Peptide Receptor Radionuclide Therapy for the Treatment of Pancreatic Neuroendocrine Tumors: Recent Insights.
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ABSTRACT:
SUBMITTER: Starr JS
PROVIDER: S-EPMC7205451 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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Peptide Receptor Radionuclide Therapy for the Treatment of Pancreatic Neuroendocrine Tumors: Recent Insights.
Starr Jason S JS Sonbol Mohamad Bassam MB Hobday Timothy J TJ Sharma Akash A Kendi Ayse Tuba AT Halfdanarson Thorvardur R TR
OncoTargets and therapy 20200428
Peptide receptor radionuclide therapy (PRRT) is a paradigm shifting approach to the treatment of neuroendocrine tumors. Although there are no prospective randomized trials directly studying PRRT in pancreatic neuroendocrine tumors (panNETs), there are data to suggest benefit in this patient population. Collectively, the data, consisting of two prospective and six retrospective studies, show a median PFS ranging from 20 to 39 months and a median OS ranging from 37 to 79 months. There are ongoing ...[more]
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Project description:Since its approval in 2018 by the US Food and Drug Administration, peptide receptor radionuclide therapy (PRRT) has become a mainstay in the treatment of neuroendocrine tumors. Lutetium-177-DOTATATE, the only approved agent, is indicated for the treatment of gastroenteropancreatic-neuroendocrine tumors. Although patient selection appears straightforward with somatostatin receptor-positron emission tomography, there is considerable complexity when deciding which patients to treat and when to start PRRT. Herein, we review the many factors that affect patient selection, focusing on the optimal patients to treat. Although significant effort has been expended to determine which patients benefit the most from PRRT, a validated predictive biomarker remains elusive. Although PRRT has been used for more than 2 decades in Europe and standards of care exist for safe treatment, there remain numerous questions regarding when PRRT should be used relative to other treatments. It is important to remember that multidisciplinary discussions are essential. Currently, there are a number of ongoing studies looking to assess the efficacy of PRRT compared with other treatment options and to optimize treatment through combination therapy, different dosing strategies, or use of different radionuclides and radioligands.
| S-EPMC9390818 | biostudies-literature
Project description:Peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTATATE has been approved for the treatment of gastroenteropancreatic NETs. An understanding of benefits and risks is important for the appropriate implementation of this therapy. This review summarizes study data supporting the use of radiolabeled somatostatin analogs for the treatment of advanced NETs and highlights risks, including potential toxicities in specific populations. Key ongoing clinical trials, including randomized studies, are designed to better define the position of PRRT within the broader therapeutic landscape. Preclinical and early-phase human studies are focused on the development of novel somatostatin-receptor agonists and antagonists, new radionuclides, and radiosensitizing combination therapies.
| S-EPMC8118168 | biostudies-literature
Project description:IntroductionNeuroendocrine neoplasms including neuroendocrine tumors (NETs) are often diagnosed as primary disseminated or inoperable. In those cases, systemic extensive therapy is necessary, but radical treatment is unlikely. As described in the literature, in some selected cases, peptide receptor radionuclide therapy (PRRT) may be used as a first-line/neoadjuvant therapy that allows further successful surgery. Such treatment may enable a reduction of total tumor burden or allow a radical treatment which improves the final outcomes.AimThis study aims to assess whether neoadjuvant PRRT could be a treatment option for patients with initially unresectable NETs.MethodsAmong the group of 114 patients treated with PRRT between the years 2005 and 2020, in 32 cases, it was the first-line therapy, mainly due to massive disease burden at the time of diagnosis. Among them, nine patients received PRRT as the first-line treatment due to the primary inoperable tumors with the intention of preoperative reduction of the tumor size in order to allow for a surgical treatment.ResultsNeoadjuvant PRRT enabled surgery in four out of nine (45%) patients. Finally, in two out of four cases, the goal (radical surgery) has been achieved.ConclusionPRRT may be considered not only as a palliative but also as a neoadjuvant therapy in advanced, somatostatin-positive NETs that were initially inoperable.
