Tumor Mutational Burden Associated With Response to Hyperthermic Intraperitoneal Chemotherapy.

Lisi Zeng,Hongsheng Tang,Yang Shao,Jin Li,Huiyan Liu,Weiwen Cui,Kaihua Liu,Qianghua Xia,Shuzhong Cui,Tianpei Guan,Ziying Lei,Jiali Luo,Quanxing Liao,Jinxia Huang,Juncai Wen,Xubo Huang,Yun Tian

doi:10.3389/fonc.2022.796263

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.

Highlights

Gastric cancer is among the most common cancer types and a leading cause of cancer death in both men and women worldwide [1], especially in Asian countries, which imposes a considerable global health burden
We found that genes GPI, PCDH9, and C21ORF140 harbored mutations in three or more no durable benefit (NDB) patients but none in the durable clinical benefit (DCB) group, and further statistical analyses of collapsing variants to the gene level showed a significant negative correlation with Hyperthermic intraperitoneal chemotherapy (HIPEC) response (p < 0.05)
Within our discovery cohort and a replication cohort, we found a significant association between high tumor mutational burden (TMB) and patients’ beneficial treatment effect

Summary

Introduction

Gastric cancer is among the most common cancer types and a leading cause of cancer death in both men and women worldwide [1], especially in Asian countries, which imposes a considerable global health burden. When gastric cancer is diagnosed, patients are often already at an advanced stage. Surgical resection is a curative therapeutic approach for gastric cancer and confers good outcome for early-stage gastric cancer. The survival rate for patients with metastatic gastric cancer is very low, ranging from 4 to 12 months [1], despite the successful application of modern chemotherapy to other solid tumors. Gastric 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; not all patients demonstrate response to HIPEC

Methods

Results

Discussion

Conclusion