分子与遗传医学

Usefulness and Applicability of Next Generation Sequencing in Neuroendocrine Neoplasms

Abstract

Manyanont S, Winter K and Trikalinos NA

Background: Neuroendocrine neoplasms (NENs) are rare tumors that can arise anywhere in the body and treatment options are limited due to their rarity. Knowledge of their mutational status might allow for tumor agnostic treatments, suggest a familial component or aid in enrollment in clinical trials, especially in the metastatic setting.

Objective: We aimed to evaluate the clinical relevance of results from next generation sequencing (NGS) in NEN patients and determine their applicability to patient management.

Patients and methods: Eligible NEN patients on an institutional, IRB approved protocol, who had NGS as standard of care and were treated in the past 24 months, were included. Tumors were categorized by location and histologic grade. We explored the actual and theoretical eligibility for tumor agnostic treatments and enrollment in clinical trials as available on clinicaltrials.gov.

Results: Between August 2017 and July 2019 a total of 107 patients were eligible. Globally 102 clinical trials included patients with NEN and specific mutations. NGS detected one (1%) case of MSI high and one (1) TRK fusion positive tumor, eligible for checkpoint inhibitor and TRK inhibitor therapy respectively. Moreover, tumor NGS identified 16 (15%) cases of MEN1, 1 (1%) of RET, 2 (2%) of NF1 and 3 (2.8%) of MUTYH, 2 (2%) TSC or TSC2, BRCA in 1 (1%). These patients were appropriately referred to genetic counseling. About 51.5% of patients would in theory be eligible for an investigational treatment based on NGS and global clinical trial availability. Fifty two of 107 patients (48.5%) would not have been eligible for a clinical trial with reasons varying between no mutations (24%), sample failure (8.4%) or nonactionable mutations (15.9%).

Conclusion: NGS can point to clinical trial eligibility and guide genetic counseling and should probably be considered as a standard approach in the evaluation of new metastatic NEN patients.