Ascites and Serial Plasma Circulating Tumor DNA for Predicting the Effectiveness of Hyperthermic Intraperitoneal Chemotherapy in Patients With Peritoneal Carcinomatosis.

Xiaolin Pu,Xiaoying Wang,Hua Jiang,Zongyuan Li

doi:10.3389/fonc.2022.791418

Abstract

PurposeWe investigated the value of ascites and serial plasma circulating tumor DNA (ctDNA) for predicting response to hyperthermic intraperitoneal chemotherapy (HIPEC), monitoring tumor burden, and predicting prognosis in patients with peritoneal carcinomatosis (PC).Experimental DesignIn this observational study, 19 patients with PC were enrolled. Serial plasma ctDNA was analyzed using next-generation sequencing. The molecular tumor burden index (mTBI) was used to detect ctDNA, and concurrent changes in the dominant clone variant allele frequency (VAF) and common tumor markers were used as controls. The correlation between ascites and plasma ctDNA comutated genes was expressed by VAF. The overall response rate (complete response + partial response) after HIPEC was determined. Ascites progression-free survival (PFS) and overall survival (OS) were determined, and potential correlations between these outcomes and change in mTBI (△mTBI), change in sum-VAF (△sum-VAF), dominant close VAF, and tumor markers were assessed.ResultsThe overall response rate at 1 month after HIPEC was 100%. The △mTBI (r = 0.673; P = 0.023) and △sum-VAF (r = 0.945; P <0.001) were significantly positively correlated with ascites PFS; these correlations were stronger than those of the dominant clone VAF (r = 0.588; P = 0.057) and tumor markers in the same period (r =0.091; P = 0.790). Patients with a low baseline mTBI (<0.67) demonstrated significantly longer ascites PFS (P = 0.003; HR = 0.157; 95% CI: 0.046–0.540) and OS (P = 0.017; HR = 0.296; 95% CI: 0.109–0.804) than those with a high baseline mTBI (≥0.67). Consistent mutations were detected in plasma and ascites (r = 0.794; P = 0.001).ConclusionA real-time serial plasma ctDNA assay accurately reflected tumor burden. The △mTBI and △sum-VAF can be used as predictors of HIPEC efficacy in patients with PC. A high baseline mTBI may be a negative risk factor for prognosis.

Highlights

Gastric cancer, colorectal cancer, ovarian cancer, peritoneal false myxoma, peritoneal malignant mesothelioma, and the local progression of primary peritoneal carcinoma can lead to the development of peritoneal surface tumors, a condition usually referred to as peritoneal carcinomatosis (PC)
We found that dynamic Circulating tumor DNA (ctDNA) monitoring using a series of plasma samples can be helpful in predicting the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC), which is consistent with the results of previous studies [18,19,20,21]
We found that △molecular tumor burden index (mTBI) and △sum-variant allele frequency (VAF) were significantly more predictive of efficacy than changes in tumor markers and the dominant clone VAF

Summary

Introduction

Colorectal cancer, ovarian cancer, peritoneal false myxoma, peritoneal malignant mesothelioma, and the local progression of primary peritoneal carcinoma can lead to the development of peritoneal surface tumors, a condition usually referred to as peritoneal carcinomatosis (PC). The prognosis for affected patients is poor, with a median survival of approximately 6 months [1,2,3]. Patients with this condition often receive palliative treatment. PC has been considered widespread metastasis, but the condition is considered a local disease and is treated . Since hyperthermic intraperitoneal chemotherapy (HIPEC) was first used to treat peritoneal pseudomyxoma in 1980 [4], this treatment has been gradually popularized for the treatment of patients with multiple malignant tumors with peritoneal metastasis such as PC

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