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

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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.

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Most cited references 32

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Placebo-Controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octreotide LAR in the Control of Tumor Growth in Patients with Metastatic Neuroendocrine Midgut Tumors (PROMID): Results of Long-Term Survival

Anja Rinke, Michael Wittenberg, Carmen Schade-Brittinger … (2016)

Background: Somatostatin analogs have been shown to control the growth of well-differentiated metastatic neuroendocrine tumors. Their effect on overall survival is a matter of debate. We analyzed the prognostic significance of early treatment with octreotide LAR and of hepatic tumor load in the PROMID trial cohort. Patients and Methods: Between 2001 and 2008, 85 treatment-naïve patients were randomly assigned to monthly octreotide LAR 30 mg or placebo until tumor progression or death. Post-study treatment was at the discretion of the investigator. Upon disease progression, 38 out of 43 placebo patients (88.4%) received octreotide LAR. For survival, patients were followed until May 2014. Results: Forty-eight out of 85 patients (56.5%) died. In 38 patients (79.2%), death was tumor related. The median overall survival (84.7 and 83.7 months) was only slightly different in patients assigned to octreotide and placebo [HR = 0.83 (95% CI: 0.47-1.46); p = 0.51]. The median overall survival was 84.7 months for all 85 patients, 107.6 months in the low-tumor-load (n = 64) and 57.5 months in the high-tumor-load (n = 21) subgroups [HR = 2.49 (95% CI: 1.36-4.55); p = 0.002]. There was a trend towards improved overall survival in patients with a low hepatic tumor load receiving octreotide compared to placebo [‘median not reached' and 87.2 months; HR = 0.59 (95% CI: 0.29-1.2); p = 0.142]. Conclusion: The extent of tumor burden is a predictor for shorter survival. Overall survival was similar in patients receiving octreotide LAR or placebo treatment at randomization. Crossover of the majority of placebo patients to octreotide LAR may have confounded the data on overall survival.

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Author and article information

Journal

Journal ID (nlm-ta): Oncotarget

Journal ID (iso-abbrev): Oncotarget

Journal ID (publisher-id): Oncotarget

Journal ID (publisher-id): ImpactJ

Title: Oncotarget

Publisher: Impact Journals LLC

ISSN (Electronic): 1949-2553

Publication date Collection: 30 March 2018

Publication date (Electronic): 15 February 2018

Volume: 9

Issue: 24

Pages: 16932-16950

Affiliations

¹ THERANOSTICS Center for Molecular Radiotherapy, Zentralklinik Bad Berka GmbH, Bad Berka, Germany

² Department of General and Visceral Surgery, Zentralklinik Bad Berka GmbH, Bad Berka, Germany

³ Clinic for Nuclear Medicine, Charité, Berlin, Germany

⁴ Center of Molecular Imaging, Zentralklinik Bad Berka GmbH, Bad Berka, Germany

⁵ Lohmann and Birkner, Berlin, Germany

⁶ Department of Radiology, GROW - School for Oncology and Developmental Biology, Maastricht University Hospital, Maastricht, The Netherlands

⁷ Department of Radiation Oncology (The D-Lab), GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands

⁸ Department of Gastroenterology/Endocrinology, Center for Neuroendocrine Tumors Bad Berka – ENETS Center of Excellence, Zentralklinik Bad Berka GmbH, Bad Berka, Germany

Author notes

Correspondence to: Dieter Hörsch, dieter.hoersch@ 123456zentralklinik.de

Article

Publisher ID: 24524

DOI: 10.18632/oncotarget.24524

PMC ID: 5908296

PubMed ID: 29682195

SO-VID: 44c00471-e386-45b3-a8b6-60338f93a588

License:

This article is distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.