| S-EPMC8633407 | biostudies-literature
Project description:Pancreatic neuroendocrine tumors (PNETs) are described by the World Health Organization (WHO) classification by grade (1-3) and degree of differentiation. Grade 1 and 2; well differentiated PNETs are often characterized as relatively "indolent" tumors for which locoregional therapies have been shown to be effective for palliation of symptom control and prolongation of survival even in the setting of advanced disease. The treatment of liver metastases includes surgical and non-surgical modalities with varying degrees of invasiveness; efficacy; and risk. Most of these modalities have not been prospectively compared. This paper reviews literature that has been published on treatment of pancreatic neuroendocrine liver metastases using surgery; liver directed embolization and peptide receptor radionuclide therapy (PRRT). Surgery is associated with the longest survival in patients with resectable disease burden. Liver-directed (hepatic artery) therapies can sometimes convert patients with borderline disease into candidates for surgery. Among the three embolization modalities; the preponderance of data suggests chemoembolization offers superior radiographic response compared to bland embolization and radioembolization; but all have similar survival. PRRT was initially approved as salvage therapy in patients with advanced disease that was not amenable to resection or embolization; though the role of PRRT is evolving rapidly.
| S-EPMC9599940 | biostudies-literature
Project description:BackgroundPeptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs is an innovative treatment for advanced somatostatin-positive neuroendocrine tumors (NETs). PRRT cannot be performed in Japan because there is no approval or insurance cover so far.MethodsWe relied on foreign institutions to perform PRRT for Japanese patients with NETs. We retrospectively evaluated the safety and efficacy of PRRT. The inclusion criteria were pathologically confirmed well-differentiated NET and visible tumor uptake on pre-therapeutic somatostatin receptor scintigraphy. 177 Lu-DOTA-TOC was used as the standard treatment, and patients received three infusions every 8 weeks. Until the end of 2017, combination treatment with 90 Y and 177 Lu-DOTA-TOC was performed using the same protocol.ResultsThirty-five patients were evaluated, and the primary lesions were pancreas, rectum, small intestine, stomach, and other locations. The partial response rate was 42.9%. Progression-free survival (PFS) was 12.8 months and overall survival was 42.8 months. There was no significant difference in PFS between front-line and late-line PRRT (11.0 months vs 28.0 months; P = .383). Severe adverse events included lymphocytopenia (20.0%) and thrombocytopenia (5.7%). Myelodysplastic syndrome occurred in one case.ConclusionPRRT was effective and safe for Japanese patients with advanced NETs. PRRT was equally effective as front-line and late-line treatment.
| S-EPMC9292713 | biostudies-literature
Project description:Peptide receptor activation therapy (PRRT) is a promising treatment option for metastatic neuroendocrine tumors (NETs). However, predicting tumor shrinkage before treatment is challenging. We analyzed the shrinkage rate of each metastatic tumor lesion to identify predictive factors related to shrinkage. Patients with metastatic NET who underwent PRRT were included in this retrospective study. For each patient, between one to five metastatic lesions were selected in descending order of size, and the change in the maximum tumor diameter after treatment was defined as the shrinkage rate per lesion (L-SR). We analyzed the relationship between pretreatment clinicopathological factors and L-SR. The median L-SR of all 75 lesions in 20 patients was 20% (95% CI: 4.8-26.1%). While previous treatment with cytotoxic agents (34.4%, p < 0.05) and primary tumor of the pancreas (27.8%, p < 0.05) were significantly favorable factors, a primary tumor of the rectum was significantly more resistant to shrinkage (-20.5%, p < 0.001). Therefore, lesion-based analysis of PRRT for NETs showed that pancreatic NET and previous treatment with cytotoxic agents were favorable factors for tumor shrinkage; however, rectal NET was a factor associated with resistance to shrinkage.
