lutetium-lu-177-dotatate and Stomach-Neoplasms

Topics: Humans; Intestinal Neoplasms; Magnetic Resonance Imaging; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Radiopharmaceuticals; Receptors, Peptide; Stomach Neoplasms; Tomography, X-Ray Computed

Peptide receptor radionuclide therapy (PRRT) with [. Promising results were published regarding PRRT in other NENs, including lung NENs or high-grade NENs, and applying PRRT as neoadjuvant or salvage therapy. Furthermore, a diversity of strategic approaches, including dosimetry, somatostatin receptor antagonists, somatostatin receptor upregulation, radiosensitization, different radionuclides, albumin binding, alternative renal protection, and liver-directed therapy in combination with PRRT, have the potential to improve the outcome of PRRT. Also, novel biomarkers are presented that could predict response to PRRT. Multiple preclinical and early clinical studies have shown encouraging potential to advance the clinical outcome of PRRT in NEN patients. However, at this moment, most of these strategies have not yet reached the clinical setting of randomized phase III trials.

Topics: Humans; Intestinal Neoplasms; Neoadjuvant Therapy; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Radioisotopes; Receptors, Peptide; Receptors, Somatostatin; Salvage Therapy; Somatostatin; Stomach Neoplasms

Neuroendocrine tumors (NETs) are heterogeneous malignancies arising from the diffuse neuroendocrine system. They frequently originate in the gastroenteropancreatic (GEP) tract and the bronchopulmonary tree, and their incidence has steadily increased in the last 3 decades. Fundamental biologic and genomic differences underlie the clinical heterogeneity of NETs, and distinct molecular features characterize NETs of different grades and different primary sites. Although surgery remains the cornerstone of treatment for localized tumors, systemic treatment options for patients with metastatic NETs have expanded considerably. Somatostatin analogs have demonstrated both antisecretory and antitumor efficacy. Peptide receptor radionuclide therapy with lutetium-177 dotatate (

Topics: Antineoplastic Agents; Biomarkers, Tumor; Cytoreduction Surgical Procedures; Humans; Incidence; Intestinal Neoplasms; Medical Oncology; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Patient Selection; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Stomach Neoplasms; Treatment Outcome

Topics: Humans; Intestinal Neoplasms; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Radioisotopes; Stomach Neoplasms

Neuroendocrine tumors (NETs) are a group of biologically and clinically heterogeneous neoplasms arising from the diffuse neuroendocrine system. In the last few years, advances in our understanding of the biology of these tumors have translated into an expansion of treatment options for patients with NETs. Current treatment modalities include somatostatin analogs (SSAs), radiolabeled SSAs, targeted agents, cytotoxic drugs and liver-directed therapies for the management of metastatic disease.. Recent studies have expanded the role of SSAs in gastroenteropancreatic (GEP)-NETs, and everolimus has shown robust antitumor activity across a broad range of NETs of the lung and GEP tract. The radiolobeled SSA Lu-DOTATATE has been investigated in a randomized phase III trial, and has demonstrated exceptional efficacy and tolerability in patients with progressive midgut NETs. The new serotonin inhibitor telotristat etiprate has shown significant activity in the palliation of symptoms of carcinoid syndrome, and its approval by regulatory authorities is expected soon.. The field of NETs has been transformed from one dominated by limited treatment options to one characterized by an increasing number of therapeutic agents and active clinical trials. Navigating the current therapeutic algorithm may be challenging, and requires an understanding both of the heterogeneity of NETs and of characteristics that are shared by NETs across tumor subtypes.

