Abstract
To date, limited data are available concerning peptide receptor radionuclide therapy (PRRT) of grade 3 (G3) neuroendocrine neoplasms (NENs) with a Ki-67 proliferation index of >20%. The purpose of this study was to analyze the long-term outcome, efficacy and safety of PRRT in patients with SSTR-expressing G3 NEN. Methods: A total of 69 patients (M=41 males; age 28-81 years) received PRRT with lutetium-177 (177Lu) and/or yttium-90 (90Y) labeled somatostatin analogs (DOTATATE or DOTATOC). Twenty-two patients had radiosensitising chemotherapy. Kaplan–Meier analysis was performed to calculate progression-free survival (PFS) and overall survival (OS), defined from start of PRRT, including a subgroup analysis for patients with a Ki-67 of ≤55% and >55%. Treatment response was evaluated according to RECIST 1.1 as well as by molecular imaging criteria (EORTC). Short and long-term toxicity was documented (CTCAE v.5.0) using a structured database (comprising over 250 items per patient) and retrospectively analyzed. Results: Forty-six patients had pancreatic, 11 CUP, 6 midgut, 3 gastric, and 3 rectal NEN. Median follow-up was 94.3 months. The median PFS was 9.6 months and median OS was 19.9 months. For G3 NEN with a Ki-67 ≤55% (n = 53), the median PFS was 11 months and median OS 22 months. Patients with a Ki-67 >55% (n = 11), had a median PFS of 4 months and a median OS of 7 months. For those patients with positive SSTR imaging, but no FDG uptake, the median PFS was 24 months and median OS was 42 months. A significant difference was found for both, PFS and OS, with a median PFS of 16 vs 5 months and a median OS of 27 vs 9 months for a SUVmax >15.0 and a SUVmax ≤15.0 on SSTR-PET, respectively. In the group with FDG scored as 3-4, the median PFS was 7.1 months and the median OS 17.2 months. For FDG scored as 0-2, the median PFS was 24.3 months and the median OS 41.6 months. PRRT was well-tolerated by all patients; no grade 3 or grade 4 hematotoxicity occurred and no clinically significant decline in renal function was observed. There was no hepatotoxicity. Conclusion: PRRT was tolerated well without significant adverse effects and is efficacious in G3 NEN with promising clinical outcome, especially in patients with a Ki-67 index of ≤55% and even in patients who have failed chemotherapy. Baseline FDG along with SSTR molecular imaging is useful to stratify those G3-NEN patients with high uptake on SSTR PET/CT and no or minor FDG-avidity, a mismatch pattern which is associated with a better long term prognosis.
- Neuroendocrine
- Oncology: Endocrine
- Radionuclide Therapy
- G3
- lutetium-177(177Lu)
- neuroendocrine neoplasms (NENs)
- peptide receptor radionuclide therapy (PRRT)
- yttrium-90(90Y)
- Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.