Genomic profiling of small bowel adenocarcinoma: Insights from a comparative analysis with gastric and colorectal cancer and opportunities for targeted therapy

Background

Small bowel adenocarcinomas (SBAs) are rare cancers with significantly lower incidence, later stage at diagnosis, and worse overall survival than other intestinal derived cancers including colorectal cancer (CRC). To date, comprehensive genomic characterization and identification of targetable genomic alterations in SBA is lacking.

Methods

We prospectively analyzed clinical samples from 358 patients with SBA, 6,353 patients with CRC, and 889 patients with gastric carcinoma (GC) using hybrid-capture based comprehensive genomic profiling (CGP).

Results

We compared available clinical features and complete molecular profiles for SBA, CRC and GC patients. In all three series the majority were male (52-55%) and SBA patients tended to be marginally older (median 60 years old). APC alterations were less frequent in SBA (27%) than in CRC (76%) (P 

Conclusions

This study presents the first large scale genomic comparison of SBA with CRC and GC, as well as a comparison of unspecified SBAs with tumors of the duodenum. Higher incidence of microsattelite instability in SBA suggests that an important subset of these patients may benefit from treatment with anti-PD-1/PD-L1 therapies. The use of CGP during the course of clinical care identifies targetable genomic alterations across intestinal tumor types and allows patients to be matched with appropriate targeted therapies.

Clinical trial identification

Legal entity responsible for the study

Foundation Medicine, Inc.

Funding

Foundation Medicine, Inc.

Disclosure

A.B. Schrock, J. Sun, P. Stephens, J.S. Ross, V.A. Miller, S.M. Ali: Employee at Foundation Medicine. Stock ownership: Foundation Medicine. All other authors have declared no conflicts of interest.