Department of Radiation Oncology and Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, Heidelberg, Germany; Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany; National Center for Tumor Diseases (NCT), Heidelberg, Germany.
Department of Radiation Oncology and Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, Heidelberg, Germany; Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany; National Center for Tumor Diseases (NCT), Heidelberg, Germany; Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Radiother Oncol. 2024 Dec;201:110579. doi: 10.1016/j.radonc.2024.110579. Epub 2024 Oct 10.
Late-occurring contrast-enhancing brain lesions (CEBLs) have been observed on MRI follow-up in low-grade glioma (LGG) patients post-proton therapy. Predictive risk-models for this endpoint identified a dose-averaged linear energy transfer (LET)-dependent proton relative biological effectiveness (RBE) effect on CEBL occurrence and increased radiosensitivity of the cerebral periventricular region (VP). This work aimed to design a stable risk-minimizing treatment planning (TP) concept addressing these intertwined risk factors through a classically formulated optimization problem.
The concept was developed in RayStation-research 11B IonPG featuring a variable-RBE-based optimizer involving 20 LGG patients with varying target volume localizations and risk-factor contributions. Classical cost functions penalizing dose, dose-volume-histogram points, and equivalent uniform dose were used to formulate the optimization problem, and a new set of structures was introduced to actively spare the VP, control high LET regions, and de-escalate the dose outside the gross tumor volume. Target volume coverage and organ-at-risk sparing were robustly evaluated, and Normal Tissue Complication Probabilities (NTCP) for CEBL occurrence were quantified.
The concept yielded stable optimization outcomes for all considered subjects. Risk hot spots were successfully mitigated, and an NTCP reduction of up to 79 % was observed compared to conventional TP while maintaining target coverage, demonstrating the feasibility of the chosen model-based approach.
With the proposed TP protocol, we close the gap between predictive risk-modeling and practical risk-mitigation in the clinic and provide a concept for CEBL avoidance with the potential to advance treatment precision for LGG patients.
质子治疗后，低级别胶质瘤（LGG）患者的 MRI 随访中观察到迟发性增强脑病变（CEBL）。预测该终点的风险模型确定了剂量平均线性能量传递（LET）依赖性质子相对生物效应（RBE）对 CEBL 发生的影响，以及大脑脑室周围区域（VP）的放射敏感性增加。这项工作旨在通过经典优化问题设计一种稳定的风险最小化治疗计划（TP）概念，以解决这些相互交织的风险因素。
该概念是在 RayStation-research 11B IonPG 中开发的，具有基于可变 RBE 的优化器，涉及 20 名具有不同靶区定位和风险因素贡献的 LGG 患者。经典的成本函数惩罚剂量、剂量-体积直方图点和等效均匀剂量，用于制定优化问题，并引入了一组新的结构，以主动保护 VP、控制高 LET 区域和降低肿瘤体积外的剂量。对靶区覆盖率和器官风险保护进行了稳健评估，并量化了 CEBL 发生的正常组织并发症概率（NTCP）。
该概念为所有考虑的患者都产生了稳定的优化结果。成功减轻了风险热点，与传统 TP 相比，观察到 NTCP 降低了高达 79%，同时保持了靶区覆盖，证明了所选基于模型方法的可行性。
通过提出的 TP 方案，我们缩小了预测风险模型和临床实际风险缓解之间的差距，并提供了一种避免 CEBL 的概念，有可能提高 LGG 患者的治疗精度。
