Validating ctDNA in GE Cancer: Steps Toward Clinical Integration

In an interview with Targeted Oncology, Rutika Mehta, MD, MPH, associate professor of medicine and attending physician at Weill Cornell Medicine and NewYork-Presbyterian Hospital, discusses the key research gaps that must be addressed before circulating tumor DNA (ctDNA) testing can be more broadly integrated into routine clinical care for patients with gastroesophageal cancer.

Watch part 1 and part 2 of Dr Mehta’s interview.

While existing data support the potential value of ctDNA-based detection of minimal residual disease (MRD) in the locally advanced setting, Mehta notes that additional evidence is particularly needed in metastatic disease. As new systemic therapies continue to emerge, understanding how MRD testing interacts with these treatment strategies will be critical. 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.

Mehta highlights important limitations of her team’s study, which was published in Cancer. The analysis was retrospective, with ctDNA samples collected at varying time points rather than through a standardized prospective protocol. As a result, the study included a relatively small patient population. Despite these limitations, the findings provided several important signals regarding the prognostic value of MRD dynamics during treatment.

One key study observation was that patients whose MRD status converted from positive to negative—indicating clearance of detectable ctDNA—tended to experience more favorable outcomes compared with those who remained persistently MRD-positive.¹ In addition, large reductions in ctDNA levels appeared to correlate with improved prognosis. Specifically, 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.

According to Mehta, these findings underscore the need for prospective trials that systematically evaluate ctDNA monitoring during treatment. Such studies could help validate MRD dynamics as a clinically actionable biomarker and support broader adoption of ctDNA-guided strategies in gastroesophageal cancer management.

Read the full interview here.

REFERENCE

1. Mehta R, Rivero‐Hinojosa S, Dayyani F, et al. Circulating tumor DNA informs clinical practice in patients with recurrent/metastatic gastroesophageal cancers. Cancer. 2026;132(1). doi:10.1002/cncr.70242