Studies Link Dynamic ctDNA Monitoring to Treatment Response in Gastroesophageal and Rectal Cancers
Studies in gastroesophageal and locally advanced rectal cancers linked dynamic ctDNA monitoring to treatment response and prognosis. MRD clearance, more than 90% ctDNA declines, and early ctDNA clearance were associated with better outcomes.
Dynamic ctDNA monitoring was linked to treatment response and prognosis in studies of gastroesophageal cancer and locally advanced rectal cancer. Findings from a retrospective analysis in gastroesophageal cancer and a biomarker substudy of the randomized COPEC trial in rectal cancer supported calls for prospective trials and ctDNA-guided treatment strategies.
In gastroesophageal cancer, existing data supported the potential value of ctDNA-based detection of minimal residual disease (MRD) in the locally advanced setting, while additional evidence was particularly needed in metastatic disease. A retrospective study published in Cancer found that patients whose MRD status converted from positive to negative, indicating clearance of detectable ctDNA, tended to experience more favorable outcomes than those who remained persistently MRD-positive. Patients who experienced more than a 90% decline in ctDNA values had better outcomes than those whose ctDNA levels remained stable or increased over time.
The gastroesophageal cancer analysis included ctDNA samples collected at varying time points rather than through a standardized prospective protocol, resulting in a relatively small patient population. The findings nevertheless provided signals regarding the prognostic value of MRD dynamics during treatment and underscored the need for prospective trials that systematically evaluate ctDNA monitoring during treatment.
In locally advanced rectal cancer, a biomarker substudy of the multicenter randomized COPEC trial enrolled 153 patients with low-/intermediate-risk disease. Plasma samples, totaling 526, were collected at baseline and after each cycle of neoadjuvant chemotherapy, and ctDNA was analyzed via tumor-informed sequencing. Patients were classified by dynamic status into high-risk groups with delayed or no clearance and recurred positivity, and low-risk groups with early clearance and persistent negativity.
No patient with high-risk ctDNA dynamics achieved a major pathologic response, defined as pathologic tumor regression grade 0 to 1. The poor response rate was 59.4% in the high-risk group versus 12.4% in the low-risk group, with high-risk dynamic ctDNA status identified as a strong independent predictor of poor response, with an odds ratio of 11.69 and a 95% confidence interval of 5 to 27.25. Delayed or no clearance and recurred positivity were also significant risk factors, and a single preoperative ctDNA-positive result predicted poor response with an odds ratio of 11.27.
The rectal cancer study said dynamic ctDNA monitoring identified patients at high risk for neoadjuvant chemotherapy failure as early as two cycles into treatment, which could form the basis for an adaptive trial design and eventual personalization of therapy selection. In gastroesophageal cancer, future research may help clarify whether ctDNA monitoring can serve as a reliable biomarker for treatment response, prognosis, and clinical decision-making in patients receiving modern therapeutic regimens.