Circulating Tumor DNA Response and Minimal Residual Disease Assessment in DNA Polymerase Epsilon-Mutated Colorectal Cancer Undergoing Immunotherapy

Exonuclease domain mutation (EDM) in polymerase epsilon (POLE)-mutated colorectal cancer patients is characterized by specific clinical features and a very high tumor mutation burden (TMB). The therapeutic effectiveness of immune checkpoint inhibitors (ICIs) for the treatment of colorectal cancer in patients with POLE mutations is poorly defined. Our case represents a young-onset colon cancer patient who has had a continued response to programmed cell death protein 1 (PD1) blockade alongside clearance of circulating tumor DNA (ctDNA) using a tumor-informed approach. Utilizing ctDNA kinetics to assess minimal residual disease (MRD) in the context of colorectal cancer is a very important topic. Furthermore, utilizing ctDNA kinetics in response to immunotherapy is something that is relevant to all tumor types undergoing immunotherapy. Recently, several landmark articles have proposed this as a promising approach. There is, however, limited information in the literature showing the feasibility of such an approach. Our case report is going to be of value, both from a scientific as well as a clinical standpoint. This is particularly relevant given the rise of colorectal cancers in young individuals.