Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom.
Department of Radiotherapy Physics, University College London Hospitals NHS Foundation Trust, London, United Kingdom.
Acta Oncol. 2019 Dec;58(12):1765-1774. doi: 10.1080/0284186X.2019.1653496. Epub 2019 Aug 20.
Pediatric craniopharyngioma, adult base-of-skull sarcoma and chordoma cases are all regarded as priority candidates for proton therapy. In this study, a dosimetric comparison between volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT) was first performed. We then investigated the impact of physical and biological uncertainties. We assessed whether IMPT plans remained dosimetrically superior when such uncertainty estimates were considered, especially with regards to sparing organs at risk (OARs). We studied 10 cases: four chondrosarcoma, two chordoma and four pediatric craniopharyngioma. VMAT and IMPT plans were created according to modality-specific protocols. For IMPT, we considered (i) variable RBE modeling using the McNamara model for different values of (/), and (ii) robustness analysis with ±3 mm set-up and 3.5% range uncertainties. When comparing the VMAT and IMPT plans, the dosimetric advantages of IMPT were clear: IMPT led to reduced integral dose and, typically, improved CTV coverage given our OAR constraints. When physical robustness analysis was performed for IMPT, some uncertainty scenarios worsened the CTV coverage but not usually beyond that achieved by VMAT. Certain scenarios caused OAR constraints to be exceeded, particularly for the brainstem and optical chiasm. However, variable RBE modeling predicted even more substantial hotspots, especially for low values of (/). Variable RBE modeling often prompted dose constraints to be exceeded for critical structures. For base-of-skull and pediatric craniopharyngioma cases, both physical and biological robustness analyses should be considered for IMPT: these analyses can substantially affect the sparing of OARs and comparisons against VMAT. All proton RBE modeling is subject to high levels of uncertainty, but the clinical community should remain cognizant possible RBE effects. Careful clinical and imaging follow-up, plus further research on end-of-range RBE mitigation strategies such as LET optimization, should be prioritized for these cohorts of proton patients.
儿科颅咽管瘤、成人颅底肉瘤和脊索瘤病例均被视为质子治疗的优先候选者。在本研究中，我们首次对容积调强弧形治疗（VMAT）和强度调制质子治疗（IMPT）进行了剂量学比较。然后，我们研究了物理和生物不确定性的影响。我们评估了在考虑这些不确定性估计时，IMPT 计划是否仍然在剂量学上具有优势，特别是在保护危及器官（OARs）方面。我们研究了 10 个病例：4 例软骨肉瘤、2 例脊索瘤和 4 例儿科颅咽管瘤。根据特定模式的方案创建了 VMAT 和 IMPT 计划。对于 IMPT，我们考虑了（i）使用 McNamara 模型针对不同 (/）值的可变 RBE 建模，以及（ii）带有±3mm 设置和 3.5%范围不确定性的稳健性分析。在比较 VMAT 和 IMPT 计划时，IMPT 的剂量学优势显而易见：与我们的 OAR 约束相比，IMPT 导致积分剂量降低，通常可以改善 CTV 覆盖。当对 IMPT 进行物理稳健性分析时，某些不确定性情况会降低 CTV 覆盖范围，但通常不会超过 VMAT 的水平。某些情况会导致 OAR 约束被超出，特别是对于脑干和视神经交叉。然而，可变 RBE 建模预测了更多的热点，尤其是对于低值 (/）。可变 RBE 建模通常会导致危及器官的剂量限制被超出。对于颅底和儿科颅咽管瘤病例，质子治疗的物理和生物稳健性分析都应该被考虑：这些分析会对 OAR 的保护和与 VMAT 的比较产生重大影响。所有质子 RBE 建模都存在高度的不确定性，但临床医生应该意识到可能的 RBE 影响。对于这些质子患者群体，应优先进行仔细的临床和影像学随访，以及进一步研究末端 RBE 缓解策略，如 LET 优化。