Topics: Clinical Trials, Phase III as Topic; Humans; Intestinal Neoplasms; Lutetium; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Radiopharmaceuticals; Randomized Controlled Trials as Topic; Somatostatin; Stomach Neoplasms

7.4 GBq of. A substantial effect of AA co-infusion on

Topics: Adult; Aged; Aged, 80 and over; Amino Acids; Antineoplastic Agents; Female; Humans; Infusions, Intravenous; Intestinal Neoplasms; Kidney; Lymphocyte Count; Male; Middle Aged; Models, Biological; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Stomach Neoplasms

Aim of this study was to evaluate the effectiveness of non-carrier added (n. c. a.) [177Lu]DOTA-TATE in inoperable liver metastases, positive for sst2 receptor overexpression (verified by Octreoscan and confirmed by biopsy) due to neuroendocrine gastroenteropancreatic (GEP) tumors. [177Lu]DOTA-TATE has been infused after selective catheterization of the hepatic artery, minimising in parallel the toxicity of non-target tissues.. The dose per session administered to each patient (12 cases in total) was 7400 MBq (200 mCi). Repetitions did not exceed 6-fold with treatment intervals of 5-8 weeks. Response assessment was classified according to the therapeutic benefit. Absorbed doses delivered to metastases, kidneys and red marrow were calculated according to OLINDA 1.1 program and the derived values were correlated to the Response Evaluating Criteria in Solid Tumors (RECIST). CT/MRI scans were performed as baseline before, during and after the end of treatment and monthly ultrasound images for follow-up estimation and measurements. Toxicity (World Health Organization criteria) was measured using blood and urine tests of renal, hepatic and bone marrow function.. None of the patients resulted complete response (0.0%); partial response was assessed in 8 (66.7%), disease stabilization in 3 (25%) and progressive disease in 1(8.3%). A 14-month median survival time was estimated for all patients, so far. Eight of 12 (66.7%) showed a mean target diameter shrinkage ranging from 33% to 45%. The organ average radiation dose estimation was found as follows: a) liver tumor 20.8 mGy/MBq; b) liver 0.14 mGy/MBq; c) kidneys 0.41 mGy/MBq; d) spleen 1.4 mGy/MBq; and f) bone marrow 0.022 mGy/MBq. The average absorbed dose per session to a tumor for a spherical mass of 20 g was estimated to be 20.8 mGy/MBq, depending on the histotype of the tumor. WHO toxicity grade 2 to 3 erythro-, leuko- and thrombo-cytopenia occurred in 9 (75%) cases observed about after the third session.. In unresectable metastatic liver lesions positive for somatostatin receptors repeated, trans-hepatic high doses of [177Lu]DOTA-TATE resulted in a more than promising therapeutic outcome with a partial response in 75% of the treated patients. Given the loco-regional modality character of the administration technique, no nephro-toxicity has been so far observed whereas a remarkable myelotoxicity was noticed.

Topics: Adult; Aged; Female; Hepatic Artery; Humans; Infusions, Intra-Arterial; Intestinal Neoplasms; Liver Neoplasms; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Radiopharmaceuticals; Stomach Neoplasms; Treatment Outcome

Neuroendocrine tumors (NETs) are rare, but the incidence and prevalence of NETs are increasing in the United States. While surgery is the preferred treatment for NETs, it is not a viable option for metastatic disease. Lutathera (177Lu-DOTATATE) is approved by the United States Food and Drug Administration and the European Medicines Agency for the treatment of gastroenteropancreatic (GEP)-NETs in adults. There is limited information on GEP-NET treatment responses to Lutathera.Our institution launched a peptide receptor radionuclide therapy (PRRT) service line using Lutathera with involvement from a multidisciplinary team and complete collaboration between hospital administration and clinical providers. A prospective registry study was also established in order to collect patient demographics and clinical data regarding the treatment of GEP primary NETs with Lutathera.Between August 2018 and July 2020, 35 GEP-NET patients were treated with Lutathera, of which 65.71% received 4 complete cycles and 25.71% received 3 cycles; 5.71% and 2.86% received 2 and 1 cycles of PRRT, respectively. Most adverse events during the course of our study were low grade using the common terminology criteria for adverse events system. Of the patients who completed all 4 cycles: 22% showed partial response to Lutathera, 44% showed stable disease, and 13% showed disease progression based on a qualitative assessment of positron emission tomography/computed tomography imaging.From our experience, Lutathera was well tolerated in patients with GEP-NET. Additional studies are needed to examine long-term clinical and patient-reported outcomes associated with GEP-NET treatment as well as financial considerations for hospitals embarking on a PRRT program.

Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Intestinal Neoplasms; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Positron-Emission Tomography; Prospective Studies; Radioactive Tracers; Radioisotopes; Receptors, Peptide; Stomach Neoplasms; Treatment Outcome

Peptide receptor radionuclide therapy is a targeted therapy used to treat unresectable somatostatin receptor-positive neuroendocrine tumors. The objective of this study was to evaluate response rates among neuroendocrine tumors of different primaries and identify factors relevant to future treatment strategies.. We retrospectively reviewed patients who received peptide receptor radionuclide therapy for neuroendocrine tumors from 2018 to 2019 at our institution. Patients were assessed with computed tomography/magnetic resonance imaging and. Twenty-seven patients underwent 92 cycles of peptide receptor radionuclide therapy: pancreas (n = 11), small bowel (n = 7), and other (n = 9) neuroendocrine tumors. Overall, 30% (8 of 27) had partial response, 59% (16 of 27) stable disease, and 11% (3 of 27) progressed. Pancreatic neuroendocrine tumors responded differently from small bowel neuroendocrine tumors regardless of cycle number (P = .01). The majority of pancreatic neuroendocrine tumors (6 of 11) had partial response to peptide receptor radionuclide therapy, while all small bowel neuroendocrine tumors had stable disease. Pancreatic neuroendocrine tumors stable after 2 cycles were more likely to respond to additional cycles versus other neuroendocrine tumors (probability: 60% vs 11%).. Patients with unresectable advanced or metastatic pancreatic neuroendocrine tumors may benefit from a full course of peptide receptor radionuclide therapy, whereas other neuroendocrine tumors appear less likely to respond. Large prospective studies are needed to confirm these findings.

Topics: Aged; Coordination Complexes; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Intestinal Neoplasms; Male; Middle Aged; Neoplasm Staging; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Positron-Emission Tomography; Response Evaluation Criteria in Solid Tumors; Retrospective Studies; Stomach Neoplasms; Treatment Outcome

Patients with WD-GEP-NET who benefited from a pretherapeutic 68Ga-DOTATOC PET/CT and a 177Lu-DOTATATE SPECT/CT after the cycle 1 of peptide receptor radionuclide therapy were prospectively included. SPECT/CT acquisitions were performed on a system calibrated with a conversion factor of 9.48 counts/MBq per second and were reconstructed with an iterative algorithm allowing quantification using the SPECTRA Quant software (MIM Software, Cleveland, OH). For each patient, different SUV parameters were recorded on both PET/CT (Ga parameters) and SPECT/CT (Lu parameters) for comparison: physiological uptakes (liver/spleen), tumor uptake (1-10/patient; SUVmax, SUVmean, SUVpeak, MTV), tumor-to-liver and tumor-to-spleen ratios according to liver/spleen SUVmax and SUVmean (TLRmax, TLRmean, TSRmax, and TSRmean, respectively).. Ten patients (8 female; 2 male) aged from 50 to 83 years presenting with a metastatic progressive WD-GEP-NET (7 small intestine, 2 pancreas, 1 rectum) were included. Median values of lesional Lu-SUV were significantly lower than the corresponding Ga-SUV (P < 0.001), whereas median values of lesional Lu-MTV, Lu-TLR, and Lu-TSR were significantly higher than the corresponding Ga-MTV, Ga-TLR, and Ga-TSR (P < 0.02). Pearson correlation coefficients were strong for both SUV and MTV parameters (0.779-0.845), weak for TLR parameters (0.365-0.394), and moderate-to-strong for TSR parameters (0.676-0.750).. Our results suggest the feasibility of 177Lu-DOTATATE SPECT/CT quantification in clinical practice and show a strong correlation of several SUV-based parameters with the corresponding in 68Ga-DOTATOC PET/CT.

