A novel framework for thermoradiotherapy treatment planning

Purpose Thermoradiotherapy combines radiotherapy with hyperthermia to increase therapeutic effectiveness. Currently, both modalities are optimized separately and in state-of-the-art research the enhanced therapeutic effect is evaluated using equivalent radiation dose in 2-Gy fractions (EQD2). This study proposes a novel thermoradiotherapy treatment planning framework with voxelwise EQD2 radiotherapy optimizing including thermal radiosensitization and direct thermal cytotoxicity. Methods To demonstrate proof-of-concept of the planning framework, three strategies consisting of 20 radiotherapy fractions were planned for four prostate cancer cases with substantially different temperature distributions: (1) Conventional radiotherapy plan of 60 Gy combined with four hyperthermia sessions (RT60+HT), (2) standalone uniform dose escalation to 68 Gy without hyperthermia (RT68), and (3) uniform target EQD2 that maximizes the tumor control probability (TCP) accounting for voxelwise thermal effects of four hyperthermia sessions without increasing normal tissue doses (RTHT+HT). Assessment included dose, EQD2, TCP, and rectal normal tissue complication probability (NTCP), alongside robustness analyses for TCP and NTCP against parameter uncertainties. Results The estimated TCP of around 76% for RT60 without hyperthermia was increased to an average of 85.9% (range: 81.3-90.5%) for RT60+HT, 92.5% (92.4-92.5%) for RT68 and 94.4% (91.7-96.6%) for RTHT+HT. The corresponding averaged rectal NTCPs were 8.7% (7.9-10.0%), 14.9% (13.8-17.1%) and 8.4% (7.5-9.7%), respectively. RT68 and RTHT+HT exhibited slightly enhanced TCP robustness against parameter uncertainties compared to RT60+HT, while RT68 presented higher and less robust rectal NTCP values compared to the other planning strategies. Conclusions This study introduces an innovative thermoradiotherapy planning approach, integrating thermal effects into EQD2-based radiotherapy optimization. Results demonstrate an ability to achieve enhanced and uniform target EQD2 and TCP across various temperature distributions without elevating normal tissue EQD2 or NTCP compared to conventional methods. While promising for improving clinical outcomes, realizable enhancements depend on accurate tumor- and tissue-specific data and precise quantification of hyperthermic effects, which are seamlessly integrable in the planning framework as they emerge.