Dynamic changes in longitudinal circulating tumour DNA profile during metastatic colorectal cancer treatment

Sheehyun Kim, Yoojoo Lim, Jun Kyu Kang, Hwang Phill Kim, Hanseong Roh, Su Yeon Kim, Dongin Lee, Duhee Bang, Seung Yong Jeong, Kyu Joo Park, Sae Won Han, Tae You Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Circulating tumour DNA (ctDNA) has been spotlighted as an attractive biomarker because of its easy accessibility and real-time representation of tumour genetic profile. However, the clinical utility of longitudinal ctDNA monitoring has not been clearly defined. Methods: Serial blood samples were obtained from metastatic colorectal cancer patients undergoing first-line chemotherapy. ctDNA was sequenced using a targeted next-generation sequencing platform which included 106 genes. Changes in ctDNA profile and treatment outcome were comprehensively analysed. Results: A total of 272 samples from 62 patients were analysed. In all, 90.3% of patients had detectable ctDNA mutation before treatment. ctDNA clearance after chemotherapy was associated with longer progression-free survival which was independent of radiological response (adjusted hazard ratio 0.22, 95% confidence interval 0.10–0.46). Longitudinal monitoring was able to detect ctDNA progression which preceded radiological progressive disease (PD) in 58.1% (median 3.3 months). Diverse resistant mutations (34.9%) and gene amplification (7.0%) at the time of PD were discovered. For 16.3% of the PD patients, the newly identified mutations could be potential candidates of targeted therapy or clinical trial. Conclusion: ctDNA profile provided a more accurate landscape of tumour and dynamic changes compared to radiological evaluation. Longitudinal ctDNA monitoring may improve personalised treatment decision-making.

Original languageEnglish
JournalBritish journal of cancer
DOIs
Publication statusAccepted/In press - 2022

Bibliographical note

Funding Information:
This study was supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI18C2282).

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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