Results and adverse events of personalized peptide receptor radionuclide therapy with 90Yttrium and 177Lutetium in 1048 patients with neuroendocrine neoplasms.

Richard P Baum,Karin Niepsch,Philippe Lambin,Aviral Singh,Franz C Robiller,Merten Hommann,Dirk Mueller,Arthur Jochems,Harshad R Kulkarni,Daniel Kaemmerer,Holger Franz,Vikas Prasad,Dieter Hörsch

doi:10.18632/oncotarget.24524

Abstract

IntroductionPeptide receptor radionuclide therapy (PRRT) of patients with somatostatin receptor expressing neuroendocrine neoplasms has shown promising results in clinical trials and a recently published phase III study.MethodsIn our center, 2294 patients were screened between 2004 and 2014 by 68Ga somatostatin receptor (SSTR) PET/CT. Intention to treat analysis included 1048 patients, who received at least one cycle of 90Yttrium or 177Lutetium-based PRRT. Progression free survival was determined by 68Ga SSTR-PET/CT and EORTC response criteria. Adverse events were determined by CTCAE criteria.ResultsOverall survival (95% confidence interval) of all patients was 51 months (47.0-54.9) and differed significantly according to radionuclide, grading, previous therapies, primary site and functionality. Progression free survival (based on PET/CT) of all patients was 19 months (16.9-21), which was significantly influenced by radionuclide, grading, and origin of neuroendocrine neoplasm. Progression free survival after initial progression and first and second resumption of PRRT after therapy-free intervals of more than 6 months were 11 months (9.4-12.5) and 8 months (6.4-9.5), respectively. Myelodysplastic syndrome or leukemia developed in 22 patients (2.1%) and 5 patients required hemodialysis after treatment, other adverse events were rare.ConclusionPRRT is effective and overall survival is favorable in patients with neuroendocrine neoplasms depending on the radionuclide used for therapy, grading and origin of the neuroendocrine neoplasm which is not exactly mirrored in progression free survival as determined by highly sensitive 68Ga somatostatin receptor PET/CT using EORTC criteria for determining response to therapy.

Highlights

Peptide receptor radionuclide therapy (PRRT) of patients with somatostatin receptor expressing neuroendocrine neoplasms has shown promising results in clinical trials and a recently published phase III study
Progression free survival of all patients was 19 months (16.9-21), which was significantly influenced by radionuclide, grading, and origin of neuroendocrine neoplasm
Myelodysplastic syndrome or leukemia developed in 22 patients (2.1%) and 5 patients required hemodialysis after treatment, other adverse events were rare

Summary

Introduction

Peptide receptor radionuclide therapy (PRRT) of patients with somatostatin receptor expressing neuroendocrine neoplasms has shown promising results in clinical trials and a recently published phase III study. Neuroendocrine neoplasms (NENs) arise most frequently in the gastroentero-pancreatic system and lungs. These neoplasms originate in scattered endocrine cells of the diffuse neuroendocrine system and are biologically very heterogeneous [1]. Two groups of NEN behave biologically and clinically distinctively different; the well differentiated slowly growing neuroendocrine tumors with an excellent to good prognosis and poorly differentiated fast growing neuroendocrine carcinomas with a poor prognosis. Neuroendocrine carcinomas are defined by small or large cell morphology. The new WHO classification of pancreatic NENs includes the newly created well differentiated neuroendocrine tumors with a proliferation of up to 50% as neuroendocrine tumor G3 [2, 3]. NENs may be functionally active due to the autonomous secretion of biogenic amines or peptide hormones such as serotonin, gastrin or insulin causing characteristic functional syndromes [4]

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