Dale Jon Espen, Molinelli Silvia, Vischioni Barbara, Vitolo Viviana, Bonora Maria, Magro Giuseppe, Mairani Andrea, Hasegawa Azusa, Ohno Tatsuya, Dahl Olav, Valvo Francesca, Fossati Piero
Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway.
Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.
Front Oncol. 2020 Nov 24;10:531344. doi: 10.3389/fonc.2020.531344. eCollection 2020.
The Italian (CNAO) has applied dose constraints for carbon ion RT (CIRT) as defined by Japan's (NIRS). However, these institutions use different models to predict the (RBE). CNAO applies the (LEM I), which in most clinical situations predicts higher RBE than NIRS's (MKM). Equal constraints therefore become more restrictive at CNAO. Tolerance doses for the brainstem have not been validated for LEM I-weighted dose ( ). However, brainstem constraints and a (NTCP) model were recently reported for MKM-weighted dose ( ), showing that a constraint relaxation to <30 Gy (RBE) and <40 Gy (RBE) was feasible. The aim of this work was to evaluate the brainstem NTCP associated with CNAO's current clinical practice and to propose new brainstem constraints for LEM I-optimized CIRT at CNAO.
We reproduced the absorbed dose of 30 representative patient treatment plans from CNAO. Subsequently, we calculated both and , and the relationship between and for various brainstem dose metrics was analyzed. Furthermore, the NTCP model developed for was applied to estimate the NTCPs of the delivered plans.
The translation of CNAO treatment plans to confirmed that the former CNAO constraints were conservative compared with constraints. Estimated NTCPs were 0% for all but one case, in which the NTCP was 2%. The relationship / could be described by a quadratic regression model which revealed that the validated constraints corresponded to <41 Gy (RBE) (95% CI, 38-44 Gy (RBE)) and <49 Gy (RBE) (95% CI, 46-52 Gy (RBE)).
Our study demonstrates that RBE-weighted dose translation is of crucial importance in order to exchange experience and thus harmonize CIRT treatments globally. To mitigate uncertainties involved, we propose to use the lower bound of the 95% CI of the translation estimates, , <38 Gy (RBE) and <46 Gy (RBE) as brainstem dose constraints for 16 fraction CIRT treatments optimized with LEM I.
意大利国立肿瘤研究所(CNAO)已采用日本国立放射科学研究所(NIRS)定义的碳离子放疗(CIRT)剂量限制。然而,这些机构使用不同模型来预测相对生物学效应(RBE)。CNAO应用线性能量传递模型I(LEM I),在大多数临床情况下,该模型预测的RBE高于NIRS的多能模型(MKM)。因此,相同的限制在CNAO变得更具限制性。尚未对脑干的耐受剂量进行LEM I加权剂量()的验证。然而,最近报道了针对MKM加权剂量()的脑干限制和正常组织并发症概率(NTCP)模型,表明将限制放宽至Dmax<30 Gy(RBE)和Dmean<40 Gy(RBE)是可行的。本研究的目的是评估与CNAO当前临床实践相关的脑干NTCP,并为CNAO的LEM I优化CIRT提出新的脑干限制。
我们重现了CNAO的30个代表性患者治疗计划的吸收剂量。随后,我们计算了Dmax和Dmean,并分析了各种脑干剂量指标下Dmax与Dmean之间的关系。此外,应用针对MKM开发的NTCP模型来估计所交付计划的NTCP。
将CNAO治疗计划转换为MKM证实,与MKM限制相比,CNAO以前的限制较为保守。除1例NTCP为2%外,所有病例的估计NTCP均为0%。Dmax/Dmean关系可用二次回归模型描述,该模型表明,经验证的MKM限制对应于Dmax<41 Gy(RBE)(95%置信区间,38 - 44 Gy(RBE))和Dmean<49 Gy(RBE)(95%置信区间,46 - 52 Gy(RBE))。
我们的研究表明,为了交流经验并在全球范围内协调CIRT治疗,RBE加权剂量转换至关重要。为了减轻所涉及的不确定性,我们建议将转换估计值95%置信区间的下限,即Dmax<38 Gy(RBE)和Dmean<46 Gy(RBE)用作LEM I优化的16分割CIRT治疗的脑干剂量限制。