Comparing Baseline VAF in Circulating tumor DNA and Tumor Tissues Predicting Prognosis of Patients with Colorectal Cancer Liver Metastases After Curative Resection.

INTRODUCTION: The prognostic value of baseline variant allele frequency (VAF) in circulating tumor DNA (ctDNA) of colorectal cancer liver metastases (CRLM) patients after curative resection was rarely investigated.

METHODS: A single-center prospective study was performed to investigate the prognostic impact of baseline VAF in ctDNA and matched tumor tissues of CRLM patients after curative resection between May 2019 and May 2021 by the Illumina NovoSeq 6000 platform. The relationship of the tumor burden score (TBS) and the VAF in ctDNA and matched tumor tissues was evaluated by the Pearson correlation method. The survival curves of recurrence-free survival (RFS) and overall survival (OS) were plotted. Factors associated with RFS were calculated using Cox regression analysis, and an integrated prognostic model using significant baseline variables was proposed.

RESULTS: There were 121 patients with baseline ctDNA and matched tumor tissues enrolled in the study. A total of 417 mutations spanning 20 genes were identified in baseline tumor tissues of 119/121 (98.3%) cases. The overall mutations in tumor tissues were completely covered by ctDNA in 52 of 121(43.0%) patients. Baseline VAF in ctDNA but not in tumor tissues was significantly correlated to TBS of CRLM (R=0.36, p<0.001). Significantly longer RFS but not OS was observed in patients with lower VAF in ctDNA compared to those with higher one (p<0.001 and p=0.33 respectively). Multivariate Cox regression analysis showed higher VAF in baseline ctDNA was an independent risk factor for RFS. An integrated prognostic model including baseline metastasis location and VAF in ctDNA outperformed the traditional CRS model in predicting RFS.

CONCLUSION: Baseline VAF in ctDNA but not in tumor tissues influenced RFS of CRLM patients after curative resection.