890MO - Mutation spectrum in liquid versus solid biopsies from advanced digestive neuroendocrine carcinoma patients

Background

Digestive neuroendocrine carcinoma (NEC) are currently defined by the presence of a poorly differentiated neuroendocrine phenotype and a high proliferation rate (Ki-67>20%). Most digestive NEC are diagnosed with metastatic disease with survival less than 1 year if medically treated. Frequently only minor biopsies are available for further molecular diagnostics. The molecular characteristics of digestive NEC has recently been described, but data on applicability of liquid biopsies in digestive NEC is very limited.

Methods

We performed massive parallel sequencing of 76 cancer related genes in plasma ctDNA from 50 patients with advanced digestive NEC and compared findings to previous analyses performed in matched FFPE tumour biopsies. Optimal filters were used, including data from WBC as filter for removal of SNPs.

Results

Among the 50 patients, 46 had metastatic disease and 4 locoregional disease at the time of plasma sampling. We detected a total of 178 somatic mutations in the liquid biopsies. Out of these, 127 (71%) were also detected in the solid biopsies. In the same 76 genes, we previously detected 199 somatic mutations (SNVs) in the tumor biopsies. Thus, 64% (127 out of 199) of mutations in solid biopsies were also found in the liquid biopsies. The concordance was higher in patients with liver metastases (p= p=1.5x10^-5), while it was similar between digestive NEC with different primary sites, except for a lower concordance in esophageal cases (p=0.001). Concordance was not associated with tumor mutational burden (TMB). Tumour tissue mutations also detected in liquid biopsies was lower for MSI (40%) versus MSS tumours (70%; p=7.8x10^-4). Applying a predefined set of criteria, we identified potentially targetable mutations in plasma of 26 (52%) of digestive NEC patients; 9 patients (18%) had potentially targetable mutation detected only in liquid biopsies.

Conclusions

We found liquid biopsy analyses to be an applicable alternative to solid biopsies in digestive NEC patients. Liquid biopsies could be used for biomarker assessment in clinical trials for these patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Helse Bergen, Haukeland University Hospital, Bergen, Norway.

Funding

Helse Bergen, Haukeland University Hospital, Bergen, Norway.

Disclosure

T. Grob: Financial Interests, Personal and Institutional, Research Grant: Roche. All other authors have declared no conflicts of interest.