lutetium-lu-177-dotatate and Carcinoma--Neuroendocrine

It has been shown that a subgroup of patients with differentiated thyroid cancer (DTC) and medullary thyroid carcinoma (MTC) would progress to advanced stages of thyroid cancer. Therefore, the present study was done to systematically review available evidence in order to investigate efficacy and safety of peptide receptor radionuclide therapy (PRRT) in the patients with advanced radioiodine refractory differentiated thyroid cancer (RR-DTC) and metastatic MTC.. For this purpose, relevant studies investigated safety and efficacy of PRRT in the patients with advanced RR-DTC and metastatic MTC were identified by searching Medline (Pubmed, Ovid, and Ebsco), Scopus, Embase, Web of Science, and Cochrane Library databases (from database inception to March 24, 2021). The review was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Searching was done independently by two investigators. Two researchers independently extracted the data and any disagreement was adjudicated by consensus. Quality of the studies was assessed using the tool of case reports/series in systematic reviews.. Among 2284 related papers, 41 papers met the inclusion criteria. A total of 157 patients with RR-DTC were treated with PPRT. Biochemical and objective responses (partial and complete) were observed in 25.3 and 10.5% of patients, respectively. Among 220 patients with metastatic MTC, biochemical and objective responses were observed in 37.2 and 10.6% of the patients, respectively. Forty-six deaths were reported in 95 patients with advanced RR-DTC. In addition, 63 deaths were observed in 144 patients with metastatic MTC. Major side effects were reported in 124 patients treated with. Findings of the study revealed that in the absence of the established treatment for the patients with RR-DTC and metastatic MTC, PRRT could be effective with few adverse events.. PROSPERO registration number: CRD42019125245 .

Topics: Carcinoma, Neuroendocrine; Hematologic Diseases; Humans; Iodine Radioisotopes; Octreotide; Organometallic Compounds; Radiation Injuries; Radiation Tolerance; Radiopharmaceuticals; Renal Insufficiency; Thyroid Neoplasms; Treatment Outcome; Yttrium Radioisotopes

Topics: Carcinoid Tumor; Carcinoma, Neuroendocrine; Clinical Trials as Topic; Humans; Lung Neoplasms; Molecular Targeted Therapy; Neoplasm Staging; Octreotide; Organometallic Compounds; Peptides; Receptors, Somatostatin; Somatostatin; Treatment Outcome

Pancreatic malignancies, the fourth leading cause of cancer deaths, have an aggressive behavior with poor prognosis, resulting in a 5-year survival rate of only 4%. It is typically a silent malignancy until patients develop metastatic disease. Targeted radionuclide therapies of cancer such as radiolabeled peptides, which bind to the receptors overexpressed by cancer cells and radiolabeled antibodies to tumor-specific antigens provide a viable alternative to chemotherapy and external beam radiation of metastatic cancers. Multiple clinical trials of targeted radionuclide therapy of pancreatic cancer have been performed in the last decade and demonstrated safety and potential efficacy of radionuclide therapy for treatment of this formidable disease. Although a lot of progress has been made in treatment of pancreatic neuroendocrine tumors with radiolabeled (90)Y and (177)Lu somatostatin peptide analogs, pancreatic adenocarcinomas remain a major challenge. Novel approaches such as peptides and antibodies radiolabeled with alpha emitters, pre-targeting, bispecific antibodies and biological therapy based on the radioactive tumorlytic bacteria might offer a potential breakthrough in treatment of pancreatic adenocarcinomas.

Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal; Carcinoma, Neuroendocrine; Clinical Trials as Topic; Humans; Listeria; Molecular Targeted Therapy; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Radioisotopes; Radionuclide Imaging; Radiopharmaceuticals; Rhenium

Peptide receptor radionuclide therapy is a new treatment modality for patients with inoperable or metastasised neuroendocrine gastroenteropancreatic tumours. After the successful implementation of somatostatin receptor scintigraphy in daily clinical practice, the next logical step was to increase the radiation dose of the administered radiolabelled somatostatin analogue in an attempt to induce tumour shrinkage. Since then, an increasing number of patients has been successfully treated with this approach, resulting in a substantial numbers of patient with objective tumour shrinkage. Serious side-effects have been rare. This article reviews the effectiveness of the different radiolabelled somatostatin analogues used, the currently known side-effects and the survival data available. Furthermore, clinical issues, including indication and timing of therapy, are discussed. Finally, important directions for future research are briefly mentioned to illustrate that, although the currently available results already suggest a favourable outcome compared with other systemic therapies, new strategies are being developed to increase efficacy.

Topics: Animals; Carcinoma, Neuroendocrine; Gastrointestinal Neoplasms; Humans; Indium Radioisotopes; Lutetium; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Patient Selection; Pentetic Acid; Peptides, Cyclic; Quality of Life; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Peptide; Receptors, Somatostatin; Somatostatin; Treatment Outcome; Yttrium Radioisotopes

Medullary thyroid cancer (MTC) is a rare but potentially life-threatening disease with limited therapeutic options. As a neuroendocrine tumor, MTC expresses somatostatin receptors, and therefore, somatostatin-labeled radiopharmaceuticals could be used to treat patients with MTC.. The aims of this study were to evaluate tumor shrinkage after Lu-DOTATATE treatment, to analyze the impact on quality of life as accessed by the SF-36 questionnaire, and to demonstrate a possible prognostic role for In-DTPA-octreotide uptake in patients with MTC.. Patients with progressive MTC underwent evaluation using In-DTPA-octreotide. Patients who demonstrated In-DTPA-octreotide uptake were treated with 4 cycles of 200 mCi of Lu-DOTATATE and were evaluated using CT scans over 8 to 12 months of treatment.. Of the 16 patients initially enrolled, 9 (56.25%) had lesions that were observed in the In-DTPA-octreotide scans and were eligible for therapy with Lu-DOTATATE. Three patients had a partial response, 3 patients were classified as having stable disease and, 1 patient had a progressive disease. All responders indicated improvement in quality of life 6 to 12 months after therapy.. Treatment with Lu-DOTATATE seems to be an alternative therapy for somatostatin receptor-positive tumors, with very mild adverse effects and quality-of-life improvement, at least during a short-term period. Further studies are needed to determine long-term benefits and to identify which patients are more likely to respond to this modality of therapy.

