Biological adaptive radiotherapy for short-time dose compensation in lung SBRT patients

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_50% of the gross tumor volume (GTV) and from 16.4% to 24.9% for D_98% of the PTV. After applying BART, the differences were minimized to -1.5% to -0.6% for D_50% of the GTV and -0.1% to 0.9% for D_98% 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_50% of the GTV and -12.3% to -7.3% for D_98% of the PTV. The volume differences between the BART plan and the plan without interruption remained within -0.8% to -0.4% for V_5Gy and -0.2% to 0.0% for V_20Gy, while differences between the BART and compensated PD plans were similarly small. The maximum dose to the spinal cord (D_0.1cc) 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.