Early biomarkers of therapeutic responses could help optimize the treatment of metastatic colorectal cancer (mCRC). This prospective exploratory study was designed to explore the serial changes in plasma-circulating tumor DNA (ctDNA) as an early marker of therapeutic response to systemic treatment in mCRC.
Forty-seven mCRC patients receiving standard first-line therapy every two weeks were enrolled. Somatic mutations in plasma ctDNA were detected serially before each of the first four cycles via next-generation sequencing, and the mutation of maximal frequency in pretreatment ctDNA was selected as the candidate mutation for analysis. Radiologic responses were assessed after the fourth cycle.
The results indicated that mutations in pretreatment ctDNA could be detected in 45 (95.7%) patients. Among the 41 patients monitored serially, imaging after four cycles of treatment showed 17 PR, 18 SD, and 6 PD cases. Changes in ctDNA could differentiate patients with progressive disease two cycles (approximately four weeks) earlier than the changes in CEA and CA19-9 levels could, and changes in ctDNA levels as early as prior to cycle 2 predicted the radiologic responses after cycle 4. A log2 value of fold-change in ctDNA after cycle 1 (log2 (C1/C0)) > -0.832 predicted progressive disease, with a sensitivity and specificity of 100.0% (95%CI: 54.1-100.0%) cand 85.7% (95%CI: 69.7-95.2%), respectively, and an accuracy of 87.8% (95%CI: 73.8-95.9%). Patients with ctDNA log2 (C1/C0) > -0.832 showed significantly worse progression-free survival than did those with log2 (C1/C0) ≤ -0.832 (median 2.5 versus 9.0 months; P = 0.016).
The present exploratory study suggests that early changes in ctDNA that are detected via targeted sequencing might potentially predict later radiologic responses in mCRC.
Clinical trial identification
Legal entity responsible for the study
Peking Union Medical College Hospital.
Has not received any funding.
All authors have declared no conflicts of interest.