Diagnostic and therapeutic impact of genomic testing in neuroendocrine neoplasms

Neuroendocrine neoplasms (NENs) are a diverse group of rare cancers with high heritability and limited treatment options for metastatic disease. Genomic testing guidelines for patients with NENs are limited to germline testing in high-risk individuals and tumour mutational burden (TMB) in a subset of patients. Here, we assess the prevalence of clinically actionable somatic variants using gene panel testing in the AACR GENIE database, and our real-world experience using additional genomic testing methodologies such as whole genome sequencing (WGS) and circulating tumour DNA sequencing for patients with NENs. The AACR GENIE database contained large panel data for 2,838 samples representing 26 different NEN subtypes. Of the samples, 19.1% had an OncoKB-defined actionable variant; however, only 1.6% were Level 1. TMB ≥ 10 mut/Mb was found in 21% of the assessable AACR GENIE cohort, mostly in NEC subtypes. Our institutional cohort of 30 patients was analysed using tumour-normal WGS in 24/33 testing episodes. Eight of thirty patients (27%) had variant-based clinical trial recommendations made. Seven of twenty-four WGS cases (29%) had clinically reportable germline variants identified. Circulating tumour DNA testing (n = 5/33) was used to sequence patients with uncontrolled hormone syndromes and when adequate tissue was not available. In selected patients with certain metastatic NET subtypes or NECs, our data support consideration of comprehensive tumour-normal genomic testing.