Association of high postoperative physical activity with ctDNA MRD positivity and recurrence-free survival across solid tumors: The SCRUM-MONSTAR LIFELOG study.

Abstract

10540 Background: Physical activity is associated with improved survival across multiple cancer types, yet its relationship with molecular residual disease (MRD) detected by circulating tumor DNA (ctDNA) remains unclear. We examined whether objectively measured physical activity correlates with postoperative ctDNA status. Methods: The LIFELOG study, ancillary to MONSTAR-SCREEN-3, enrolled patients who underwent curative surgery for solid tumors. Participants wore a wrist-based device targeting 1 month during the early postoperative period. Accelerometer and photoplethysmography data were processed to derive metrics including mean acceleration, moderate-to-vigorous physical activity (MVPA) percentage, longest MVPA bout, and high-intensity heart rate zone percentage. K-means clustering (k=3) classified patients into activity phenotypes. ctDNA was assessed serially using an ultra-sensitive whole-genome sequencing-based MRD assay (Myriad Genetics). ctDNA positivity at 1 and 3 months postoperatively were compared between activity phenotypes, with overlap weighting used to adjust for potential confounders. Results: Of 127 enrolled patients, 4 were excluded due to no device data, leaving 123 for analysis. Adequate wear time (≥10 hours/day on ≥3 days/week) was achieved in 113 patients (91.9%). Cancer types included colorectal (n=29), urothelial (n=24), hepatocellular (n=13), gastric (n=11), renal (n=11), and others (n=35). Median age was 70.1 years; 57.7% were male; 46.3% had stage III-IV disease. Clustering identified three phenotypes: Cluster 1 (high activity; n=10), Cluster 2 (moderate; n=53), and Cluster 3 (low; n=60). Activity metrics differed across clusters (any P<0.001). Cluster 3 had significantly inferior recurrence-free survival compared with Clusters 1+2 (hazard ratio 4.01; 95% confidence interval, 1.10-14.6; P=0.035). Postoperative ctDNA positivity was significantly higher in Cluster 3 compared with Clusters 1+2 at both 1 month (32.5% vs 6.4%; P=0.002) and 3 months (30.0% vs 2.4%; P<0.001). At 3 months, this difference persisted after adjustment for age, sex, adjuvant chemotherapy, stage, and cancer type (P=0.003). Among 80 patients with evaluable ctDNA data at both 1 and 3 months, of 15 patients who were ctDNA-positive at 1 month; conversion to ctDNA-negative at 3 months was observed in 66.7% in Clusters 1+2 versus 16.7% in Cluster 3 (P=0.15). Of 65 patients who were ctDNA-negative at 1 month; conversion to ctDNA-positive at 3 months was observed in 0% in Clusters 1+2 versus 7.7% in Cluster 3 (P=0.16). Conclusions: Lower objectively measured physical activity was associated with higher postoperative ctDNA positivity rates and inferior recurrence-free survival. These findings warrant validation in larger cohorts and investigation of exercise-based interventions in postoperative cancer care.