Main Session
Sep 28
PQA 03 - Digital Health Innovation and Informatics, Patient Safety & Quality, and Radiation and Cancer Biology

2604 - A Functional Imaging-Guided Framework for Evaluating TCP and NTCP in Proton FLASH Radiotherapy

10:45am - 12:00pm ET
Poster Hall - Exhibit Hall A
Screen: 9
POSTER

Presenter(s)

Shucheng Shen, - Department of Graduate, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan,

S. Shen1, M. Li2, S. Sun3, W. Ruozheng4, T. Dai5, and Y. Yin1; 1Department of Radiation Oncology Physics and Technology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 2Department of Radiation Oncology Physics and Technology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, jinan, China, 3Department of Radiation Physics, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, jinan, China, 4Tumor Hospital of Xinjiang Uygur Autonomous Region, wulumuqi, xinjiang, China, 5Thayer School of Engineering, Dartmouth College, Hanover, NH

Purpose/Objective(s): To establish a novel evaluation framework that integrates individualized FMISO-PET functional imaging into Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) modeling for proton FLASH radiotherapy. This approach provides a first-of-its-kind quantitative basis for personalized efficacy prediction and clinical decision-making.

Materials/Methods: A FLASH sparing model was developed based on oxygen depletion kinetics to calculate voxel-level FLASH Sparing Effect (FSE) as a function of partial pressure of oxygen (PO2) and dose rate. We utilized a voxel-wise mapping technique to convert patient-specific FMISO-PET uptake values into 3D PO2 distributions. FLASH physical doses were converted to conventional equivalent doses (Deq) and subsequently to EQD2. Quantitative assessment of TCP and NTCP (for grade =2 radiation pneumonitis) was performed using generalized Equivalent Uniform Dose (gEUD), accounting for the heterogeneous oxygen landscape in non-small cell lung cancer (NSCLC) patients.

Results:

  • Voxel-Level Heterogeneity: FSE demonstrated a strong PO2 dependence, exceeding 1.7 in well-oxygenated normal tissues (PO2˜ 40 mmHg) while remaining near 1.0 in hypoxic tumor regions, directly revealing the biological "masking" effect of hypoxia on FLASH.

  • Expanded Therapeutic Window: Theoretical modeling indicated a relative reduction in NTCP of approximately 90% with only a minimal relative decrease in TCP (˜ 3%), significantly broadening the therapeutic index.

  • Patient-Specific Validation: Validation in NSCLC patients showed that central lesions benefited more significantly from FLASH (87-88% NTCP reduction) than peripheral lesions (83% reduction) due to the larger volume of normal tissue exposure. Individualized TCP variations (1–21% reduction) highlighted the necessity of PET-guided planning.

Conclusion: This study presents the first framework to quantify the FLASH effect by integrating patient-specific functional imaging with clinical prediction models. It offers a powerful tool for biological dose optimization and personalized treatment strategies in the era of proton FLASH therapy.