| S-EPMC9313286 | biostudies-literature
Project description:ImportancePeptide receptor radionuclide therapy (PRRT) is approved in the US for treatment of gastroenteropancreatic neuroendocrine tumors (NETs), but data on PRRT outcomes within US populations remain scarce.ObjectiveTo analyze the first 2 years of PRRT implementation at a US-based NET referral center.Design, setting, and participantsThis cohort study was conducted using medical records of patients with metastatic NET receiving PRRT from 2018 through 2020 in a NET program at a tertiary referral center. Included patients were those at the center with metastatic NETs who received at least 1 dose of PRRT over the study period. Laboratory toxic effects were assessed using Common Terminology Criteria for Adverse Events version 5.0. Tumor response was determined using Response Evaluation Criteria in Solid Tumors 1.1. Survival analysis was conducted to identify factors associated with progression-free survival (PFS) and overall survival. Data were analyzed from August 2018 through August 2020.ExposuresReceiving 4 cycles of lutetium-177-dotatate infusion, separated by 8-week intervals targeted to 7.4 GBq (200 mCi) per dose.Main outcomes and measuresData were compared from before and after PRRT to determine hematologic, liver, and kidney toxic effects and to assess tumor progression and patient survival.ResultsAmong 78 patients receiving at least 1 dose of PRRT, median (interquartile range) age at PRRT initiation was 59.8 (53.5-69.2) years and 39 (50.0%) were men. The most common primary NET sites included small bowel, occurring in 34 patients (43.6%), and pancreas, occurring in 22 patients (28.2%). World Health Organization grade 1 or 2 tumors occurred in 62 patients (79.5%). Among all patients, 56 patients underwent pretreatment with tumor resection (71.8%), 49 patients received nonsomatostatin analogue systemic therapy (62.8%), and 49 patients received liver-directed therapy (62.8%). At least 1 grade 2 or greater toxic effect was found in 47 patients (60.3%). Median PFS was 21.6 months for the study group, was not reached by 22 months for patients with small bowel primary tumors, and was 13.3 months for patients with pancreatic primary tumors. Having a small bowel primary tumor was associated with a lower rate of progression compared with having a pancreatic primary tumor (hazard ratio, 0.19; 95% CI, 0.07-0.55; P = .01). Median overall survival was not reached.Conclusions and relevanceThis cohort study of patients with metastatic NETs found that PRRT was associated with laboratory-measured toxic effects during treatment for most patients and an overall median PFS of 21.6 months. Patients with small bowel NETs had longer PFS after PRRT compared with patients with pancreatic NETs.
| S-EPMC7988364 | biostudies-literature
Project description:Purpose: To develop a care process model for the delivery of peptide receptor radionuclide therapy (PRRT) with lutetium-177 (177Lu)-Dotatate for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Methods: A multidisciplinary, structured PRRT process model was established. Over the last 9 months, meetings were held bi-weekly to discuss the logistics of clinical trials. Meetings are still held regularly at the Mayo Clinic Florida to discuss plans regarding commercially available PRRT treatments. The process model has evolved as we have treated patients on both clinical trials and commercial treatments. Results: An effective process model was formulated. We had 5 patients on our Expanded Access Program (EAP) clinical trial. Our ability to be a part of the EAP allowed us to understand the mechanics of how to treat these patients, and what was involved before it became commercially available. Since commercial availability of the 177Lu-Dotatate, more than 50 treatments (>20 patients) have already been completed, with several new patients getting started on treatment every week. Our nuclear medicine department receives continual requests to schedule new patients for PRRT. This can be attributed to our streamlined approach in delivering PRRT to our patients. Conclusion: A thorough procedural approach was formulated to provide patients with PRRT. Experiences and challenges led to refinement, which has allowed the process to advance. This development could lead to better patient outcomes, treatment efficiency, and a reference standard for other institutions trying to develop this at their location.
