Tumor Mutational Burden Associated With Response to Hyperthermic Intraperitoneal Chemotherapy

Abstract

BackgroundGastric cancer (GC) is one of the most common cancer types, especially in Asian countries. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to improve the progression-free survival among gastric cancer patients with peritoneal metastases; however, not all patients demonstrate response to HIPEC.MethodsBiomarkers are needed to select patients for effective treatment of HIPEC. Here, we performed whole-exome sequencing on tumor samples from 18 gastric cancer patients who received HIPEC treatment and assessed the association between genomic mutation features and progression-free survival. Exome sequencing was further conducted on tumor samples from additional 15 gastric cancer patients as a replication study.ResultsThe tumor mutational burden (TMB) was significantly higher in the group of patients with a better response to HIPEC treatment than that of the others. Kaplan–Meier survival curve showed that patients with high TMB had a significantly longer survival time than that in patients with low TMB. This discovery was validated in the replication cohort. Genes bearing mutations recurrently and selectively in patients with better response to HIPEC were found in the two cohorts.ConclusionWe found that higher TMB is significantly associated with better response to HIPEC. Our results provide useful hints for prognostic stratification of HIPEC treatment.

Genetic alterations in peritoneal metastatic tumors predicted the outcomes for hyperthermic intraperitoneal chemotherapy

“…Our results indicated that TMB was higher in non-responders than that in responders, which is consistent with a previous finding of colorectal PM treated with CRS/HIPEC ( 48 ). Conversely, the correlation between high TMB and better responses to HIPEC was reported in gastric PM patients ( 49 ). The inconsistent results might be due to the tumor heterogeneity.…”

Consensus Guideline for the Management of Colorectal Cancer with Peritoneal Metastases

“…Standard molecular analysis should be conducted, which includes assessing for microsatellite instability (MSI), RAS mutations (KRAS, NRAS, and HRAS), BRAF mutations, ERBB2 (formerly HER2) status, and tumor mutational burden (TMB) by next-generation sequencing (NGS) [31] [32]. NGS also has the potential to identify sequence variations, such as ERBB2 amplifications or NTRK gene fusions [33].…”