Topics: Aged; Aged, 80 and over; Biological Transport; Feasibility Studies; Female; Humans; Intestinal Neoplasms; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Positron Emission Tomography Computed Tomography; Receptors, Peptide; Single Photon Emission Computed Tomography Computed Tomography; Stomach Neoplasms

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

Two radiosensitizing chemotherapeutic drugs, capecitabine (CAP) and temozolomide (TEM), are administered concurrently to enhance the therapeutic efficacy of peptide receptor radionuclide therapy (PRRT). This study aims to assess the biodistribution and normal-organ and tumor radiation dosimetry for Lu-177 DOTATATE administered concurrently with CAP/TEM.. 20 patients with non-resectable histologically confirmed gastroenteropancreatic neuroendocrine tumors with normal kidney function, a normal haematological profile and somatostatin receptor expression of the tumor lesions, as scintigraphically assessed by a Ga-68 DOTANOC scan, were included in two groups-case group (n = 10) and control group (n = 10). Patients included in case group were those who were advised concomitant CAPTEM therapy by the treating medical oncologist. Patients were administered CAP orally at a dose of 600mg m. Physiological uptake of Lu-177 DOTATATE was seen in all patients in liver, spleen kidneys, and bone marrow. Radiation absorbed doses (mean ± standard deviation) were obtained as 0.29 ± 0.12 mGy/MBq for kidneys, 0.30 ± 0.18 mGy/MBq for liver, 0.63 ± 0.37 mGy/MBq for spleen, 0.019 ± 0.001 mGy/MBq for bone marrow and 3.85 ± 1.74 mGy/MBq for tumours in the case group and they were 0.31± 0.26, 0.24 ± 0.14, 0.64 ± 0.42, 0.017 ± 0.016, 5.6 ± 11.27 mGy/MBq in kidneys, liver, spleen, bone marrow and neuroendocrine tumour, respectively, in the control group. Mann-Whitney U test between the variables of two groups showed an insignificant difference (p > 0.05).. The authors demonstrated no significant difference between the tumor and organ doses with Lu-177 DOTATATE in the patients treated with and without concomitant chemotherapy.. To our knowledge, this is the first dedicated study exhibiting dosimetric analysis in patients undergoing PRRT in combination with chemotherapy.

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Capecitabine; Case-Control Studies; Chemoradiotherapy; Dacarbazine; Drug Administration Schedule; Female; Humans; Intestinal Neoplasms; Liver; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Prospective Studies; Radiation-Sensitizing Agents; Radiometry; Radiopharmaceuticals; Radiotherapy Dosage; Spleen; Stomach Neoplasms; Temozolomide; Tissue Distribution

Topics: Consent Forms; Humans; Intestinal Neoplasms; Neuroendocrine Tumors; Nuclear Medicine; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Practice Guidelines as Topic; Radiotherapy; Receptors, Somatostatin; Stomach Neoplasms

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

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

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Bronchial Neoplasms; Female; Humans; Intestinal Neoplasms; Kaplan-Meier Estimate; Leukemia; Male; Middle Aged; Myelodysplastic Syndromes; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Outcome Assessment, Health Care; Pancreatic Neoplasms; Radiopharmaceuticals; Stomach Neoplasms; Time Factors; Treatment Outcome

