Kawahara Daisuke, Koganezawa Akito S, Yamaguchi Hikaru, Wada Takuya, Murakami Yuji
Department of Radiation Oncology, Hiroshima University Hospital, Hiroshima, Japan.
Department of Information and Electronic Engineering, Faculty of Science and Engineering, Teikyo University, Tochigi, Japan.
Med Phys. 2025 Apr 14. doi: 10.1002/mp.17820.
Conventional adaptive radiation therapy (ART) primarily focuses on adapting to anatomical changes during radiation therapy but does not account for biological effects such as changes in radiosensitivity and tumor response, particularly during treatment interruptions. These interruptions may allow sublethal damage repair in tumor cells, reducing the effectiveness of stereotactic body radiation therapy (SBRT).
The aim of this study was to develop and evaluate a novel biological adaptive radiotherapy (BART) framework to compensate for the biological effects of radiation interruptions during SBRT for lung cancer.
This study involved lung SBRT patients using volumetric modulated arc therapy. We evaluated the biological dose loss using a microdosimetric kinetic model during four interruption durations (30, 60, 90, and 120 min). The reduction in the biological dose due to interruptions was calculated. The physical dose was calculated from the decreased biological dose in the in-house software, which was incorporated into the TPS. The optimization process was conducted for dose compensation in the TPS. To quantitatively assess the impact of BART on dose distribution, we evaluated the differences in target dose coverage and organ-at-risk (OAR) exposure between the original plan (without interruption), the plan with interruption, the BART plan, and the plan summing the dose before the interruption and the physical dose after compensation (compensated PD plan). The compensated PD plan assumed no biological dose reduction before the interruption.
Without BART compensation, interruptions of 30, 60, 90, and 120 min resulted in biological dose reductions, ranging from 12.1% to 19.0% for D of the gross tumor volume (GTV) and from 16.4% to 24.9% for D of the PTV. After applying BART, the differences were minimized to -1.5% to -0.6% for D of the GTV and -0.1% to 0.9% for D of the PTV. In contrast, the compensated PD plan exhibited larger residual deviations, with dose differences ranging from -9.9% to -14.0% for D of the GTV and -12.3% to -7.3% for D of the PTV. The volume differences between the BART plan and the plan without interruption remained within -0.8% to -0.4% for V and -0.2% to 0.0% for V, while differences between the BART and compensated PD plans were similarly small. The maximum dose to the spinal cord (D) also remained within -0.2 to 0.1 Gy for the BART plan relative to the plan without interruption and -0.1 to -0.5 Gy compared to the compensated PD plan. These results confirm that the OAR doses remained within clinically acceptable constraints across all evaluated plans.
This study demonstrated that the BART framework effectively compensates for the biological dose reduction caused by interruptions during lung cancer SBRT. BART successfully maintained target dose coverage and minimized biological dose loss for the target, while keeping OAR doses within safe limits, including for the lungs and spinal cord. The introduction of BART marks a significant advancement in adaptive radiotherapy, offering a comprehensive approach to managing interruptions and improving clinical outcomes.
传统的自适应放射治疗(ART)主要侧重于适应放射治疗期间的解剖学变化,但未考虑生物效应,如放射敏感性和肿瘤反应的变化,尤其是在治疗中断期间。这些中断可能使肿瘤细胞中的亚致死损伤得以修复,降低立体定向体部放射治疗(SBRT)的有效性。
本研究的目的是开发并评估一种新型的生物自适应放射治疗(BART)框架,以补偿肺癌SBRT期间放射中断的生物效应。
本研究纳入了采用容积调强弧形治疗的肺癌SBRT患者。我们使用微剂量动力学模型评估了四个中断时长(30、60、90和120分钟)期间的生物剂量损失。计算了因中断导致的生物剂量减少量。根据内部软件中降低后的生物剂量计算物理剂量,并将其纳入治疗计划系统(TPS)。在TPS中进行剂量补偿的优化过程。为了定量评估BART对剂量分布的影响,我们评估了原始计划(无中断)、有中断计划、BART计划以及将中断前剂量与补偿后的物理剂量相加的计划(补偿后的物理剂量计划)之间靶区剂量覆盖和危及器官(OAR)受照剂量的差异。补偿后的物理剂量计划假定中断前生物剂量无减少。
在没有BART补偿的情况下,30、60、90和120分钟的中断导致生物剂量减少,大体肿瘤体积(GTV)的D值减少幅度为12.1%至19.0%,计划靶体积(PTV)的D值减少幅度为16.4%至24.9%。应用BART后,GTV的D值差异最小化至-1.5%至-0.6%,PTV的D值差异最小化至-0.1%至0.9%。相比之下,补偿后的物理剂量计划表现出更大的残余偏差,GTV的D值差异范围为-9.9%至-14.0%,PTV的D值差异范围为-12.3%至-7.3%。BART计划与无中断计划之间的体积差异,V值保持在-0.8%至-0.4%之间,V值保持在-0.2%至0.0%之间,而BART计划与补偿后的物理剂量计划之间的差异同样较小。相对于无中断计划,BART计划对脊髓的最大剂量(D)也保持在-0.2至0.1 Gy范围内,与补偿后的物理剂量计划相比为-0.1至-0.5 Gy。这些结果证实,在所有评估计划中,OAR剂量均保持在临床可接受的范围内。
本研究表明,BART框架有效补偿了肺癌SBRT期间中断导致的生物剂量减少。BART成功维持了靶区剂量覆盖,并将靶区的生物剂量损失降至最低,同时将OAR剂量保持在安全范围内,包括肺部和脊髓。BART的引入标志着自适应放射治疗的重大进展,为管理中断和改善临床结果提供了一种全面的方法。