Topics: Adult; Aged; Carcinoma, Neuroendocrine; Female; Humans; Male; Middle Aged; Octreotide; Organometallic Compounds; Pentetic Acid; Quality of Life; Radiopharmaceuticals; Thyroid Neoplasms; Tomography, X-Ray Computed

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

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

Topics: Aged; Air Pollutants, Radioactive; Carcinoma, Neuroendocrine; Cremation; Environmental Exposure; Humans; Male; Occupations; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Radiation Exposure; Radiometry; Radiopharmaceuticals; Technetium

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

Peptide receptor radionuclide therapy (PRRT) for the treatment of neuroendocrine tumours (NET) has been explored for almost two decades, but there are still few trials that have exclusively investigated well-differentiated and moderately differentiated NET arising from the respiratory tree. Thus, the aim of this study was to explore the outcome in patients affected by bronchopulmonary carcinoid (BPC) following PRRT.. We retrospectively analysed 114 patients with advanced stage BPC consecutively treated with PRRT at the European Institute of Oncology, Milan, from 1997 to 2012 and followed until October 2014. The objective responses, overall survival (OS) and progression-free survival (PFS) were rated, and three different PRRT protocols ((90)Y-DOTATOC vs. (177)Lu-DOTATATE vs. (90)Y-DOTATOC + (177)Lu-DOTATATE) were compared with regard to their efficacy and tolerability.. The median OS (evaluated in 94 of the 114 patients) was 58.8 months. The median PFS was 28.0 months. The (177)Lu-DOTATATE protocol resulted in the highest 5-year OS (61.4%). Morphological responses (partial responses + minor responses) were obtained in 26.5% of the cohort and were associated with longer OS and PFS. The (90)Y-DOTATOC + (177)Lu-DOTATATE protocol provided the highest response rate (38.1%). Adverse events were mild in the majority of patients. However, haematological toxicity negatively affected survival. No severe (grade 3/4) serum creatinine increase was observed. Patients treated with (90)Y-DOTATOC alone more frequently showed a mild/moderate decrease in renal function. In patients treated with chemotherapy before PRRT had a shorter OS and PFS, and a higher risk of developing nephrotoxicity.. In a large cohort of patients with advanced BPC treated in a "real-world" scenario and followed up for a median of 45.1 months (range 2-191 months), PRRT proved to be promising in prolonging survival and delaying disease progression. Despite the potential selection biases, considering the risk-benefit ratio, (177)Lu-DOTATATE monotherapy seems the best option for PRRT. Our results indicate that the use of PRRT in earlier stages of the disease could provide a more favorable outcome.

Topics: Aged; Carcinoid Tumor; Carcinoma, Neuroendocrine; Cohort Studies; Creatinine; Data Collection; Disease Progression; Disease-Free Survival; Europe; Female; Follow-Up Studies; Humans; Lutetium; Male; Middle Aged; Neoplasm Recurrence, Local; Neuroendocrine Tumors; Octreotide; Odds Ratio; Organometallic Compounds; Radioimmunotherapy; Radioisotopes; Radiopharmaceuticals; Receptors, Peptide; Retrospective Studies; Treatment Outcome

Topics: Bone Neoplasms; Carcinoma, Neuroendocrine; Decision Making; Fluorides; Fluorine Radioisotopes; Humans; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Organophosphorus Compounds; Pain; Positron-Emission Tomography; Precision Medicine; Thyroid Neoplasms; Tomography, X-Ray Computed

Two patients diagnosed with metastatic medullary thyroid carcinoma (MTC) were referred for peptide receptor radionuclide therapy (PRRT) with Lu-[DOTA,Tyr]octreotate (DOTATATE). Each patient was treated with 4 doses of Lu-DOTATATE given 2 months apart. One patient achieved stable disease for 10 months then chose to pursue surgery, and the other achieved stable disease for 9 months on imaging; however, calcitonin continued to rise. The use of Lu-DOTATATE PRRT therapy in the management of MTC warrants further research.

Topics: Adult; Aged; Carcinoma, Neuroendocrine; Female; Humans; Male; Octreotide; Organometallic Compounds; Radiopharmaceuticals; Thyroid Neoplasms

A 48-year-old man presenting with upper abdominal pain was diagnosed with neuroendocrine tumor after biopsy of a paragastric mass with multiple liver metastases. (68)Ga-DOTATATE PET/CT showed intense uptake in the paragastric tumor and in multiple liver metastases not allowing primary surgery. Two cycles with cumulative 14.6 GBq (177)Lu-DOTATATE were given resulting in a considerable improvement. Subsequent surgery resulted in a complete remission as demonstrated by (68)Ga-DOTATATE PET/CT. Usually, peptide receptor radionuclide (PRRT) therapy is considered a palliative treatment. Few patients demonstrate a very favorable response allowing resection of the primary tumor after downstaging metastatic disease burden.

Topics: Carcinoma, Neuroendocrine; Humans; Liver Neoplasms; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Radiopharmaceuticals; Remission Induction