In a cohort biomarker study reported in JAMA Oncology, Tie et al showed that the circulating tumor DNA (ctDNA)-positive status after surgery and chemotherapy was associated with an increased risk of disease recurrence in patients with stage III colon cancer.
Study Details
The Australian multicenter study included 100 consecutive patients with newly diagnosed stage III colon cancer with R0 resection. All patients had a treatment plan for 24 weeks of standard adjuvant chemotherapy from November 2014 through May 2017. Patients with another malignant neoplasm diagnosed within the prior 3 years were excluded. Serial plasma samples were collected after surgery and after chemotherapy. Somatic mutations in individual patient tumors were identified by massively parallel sequencing of 15 genes commonly mutated in colorectal cancer, and personalized assays were used to quantify ctDNA.
The primary objective was assessment of ctDNA and recurrence-free interval.
KEY POINTS
- Postsurgical ctDNA-positive status was significantly associated with greater risk of recurrence.
- ctDNA-positive status after adjuvant chemotherapy was significantly associated with greater risk of recurrence.
ctDNA Status and Recurrence Risk
Among 96 evaluable patients, median follow-up was 28.9 months. At least one somatic mutation was identified in tumors of all 96 patients. ctDNA was detected in 20 (21%) of 96 postsurgical samples and was associated with inferior recurrence-free interval (hazard ratio [HR] = 3.8, P < .001). Estimated 3-year recurrence-free rates were 47% in patients with positive findings vs 76% in those with negative findings.
ctDNA was detected in 15 (17%) of 88 postchemotherapy samples and was associated with inferior recurrence-free interval (HR = 6.8, P < .001). Estimated 3-year recurrence free rates were 30% in patients with detectable ctDNA after chemotherapy vs 77% in those with undetectable ctDNA levels.
On multivariate analysis, postsurgical ctDNA-positive status was an independent predictor of recurrence after adjustment for clinicopathologic risk factors (HR = 7.5, P < .001).
The investigators concluded, “Results suggest that ctDNA analysis after surgery is a promising prognostic marker in stage III colon cancer. Postchemotherapy ctDNA analysis may define a patient subset that remains at high risk of recurrence despite completing standard adjuvant treatment. This high-risk population presents a unique opportunity to explore additional therapeutic approaches.”
Jeanne Tie, MD, of the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, Victoria, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by the Victorian Cancer Agency, US National Institutes of Health, Virginia and D. K. Ludwig Fund for Cancer Research, and John Templeton Foundation. For full disclosures of the study authors, visit jamanetwork.com.
