OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology - OncoRay, Dresden, Germany.
OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology - OncoRay, Dresden, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; National Center for Tumour Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and; Helmholtz Association / Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany; German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Radiother Oncol. 2023 Jan;178:109422. doi: 10.1016/j.radonc.2022.11.011. Epub 2022 Nov 23.
Currently, there is an intense debate on variations in intra-cerebral radiosensitivity and relative biological effectiveness (RBE) in proton therapy of primary brain tumours. Here, both effects were retrospectively investigated using late radiation-induced brain injuries (RIBI) observed in follow-up after proton therapy of patients with diagnosed glioma.
In total, 42 WHO grade 2-3 glioma patients out of a consecutive patient cohort having received (adjuvant) proton radio(chemo)therapy between 2014 and 2017 were eligible for analysis. RIBI lesions (symptomatic or clinically asymptomatic) were diagnosed and delineated on contrast-enhanced T1-weighted magnetic resonance imaging scans obtained in the first two years of follow-up. Correlation of RIBI location and occurrence with dose (D), proton dose-averaged linear energy transfer (LET) and variable RBE dose parameters were tested in voxel- and in patient-wise logistic regression analyses. Additionally, anatomical and clinical parameters were considered. Model performance was estimated through cross-validated area-under-the-curve (AUC) values.
In total, 64 RIBI lesions were diagnosed in 21 patients. The median time between start of proton radio(chemo)therapy and RIBI appearance was 10.2 months. Median distances of the RIBI volume centres to the cerebral ventricles and to the clinical target volume border were 2.1 mm and 1.3 mm, respectively. In voxel-wise regression, the multivariable model with D, D × LET and periventricular region (PVR) revealed the highest AUC of 0.90 (95 % confidence interval: 0.89-0.91) while the corresponding model without D × LET revealed a value of 0.84 (0.83-0.86). In patient-level analysis, the equivalent uniform dose (EUD, a = 11) in the PVR using a variable RBE was the most prominent predictor for RIBI with an AUC of 0.63 (0.32-0.90).
In this glioma cohort, an increased radiosensitivity within the PVR was observed as well as a spatial correlation of RIBI with an increased RBE. Both need to be considered when delivering radio(chemo)therapy using proton beams.
目前，在原发性脑肿瘤的质子治疗中，关于颅内放射敏感性和相对生物效应（RBE）的变化存在激烈的争论。在这里，我们使用在 2014 年至 2017 年间接受诊断为胶质瘤的患者进行质子放射（化疗）治疗后的随访中观察到的迟发性放射性脑损伤（RIBI）来回顾性地研究这两种效应。
共有 42 名世界卫生组织（WHO）2-3 级胶质瘤患者符合分析条件，这些患者来自 2014 年至 2017 年间接受（辅助）质子放射（化疗）的连续患者队列。在随访的头两年，通过对比增强 T1 加权磁共振成像扫描来诊断和描绘 RIBI 病变（有症状或无症状）。在体素和患者水平的逻辑回归分析中，测试了 RIBI 位置和发生与剂量（D）、质子剂量平均线性能量传递（LET）和可变 RBE 剂量参数的相关性。此外，还考虑了解剖学和临床参数。通过交叉验证的曲线下面积（AUC）值来估计模型性能。
共诊断出 21 名患者的 64 个 RIBI 病变。质子放射（化疗）开始与 RIBI 出现之间的中位时间为 10.2 个月。RIBI 体积中心到脑室内和到临床靶区边界的中位距离分别为 2.1 毫米和 1.3 毫米。在体素水平回归中，D、D×LET 和脑室周围区域（PVR）的多变量模型显示出最高的 AUC 为 0.90（95%置信区间：0.89-0.91），而没有 D×LET 的相应模型显示 AUC 为 0.84（0.83-0.86）。在患者水平分析中，PVR 中使用可变 RBE 的等效均匀剂量（EUD，a=11）是 RIBI 的最显著预测因子，AUC 为 0.63（0.32-0.90）。
在这个胶质瘤队列中，观察到 PVR 内放射敏感性增加，以及 RIBI 与增加的 RBE 之间的空间相关性。在使用质子束进行放射（化疗）时，这两者都需要考虑。
