Circulating tumor DNA sequencing in colorectal cancer patients treated with first-line chemotherapy with anti-EGFR

Yoojoo Lim, Sheehyun Kim, Jun Kyu Kang, Hwang Phill Kim, Hoon Jang, Hyojun Han, Hyoki Kim, Min Jung Kim, Kyung Hun Lee, Seung Bum Ryoo, Ji Won Park, Seung Yong Jeong, Kyu Joo Park, Gyeong Hoon Kang, Sae Won Han, Tae You Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Circulating tumor DNA (ctDNA) may reveal dynamic tumor status during therapy. We conducted serial ctDNA analysis to investigate potential association with clinical outcome in metastatic colorectal cancer (mCRC) patients receiving chemotherapy. Tissue KRAS/NRAS wild-type mCRC patients were enrolled and treated with first-line cetuximab-containing chemotherapy. ctDNA isolated from plasma were analyzed by next generation sequencing (NGS) with 16 targeted gene panel. Among 93 patients, 84 (90.3%) had at least 1 somatic mutation in baseline ctDNA samples (average 2.74). Five patients with KRAS or NRAS hotspot mutation in the ctDNA showed significantly worse progression-free survival (PFS) (p = 0.029). Changes in average variant allele frequency (VAF) in ctDNA showed significant correlation with tumor size change at the time of first response evaluation (p = 0.020) and progressive disease (PD) (p = 0.042). Patients whose average VAF decreased below cutoff (< 1%) at the first evaluation showed significantly better PFS (p < 0.001), and the average VAF change further discriminated the PFS in the patients in partial response (p = 0.018). At the time of PD, 54 new mutations including KRAS and MAP2K1 emerged in ctDNA. ctDNA sequencing can provide mutation profile that could better reflect tumor mutation status and predict treatment outcome.

Original languageEnglish
Article number16333
JournalScientific Reports
Volume11
Issue number1
DOIs
StatePublished - Dec 2021
Externally publishedYes

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