Lin Chien-Yu, Shen Ming-Yin, Chen William Tzu-Liang, Yang Chin-An
Integrated Precision Health and Immunodiagnostic Center, Department of Laboratory Medicine, China Medical University Hsinchu Hospital, Zhubei City 302, Taiwan.
Department of Colorectal Surgery, China Medical University Hsinchu Hospital, Zhubei City 302, Taiwan.
J Pers Med. 2023 Jun 26;13(7):1051. doi: 10.3390/jpm13071051.
mutation in tumor tissue is a well-known predictor of resistance to the treatment of anti-EGFR antibodies in metastatic colorectal cancers (mCRC). However, the prognostic value of low-frequency plasma circulating tumor DNA (ctDNA) mutation in predicting treatment resistance in pretreated mCRC patients remains controversial. This study retrospectively reviewed the clinical course, including response to anti-EGFR and anti-VEGF therapies, and changes in serum tumor marker levels along with image studies in mCRC patients with <1.5% mutations detected in plasma ctDNA by next-generation sequencing (NGS) at a single center in Taiwan. We identified six pretreated mCRC patients with low-frequency G12V/G12D/G12S/G13D mutations (variant allele frequency 0.26~1.23%) in plasma ctDNA. Co-occurring low-frequency ctDNA mutations in , , , , or were also detected. Although all six patients had treatment adjustments within one month after the ctDNA genetic test, image-evident tumor progression was noted in all patients within a median of 4 months afterwards. Re-challenge therapy with a combination of anti-EGFR, anti-VEGF, and FOLFIRI chemotherapy was found to be ineffective in a patient with 0.38% G12D mutation in baseline ctDNA. Our study suggests that the detection of low-frequency mutations in ctDNA could be used as a predictor of treatment response in mCRC patients.
肿瘤组织中的突变是转移性结直肠癌（mCRC）中抗表皮生长因子受体（EGFR）抗体治疗耐药性的一个众所周知的预测指标。然而，低频血浆循环肿瘤DNA（ctDNA）突变在预测既往治疗的mCRC患者治疗耐药性方面的预后价值仍存在争议。本研究回顾性分析了台湾某单中心通过下一代测序（NGS）在血浆ctDNA中检测到<1.5%突变的mCRC患者的临床病程，包括对抗EGFR和抗血管内皮生长因子（VEGF）治疗的反应、血清肿瘤标志物水平的变化以及影像学检查结果。我们确定了6例既往治疗的mCRC患者，其血浆ctDNA中存在低频G12V/G12D/G12S/G13D突变（变异等位基因频率为0.26%~1.23%）。同时还检测到了KRAS、NRAS、BRAF、PIK3CA或PTEN基因的低频ctDNA共突变。尽管所有6例患者在ctDNA基因检测后1个月内均进行了治疗调整，但所有患者在随后的中位4个月内均出现了影像学可见的肿瘤进展。对于基线ctDNA中存在0.38% G12D突变的患者，再次使用抗EGFR、抗VEGF和FOLFIRI化疗联合治疗无效。我们的研究表明，检测ctDNA中的低频KRAS突变可作为mCRC患者治疗反应的预测指标。
