Intensity-modulated proton therapy decreases dose to organs at risk in low-grade glioma patients: results of a multicentric in silico ROCOCO trial

Background and purpose: Patients with low-grade glioma (LGG) have a prolonged survival expectancy due to better discriminative tumor classification and multimodal treatment. Consequently, long-term treatment toxicity gains importance. Contemporary radiotherapy techniques such as intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), tomotherapy (TOMO) and intensity-modulated proton therapy (IMPT) enable high-dose irradiation of the target but they differ regarding delivered dose to organs at risk (OARs). The aim of this comparative in silico study was to determine these dosimetric differences in delivered doses. Material and methods: Imaging datasets of 25 LGG patients having undergone postoperative radiotherapy were included. For each of these patients, in silico treatment plans to a total dose of 50.4 Gy to the target volume were generated for the four treatment modalities investigated (i.e., IMRT, VMAT, TOMO, IMPT). Resulting treatment plans were analyzed regarding dose to target and surrounding OARs comparing IMRT, TOMO and IMPT to VMAT. Results: In total, 100 treatment plans (four per patient) were analyzed. Compared to VMAT, the IMPT mean dose (Dmean) for nine out of 10 (90%) OARs was statistically significantly (p Discussion: The low dose volume to the majority of OARs was significantly reduced when using IMPT compared to VMAT. Whether this will lead to a significant reduction in neurocognitive decline and improved quality of life is to be determined in carefully designed future clinical trials.

背景与目的：低级别胶质瘤（low-grade glioma, LGG）患者因肿瘤分类更精准、采用多模式治疗，生存预期得以延长。因此，长期治疗相关毒性愈发受到临床重视。当代放射治疗技术包括调强放射治疗（intensity-modulated radiotherapy, IMRT）、容积调强弧形治疗（volumetric modulated arc therapy, VMAT）、螺旋断层放疗（tomotherapy, TOMO）以及调强质子治疗（intensity-modulated proton therapy, IMPT），均可实现靶区高剂量照射，但在危及器官（organs at risk, OARs）的受照剂量方面存在差异。本计算机模拟（in silico）对比研究的目的即明确上述受照剂量的剂量学差异。
材料与方法：纳入25例接受术后放疗的低级别胶质瘤患者的影像数据集。针对每例患者，针对所研究的四种放疗方式（即IMRT、VMAT、TOMO、IMPT）分别生成靶区总剂量50.4 Gy的计算机模拟治疗计划。随后分析所生成的治疗计划的靶区及周围危及器官受照剂量，并将IMRT、TOMO、IMPT与VMAT进行对比。
结果：共分析100份治疗计划（每位患者4份）。与VMAT相比，IMPT组10个危及器官中有9个（90%）的平均剂量（Dmean）具有统计学显著差异（p
讨论：与VMAT相比，采用IMPT时多数危及器官的低剂量照射体积显著降低。这是否能显著降低神经认知功能减退并改善生活质量，尚需经过严谨设计的未来临床试验加以验证。