Department of Genomic Medicine, Seoul National University Hospital, Seoul, Korea.
IMBdx, Inc., Seoul, Korea.
Br J Cancer. 2022 Sep;127(5):898-907. doi: 10.1038/s41416-022-01837-z. Epub 2022 May 28.
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.
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.
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.
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.
循环肿瘤 DNA（ctDNA）因其易于获取和实时反映肿瘤遗传特征而成为一种有吸引力的生物标志物。然而，纵向 ctDNA 监测的临床实用性尚未明确界定。
对接受一线化疗的转移性结直肠癌患者进行了一系列血液样本采集。使用靶向下一代测序平台对 ctDNA 进行测序，该平台包括 106 个基因。综合分析 ctDNA 图谱变化和治疗结果。
共分析了 62 名患者的 272 个样本。所有患者在治疗前均检测到可检测的 ctDNA 突变，占 90.3%。化疗后 ctDNA 清除与无进展生存期延长相关，且独立于影像学反应（调整后的危险比 0.22，95%置信区间 0.10-0.46）。纵向监测能够检测到 ctDNA 进展，在 58.1%（中位时间为 3.3 个月）的患者中，ctDNA 进展先于影像学进展性疾病（PD）。在 PD 时发现了多种耐药突变（34.9%）和基因扩增（7.0%）。对于 16.3%的 PD 患者，新发现的突变可能是靶向治疗或临床试验的潜在候选药物。
ctDNA 图谱与影像学评估相比，提供了更准确的肿瘤全景和动态变化。纵向 ctDNA 监测可能改善个体化治疗决策。
