Peptide receptor radionuclide therapy (PRRT) of patients with somatostatin receptor expressing gastroenteropancreatic neuroendcrine neoplasms (NEN) has shown promising results in a recently published clinical trial (NETTER-1, NEJM, Jan 2017). In this study, we performed an intention to treat analysis in over 1000 patients with NEN (pancreas, mid-gut, lung and others) treated at our center.
From 2004, 1048 patients received at least one cycle of Yttrium-90 or Lutetium-177 based PRRT, and were included in an intention to treat analysis. Ga-68 somatostatin receptor (SSR) PET/CT was used for restaging and response to therapy assessment (EORTC criteria). Accordingly, overall survival (OS) and progression free survival (PFS) were calculated. Adverse events (hematotoxicity and nephrotoxicity) were determined by CTCAE (v4.03).
Overall survival (95% CI) was 51 months (47.0-54.9) and differed according to tumor grade, location of primary tumor, functionality, previous therapies, and the radioisotope used for PRRT. PFS was 19 months (16.9-21.0), which was influenced by tumor grade, location of primary tumor, and the radioisotope used for PRRT. PFS after initial progression and first and second resumption of PRRT, following therapy-free intervals of > 6 months, was 11 months (9.4-12.5) and 8 months (6.4-9.5), respectively. Myelodysplastic syndrome or leukemia developed in 2.1% patients. No grade 4 nephrotoxicity was observed with Lu-177. Few patients with severe renal dysfunction before PRRT, progressed to end-stage renal disease. No patient with normal renal function before PRRT developed G3 (or higher) nephrotoxicity.
PRRT is effective as it favorably prolongs the OS and PFS in patients with metastatic neuroendocrine neoplasms. However, this depends on the tumor grade, location of primary tumor, and the radionuclide used for therapy. Low rate of severe hematotoxicity were observed. There was no therapy associated severe nephrotoxicity in patients with normal renal function prior to commencement of PRRT.
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Richard P. Baum
All authors have declared no conflicts of interest.