Abstract
Peptide 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. To analyze the first 2 years of PRRT implementation at a US-based NET referral center. This 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. Receiving 4 cycles of lutetium-177-dotatate infusion, separated by 8-week intervals targeted to 7.4 GBq (200 mCi) per dose. Data were compared from before and after PRRT to determine hematologic, liver, and kidney toxic effects and to assess tumor progression and patient survival. Among 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. This 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.
Highlights
Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms, with primary tumors commonly originating in the pancreas, intestines, and lungs.[1,2,3] These tumors often present with distant metastatic disease, and given the multitude of treatment options available, treatment of metastatic disease is growing increasingly complex.[4]
Median overall survival was not reached. This cohort study of patients with metastatic neuroendocrine tumor (NET) found that peptide receptor radionuclide therapy (PRRT) was associated with laboratory-measured toxic effects during treatment for most patients and
The first randomized clinical trial assessing the efficacy of PRRT for treatment of NETs was the Neuroendocrine Tumors Therapy (NETTER-1) trial, which included patients with metastatic, welldifferentiated midgut NETs who had progressed on somatostatin analogue therapy.[12]
Summary
Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms, with primary tumors commonly originating in the pancreas, intestines, and lungs.[1,2,3] These tumors often present with distant metastatic disease, and given the multitude of treatment options available, treatment of metastatic disease is growing increasingly complex.[4]. In PRRT, a radionuclide linked to a somatostatin analogue is used, allowing for targeted delivery of radiotherapy to somatostatin receptor–expressing NETs, which represent most NETs.[10,11] The first randomized clinical trial assessing the efficacy of PRRT for treatment of NETs was the Neuroendocrine Tumors Therapy (NETTER-1) trial, which included patients with metastatic, welldifferentiated (ie, World Health Organization [WHO] grade 1 or 2) midgut NETs who had progressed on somatostatin analogue therapy.[12] In this landmark phase 3 multicenter trial, patients were randomized to receive lutetium-177-dotatate plus octreotide long-acting repeatable or high-dose octreotide long-acting repeatable alone. After results of NETTER-1 supported the effectiveness of PRRT in midgut NETs, the Food and Drug Administration (FDA) approved lutetium177-dotatate for treatment of somatostatin receptor–positive gastroenteropancreatic NETs in 2018. Since FDA approval of PRRT, efforts have been targeted at implementation of PRRT within NET clinics across the United States.[13,14] Results from a 2020 study[15] by our group suggested that PRRT could be successfully administered among a diverse US-based group of patients with NETs, and we found that patients with abnormal liver function tests before PRRT had an increased likelihood of discontinuing PRRT prior to completion of the PRRT treatment course
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
