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KMID : 0939920230550030927
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대한암학회지
2023 Volume.55 No. 3 p.927 ~ p.938
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Circulating Tumor DNA Dynamics and Treatment Outcome of Regorafenib in Metastatic Colorectal Cancer
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Lee Dae-Won
Lim Yoo-Joo
Kim Hwang-Phill
Kim Su-Yeon
Roh Han-Seong
Kang Jun-Kyu
Lee Kyung-Hun
Kim Min-Jung
Ryoo Seung-Bum
Park Ji-Won
Jeong Seung-Yong
Park Kyu-Joo
Kang Gyeong-Hoon
Han Sae-Won
Kim Tae-You
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Abstract
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Purpose : Circulating tumor DNA (ctDNA) is emerging as a valuable non-invasive tool to identify tumor heterogeneity and tumor burden. This study investigated ctDNA dynamics in metastatic colorectal cancer patients treated with regorafenib.
Materials and Methods : In this prospective biomarker study, plasma cell-free DNA (cfDNA) samples obtained at baseline, at the first response evaluation after 2 cycles of treatment, and at the time of progressive disease were sequenced using a targeted next-generation sequencing platform which included 106 genes.
Results : A total of 285 blood samples from 110 patients were analyzed. Higher baseline cfDNA concentration was associated with worse progression-free survival (PFS) and overall survival (OS). After 2 cycles of treatment, variant allele frequency (VAF) in the majority of ctDNA mutations decreased with a mean relative change of ?31.6%. Decreases in the VAF of TP53, APC, TCF7L2, and ROS1 after 2 cycles of regorafenib were associated with longer PFS. We used the sum of VAF at each time point as a surrogate for the overall ctDNA burden. A reduction in sum (VAF) of ≥ 50% after 2 cycles was associated with longer PFS (6.1 vs. 2.7 months, p=0.002), OS (11.3 vs. 5.9 months, p=0.001), and higher disease control rate (86.3% vs. 51.1%, p < 0.001). VAF of the majority of the ctDNA mutations increased at the time of disease progression, and VAF of BRAF increased markedly.
Conclusion : Reduction in ctDNA burden as estimated by sum (VAF) could be used to predict treatment outcome of regorafenib.
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KEYWORD
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ctDNA, Colorectal neoplasms, Regorafenib, Liquid biopsy
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