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 purpose of this article is to report the experience of the Portuguese Institute of Oncology - Porto in the treatment of gastroenteropancreatic neuroendocrine tumors with 177Lu-DOTA-TATE, regarding the safety and efficacy of this treatment modality.. A retrospective analysis of clinical reports of patients with gastroenteropancreatic neuroendocrine tumors undergoing treatment with 177Lu-DOTA-TATE between April 2011 and November 2013 was performed.. Thirty six cases were reviewed and 30 completed all 3 cycles of 177Lu-DOTA-TATE (83.3%). In these patients it was registered: acute side effects in 8.9% of cycles; grade 3 CTCAE liver toxicity in 13.3% of patients (all with previous abnormal liver function); absence of significant renal or hematologic toxicity; symptomatic improvement in 71.4% of patients; median overall time to progression of 25.6 months; median overall survival from diagnosis of 121.7 months. Patients with higher expression of somatostatin receptors had longer progression-free survival and overall survival times (p < 0.05).. Peptide receptor radionuclide therapy with 177Lu-DOTA-TATE is an effective, safe and well-tolerated treatment, as evidenced in our study by the following findings: symptomatic improvement in most patients and increased time to disease progression and survival (especially in those with higher sstr expression), with acute and significant subacute/chronic side effects reported only in a minority of cases.. Peptide receptor radionuclide therapy with 177Lu-DOTA-TATE is a promising treatment for patients with gastroenteropancreatic neuroendocrine tumors, with demonstrated benefits in terms of safety and efficacy.. Introdução: O objetivo deste artigo é rever a experiência do Instituto Português de Oncologia do Porto na terapêutica de tumores neuroendócrinos gastroenteropancreáticos com 177Lu-DOTA-TATE, tendo como principais pontos de análise a segurança e eficáciaterapêutica. Material e Métodos: Foi realizada uma análise retrospetiva dos processos clínicos de doentes com tumores neuroendócrinos gastroenteropancreáticos, submetidos a terapêutica com 177Lu-DOTA-TATE entre abril de 2011 e novembro de 2013. Resultados: Dos 36 casos revistos, 30 completaram os três ciclos de 177Lu-DOTA-TATE (83,3%). Nesses doentes foram registados: efeitos colaterais agudos em 8,9% dos ciclos; toxicidade hepática grau 3 CTCAE em 13,3% dos doentes (todos com alterações prévias da função hepática); ausência de toxicidade renal ou hematológica significativa; melhoria sintomática em 71,4% dos doentes; tempo mediano global desde o início da terapêutica até progressão de doença de 25,6 meses; tempo mediano global de sobrevivência desde o diagnóstico de 121,7 meses. Verificou-se um maior tempo livre de progressão de doença e de sobrevivência nos doentes com expressão elevada de recetores da somatostatina (p < 0,05). Discussão: A peptide receptor radionuclide therapy com 177Lu-DOTA-TATE apresenta respostas clínicas favoráveis com segurança e boa tolerabilidade terapêutica, conforme evidenciado no nosso estudo pelos seguintes achados: melhoria dos sintomas na maioria dos doentes e aumento significativo do tempo livre de progressão de doença e da sobrevivência (sobretudo nos doentes com expressão elevada de sstr), com efeitos colaterais agudos e subagudos/crónicos significativos numa minoria de doentes. Conclusão: A peptide receptor radionuclide therapy com 177Lu-DOTA-TATE é uma terapêutica promissora, com benefícios reais em termos de eficácia e segurança nos doentes com tumores neuroendócrinos gastroenteropancreáticos.

Topics: Humans; Intestinal Neoplasms; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Retrospective Studies; Stomach Neoplasms

Peptide receptor radionuclide therapy (PRRT) is a relatively new treatment modality for patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumours (GEP NETs). The aim of this study was to determine the time to progression of patients treated with PRRT and to identify the prognostic factors related to treatment response.. Patients with sporadic GEP NETs prospectively treated with PRRT were retrospectively analysed. The primary end point was progression-free survival (PFS).. A total of 69 patients (37 men and 32 women; 45 with pancreatic and 24 with gastrointestinal lesion; 22 NET G1 and 41 NET G2) were treated with (90)Y or (177)Lu. The objective response rate was 27.5% (partial response, PR), while 50.7% had stable disease and 23.2% had progressive disease. Significant differences in PFS were observed in relationship to the stage of the disease (44 months for stage III, 23 months for stage IV), the evidence of a PR 6 months after the end of the PRRT (39 months in patients with a PR, 22 months in patients without a PR) and previous transarterial chemoembolization (TACE, yes 13 months vs no 31 months). Stage IV, NET G2 and previous TACE were found to be significant factors for tumour progression at multivariate analysis.. Low tumour burden and a low proliferation index represent independent prognostic factors for long PFS, while previous chemoembolization techniques represent independent prognostic factors for early tumour progression and shorter PFS. Our data suggest that chemoembolization techniques to reduce the hepatic tumour burden should be avoided.

