we aimed to elucidate the prognostic value of tumor heterogeneity as assessed by somatostatin receptor (SSTR)-PET/CT. 141 patients with SSTR-expressing tumors were analyzed obtaining SSTR-PET/CT before PRRT (1-6 cycles, 177Lu somatostatin analog). Using the Interview Fusion Workstation (Mediso), a total of 872 metastases were manually segmented. Conventional PET parameters as well as textural features representing intratumoral heterogeneity were computed. The prognostic ability for PFS and overall survival (OS) were examined. After performing Cox regression, independent parameters were determined by ROC analysis to obtain cut-off values to be used for Kaplan-Meier analysis. Within follow-up (median, 43.1 months), 75 patients showed disease progression (median, 22.2 m) and 54 patients died (median, 27.6 m). Cox analysis identified 8 statistically independent heterogeneity parameters for time-to-progression and time-to-death. Among them, the textural feature Entropy predicted both PFS and OS. Conventional PET parameters failed in response prediction. Imaging-based heterogeneity assessment provides prognostic information in PRRT candidates and outperformed conventional PET parameters. Its implementation in clinical practice can pave the way for individualized patient management.

Topics: Adult; Aged; Aged, 80 and over; Disease-Free Survival; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Positron Emission Tomography Computed Tomography; Prognosis; Receptors, Somatostatin; ROC Curve; Treatment Outcome

A number of detected neuroendocrine neoplasms (NENs) has been on the increase due to our awareness of the NENs risk and the development of different imaging techniques. Therapy of NENs involves surgery, chemotherapy, "cold" somatostatin analogs (SSA), peptide receptor radionuclide therapy (PRRT) and kinase inhibitors in pancreatic NENs. The aim of this study is to assess the efficacy of SSA in combination with "hot" somatostatin analogs, and the survival rate of our patients with advanced NENs. Seventy nine patients with metastatic NEN and positive somatostatin receptor scintigraphy (SRS) were enrolled in the study. Every patient was supposed to receive a dose of 7.4 GBq/m

Topics: Adult; Aged; Aged, 80 and over; Disease Progression; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Radionuclide Imaging; Receptors, Peptide; Receptors, Somatostatin; Somatostatin; Survival Analysis; Treatment Outcome

Neuroendocrine tumors (NETs) of the skin or soft tissue are rare (mostly described as sites of metastasis), whereas primary soft-tissue NETs are extremely rare; they are usually diagnosed at advanced stages with distant metastases because of their indolent nature. We herein describe our experience with 2 such cases. In the first case, the NET originated in the retroperitoneal soft tissue, and in the second case, the patient was a middle-aged lady with NET arising from soft tissue in the pelvis. Both patients were treated with

Topics: Female; Humans; Middle Aged; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Receptors, Peptide; Receptors, Somatostatin; Soft Tissue Neoplasms; Treatment Outcome

To determine the impact of PRRT on quality of life, radiologic and metabolic response, overall survival, prognostic factors and toxicity.. Thirty-six patients treated with. From 36 patients, 55.6% were men, with a median age of 61.1 ± 11.8 years. Regarding previous treatments, 55.6% of patients underwent surgery of the primary tumor, 100% of patients were treated with long-acting somatostatin analogues, 66.7% of patients were treated with everolimus, 27.8% of patients were treated with tyrosine kinase inhibitor, and 27.8% of patients were treated with interferon. One patient received radioembolization, three patients received chemoembolization, six patients received chemotherapy. Hematological toxicity was registered in 14 patients (G1-G2: 55.5% and G3: 3.1%). Other events presented were intestinal suboclusion in 4 cases, cholestasis in 2 cases and carcinoid crisis in 1 case. The median follow-up time was 3 years. Currently, 24 patients completed treatment. Nineteen are alive with stable disease, two have disease progression, eight have died, and nine are still receiving treatment. The median overall survival was 12.5 mo (95% confidence interval range: 9.8-15.2), being inversely proportional to toxicity in previous treatments (. Overall survival was inversely proportional to previous toxicity, tumor grade and the presence of bone metastasis and directly proportional to matching lesion findings between Octreoscan and computed tomography pre-PRRT and primary tumor and metastasis surgery.

Topics: Aged; Female; Humans; Intestinal Neoplasms; Male; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Prognosis; Proportional Hazards Models; Radiopharmaceuticals; Spain; Stomach Neoplasms; Survival Rate; Treatment Outcome

Peptide receptor radionuclide therapy (PRRT) has been shown to be useful in inoperable/metastatic medullary thyroid carcinoma (MTC). However, the role of concomitant PRRT and low-dose capecitabine therapy has not yet been studied in these patients. This study was conducted to evaluate the efficacy and safety of this combination approach in advanced MTC.. This was a retrospective, single-centre study. Data of consecutive patients of advanced inoperable/metastatic MTC treated with concomitant Lu-DOTATATE+capecitabine, from January 2014 to August 2018, were collected and analysed for radiological, molecular and biochemical responses and treatment-related toxicity.. Eight patients with advanced MTC received a median cumulative dose of 20.9 GBq (interquartile range 8.9-27.7 GBq) Lu-DOTATATE over 1-4 cycles and 1250 mg/m capecitabine from days 0 to 14 of each PRRT cycle. Radiological response according to Response Evaluation Criteria in Solid Tumours 1.1 criteria could be assessed in seven patients. Six out of seven patients (86%) had stable disease, while disease progression was observed in 1/7 (14%) patients. However, molecular response, as per the European Organization for Research and Treatment of Cancer criteria, was observed in all the seven patients. Biochemical response with reduction in serum calcitonin levels was observed in 3/5 (60%) patients. With the exception of grade 2 anaemia in one patient, no other significant toxicity was observed in this cohort.. Our results indicate the efficacy and safety of concomitant Lu-DOTATATE and capecitabine in advanced MTC. Larger randomized controlled trials are, however, required to establish the role of capecitabine as a radiosensitizer along with PRRT in these patients.

