Minimal residual disease monitoring via ctDNA: a case report of Lynch syndrome with synchronous colorectal cancer and review of literature.

Abstract

The investigation of circulating tumor DNA (ctDNA) as a substitute for minimal residual disease (MRD) has been a central focus in various clinical trials, with findings highlighting its effectiveness as a sensitive marker for detecting recurrence. In 2018, a joint review by the American Society of Clinical Oncology and the College of American Pathologists acknowledged a lack of current evidence guiding clinical decisions regarding ctDNA. Nevertheless, there are a multitude of ongoing studies exploring the future applications of ctDNA and its role in clinical decision making for select patient populations. The case presented involves a patient with Lynch syndrome who developed synchronous left-sided colorectal cancers (CRC). Each primary malignancy exhibited a distinct mutational profile, introducing complexity to the personalized tumor-informed assays used for quantifying ctDNA levels. Initial ctDNA levels were negative until the assay was calibrated to the transverse colon primary tumor. Unfortunately, surveillance imaging showed radiographic recurrence coinciding with positive ctDNA findings. Treatment with the anti-PD-1 inhibitor pembrolizumab was initiated, resulting in the clearance of ctDNA after just four cycles. As of now, there is no radiographic or biologic evidence indicating disease recurrence. This case study sheds light on the evolving landscape and current limitations of ctDNA as a surrogate for MRD. We describe a patient with synchronous CRC who had radiographic recurrence and a negative MRD assay. Current tumor-informed assays are limited in their capacity to detect a single tumor, and by nature can miss both synchronous and metachronous malignancies. Assays tailored to multiple tumors or utilizing tumor agnostic methods should be a part of clinical decision making in this patient population.