Topics: Aged; Female; Humans; Intestinal Neoplasms; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Radiopharmaceuticals; Somatostatin; Stomach Neoplasms; Treatment Outcome; Yttrium Radioisotopes

Response Evaluation Criteria In Solid Tumors (RECIST) (unidimensional), Southwest Oncology Group (SWOG) solid tumor response criteria (bidimensional), and their modified variants are commonly used in the tumor response assessment after treatment of gastroenteropancreatic and thoracic neuroendocrine tumors (NETs). In the current study, RECIST, SWOG criteria, modified RECIST (mRECIST), and modified SWOG (mSWOG) criteria were compared in patients with NETs treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate).. Two-hundred sixty-eight Dutch patients with NETs who had been treated with (177)Lu-octreotate between January 2000 and April 2007 were studied. CT or MR imaging scans were analyzed using RECIST, SWOG criteria, mRECIST, and mSWOG criteria (including the tumor response class minor response [decrease of 13%-30% for mRECIST and 25%-50% for mSWOG]). The outcomes were correlated with progression-free survival (PFS) and overall survival (OS).. Eleven patients had an unknown tumor response and were excluded. The rates of objective response (OR) (complete response + partial response [+minor response for mRECIST/mSWOG]), stable disease, and progressive disease (PD) were 28%, 49%, and 24%, respectively, according to RECIST; 25%, 49%, and 26%, respectively, according to SWOG; 44%, 33%, and 24%, respectively, according to mRECIST; and 45%, 29%, and 26%, respectively, according to mSWOG. In patients who had OR, stable disease, or PD, the median PFS was 26-30, 27-34, and 8 mo, respectively, with any of the 4 response criteria. In patients who had OR, stable disease, or PD, the median OS was 55-57, 56-74, and 11-12 mo, respectively, with any of the 4 response criteria. Subanalyses for patients who had progression before treatment start were comparable.. Patients with PD as treatment outcome had significantly shorter PFS and OS than patients with an OR or stable disease with all 4 scoring systems. PFS and OS were comparable for patients with tumor regression and stable disease. The addition of the response class minor response did not improve the correlation with PFS and OS. The 4 scoring systems gave comparable results in terms of PFS and OS per categorized outcome.

Topics: Female; Humans; Intestinal Neoplasms; Male; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Retrospective Studies; Stomach Neoplasms; Survival Analysis; Thoracic Neoplasms; Treatment Outcome

Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues plays an increasing role in the treatment of patients with inoperable or metastasised gatroenteropancreatic neuroendocrine tumours (GEP-NETs). (90)Y-DOTATOC and (177)Lu-DOTATATE are the most used radiopeptides for PRRT with comparable tumour response rates (about 15-35%). The side effects of this therapy are few and mild. However, amino acids should be used for kidney protection, especially during infusion of (90)Y-DOTATOC. Options to improve PRRT may include combinations of radioactive labelled somatostatin analogues and the use of radiosensitising drugs combined with PRRT. Other therapeutic applications of PRRT may include intra-arterial administration, neo-adjuvant treatment and additional PRRT cycles in patients with progressive disease, who have benefited from initial therapy. Considering the mild side-effects, PRRT may well become the first-line therapy in patients with metastasised or inoperable GEP-NETs if more widespread use of PRRT can be accomplished.

Topics: Heterocyclic Compounds; Heterocyclic Compounds, 1-Ring; Humans; Intestinal Neoplasms; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Peptides, Cyclic; Radiopharmaceuticals; Receptors, Somatostatin; Retreatment; Somatostatin; Stomach Neoplasms; Yttrium Radioisotopes

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

Topics: Endocrine Gland Neoplasms; Humans; Karnofsky Performance Status; Magnetic Resonance Imaging; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Radiation Dosage; Radiopharmaceuticals; Stomach Neoplasms; Tomography, X-Ray Computed; Treatment Outcome