Antonious Z. Hazim, MD

A positive ctDNA result does not necessarily mean MRD. In NSCLC surveillance, 59% of patients with a positive methylation-based ctDNA result subsequently became negative, mostly without radiologic recurrence. Low-level signals around the assay’s detection limit were particularly unstable. In contrast, all three patients with clearly higher ctDNA fractions had confirmed recurrence. As ctDNA increasingly enters perioperative trials and potentially treatment decisions, perhaps the clinically relevant biomarker is not simply ctDNA+/−, but its level, persistence, and trajectory. A single low-level positive result may be a poor reason to label a patient as having molecular residual disease and escalate treatment. This is a small retrospective study, but an important warning against reducing MRD to a binary variable. I raised a similar concern when discussing SERENA-6. Unfortunately, it did not attract the editor’s interest at the time and was therefore not published in a “scientific journal.” Given the sometimes difficult-to-understand discretionary nature of editorial decisions, I have increasingly chosen to share some of my scientific views independently, as I did in the post below. jtocrr.org/article/S2666-364…