Annals of Laboratory Medicine

Korean Society for Laboratory Medicine (대한진단검사의학회)
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Clinical Utility of Monitoring Circulating Tumor DNA Using a Targeted Next-generation Sequencing Panel in Patients with Colorectal Cancer

  • Hyoeun Shim (Department of Laboratory Medicine, National Cancer Center) ;
  • Soobeen Heo (Targeted Therapy Branch, Research Institute, National Cancer Center) ;
  • Jiyu Sun (Integrated Biostatistics Branch, Division of Cancer Data Science, National Cancer Center) ;
  • Moon Ki Choi (Center for Colorectal Cancer, National Cancer Center) ;
  • Sung Chan Park (Center for Colorectal Cancer, National Cancer Center) ;
  • Chang Won Hong (Center for Colorectal Cancer, National Cancer Center) ;
  • Seong Hoon Kim (Organ Transplantation Center, National Cancer Center) ;
  • Seog-Yun Park (Department of Pathology, National Cancer Center) ;
  • Sun-Young Kong (Department of Laboratory Medicine, National Cancer Center) ;
  • Ji Yeon Baek (Center for Colorectal Cancer, National Cancer Center)
  • Received : 2024.11.06
  • Accepted : 2025.06.04
  • Published : 2025.07.01
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Abstract

Background: Circulating tumor DNA (ctDNA) profiling from peripheral blood allows relatively noninvasive monitoring of solid tumors; however, its utility post-surgery or chemotherapy in colorectal cancer remains underexplored. We evaluated the clinical implications of a ctDNA next-generation sequencing (NGS) panel post-surgery or chemotherapy in patients with colorectal cancer. Methods: We collected samples from 23 patients with colorectal cancer (17 men, median age 65 yrs) at baseline and post-surgery or chemotherapy at the National Cancer Center, Korea, between January 2021 and September 2023. ctDNA was analyzed using an NGS panel including 46 genes, and variant allele frequencies (VAFs) were determined. Follow-up samples were analyzed using the NGS panel or droplet digital PCR (ddPCR) when probes were available. Clinical status was compared with ctDNA results, and survival was analyzed using a time-dependent Cox model. Results: Mutations were identified in 13 out of 14 patients (92.8%) with stage II/III cancer and in all nine patients (100%) with stage IV cancer. Mutations were detected in KRAS (N=15, 65%), APC (N=8, 35%), TP53 (N=7, 30%), PIK3CA (N=5, 22%), and RET (N=4, 17%). A 1% increase in KRAS and TP53 VAFs was associated with 48% and 32% increased mortality risk, respectively. Changes in VAF correlated well with clinical findings. Conclusions: The detection of and an increase in KRAS and TP53 VAFs were associated with poor prognosis. ddPCR-based ctDNA monitoring results were comparable to those obtained with the NGS panel. ctDNA monitoring during treatment is clinically informative in managing colorectal cancer.

Keywords

Acknowledgement

This study was supported by the National Cancer Center (Goyang, Korea; grant No. 2110220).

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