Topics: Aged; Capecitabine; Carcinoma, Neuroendocrine; Dose-Response Relationship, Drug; Endpoint Determination; Humans; Male; Neoplasm Metastasis; Octreotide; Organometallic Compounds; Retrospective Studies; Safety; Thyroid Neoplasms

Perioperative mortality of patients who undergo heart valve surgery for carcinoid heart valve disease has been observed to be high (5%-10%). We investigated whether peptide receptor radiotherapy with lutetium-177 dotatate can be used safely in patients with neuroendocrine neoplasm carcinoid heart valve disease and if there is associated survival advantage by reducing overall exposure of the valves to high doses of vasoactive peptides.. Retrospective case notes review was performed on 18 neuroendocrine neoplasm patients (mean 60 years), who underwent heart valve surgery between 2003 and 2017 for carcinoid heart valve disease, 9 of whom received peptide receptor radiotherapy in addition to surgery.. All patients were treated with somatostatin receptor antagonists and underwent cardiac valvular surgery (mean two valves replaced) and three benefitted from additional coronary bypass grafting. Nine patients underwent surgery alone: in this group, the time from surgery to progression was 14 months (mean; SD 13.5 months). Nine were treated with peptide receptor radiotherapy in addition to surgery. Six underwent surgery with peptide receptor radiotherapy on progression. Time to progression from surgery to first peptide receptor radiotherapy was mean 25.1 months (SD 23.6 months). No patients developed peritreatment cardiac complications. There were no deaths within the 30-day postoperative period. Average time from surgery to last follow-up/death was 41 months (6-79) in the surgery + lutetium group and in the surgery only group 17 months (1-24). Nine patients died, five in the surgery + lutetium group and four in the surgery only group, all at greater than 1-year postsurgery.. Peptide receptor radiotherapy is safe in the setting of Carcinoid valvular heart disease in patients with controlled heart failure, PPRT can be use in the pre- and post-valve surgery period. There appears to be a survival benefit of having peptide receptor radiotherapy. Further evidence for peptide receptor radiotherapy in the neoadjuvant setting prior to cardiothoracic surgery is required.

Topics: Adult; Aged; Carcinoid Heart Disease; Female; Heart Valves; Humans; Male; Middle Aged; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Receptors, Peptide; Retrospective Studies; Safety; Time Factors; Treatment Outcome

Topics: Coronavirus Infections; COVID-19; Disease Progression; Health Services Research; History, 21st Century; Humans; Medical Oncology; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pandemics; Pneumonia, Viral; Public Health; Risk Assessment; Severe Acute Respiratory Syndrome; Somatostatin

Advanced inoperable/metastatic neuroendocrine tumors (NETs) pose a therapeutic challenge with limited treatment options. Peptide receptor radionuclide therapy (PRRT), being specific in targeting the somatostatin receptors, is a promising and viable option in this setting. In this study, we intended to evaluate the role of PRRT as the first-line systemic therapy in advanced inoperable/metastatic NETs.. Data of consecutive patients of advanced inoperable/metastatic NETs treated with first-line Lu-DOTATATE at our center, from September 2012 to August 2019, were collected and analyzed.. Forty-five patients (median age, 50 years; range, 14-72 years) with treatment-naive advanced NETs received a median cumulative dose of 27 GBq (range, 13.3-41.3 GBq; over 2-7 cycles) Lu-DOTATATE and 1250 mg/m capecitabine from days 0 to 14 of each PRRT cycle. Three patients were lost to follow-up, 2 had nonmeasurable lesions on CT, and hence, radiological response using Response Evaluation Criteria in Solid Tumors version 1.1 could be assessed in 40 patients. Twelve of 40 patients (30%) showed a partial response, whereas stable disease was observed in 22 of 40 patients (55%). Disease progression was limited to 6 of 40 patients (15%). Treatment-related adverse effects were minimal with grade 3/4 anemia, leukopenia, neutropenia, and hepatotoxicity observed in 2%, 2%, 4%, and 4% of the patients, respectively. Median progression-free survival was 48 months (95% confidence interval, 34.7-61.3 months).. Our results indicate the efficacy and safety of first-line PRRT in advanced NETs. Future randomized trials, comparing PRRT and somatostatin analogs in treatment-naive patients, are required to identify the definite sequence of treatment options for these patients.

Topics: Adolescent; Adult; Aged; Disease Progression; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Progression-Free Survival; Receptors, Peptide; Young Adult

We presented a promising result of radionuclide therapy using Lu-PSMA and Lu-DOTATATE in a patient with prostatic adenocarcinoma and neuroendocrine differentiation. Functional imaging of somatostatin receptors in patients with metastatic castration-resistant prostate cancer may pave the way toward implementation of novel radionuclide targets for the treatment of this aggressive subtype of prostate cancer.

Topics: Antigens, Surface; Carcinoma, Neuroendocrine; Glutamate Carboxypeptidase II; Humans; Male; Middle Aged; Neoplasm Metastasis; Octreotide; Organometallic Compounds; Prostatic Neoplasms, Castration-Resistant; Receptors, Somatostatin

Inoperable or metastatic paragangliomas (PGLs) and malignant pheochromocytomas (PCCs) are rare tumours with limited options for systemic treatment. Aim of this study was to assess the safety and efficacy of the radiolabelled somatostatin analogue (177LutetiumDOTA0-Tyr3)octreotate (177Lu-DOTATATE) for the treatment of PGLs and PCCs.. Patients with histologically proven inoperable or malignant PGLs and PCCs treated with 177Lu-DOTATATE at our centre were retrospectively analysed. Patients were treated with up to four cycles of 177Lu-DOTATATE with an intended dose of 7.4 Gb per cycle. Response was assessed with use of RECIST 1.1.. Thirty patients were included: 17 with parasympathetic, 10 with sympathetic PGLs and 3 with PCCs. Grade 3/4 subacute haematotoxicity occurred in 6 (20%) of patients. A reversible subacute adverse event due to cardiac failure following possible catecholamine release occurred in two patients. Best tumour response was partial response in 7 (23%) and stable disease in 20 (67%), whereas 3 (10%) patients had progressive disease. In 20 patients with baseline disease progression, tumour control was observed in 17 (85%); the median progression-free survival was 91 months in patients with parasympathetic PGLs, 13 months in patients with sympathetic PGLs and 10 months in patients with metastatic PCCs.. This study suggests that PRRT with 177Lu-DOTATATE is a safe and effective treatment option for patients with inoperable or malignant PGL and PCC.

