Purpose: Using a biologically effective dose (BED) of ~100Gy has shown promising local control and overall survival in an initial trial combining SBRT with pembro(PMID: 29437535). Since higher BED has been shown to have better control rates and may introduce additional immune response triggering, itâ€™s hypothesized that further BED increase may improve outcome for SBRT+pembro. SBRT doses are limited by dosimetric constraints of surrounding organs-at-risk (OARs). This study seeks to determine if ultra-high radiation (BED>200Gy) could be safely planned/delivered to patients receiving SBRT+pembro, while still respecting OAR tolerances.
Methods: Five patients enrolled on an institutional phase I trial investigating safety of SBRT+pembro were analyzed. Based on trial protocol, gross tumor volumes (GTVs)>65cc were decreased to a 65cc subvolume (SubGTV). Clinical plans delivered 45Gy in 3fx (BEDâ‚?10â‚Ž=112.5Gy). For this study, Eclipse AcurosXB v11 was used to plan VMAT treatments prescribing 90Gy in 3fx (BEDâ‚?10â‚Ž=360Gy) using 6FFF and 10FFF beams, to the SubGTV. OAR objectives followed trial guidelines, with a SubGTV coverage goal V1â‚?100%â‚Ž>95%, and secondary goal Vâ‚?70%â‚Ž>99%. Seven partial/full arcs, automatic NTO, both min/max MU objectives, and external/internal ring structures to control dose fall off and buildup were used. OAR tolerances were prioritized over coverage. Plans were delivered to a QA phantom and evaluated using gamma analysis.
Results: The primary coverage goal was achieved for 4/5 and 3/5 plans utilizing 6FFF and 10FFF, respectively. All plans met secondary coverage goal and OAR constraints. SubGTV Dâ‚?100%â‚Ž ranged from BEDs of 167-504Gy (6FFF) and 106-470Gy (10FFF). While 10FFF vs. 6FFF target coverage decreased, 10FFF provided improved skin-sparing and 2X dose rate. Delivered plans passed gamma analysis (3%/1mm) with average rate of 98.14%.
Conclusion: VMAT plans with doses of BEDâ‚?10â‚Ž>300Gy to a GTV subvolume, while sufficiently sparing OARs, are feasible. This could provide better disease control and improve efficacy of concomitant SBRT and immunotherapy.
Not Applicable / None Entered.