| S-EPMC6333662 | biostudies-literature
Project description:BACKGROUND:Peptide receptor radionuclide therapy (PRRT) is an approved treatment modality for gastroenteropancreatic neuroendocrine tumours (GEP NETs), Although Phase III randomised clinical trial data is not available for NETs of other site of origin, in practice, PRRT is used more widely in clinical practice, based on its mechanism of targeting the somatostatin receptor. Use of PRRT for lung (bronchial) NET, specifically typical and atypical carcinoid (TC, AC), has been reported only in small retrospective case series. This multicentre study adds to the evidence regarding utility of PRRT for lung NETs. MATERIALS AND METHODS:A retrospective chart review of patients with TC and AC who received 177Lu-dotatate PRRT between January 2002 and June 2019 in six hospitals across Australia was undertaken. Data regarding demographics, efficacy and toxicity was evaluated at each site by the treating clinician. RESULTS:Forty-eight patients (32 AC, 15 TC, 1 unclassified) received a median of four 177Lu-dotatate treatments. There was a median of one prior line of systemic treatment (range: 0-3). The response rate to 177Lu-dotatate was 33%, with a median overall survival of 49 months (range of 3-91), at a median follow up of 33 months. This compares favourably with GEP NET. Overall toxicity was recorded as modest. CONCLUSIONS:177Lu-dotatate PRRT in patients with lung NETs is used in real world practice, where it appears well-tolerated with some efficacy. Further evidence could be obtained through a global prospective clinical or registry trial.
| S-EPMC7343632 | biostudies-literature
Project description:ImportanceDespite the benefit of peptide receptor radionuclide therapy (PRRT) for patients with well-differentiated neuroendocrine tumors (WD NETs), no clinical metric to anticipate benefit from the therapy for individual patients has been previously defined.ObjectiveTo assess whether the prognostic ability of the clinical score (CS) could be validated in an external cohort of patients with WD NETs.Design, setting, and participantsThis multicenter cohort study's analysis included patients with WD NETs who were under consideration for peptide receptor radionuclide therapy (PRRT) with lutetium-177 (177Lu)-dotatate between March 1, 2016, and March 17, 2020. The original cohort included patients from Vanderbilt-Ingram Cancer Center. The validation cohort included patients from Ochsner Medical Center, Markey Cancer Center, and Rush Medical Center. Patients with paragangliomas, pheochromocytomas and neuroblastomas were excluded. Statistical analysis was performed from June to November 2021.ExposuresPRRT with 177Lu-dotatate or alternate therapies such as everolimus, sunitinib, or capecitabine plus temozolomide.Main outcomes and measuresThe primary outcome was progression-free survival (PFS) and was estimated by the Kaplan-Meier method; a Cox proportional-hazards model adjusting for primary tumor site, tumor grade, and number of PRRT doses administered was used to analyze association between CS and outcomes.ResultsA total of 126 patients (median age [IQR] age: 63.6 [52.9-70.7] years; 64 male individuals) were included in the validation cohort, and the combined cohort (validation and original cohorts combined) had a total of 248 patients (median [IQR] patient age: 63.3 [53.3-70.3] years; 126 male individuals). In the validation cohort, on multivariable analysis, for each 2-point increase in CS, PFS decreased significantly (hazard ratio, 2.61; 95% CI, 1.64-4.16). After finding an association of the CS with PFS in the validation cohort, the original and validation cohorts were combined into the cohort for this analysis. On multivariable analysis, for each 2-point increase in CS, PFS decreased significantly (hazard ratio, 2.52; 95% CI, 1.89-3.36).Conclusions and relevanceIncreases in CS were associated with worsening PFS in the validation cohort, validating findings from the original cohort. These findings suggest that the CS, to our knowledge, represents the first clinical metric to estimate anticipated benefit from PRRT for patients with WD NETs and may be a clinical tool for patients being considered for PRRT.
| S-EPMC8771294 | biostudies-literature