Measurable imaging-based changes in enhancement of intrahepatic cholangiocarcinoma after radiotherapy reflect physical mechanisms of response
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.
Authors
- Michael Kevin Rooney (ORCID: https://orcid.org/0000-0002-2860-4653)
- Yun Shin Chun (ORCID: https://orcid.org/0000-0003-1384-8927)
- Emma B. Holliday (ORCID: https://orcid.org/0000-0002-4362-461X)
- Hop S. Tran Cao (ORCID: https://orcid.org/0000-0001-8612-8272)
- Ethan B. Ludmir (ORCID: https://orcid.org/0000-0002-5472-5344)
- Eugene J. Koay (ORCID: https://orcid.org/0000-0001-7675-3461)
- Hyunseon C. Kang (ORCID: https://orcid.org/0000-0001-5313-3526)
- Kanwal P. S. Raghav (ORCID: https://orcid.org/0000-0003-1311-4173)
- Vittorio Cristini (ORCID: https://orcid.org/0000-0002-7909-4278)
- Bruno Calazans Odisio (ORCID: https://orcid.org/0000-0002-1771-8233)
- Sonal S. Noticewala (ORCID: https://orcid.org/0000-0002-3153-0317)
- Prashant Dogra (ORCID: https://orcid.org/0000-0001-6722-7371)
- Mohamed Zaid (ORCID: https://orcid.org/0000-0002-8615-2456)
- Ahmed Omar Kaseb (ORCID: https://orcid.org/0000-0002-9491-0587)
- Dalia Elganainy (ORCID: https://orcid.org/0000-0003-4427-986X)
- Milind M. Javle (ORCID: https://orcid.org/0000-0001-9158-0941)
- Sunyoung S. Lee (ORCID: https://orcid.org/0000-0002-5954-5991)
- Grace L. Smith (ORCID: https://orcid.org/0000-0002-3171-2911)
- Kevin Sun (ORCID: https://orcid.org/0000-0003-3230-4319)
- Timothy Eric Newhook (ORCID: https://orcid.org/0000-0001-6663-459X)
- Albert C. Koong (ORCID: https://orcid.org/0000-0001-9824-1643)
- Ching‐Wei D. Tzeng (ORCID: https://orcid.org/0000-0001-6035-7288)
- Priya Bhosale (ORCID: https://orcid.org/0000-0003-4014-4941)
- Prajnan Das (ORCID: https://orcid.org/0000-0002-3845-0707)
- Bruce D. Minsky (ORCID: https://orcid.org/0000-0001-8434-7930)
- Brian De (ORCID: https://orcid.org/0000-0003-3468-3359)
- Zhihui Wang (ORCID: https://orcid.org/0000-0002-1212-8525)
- Charles Wang (ORCID: https://orcid.org/0000-0002-9865-1658)
- Enoch Chang (ORCID: https://orcid.org/0000-0002-2879-5445)
- J.-N. Vauthey
- Ahmed Amer
Institutions
- University of Southern California (US)
- Houston Methodist (US)
- The University of Texas MD Anderson Cancer Center (US)
- Cornell University (US)
Publication Details
- Journal
- npj Systems Biology and Applications
- Published
- 2025-12-12
- DOI
- https://doi.org/10.1038/s41540-025-00616-9
- Primary Topic
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Pancreatic Cancer Action Network
- RSNA Research and Education Foundation
- Radiological Society of North America
- Khalifa Bin Zayed Al Nahyan Foundation
- Warren Y. Soper Charitable Trust
- National Institutes of Health
- University of Texas MD Anderson Cancer Center
- National Cancer Institute