Topics: Adrenal Gland Neoplasms; Adult; Aged; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Octreotide; Organometallic Compounds; Paraganglioma; Pheochromocytoma; Radiation Dosage; Radioisotopes; Receptors, Peptide; Retrospective Studies; Treatment Outcome

A 77-year-old man with a history of metastatic Merkel cell carcinoma and debilitating painful cutaneous lesions was referred to our nuclear medicine department for peptide receptor radionuclide therapy with Lu-DOTATATE as ultimate therapeutic option. Post-treatment whole body scan showed multiple zones of Lu-DOTATATE uptake in the metastatic regions, which revealed significant improvement within the next 10 days of therapy. Peptide receptor radionuclide therapy in metastatic Merkel cell carcinoma is an effective therapeutic option that should be considered in earlier stages of the disease.

Topics: Aged; Carcinoma, Merkel Cell; Humans; Male; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Organotechnetium Compounds; Positron-Emission Tomography; Radiopharmaceuticals; Whole Body Imaging

There is convincing evidence that peptide receptor radionuclide therapy (PRRT) using. In our study, 70 patients (39 men or 31 female) suffering from midgut NET were included, with a mean age of 64.2 years. Functional performance was assessed by the index of the Eastern Cooperative of Oncology Group (ECOG). Thirty-three patients (47%) showed ECOG 0, 31 patients (44%) ECOG 1, and six patients (9%) ECOG 2. Health-related QoL was assessed by the EORTC QLQ-C30 questionnaire filled in at baseline and 3 months after each PRRT cycle.. The median cumulative administered activity was 27.4 GBq. Global health status significantly improved compared to baseline status after 1st (p = 0.05), 2nd (p = 0.004), and 3rd (p = 0.04) treatment cycle. Analyzing specific aspects of QoL, emotional functioning significantly improved after 1st and 2nd treatment cycle (both p < 0.001) as well as after 3rd cycle (p = 0.001). With regard to cognitive functioning, there was a significant improvement after 1st and 2nd treatment cycle (p = 0.003 and p = 0.05 respectively). With regard to alleviation of somatic symptoms, a significant reduction in pain and diarrhea was observed after the 2nd cycle (p = 0.038) and 3rd cycle (p = 0.036). Furthermore, changes in QoL in relation to functional performance status as assessed by ECOG were analyzed. There were no significant differences with regard to QoL alterations between patients with high (ECOG 0 or 1) and moderate performance status.. Our study confirmed an equally positive effect of PRRT on quality of life in midgut NET patients with high or moderate functional status in terms of increasing global health, functional status, and alleviating symptoms.

Topics: Adult; Aged; Aged, 80 and over; Disease-Free Survival; Female; Humans; Intestinal Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Quality of Life; Radiopharmaceuticals; Receptors, Peptide; Retrospective Studies; Treatment Outcome

Primary neuroendocrine tumours (NETs) of mediastinum are unusual tumours with aggressive biological behaviour with limited treatment options and guarded prognosis.. Twenty-seven patients with histopathologically and radiologically proven metastatic or advanced mediastinal NET, who had undergone 177Lu-DOTATATE PRRT, were included in this retrospective analysis. Descriptive statistics was employed to calculate the cumulative overall survival (OS) and progression-free survival (PFS), determining correlation and strength of correlation between different variables with OS and PFS and finally, predictors of outcome (OS and PFS).. In all 27 patients enrolled and analyzed, complete symptomatic response was observed in 10 patients (37%), partial response in seven patients (25.9%), symptomatically stable disease in four patients (14.8%), and symptoms progressed or worsened in six patients (22.2%). Metabolic response evaluation demonstrated complete metabolic response in one patient (3.7%), partial metabolic response was seen in nine patients (33.3%), metabolically stable disease was seen in five patients (18.5%), and 12 patients (44.4%) showed metabolic disease progression. None of the patients achieved complete anatomical/morphological response, six (22.2%) showed partial response, seven (25.9%) showed stable disease, and in 14 patients (51.9%), there was morphological disease progression. At the time of analysis, 10 patients (37%) succumbed to the disease. The median PFS was 36 months and the median OS was 66 months. Bivariate analysis showed significant level of association of PFS with surgical intervention, higher cumulative PRRT dose, metabolic response, smaller sized primary lesion, and low lesional FDG uptake. With regard to OS, higher cumulative PRRT dose, low FDG uptake and longer PFS showed significant association.. Previous surgical intervention (including debulking surgery with R1 resection), higher cumulative dose of PRRT, and low FDG uptake of the tumour are associated with prolonged OS and PFS in patients with metastatic or advanced mediastinal NETs and were independent favourable prognostic markers.

Topics: Adolescent; Adult; Coordination Complexes; Female; Humans; Kaplan-Meier Estimate; Male; Mediastinal Neoplasms; Middle Aged; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Prognosis; Receptors, Peptide; Retrospective Studies; Treatment Outcome; Young Adult

Fractionated therapy with. Cross-dose to kidneys in the majority of patients were less than 2% and almost all cross-doses were less than 10%. Cross-dose exceeded 10% only in rare cases of patients with high tumor burden and low absorbed doses to kidneys.. The absorbed dose from

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Gastrointestinal Neoplasms; Humans; Kidney; Male; Middle Aged; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Organs at Risk; Radiometry; Radiotherapy; Young Adult

Functioning and symptomatic disease resistant to conventional therapies constitutes a subset amongst neuroendocrine tumors (NETs) that are commonly considered for peptide receptor radionuclide therapy (PRRT). The aim of this study was to evaluate the efficacy of Lu-DOTATATE PRRT in this group with objective assessment criteria.. A total of 46 patients with refractory or progressive symptomatic GEP-NETs (previously treated at various stages with long-acting octreotide, chemotherapy, multikinase inhibitors, etc.) who had undergone treatment with PRRT were retrospectively analyzed. These patients were evaluated for response on three scales: clinical, biochemical parameters (tumor marker levels), and imaging (functional molecular and contrast enhanced anatomic). They were classified as complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD) on each scale. Furthermore, the patients were classified as (a) those who gained benefit from PRRT and (b) those who were nonresponders using predefined criteria.. Ninety-one percent of the patient population had liver metastases, with a mean serum chromograninA level of 3307 U/ml, consistent with high volume tumor burden and refractory symptoms. Clinical symptomatic response on an analogue scale showed 54% CR, 35% PR, and 6% SD, whereas 4% showed worsening of symptoms. Biochemically, 17% CR, 28% PR, and 28% SD were observed, whereas 12% showed PD. On evaluation by imaging (PERCIST and RECIST 1.1 criteria), we observed 4% CR, 39% PR, and 36% SD, whereas 19% showed PD. The clinical scale showed the highest overall benefit of 95.6% in the population studied.. The data support the evidence that PRRT could be potentially beneficial in resistant, refractory, and progressive symptomatic groups of GEP-NETs with functional disease burden. The use of a multidimensional response evaluation should be adopted (rather than only anatomical-functional imaging) and needs to be considered while managing this subset of patients.

