背景:经典的辐射协议是由在目标上均匀递送的物理剂量引导的。选择方案以将正常组织并发症概率(NTCP)保持在可接受的水平。与目标体积相邻的危险器官(OAR)可能导致肿瘤剂量不足和肿瘤控制概率(TCP)降低。我们研究的目的是探索基于生物学的剂量递增:通过保持OAR的NTCP恒定,辐射剂量要最大化,允许导致不均匀的剂量分布。
方法:我们使用了25只患有脑肿瘤的狗的计算机断层扫描数据集,先前用10x4Gy(40Gy至PTVD50)治疗。我们为每位患者制定了3个计划:A)原始治疗计划,剂量分布均匀,B)异质剂量分布,严格遵守与A)中相同的NTCP,和C)粘附于NTCP<5%的异质剂量分布。对于计划比较,计算TCP和TCP等效剂量(导致相同TCP的均匀目标剂量)。为了能够在计划优化中使用肿瘤靶的广义等效均匀剂量(gEUD)度量,计算的TCP值用于获得体积效应参数a。
结果:如预期的,所有OAR的NTCP与计划A)到B)没有区别。在计划C)中,然而,NTCPs显著高于大脑(平均2.5%(SD±1.9,95CI:1.7,3.3),p<0.001),视交叉(平均2.0%(SD±2.2,95CI:1.0,2.8),p=0.010)与计划A)相比,但是没有发现脑干的显著增加。对于25名被评估患者中的24名,与同质计划A)相比,异质计划B)和C)导致目标剂量增加和预计TCP增加。此外,预测的个体TCP值作为剂量函数的分布与群体TCP模型非常吻合.
结论:我们的研究是风险适应性辐射剂量优化的第一步。该策略利用基于TCP和NTCP的生物目标函数而不是基于物理剂量约束的目标函数。
BACKGROUND: Classical radiation protocols are guided by physical dose delivered homogeneously over the target. Protocols are chosen to keep normal tissue complication probability (NTCP) at an acceptable level. Organs at risk (OAR) adjacent to the target volume could lead to underdosage of the tumor and a decrease of tumor control probability (TCP). The intent of our
study was to explore a biology-based dose escalation: by keeping NTCP for OAR constant, radiation dose was to be maximized, allowing to result in heterogeneous dose distributions.
METHODS: We used computed tomography datasets of 25 dogs with brain tumors, previously treated with 10x4 Gy (40 Gy to PTV D50). We generated 3 plans for each patient: A) original treatment plan with homogeneous dose distribution, B) heterogeneous dose distribution with strict adherence to the same NTCPs as in A), and C) heterogeneous dose distribution with adherence to NTCP <5%. For plan comparison, TCPs and TCP equivalent doses (homogenous target dose which results in the same TCP) were calculated. To enable the use of the generalized equivalent uniform dose (gEUD) metric of the tumor target in plan optimization, the calculated TCP values were used to obtain the volume effect parameter a.
RESULTS: As intended, NTCPs for all OARs did not differ from plan A) to B). In plan C), however, NTCPs were significantly higher for brain (mean 2.5% (SD±1.9, 95%CI: 1.7,3.3), p<0.001), optic chiasm (mean 2.0% (SD±2.2, 95%CI: 1.0,2.8), p=0.010) compared to plan A), but no significant increase was found for the brainstem. For 24 of 25 of the evaluated patients, the heterogenous plans B) and C) led to an increase in target dose and projected increase in TCP compared to the homogenous plan A). Furthermore, the distribution of the projected individual TCP values as a function of the dose was found to be in good agreement with the population TCP model.
CONCLUSIONS: Our
study is a first step towards risk-adaptive radiation dose optimization. This strategy utilizes a biologic objective function based on TCP and NTCP instead of an objective function based on physical dose constraints.