Clinical Application of Comprehensive Genomic Profiling Tests for Diffuse Gliomas

Abstract

Simple SummaryCancer patients suffer from recurrence after the completion of standard treatments and exhaustion of treatment options. The comprehensive genomic profiling test (CGPT) is a platform that enables those patients to access the eligible promising therapeutic agents based on their genomic aberrations, using next-generation sequencing. Though CGPTs have been utilized since 2019 in Japan, only limited findings have been available about their use for glioma patients. The aim of this study was to reveal the comprehensive results of CGPT in glioma patients, especially the clinical actionability, which means the probability of being able to receive appropriate molecular targeting therapeutic agents. In our cohort, the clinical actionability was 18.5%, which was compatible with the results of previous reports for tumors other than glioma. We confirmed that CGPT is also useful for glioma patients, and our result will encourage a future increase of CGPT use in our clinical practices.Next-generation sequencing-based comprehensive genomic profiling test (CGPT) enables clinicians and patients to access promising molecularly targeted therapeutic agents. Approximately 10% of patients who undergo CGPT receive an appropriate agent. However, its coverage of glioma patients is seldom reported. The aim of this study was to reveal the comprehensive results of CGPT in glioma patients in our institution, especially the clinical actionability. We analyzed the genomic aberrations, tumor mutation burden scores, and microsatellite instability status. The Molecular Tumor Board (MTB) individually recommended a therapeutic agent and suggested further confirmation of germline mutations after considering the results. The results of 65/104 patients with glioma who underwent CGPTs were reviewed by MTB. Among them, 12 (18.5%) could access at least one therapeutic agent, and 5 (7.7%) were suspected of germline mutations. A total of 49 patients with IDH-wildtype glioblastoma showed frequent genomic aberrations in the following genes: TERT promoter (67%), CDKN2A (57%), CDKN2B (51%), MTAP (41%), TP53 (35%), EGFR (31%), PTEN (31%), NF1 (18%), BRAF (12%), PDGFRA (12%), CDK4 (10%), and PIK3CA (10%). Since glioma patients currently have very limited standard treatment options and a high recurrence rate, CGPT might be a facilitative tool for glioma patients in terms of clinical actionability and diagnostic value.