Abstract
Escalated doses of radiotherapy associate with improved local control and overall survival (OS) in intrahepatic cholangiocarcinoma (iCCA), but personalization remains limited because conventional size-based CT criteria correlate poorly with outcomes. We hypothesized that quantitative enhancement measurements would better predict clinical outcomes and guide individualized RT optimization. In a retrospective cohort of 154 patients, we analyzed pre- and post-RT CT scans using quantitative European Association for Study of Liver (qEASL) to derive viable tumor volumes, comparing enhancement-based metrics with size-based RECIST and linking them to outcomes via survival and mathematical modeling. Change in enhancement volume was strongly associated with OS after adjustment, outperforming RECIST, and a ≥ 33% reduction optimally distinguished responders. From modeling analyses, the patient-specific tumor growth rate parameter emerged as the dominant mechanistic predictor, achieving 80.5% classification accuracy. Importantly, CT-derived mathematical parameters from this framework may inform RT planning and dose adaptation, particularly for resistant tumors, by bridging imaging with mechanistic insight.