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. 2018 Feb 15;9(24):16932-16950.
doi: 10.18632/oncotarget.24524. eCollection 2018 Mar 30.

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

Richard P Baum  1 , Harshad R Kulkarni  1 , Aviral Singh  1 , Daniel Kaemmerer  2 , Dirk Mueller  1 , Vikas Prasad  3 , Merten Hommann  2 , Franz C Robiller  4 , Karin Niepsch  1 , Holger Franz  5 , Arthur Jochems  6 , Philippe Lambin  6   7 , Dieter Hörsch  8
Affiliations

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

Richard P Baum et al. Oncotarget. .

Abstract

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.

Methods: In 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.

Results: Overall 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.

Conclusion: PRRT 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.

Keywords: functional syndromes; neuroendocrine tumors; peptide receptor radionuclide therapy; survival.

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Conflict of interest statement

CONFLICTS OF INTEREST R.P. Baum received honoraria from Ipsen Pharma, ROTOP Pharmaka, OctreoPharm Sciences GmbH and Advanced Accelerator Applications outside the submitted work; H.R. Kulkarni has nothing to disclose; K. Niepsch has nothing to disclose; D. Kaemmerer received travel support by the companies IPSEN Pharma GmbH and Pfizer; D. Mueller is inventor of the herein mentioned NaCl based 68Ga labeling method. In some countries, patent applications have been registered; V. Prasad has nothing to disclose; M. Hommann has nothing to disclose; F. Robiller has nothing to disclose; A. Singh has nothing to disclose; H. Franz reports personal fees from Zentralklinik Bad Berka, during the conduct of the study; A. Jochems has nothing to disclose; P. Lambin is member is the Scientific advisory board of the companies DNAmito and Oncoradiomics and is inventor of several radiomics patents; D. Hörsch reports personal fees from Lexicon Pharma Inc, grants and personal fees from Ipsen Pharma Inc, during the conduct of the study; grants and personal fees from Novartis Pharma Inc, personal fees from Pfizer Pharma Inc, grants and personal fees from Ipsen Pharma Inc, personal fees from Lexicon Pharma Inc, outside the submitted work.

Figures

Figure 1
Figure 1. Flow chart of trial characteristics
Figure 2
Figure 2
Kaplan-Meier plots of overall survival (A) and progression-free survival 1 (B) after start of PRRT.
Figure 3
Figure 3
Kaplan-Meier plots of overall survival according to radioisotope (A) and grading (B).
Figure 4
Figure 4
Kaplan-Meier plots of overall survival according to number of previous therapies (A) and primary tumors (B).
Figure 5
Figure 5
Kaplan-Meier plots of progression-free survival 1 according to radioisotope (A) and grading (B).
Figure 6
Figure 6
Kaplan-Meier plots of progression-free survival 1 according to primary tumors (A) and number of previous therapies (B).
Figure 7
Figure 7
Kaplan-Meier plots of progression-free survival 2 (A) and 3 (B) after re-start of PRRT.
See this image and copyright information in PMC

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