Serial Monitoring of Circulating Tumor DNA in Patients With Metastatic Colorectal Cancer to Predict the Therapeutic Response

Frontiers in Genetics

Nan Li¹  Jianfeng Zhou²  Zhao Sun²  Yanping Zhou²  Yuejuan Cheng²  Chunmei Bai²  Ning Jia²  Xin Gao³  Wei Chen⁴  Xueliang Wang⁴  Rong Shi⁴  Chunying Shen⁴ 

[1] Clinical Epidemiology Research Center, Peking University Third Hospital, Beijing, China;Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China;Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China;San Valley Biotechnology Incorporated, Beijing, China;

关键词: liquid biopsy;    circulating tumor DNA;    metastatic colorectal cancer;    therapeutic response;    biomarker;   

DOI  :  10.3389/fgene.2019.00470

来源: DOAJ

【 摘 要 】

Early biomarkers of therapeutic responses can help optimize the treatment of metastatic colorectal cancers (mCRC). In this prospective exploratory study, we examined serial changes of plasma-circulating tumor DNA (ctDNA) in 41 mCRC patients receiving first-line chemotherapies and tested its association with treatment outcomes according to radiological assessments. Using next-generation sequencing technologies, we profiled somatic mutations in 50 cancer-related genes in ctDNA before each of the first four treatment cycles. We observed mutations in 95.7% of pre-treatment ctDNA samples. Using mutations of the maximal frequency in each pre-treatment plasma ctDNA sample as the candidate targets, we computed log2 fold changes of ctDNA levels between adjacent treatment cycles. We found that ctDNA reductions as early as prior to cycle 2 predicted responses after cycle 4. Log2 fold changes of ctDNA after cycle 1 (ctDNA log2 (C1/C0)) > −0.126 predicted progressive disease, with an accuracy of 94.6%. These patients also showed significantly worse progression-free survival than those with ctDNA log2 (C1/C0) ≤ −0.126 (median 2.0 vs. 9.0 months; P = 0.007). Together, the present exploratory study suggests that early changes in ctDNA levels detected via targeted sequencing are potential biomarkers of future treatment responses in mCRCs.

【 授权许可】

Unknown