Clinical and diagnostic utility of genomic profiling for digestive cancers: real-world evidence from Japan

Abstract

Abstract Background Since 2019, cancer genome panel testing in Japan has been covered under healthcare insurance. However, the usefulness of comprehensive genomic profiling (CGP) in the Japanese healthcare insurance system remains insufficiently explored. Therefore, herein, we conducted a large-scale study to determine the usefulness of CGP in digestive cancer diagnosis and established a diagnostic flow chart based on alterations in core digestive cancer-related genes. Methods We recruited 1587 patients with various cancers and subjected them to the FoundationOne CDx assay at the Keio PleSSision Group (19 hospitals) in Japan from March 2020 to October 2022. Potentially actionable genomic alterations of biological significance and actionable genomic alterations were defined using the scoring system we developed. We analyzed the detection rate of potentially actionable genomic alterations, actionable genomic alterations, and alterations equivalent to companion diagnosis (CDx), as well as the signaling pathways associated with these alterations in each digestive cancer. Results The detection rate of potentially actionable genomic alterations, actionable genomic alterations, and alterations equivalent to CDx in the 547 digestive cancers was 99.5%, 62.5%, and 11.5%, respectively. APC alterations were frequent in colorectal cancers, KRAS alterations in pancreatic cancer, and CDKN2A alterations in biliary cancers. Histologically, most digestive cancers, except esophageal cancer, were adenocarcinomas. Conclusion Based on the patterns of genomic alterations characteristic of each digestive cancer, we created a classification flowchart for digestive adenocarcinomas that may be useful in precise diagnosis. CGP has clinical and diagnostic utility in the diagnosis of digestive cancers.