Topics: Adult; Aged; Disease Progression; Female; Humans; Intestinal Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Receptors, Peptide; Retrospective Studies; Stomach Neoplasms; Young Adult

The aims of this study were to perform multiparametric response assessment of metastatic/advanced pulmonary neuroendocrine tumors (NETs) to Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) (clinical, biochemical, molecular/structural imaging, and survival assessment) and to study the relationship between response, mortality, and overall survival with dual-tracer molecular imaging parameters.. Twenty-two patients (6 women, 16 men; median age, 44 years; range, 16-72 years) of histopathologically proven pulmonary NETs with metastatic/advanced disease were included and analyzed retrospectively. Lu-DOTATATE PRRT was administered using standardized protocol (150 mCi [5.55 GBq] per cycle, cycles repeated at 12-16 weeks' intervals [range, 1-5 cycles; average, 4 cycles]) with amino acid-based renal protection. Assessment with Tc-HYNIC-TOC (in the initial years of PRRT development, n = 11)/Ga-DOTATATE PET/CT (presently, n = 11) and F-FDG PET/CT (n = 22), symptomatic and biochemical parameters (serum CgA and urinary 5-HIAA levels), and anatomical response using contrast-enhanced CT (after 3 cycles) was part of routine pretreatment and response evaluation. The patients were designated as responders and nonresponders based on predefined response assessment criteria. Kaplan-Meier product-limit method was calculated for overall survival (OS) curve after the first PRRT, and corresponding 95% confidence intervals (95% CIs) were estimated for annual survival at 1, 2, 3, and 4 years. The various prognostic variables were also investigated for association with mortality, OS, and treatment response following PRRT.. Of 22 patients, 6 had undergone surgical resection of primary tumors. All patients were symptomatic before start of PRRT. Two patients did not qualify for PRRT, and 1 received single cycle with follow-up less than 3 months, hence excluded from the present analysis. Thus, a total 19 patients were analyzed in our study. Symptomatic response following PRRT was observed in 15 (79%) of 19 patients. Based on predefined 3-scale response evaluation criteria, of 19 patients, 12 patients (63%) were finally characterized as responders, and 7 patients (37%) were overall nonresponder to PRRT. All 7 nonresponders had moderate to intense FDG-avid primary lung lesion (SUVmax >5 in 4 of 7 patients), and 5 had FDG-avid metastatic liver disease (SUVmax >5). Peptide receptor radionuclide therapy was well tolerated in all with no major hematologic and renal toxicity (except for 2 patients showing mild grade I renal and hematologic toxicity in the initial cycles and recovery in subsequent follow-up). Seven (37%) of 19 died at the time of analysis. The observed annual OS rates were as follows: 1 year: 94.7% (95% CI, 68.1%-99.2%), 2 years: 66% (95% CI, 35.5%-84.5%), 3 years: 57.7% (95% CI, 28-78.9%), and 4 years: 38.5% (95% CI, 8.1%-69.5%); median OS was 40 months with 39% (95% CI, 13.1%-64.8%). In conclusion, Lu-DOTATATE PRRT was found safe and well tolerated in receptor-positive pulmonary NET. FDG positivity appeared to forecast aggressive tumor behavior.

Topics: Adolescent; Adult; Aged; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Positron Emission Tomography Computed Tomography; Prognosis; Receptors, Peptide; Retrospective Studies; Treatment Outcome; Young Adult

Topics: Female; Humans; Intestinal Neoplasms; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Positron Emission Tomography Computed Tomography; Protein Kinase Inhibitors; Radiopharmaceuticals; Stomach Neoplasms

Lutetium-177 DOTA-D-Phe1-Tyr3-octreotide (Lu-DOTATATE) is a treatment option for patients with well-differentiated metastatic neuroendocrine tumours. Our centre started administering this therapy in 2012. The aim of this study was therefore to analyse the first cohort of patients treated with Lu-DOTATATE to determine its early efficacy and toxicity.. We retrospectively analysed patient, tumour and treatment characteristics, end-of-treatment outcome, time to progression and toxicity in 79 consecutive patients treated with Lu-DOTATATE who had progressive NET according to Response Evaluation Criteria in Solid Tumours criteria. Follow-up time was 12-40 months. Study of Kaplan-Meier plots, analysis of time to progression and multiple regression analysis of factors predictive of time to progression were performed.. At end-of-treatment radiological restaging, 13% of patients were found to have partial response and 64% to have stable disease; 23% of patients progressed through treatment. Overall, 47% of patients demonstrated a reduction in chromogranin A levels. The overall estimated median time to progression from the start of treatment was 28 months for the entire cohort and 31, 30 and 5 months for those with partial response, stable disease and progressive disease, respectively. On multivariate regression analysis, higher grade of tumour was found to be significantly associated with shorter progression-free survival. Three patients experienced grade 1 haematotoxicity, five grade 1 nephrotoxicity and one grade 2 nephrotoxicity.. Early outcomes of patients treated with Lu-DOTATATE are similar to those in previously published series in terms of end-of-treatment efficacy and toxicity. This provides further evidence that this is a safe and efficacious form of treatment for patients with progressive metastatic neuroendocrine tumours.

Topics: Adult; Aged; Aged, 80 and over; Disease Progression; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Radiotherapy Dosage; Retrospective Studies

Peptide receptor radionuclide therapy targets highly expressed somatostatin receptors in well-differentiated neuroendocrine tumors, producing stability or a partial response in most patients with inoperable or metastatic disease. However, neuroendocrine tumors showing increased

Topics: Adult; Capecitabine; Combined Modality Therapy; Fluorodeoxyglucose F18; Humans; Male; Mediastinal Neoplasms; Neoplasm Metastasis; Octreotide; Organometallic Compounds; Paraganglioma; Positron Emission Tomography Computed Tomography; Radiotherapy, Image-Guided

Pancreatic neuroendocrine tumors (pNET) are rare slowly growing tumors with a high metastatic potential. Peptide receptor radionuclide therapy (PRRT) with radiolabeled analogues has been developed as a new tool for the management of metastatic well-differentiated (grade 1 and 2) neuroendocrine tumors expressing somatostatin receptor (SSTR2). Chemotherapy is the mainstay in the management of grade 3 (G3) unresectable pancreatic neuroendocrine carcinoma (pNEC). To date, no study has evaluated the efficacy of PRRT in such tumors.. We describe a case of a progressive G3 pNEC with huge liver metastases successfully treated with PRRT (Lu DOTATATE).. Complete remission was obtained for 3 years. Indeed, the mitotic index was low (as G2 tumors) but with a very high Ki-67 index (45%-70%). Such discordance between the proliferative markers should consider the use of PRRT before chemotherapy in unresectable metastatic G3 tumors expressing SSTR2.. This case supports the hypotheses highlighting the heterogeneity of G3 pNEC. The latter should be subdivided into 2 distinct categories: proliferation-discordant (well differentiated) and concordant (poorly differentiated) NEC. PRRT could be suggested for the former group before the conventional chemotherapy.

