Circulating tumor DNA dynamics and response to immunotherapy in colorectal cancer

Abstract

Circulating tumor DNA (ctDNA) is increasingly being investigated as a tool to detect minimal residual disease in resected, stage I-III colorectal cancer. Recent ctDNA studies have indicated that detection of ctDNA following surgery for resectable colorectal cancer confers a significantly higher risk of recurrence than those with negative ctDNA postoperatively. In those with postoperative ctDNA positivity, clearance of minimal residual disease with adjuvant chemotherapy is a positive prognostic indicator. Lastly, ctDNA has demonstrated superior sensitivity to the conventional blood tumor marker carcinoembryonic antigen (CEA) and can offer median lead times of up to 11 months for radiographic detection of recurrence during the surveillance of resected, stage I-III colorectal cancer. In metastatic colorectal cancer (mCRC), there is growing evidence to suggest that plasma ctDNA can be used to monitor tumor response to conventional chemotherapy as well. The present case series demonstrated that plasma ctDNA is a predictor of tumor response to immunotherapy in patients with mCRC that are microsatellite stable or microsatellite instability high. Plasma ctDNA could serve as a dynamic marker of immunotherapy response even in colorectal tumors that were CEA non-producers. Overall, these findings add to ongoing efforts to establish the role of plasma ctDNA in monitoring response to immunotherapy in CRC.

Predictive biomarkers of colon cancer immunotherapy: Present and future

“…In this study, patients’ KRAS, NRAS, BRAF, and EGFR-S492R mutation was analyzed through ctDNA, and the result show patients with RAS/BRAF WT ctDNA presented with better mOS and mPFS compared to patients with mutated ctDNA. These findings presented the potential role of ctDNA for colon cancer immunotherapy ( 181 ). However, the reports of ctDNA in the immunotherapy of colon cancer are still limited and ctDNA’s predictive role in immunotherapy needs to be verified by larger clinical studies.…”

POLE-Mutant Colon Cancer Treated with PD-1 Blockade Showing Clearance of Circulating Tumor DNA and Prolonged Disease-Free Interval

“…Furthermore, it is noteworthy that ctDNA was a more reliable marker for disease activity in this patient than CEA, which remained low throughout the treatment course due to his non-CEA-producing tumor. Early studies have suggested that plasma ctDNA could serve as a dynamic marker of tumor response to immunotherapy in patients with metastatic colorectal cancer that is both MSS and MSI-high [41]. A large, multicenter, prospective, observational study enrolling over 1500 patients with solid tumors is underway to evaluate the clinical utility of serial plasma ctDNA assessments on clinical decision-making inclusive of the continuation/discontinuation or intensification/de-intensification of immunotherapy in these patients [42].…”

Developments and current status of cell‐free DNA in the early detection and management of hepatocellular carcinoma

“…Conversely, an elevation in mSEPT9 levels aligns with tumor progression during immunotherapy. 69 However, it is worth noting that a corresponding investigation specific to HCC is lacking. There remains an unaddressed gap in clinical research pertaining to ctDNA in the context of immune checkpoint blockade therapy for patients with HCC.…”

“…The utilization of the methylated SEPTIN9 gene (mSEPT9) is prevalent in colorectal cancer, where a reduction in mSEPT9 levels is established as a sign of a positive tumor response to immunotherapy. Conversely, an elevation in mSEPT9 levels aligns with tumor progression during immunotherapy 69 . However, it is worth noting that a corresponding investigation specific to HCC is lacking.…”