Analysis of circulating tumor DNA identifies distinct therapeutic response to intraperitoneal and intravenous paclitaxel plus S-1 in gastric cancer patients with peritoneal metastasis

Background:Circulating tumor DNA (ctDNA) is a promising technique for predicting curative effects and monitoring tumor recurrence. The utility of ctDNA for gastric cancer with peritoneal dissemination remains elusive. Objectives:To assess the feasibility of ctDNA in predicting tumor response to chemotherapy in gastric cancer with peritoneal dissemination. Design:This was a prospective study.Methods:We enrolled 30 patients with gastric cancer peritoneal metastasis, treated with intraperitoneal and intravenous paclitaxel plus S-1. Peripheral blood samples of patients were prospectively collected at baseline, after treatment initiation accompanied by computed tomography scan and disease progression. Mutational profiles from ctDNA were analyzed to evaluate its association with chemotherapeutic response. Results:Tumor protein 53 (TP53) was the most frequently altered gene at baseline blood samples. Although baseline TP53 mutation was not related to therapeutic response, patients with TP53 mutation had worse progression-free survival (PFS) and overall survival (OS). Additionally, baseline ctDNA content fraction (CCF) was found to be significantly lower in responders than non-responders. Meanwhile, patients with high CCF had a trend of worse PFS and OS. Combining TP53 alteration and CCF, the prognosis of TP53-wt patients could be further stratified. Patients with CCF-low_TP53-wt had markedly longer survival than those with CCF-high_TP53-wt. Conclusion:Our study highlighted the significance of ctDNA in predicting potential clinical outcomes in gastric cancer patients during chemotherapy.Trial registration:ChiCTR-IIR-16009802 (Chinese Clinical Trial Registry).