Topics: Carcinoma, Neuroendocrine; Female; Humans; Liver Neoplasms; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Prognosis; Receptors, Somatostatin

A 70-year-old woman presented with frequent episodes of hypoglycemia. Imaging revealed a 6-cm pancreatic mass with several liver lesions. The pancreatic mass was resected and confirmed to be a well-differentiated insulinoma. Surgery improved but did not resolve her hypoglycemic episodes, and she was referred for peptide receptor radionuclide therapy with 177Lu-DOTATATE to treat her residual disease. A modified protocol with a continuous IV dextrose infusion was used, and the treatments were well tolerated. After 4 induction and 2 maintenance treatments, her hypoglycemic symptoms resolved completely and her disease stabilized. She has been progression free for 24 months.

Topics: Aged; Female; Humans; Insulinoma; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Receptors, Peptide

Our objective was to assess the renal toxicity profile of (177)Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in patients with a metastatic neuroendocrine tumor (NET) and a single functioning kidney.. This was a retrospective analysis of NET patients who had undergone (177)Lu-DOTATATE PRRT at a large tertiary-care center. All patients selected for the study had somatostatin receptor-positive NETs, had received at least 3 cycles of (177)Lu-DOTATATE PRRT, and had a documented single functioning kidney. The analyzed parameters included patient characteristics, metastatic burden, renal characteristics at diagnosis and during therapy, and nephrotoxic factors. For the renal assessment, the following characteristics were studied before each PRRT cycle: glomerular filtration rate (GFR) as estimated by (99m)Tc-diethylenetriamine pentaacetic acid renography, effective renal plasma flow (ERPF) as measured by (99m)Tc-ethylenedicysteine renography, and blood urea and serum creatinine levels. Renal toxicity was evaluated using version 4.0 of the Common Terminology Criteria for Adverse Events (NCI-CTCAE score). The percentage reduction in GFR and ERPF was also assessed. Filtration fraction was calculated to clarify whether there was a relatively greater reduction in one index of renal function than in the other.. At the time of analysis, 6 patients met the inclusion criteria, having received between 3 and 5 cycles of therapy with a cumulative activity of 16.6-36.2 GBq. The duration of follow-up ranged from 12 to 56 mo. The overall toxicity profile (as per the NCI-CTCAE score) showed no acute renal toxicity in any patient. Regarding overall chronic renal toxicity, 3 patients had none, 1 patient had grade II, and 2 patients had grade I. All patients with overall chronic renal toxicity showed compromised renal function at the outset (baseline). The 2 patients with grade I chronic renal toxicity after PRRT had grade II at baseline and gradual improvement over the subsequent cycles. One patient with grade II at baseline showed transient worsening to grade III after the first cycle followed by gradual improvement and a return to baseline after the second cycle. Only 2 patients showed a reduction in GFR (5.3% in one and 13.84% in the other). Four patients showed a reduction in ERPF (31.4% in the patient with the greatest reduction), and all had a rise in filtration fraction signifying that tubular parameters were more affected than glomerular parameters.. With proper renal protection and dose fractionation, it is feasible to use (177)Lu-DOTATATE PRRT in patients with NET and a single functioning kidney. Further studies are required to assess the long-term renal consequences of changes in ERPF and filtration fraction in these patients.

Topics: Adult; Female; Glomerular Filtration Rate; Humans; Kidney; Male; Middle Aged; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Receptors, Peptide; Retrospective Studies; Safety

Differentiated thyroid carcinoma (DTC) has good prognosis but 5% of the patients already have distant metastasis at the diagnosis. Tumour cells can lose their iodine uptake ability and enter a state of dedifferentiation. Treatment for differentiated thyroid carcinoma that is not suitable for the local surgery and unresponsive to radioactive iodine uptake is not always easy for physicians. We present a case of a 64-year-old man who had total thyroidectomy surgery and central lymph node dissection with diagnosis of multinodular goitre disease. Histopathological evaluation was papillary thyroid cancer with tall cell variant. Treatment using 150 mCi radioiodine was administered to the patient three times but could not effect a cure. We performed Ga-68 labelled DOTATE (synthetic somatostatin analogue peptide). This provided a good outcome. As evident from our case, Lu-177 radionuclide labelled synthetic somatostatin analogue peptides have therapeutic effect on radioiodine refractory DTC, as an alternative treatment modality.

Topics: Aged; Carcinoma; Carcinoma, Papillary; Goiter, Nodular; Humans; Iodine Radioisotopes; Male; Neoplasm Metastasis; Octreotide; Organometallic Compounds; Peptides; Positron Emission Tomography Computed Tomography; Somatostatin; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyroidectomy

