热放射治疗将放射治疗与热疗相结合以提高治疗效果。目前，两种治疗方式均分别进行优化，并且在最先进的研究中，使用 2 Gy 分数 (EQD2) 中的等效辐射剂量来评估增强的治疗效果。本研究提出了一种新颖的热放射治疗计划框架，采用体素 EQD2 放射治疗优化，包括热放射增敏和直接热细胞毒性。为了证明该计划框架的概念验证，针对 4 例前列腺癌病例计划了由 20 个放射治疗部分组成的三种策略，其中不同的温度分布：(1) 60 Gy 的常规放疗计划结合四次热疗 (RT60 HT)，(2) 独立均匀剂量升级至 68 Gy，无热疗 (RT68)，(3) 使肿瘤最大化的统一目标 EQD2控制概率 (TCP) 解释了四次热疗过程的体素热效应，而不增加正常组织剂量 (RTHT HT)。评估包括剂量、EQD2、TCP 和直肠正常组织并发症概率 (NTCP)，以及针对参数不确定性对 TCP 和 NTCP 进行稳健性分析。未进行热疗的 RT60 的估计 TCP 约为 76%，增加至平均 85.9%（范围：RT60 HT 为 81.3-90.5%)，RT68 为 92.5% (92.4-92.5%)，RTHT HT 为 94.4% (91.7-96.6%)。相应的平均直肠 NTCP 分别为 8.7% (7.9-10.0%)、14.9% (13.8-17.1%) 和 8.4% (7.5-9.7%)。与 RT60 HT 相比，RT68 和 RTHT HT 对参数不确定性的 TCP 鲁棒性略有增强，而与其他计划策略相比，RT68 的直肠 NTCP 值更高且鲁棒性较差。本研究引入了一种创新的热放射治疗计划方法，将热效应集成到基于 EQD2 的方法中放射治疗优化。结果表明，与传统方法相比，能够在各种温度分布下实现增强且均匀的目标 EQD2 和 TCP，而不会提高正常组织 EQD2 或 NTCP。虽然有望改善临床结果，但可实现的增强取决于准确的肿瘤和组织特异性数据以及热效应的精确量化，这些数据在出现时可以无缝集成到规划框架中。版权所有 © 2024。由 Elsevier Inc. 出版。

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.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.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.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.Copyright © 2024. Published by Elsevier Inc.