We assessed
177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in the neoadjuvant setting in patients with gastroenteropancreatic
neuroendocrine tumors (GEP-NETs). We also evaluated the variables associated with resectability of the primary
tumor after PRRT. Methods: This study included 57 GEP-NET patients who had a primary
tumor that was unresectable (because of vascular involvement as defined using the pancreatic ductal
adenocarcinoma criteria of the National Comprehensive
Cancer Network) and who underwent
177Lu-DOTATATE therapy without any prior surgery. They were categorized into 2 groups: 23 patients without liver
metastases (group 1) and 34 patients with potentially resectable liver
metastases (group 2).
177Lu-DOTATATE was administered with mixed
amino acid-based renal protection at a dose of 7.4 GBq (200 mCi) per cycle. Surgical resectability was evaluated using triphasic contrast-enhanced abdominal CT imaging at 3 different time points during the PRRT course. Four broad categories of overall PRRT response were evaluated. The Kaplan-Meier product-limit method was used to calculate progression-free survival (PFS) and overall survival (OS). Associations between variables and a resectable primary
tumor after PRRT were analyzed using the χ2 test, with a P value of less than 0.05 considered statistically significant. Results: After
177Lu-DOTATATE therapy, the unresectable primary
tumor became resectable in 15 of 57 (26.3%) patients (7 patients in group 1 and 8 patients in group 2). A complete or partial response to PRRT was seen in 48 patients (84%), 23 patients (40%), 18 patients (31%), and 23 patients (40%) using symptomatic, biochemical, molecular imaging, and anatomic imaging criteria, respectively. Estimated rates of PFS were 95% and 90% at 2 y in groups 1 and 2, respectively. The 2-y OS of the 2 groups combined was 92.1%. The rate at which the primary
tumor was resectable after PRRT was significantly higher in patients who had duodenal
neuroendocrine tumors, patients who had GEP-NETs with no regional lymph node involvement, patients for whom the primary
tumor was smaller than 5 cm, patients for whom liver
metastases were no larger than 1.5 cm, patients for whom there were no more than 3 liver
metastases, and patients for whom
18F-FDG uptake in the primary
tumor had an SUVmax of less than 5. Conclusion: In a moderate fraction of GEP-NET patients, with or without liver
metastases, whose primary
tumor was unresectable because of vascular involvement, the primary
tumor converted from unresectable to resectable after
177Lu-DOTATATE therapy, signifying that neoadjuvant PRRT can be considered in such patients. The effective control of symptoms, favorable morphologic and functional imaging response, and durable PFS and OS that we observed after
177Lu-DOTATATE PRRT may lead to less morbidity and mortality in these patients.