To assess the performance of Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in metastatic gastroenteropancreatic neuroendocrine tumor (GEP-NET) and correlate it with primary tumor site, tumor proliferation index, and dual tracer imaging characteristics.. Fifty patients (M : F 33 : 17, age: 26-71 years) with histopathologically confirmed metastatic/inoperable NETs who had undergone at least three cycles of PRRT with Lu-DOTATATE were included in the analysis. As part of the pretreatment evaluation, they underwent either Tc-HYNIC TOC (n=40)/Ga-DOTATATE PET (n=10) or fluorine-18-fluorodeoxyglucose (F-FDG) PET-computed tomography (CT). Response was assessed after three and five cycles PRRT on the basis of three parameters: (a) symptomatic and subjective scale, (b) biochemical tumor marker level, and (c) objective imaging (F-FDG/Ga DOTATATE PET/CT, Tc-HYNIC TOC, ceCT), and was categorized using predefined criteria (detailed in methods). Stable disease on imaging assessment with response on symptomatic or biochemical tumor marker scales or both were included in the responder group.. The study population was broadly classified into (a) metastatic GEP-NET with known primary (n=43 i.e. 86%), which was further subclassified according to the site of primary and (b) those with unknown primary (n=7 i.e. 14%). Symptomatic response: 96% of patients showed a symptomatic response or improvement in health-related quality of life, irrespective of tumor proliferation index, dual tracer imaging characteristics, and response or progression of disease in the scan. Biochemical tumor marker response: 83% of scan responders showed a decrease, 10% showed a stable value, and 7% showed an increase in tumor marker levels. Among the scan nonresponders, 67% patients showed a corresponding increase in the tumor marker level, 22% patient showed a decrease, whereas 11% showed stable values. Scan response: 31 out of total 50 patients (62%) showed a partial scan response with either a decrease in the number of somatostatin receptor (SSTR)-positive lesions or metabolic activity in F-FDG/Ga-DOTATATE PET-CT or both, 10 patients (20%) showed stable disease, and nine patients (18%) showed progressive disease. The higher objective partial scan response documented can be explained by the introduction of the F-FDG-PET/CT parameter as a determinant criterion. Among the responders category (n=41), 32 (78.04%) showed discordance between F-FDG-PET/CT-based and SSTR-based imaging, whereas eight out of nine patients with nonresponse category (88.89%) showed concordance between SSTR-based imaging and F-FDG-PET/CT. Conversely, 32 of 33 patients (96.97%) with SSTR/F-FDG discordance and nine out of 17 (52.94%) with concordance were finally classified as responders, whereas the remaining, that is, 1/33 (3.03%) in the 'discordant' category and 8/17 (47.06%) with imaging concordance were classified as nonresponders, respectively.. Our data show that high pretherapy F-FDG maximum standardized uptake values were associated with increased chances of treatment refractoriness in GEP-NETs. However, symptomatic improvement was observed in most cases irrespective of grade and F-FDG uptake. High pretherapy F-FDG maximum standardized uptake value in both low-grade and high-grade NET predicted a poor outcome and was associated with disease progression. Introduction of F-FDG-PET/CT parameter as a determinant of response classification increases the percentage of objective scan responders among patients with grades I and II GEP-NETs as F-FDG activity was observed to decrease before SSTR-based imaging and more frequently compared with the latter.

Topics: Adult; Aged; Biomarkers, Tumor; Cell Proliferation; Female; Humans; Intestinal Neoplasms; Male; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Positron Emission Tomography Computed Tomography; Radioactive Tracers; Receptors, Somatostatin; Stomach Neoplasms; Treatment Outcome

The aim of the study was to evaluate somatostatin receptor expression in non-I-concentrating metastatic differentiated thyroid carcinoma by Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scintigraphy and to determine the feasibility of Lu-DOTATATE (therapeutic analog) therapy in cases with positive Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scintigraphy.. In this research study, 19 patients diagnosed with differentiated thyroid carcinoma with non-iodine-concentrating metastasis with elevated serum thyroglobulin levels, attending thyroid outpatient department for follow-up, underwent Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scan for the evaluation of positivity of somatostatin receptor (SSTR). Based on the visual grading, SSTR-positive lesions were graded into 4 categories (grades I-IV) in comparison with the hepatic uptake on the scan. Patients with grades III and IV uptake in lesions (equal to or more than hepatic uptake on scan) were scheduled for Lu-DOTATATE administration. Posttherapy Lu-DOTATATE scan was undertaken during discharge from the isolation ward.. Of the 19 patients studied, 12 patients (63%) showed SSTR-positive lesion expression demonstrating uptake ranging from grade I-IV, and 7 patients (37%) did not demonstrate any tracer uptake. On a lesion-specific analysis, of the total 57 metastatic lesions, 4 lesions (7%) demonstrated grade I tracer uptake, 18 lesions (31%) grade II (less than liver), 2 lesions (3.5%) grade III (equal to liver uptake), and 1 lesion showed grade IV uptake (more than liver). Interestingly, an elevated serum chromogranin A level was documented in 3 of the patients with grades III and IV tumor uptake. A comparison of Ga-DOTATATE PET-CT and Tc-HYNIC-TOC in 4 patients who underwent both the scans demonstrated no significant differences in the tracer concentration in the metastatic lesions in any of the patients on visual grading. Based on the criterion of high tracer uptake and the patient consent, finally 2 of 3 patients were treated with Lu-DOTATATE. On follow-up after 3 months, a significant fall in serum thyroglobulin level was noted in one of the patients, and the other patient was lost to follow-up.. Avid expression of the SSTR on Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scintigraphy in non-I-concentrating metastatic differentiated thyroid cancer is observed in a relatively low fraction of patients that could favor the feasibility of Lu-DOTATATE therapy. Although seen in a small fraction, taking into account that no treatment exists in this group, somatostatin receptor-targeted imaging can be an alternative diagnostic modality in the therapeutic decision making with peptide receptor radionuclide therapy and monitoring. The documentation of elevated serum chromogranin A level in 3 patients with intense tracer uptake could suggest a possible neuroendocrine differentiation in the affected tissues leading to the expression of chromogranin A along with SSTR-avid expression. This observation needs to be explored in future studies. No definite conclusions can be drawn on the therapeutic efficacy of the Lu-DOTATATE therapy in this group at present, and more prospective research is required in this area.

Topics: Adult; Aged; Cell Differentiation; Chromogranin A; Dose Fractionation, Radiation; Feasibility Studies; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Positron-Emission Tomography; Receptors, Peptide; Receptors, Somatostatin; Thyroid Neoplasms; Tomography, X-Ray Computed; Whole Body Imaging

This report describes a case of extensive diffuse bone marrow involvement with bilateral breast metastases from duodenal neuroendocrine tumor giving rise to a superscan-like appearance on somatostatin receptor-targeted (99m)Tc-hydrazinonicotinamide-TOC scintigraphy. The metastatic lesions demonstrated partial concordance with (18)F-FDG PET/CT findings, signifying varying tumor biology and heterogeneity among metastatic lesions in the same individual, as illustrated with a dual-tracer approach. There was a dramatic symptomatic and biochemical response and better health-related quality of life with a single fraction of peptide receptor radionuclide therapy with (177)Lu-DOTATATE, and radiologically there was stable disease at that point.

