Comparing Baseline VAF in Circulating tumor DNA and Tumor Tissues Predicting Prognosis of Patients with Colorectal Cancer Liver Metastases After Curative Resection - 13/09/24

Doi : 10.1016/j.clinre.2024.102464

Ke-min Jin ^1,^{^{†
Ke-min Jin and Quan Bao have contributed equally to this work.}}, Quan bao ^1,^{^{†
Ke-min Jin and Quan Bao have contributed equally to this work.}}, Ting-ting Zhao ², Hong-wei Wang ¹, Long-fei Huang ², Kun Wang ^1,^⁎ , Bao-cai Xing ^1,^⁎
¹ Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), hepatobiliary and pancreatic surgery unit Ⅰ, Peking University Cancer Hospital & Institute, Haidian District, Beijing, China
² Research Institute, GloriousMed Clinical Laboratory Co., Ltd., Shanghai, China

^⁎Corresponding author: Prof. Kun Wang and Prof. Bao-Cai Xing, hepatobiliary and pancreatic surgery unit Ⅰ, Peking University Cancer Hospital & Institute, No. 52, Fu-Cheng-Lu Street, Beijing 100142 (PR China); Kun Wang, Tel:+8613910726401; Bao-cai Xing, Tel:±8613910721238; Fax:+8601088196567hepatobiliary and pancreatic surgery unit ⅠPeking University Cancer Hospital & InstituteNo. 52, Fu-Cheng-Lu StreetBeijing100142PR China

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Highlights

•	NGS of paired baseline serum and tumor tissues of colorectal liver metastases patients could provide prognostic value for them after curative resection.
•	Baseline VAF in ctDNA but not in tumor tissues influenced RFS of colorectal liver metastases patients after curative resection.
•	Neither baseline VAF in ctDNA nor in tumor tissues influenced OS of colorectal liver metastases patients after curative resection.

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ABSTRACT

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.