Circulating Tumor DNA Dynamics and Treatment Outcome of Regorafenib in Metastatic Colorectal Cancer
- Author:
Dae-Won LEE
1
;
Yoojoo LIM
;
Hwang-Phill KIM
;
Su Yeon KIM
;
Hanseong ROH
;
Jun-Kyu KANG
;
Kyung‑Hun LEE
;
Min Jung KIM
;
Seung-Bum RYOO
;
Ji Won PARK
;
Seung-Yong JEONG
;
Kyu Joo PARK
;
Gyeong Hoon KANG
;
Sae-Won HAN
;
Tae-You KIM
Author Information
- Publication Type:Original Article
- From:Cancer Research and Treatment 2023;55(3):927-938
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