Topics: Adult; Duodenal Neoplasms; Female; Fluorodeoxyglucose F18; Humans; Multimodal Imaging; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Organotechnetium Compounds; Positron-Emission Tomography; Receptors, Peptide; Tomography, X-Ray Computed; Treatment Outcome

Topics: Disease Management; Dose Fractionation, Radiation; Drug Administration Schedule; Hormones; Humans; Nausea; Neoplasm Metastasis; Neuroendocrine Tumors; Nuclear Medicine; Nutritional Status; Octreotide; Organometallic Compounds; Radioisotopes; Radionuclide Imaging; Receptors, Peptide; Vomiting

The aim of the study was to compare sequential (177)Lu-DOTA-TATE planar scans ((177)Lu-DOTA-TATE) in patients with metastasized neuroendocrine tumours (NET) acquired during peptide receptor radionuclide therapy (PRRT) for dosimetry purposes with the pre-therapeutic (68)Ga-DOTA-TATE positron emission tomography (PET)/CT ((68)Ga-DOTA-TATE) maximum intensity projection (MIP) images obtained in the same patients concerning the sensitivity of the different methods.. A total of 44 patients (59 ± 11 years old) with biopsy-proven NET underwent (68)Ga-DOTA-TATE and (177)Lu-DOTA-TATE imaging within 7.9 ± 7.5 days between the two examinations. (177)Lu-DOTA-TATE planar images were acquired at 0.5, 2, 24, 48 and 72 h post-injection; lesions were given a score from 0 to 4 depending on the uptake of the radiopharmaceutical (0 being lowest and 4 highest). The number of tumour lesions which were identified on (177)Lu-DOTA-TATE scans (in relation to the acquisition time after injection of the therapeutic dose as well as with regard to the body region) was compared to those detected on (68)Ga-DOTA-TATE studies obtained before PRRT.. A total of 318 lesions were detected; 280 (88%) lesions were concordant. Among the discordant lesions, 29 were (68)Ga-DOTA-TATE positive and (177)Lu-DOTA-TATE negative, whereas 9 were (68)Ga-DOTA-TATE negative and (177)Lu-DOTA-TATE positive. The sensitivity, positive predictive value and accuracy for (177)Lu-DOTA-TATE as compared to (68)Ga-DOTA-TATE were 91, 97 and 88%, respectively. Significantly more lesions were seen on the delayed (72 h) (177)Lu-DOTA-TATE images (91%) as compared to the immediate (30 min) images (68%). The highest concordance was observed for bone metastases (97%) and the lowest for head/neck lesions (75%). Concordant lesions (n = 77; mean size 3.8 cm) were significantly larger than discordant lesions (n = 38; mean size 1.6 cm) (p < 0.05). No such significance was found for differences in maximum standardized uptake value (SUV(max)). However, concordant liver lesions with a score from 1 to 3 in the 72-h (177)Lu-DOTA-TATE scan had a lower SUV(max) (n = 23; mean 10.9) than those metastases with a score of 4 (n = 97; mean SUV(max) 18) (p < 0.05).. Although (177)Lu-DOTA-TATE planar dosimetry scans exhibited a very good sensitivity for the detection of metastases, they failed to pick up 9% of lesions seen on the (68)Ga-DOTA-TATE PET/CT. Three-dimensional dosimetry using single photon emission computed tomography/CT could be applied to investigate this issue further. Delayed (72 h) images are most suitable for drawing regions of interest for dosimetric calculations.

Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Multimodal Imaging; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Positron-Emission Tomography; Radiometry; Receptors, Peptide; Retrospective Studies; Time Factors; Tomography, X-Ray Computed; Young Adult

In this technical note, an unusual discordance between diagnostic and posttherapeutic scan resulting from the use of different somatostatin receptor ligands in two settings is described. Such observation, we believe, is multifactorial, but most importantly arises due to different receptor affinity profile of the ligands and different somatostatin receptor subtype expression in different tumors. It is important for the treating physician to be aware of this phenomenon that would aid in improving our understanding of complex ligand-receptor interactions in various somatostatin receptor-positive tumors with its possible implications for therapeutic decision making with radiolabeled somatostatin receptor analogues.

Topics: Artifacts; Carcinoma, Medullary; Humans; Isotope Labeling; Male; Middle Aged; Neoplasm Metastasis; Octreotide; Organometallic Compounds; Positron-Emission Tomography; Radiation Dosage; Radiotherapy Dosage; Receptors, Somatostatin; Somatostatin; Tomography, X-Ray Computed

Quality of life (QOL) is an important outcome in cancer therapy. In this study, we investigated the QOL and symptoms after [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate) therapy in patients with inoperable or metastasized gastroenteropancreatic or bronchial neuroendocrine tumors (NETs).. Two hundred sixty-five Dutch patients completed the QOL questionnaire of the European Organization for the Research and Treatment of Cancer after being treated for NETs. ANOVA was used for statistical analyses, with a P value of 0.05 or less being considered significant. Differences of at least 10 points in global health status (GHS)/QOL scores, symptom scores, and Karnofsky performance scores (KPS) before and after therapy were regarded as indicating an improvement.. Regardless of the treatment outcome, GHS/QOL, insomnia, appetite loss, and diarrhea improved significantly in the total group. These improvements were also seen in patients with bone metastases or a decrease of 50% or more in chromogranin A. Improvement in the scores by at least 10 points was also analyzed in a subgroup of patients with decreased GHS/QOL or symptoms at the start of therapy: in 36% of these patients, GHS/QOL improved after therapy; in 49%, fatigue; in 70%, nausea plus vomiting; in 53%, pain; in 44%, dyspnea; in 59%, insomnia; in 63%, appetite loss; in 60%, constipation; and in 67%, diarrhea. Additionally, we did not see a statistically significant deterioration in patients who had GHS/QOL 100, KPS 100, or no symptoms at the start. In patients with initial stable disease or remission after treatment, GHS/QOL and KPS decreased significantly when regrowth of the tumors occurred.. GHS/QOL, KPS, and symptoms improved significantly after (177)Lu-octreotate therapy, and there was no significant decrease in QOL in patients who had no symptoms before therapy. In patients who had suboptimal scores for GHS/QOL or symptoms before therapy, a clinically significant improvement was demonstrated. Our results indicate that (177)Lu-octreotate therapy not only reduces tumors and prolongs overall survival but also improves the patients' self-assessed QOL.

