MEN1/DAXX/ATRX mutations enhance progression-free survival in gastroenteropancreatic neuroendocrine tumors treated with peptide receptor radionuclide therapy

in Endocrine-Related Cancer
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Rushabh Gujarathi Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois, USA

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Sara Abou Azar Section of Endocrine Surgery, Department of Surgery, University of Chicago, Chicago, Illinois, USA

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Joseph Tobias Section of Endocrine Surgery, Department of Surgery, University of Chicago, Chicago, Illinois, USA

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Blase N Polite Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois, USA

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Namrata Setia Department of Pathology, University of Chicago, Chicago, Illinois, USA

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Nicholas Feinberg Department of Radiology, University of Chicago, Chicago, Illinois, USA

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Daniel E Appelbaum Department of Radiology, University of Chicago, Chicago, Illinois, USA

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Xavier M Keutgen Section of Endocrine Surgery, Department of Surgery, University of Chicago, Chicago, Illinois, USA

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Chih-Yi Liao Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois, USA

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Correspondence should be addressed to C Liao: andyliao@uchicagomedicine.org
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Pre-clinical data suggest that mutations in the MEN1, DAXX, and/or ATRX genes may potentially increase radiation efficacy in cancer cells. Herein, we explore the association between response to peptide receptor radionuclide therapy (PRRT) and those mutations in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). We analyzed tissue-based next generation sequencing (NGS) assay results and clinicopathologic data from 28 patients with GEP-NETs treated with PRRT. Findings were correlated with progression-free survival (PFS) and objective response rate (ORR). Patients with mutations in MEN1, DAXX, and/or ATRX (n = 13) had a longer median PFS (26.47 vs 12.13 months; P = 0.014) than wild-type (n = 15) patients when adjusted for surgery prior to PRRT, tumor grade, and presence of TP53 mutation. Alterations in MEN1 along with a concurrent mutation in either DAXX or ATRX (n = 6) trended toward longer PFS compared to patients without concurrent mutations (31.53 vs 17.97 months; P = 0.09). ORR was higher in patients with a mutation in MEN1, DAXX, or ATRX (41.67% vs 15.38%). In pancreatic NET patients, these target mutations also showed a longer PFS (28.43 vs 9.83 months; P = 0.04). TP53 alterations showed a shorter PFS than wild-type cases (11.17 vs 20.47 months; P = 0.009). Mutations in MEN1/DAXX/ATRX are associated with improved PFS in patients with GEP-NETs receiving PRRT and might be used as a biomarker for treatment response.

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