Topics: Anorexia; Data Interpretation, Statistical; Disease Progression; Emotions; Female; Health Status; Humans; Karnofsky Performance Status; Male; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pain; Pancreatic Neoplasms; Quality of Life; Radiopharmaceuticals; Social Behavior; Stomach Neoplasms; Surveys and Questionnaires; Treatment Outcome

A patient with anaplastic meningioma and lung metastases resistant to conventional treatment underwent radiopeptide therapy with 177Lu- DOTA-octreotate in our institute. The treatment resulted in significant improvement in patient's quality of life and inhibition of tumor progression. This case may eventually help to establish the value of radiopeptide therapy in patients with this rare condition.

Topics: Blood-Brain Barrier; Coordination Complexes; Disease Progression; Female; Humans; Lung Neoplasms; Meningioma; Middle Aged; Neoplasm Metastasis; Octreotide; Positron-Emission Tomography; Quality of Life; Radiopharmaceuticals; Receptors, Peptide; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Treatment Outcome

(177)Lu-(DOTA0,Tyr3) octreotate is a new treatment modality for disseminated neuroendocrine tumors. According to a consensus protocol, the calculated maximally tolerated absorbed dose to the kidney should not exceed 27 Gy. In commonly used dosimetry methods, planar imaging is used for determination of the residence time, whereas the kidney mass is determined from a computed tomography (CT) scan.. Three different quantification methods were used to evaluate the absorbed dose to the kidneys. The first method involved common planar activity imaging, and the absorbed dose was calculated using the medical internal radiation dose (MIRD) formalism, using CT scan-based kidney masses. For this method, 2 region of interest locations for the background correction were investigated. The second method also included single-photon emission computed tomography (SPECT) data, which were used to scale the amplitude of the time-activity curve obtained from planar images. The absorbed dose was calculated as in the planar method. The third method used quantitative SPECT images converted to absorbed dose rate images, where the median absorbed dose rate in the kidneys was calculated in a volume of interest defined over the renal cortex.. For some patients, the results showed a large difference in calculated kidney-absorbed doses, depending on the dosimetry method. The 2 SPECT-based methods generally gave consistent values, although the calculations were based on different assumptions. Dosimetry using the baseline planar method gave higher absorbed doses in all patients. The values obtained from planar imaging with a background region of interest placed adjacent to the kidneys were more consistent with dosimetry also including SPECT. For the accumulated tumor absorbed dose, the first 2 of the 4 planned therapy cycles made the major contribution.. The results suggested that patients evaluated according to the conventional planar-based dosimetry method may have been undertreated compared with the other methods. Hematology and creatinine did not indicate any restriction for a more aggressive approach, which would be especially useful in patients with more aggressive tumors where there is not time for more protracted therapy.

Topics: Forecasting; Humans; Lutetium; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Radiometry; Radiopharmaceuticals; Radiotherapy Dosage

Treatment with the radiolabelled somatostatin analogue (177)Lu-octreotate results in tumour remission in 47% of patients with gastroenteropancreatic neuroendocrine tumours. Adding capecitabine to (177)Lu-octreotate, as a radio-sensitiser, may enhance these anti-tumour effects. We now present the short-term toxicity profile of this novel combination.. Seven patients were treated with 7.4 GBq (177)Lu-octreotate and capecitabine (1650 mg/m(2) per day) for 2 weeks with an intended number of four cycles. Toxicity, and especially haematological and renal parameters, were monitored on a weekly basis for the first two cycles and 4 and 6 weeks after subsequent cycles.. None of the patients had hand-foot syndrome. One patient had grade 1 stomatitis occurring after one of four cycles. Grade 3 or 4 leukopenia or neutropenia did not occur. One patient had grade 3 anaemia, but none had grade 4 anaemia. One patient had grade 2 thrombocytopenia after the fourth cycle, and one had grade 3 thrombocytopenia. Grade 4 thrombocytopenia did not occur. No significant changes in serum creatinine levels were observed. None of the patients had symptoms of cardiac ischaemia.. Treatment with the combination of (177)Lu-octreotate and capecitabine was feasible and safe considering acute and subacute side effects. We therefore started a randomised, controlled clinical trial to compare this combination with (177)Lu-octreotate as single agent with regard to anti-tumour effects and side effects.

Topics: Antimetabolites, Antineoplastic; Capecitabine; Combined Modality Therapy; Creatinine; Deoxycytidine; Fluorouracil; Gastrointestinal Neoplasms; Humans; Injections, Intravenous; Leukocyte Count; Male; Neoplasm Metastasis; Neoplasm Staging; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Platelet Count; Radioisotopes; Receptors, Somatostatin

To present a case of a young woman with Cushing syndrome caused by ectopic production of adrenocorticotropic hormone from a metastatic pancreatic gastrin-secreting endocrine carcinoma, who had a good response to combination peptide receptor radionuclide therapy.. We review the history, physical examination, laboratory investigations, and radiographic findings in this unusual patient. Moreover, the multimodal interventions are described and discussed.. In a 38-year-old woman with typical signs of cortisol excess, laboratory studies revealed diabetes mellitus, hypokalemia, and high levels of adrenocorticotropic hormone, plasma cortisol, and urinary cortisol. Abdominal computed tomography showed a 4-cm pancreatic mass and multiple metastatic lesions in the liver, and ectopic Cushing syndrome was diagnosed. Treatment consisted of surgical debulking of the tumor, ketoconazole, somatostatin analogues, chemoembolization of the liver metastatic lesions, and peptide receptor radionuclide therapy with the radiolabeled somatostatin analogues 90Y-DOTATOC ([90Y-DOTA0, Tyr3]-octreotide) and 177Lu-DOTATATE ([177Lu-DOTA0, Tyr3]-octreotate). The 5 1/2-year follow-up showed positive results, which included complete regression of all clinical and hormonal evidence of the tumor and substantial decrease in the size and number of hepatic metastatic lesions. The patient achieved and still maintains an optimal quality of life.. To the best of our knowledge, this is the first report of a multidisciplinary approach including peptide receptor radionuclide therapy with 90Y-DOTATOC and 177Lu-DOTATATE, which proved to be effective in improving clinical outcome in a case of metastatic endocrine carcinoma of the pancreas in conjunction with ectopic Cushing syndrome. In this unusual case, the patient has one of the longest durations of survival in this setting described in the literature.

Topics: Adrenocorticotropic Hormone; Adult; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Cushing Syndrome; Female; Gastrinoma; Humans; Neoplasm Metastasis; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Yttrium Radioisotopes