2029 - Are We Misrepresenting Proton Minibeam Therapy Effectiveness through Physical Dose Metrics?
Presenter(s)
K. Dere1, A. C. Usta2, R. S. Kurnaz3, L. Lin4, Y. Yang5, M. Surucu5, and S. Charyyev5; 1Minerva University, San Francisco, CA, 2Bahcesehir College, Istanbul, Turkey, 3ENKA, Kocaeli, Turkey, 4Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, 5Department of Radiation Oncology, Stanford University, Stanford, CA
Purpose/Objective(s): The conventional implementation of proton spatially fractionated radiotherapy (SFRT) uses physical collimators with millimeter apertures to generate minibeams, creating alternating regions of high-dose peaks and low-dose valleys. Current evaluation of SFRT effectiveness predominantly relies on physical quantities, particularly the peak-to-valley dose ratio (PVDRPHYS). While high PVDRPHYS and low valley doses have been correlated with improved normal tissue sparing, this physical metric-based approach provides an incomplete picture of the treatment's biological impact. In this work, we aim to quantify biological dose for proton minibeams created using physical collimators and critically evaluate the adequacy of PVDRPHYS as compared to biologically weighted PVDRRBE.
Materials/Methods: Monte Carlo simulations using TOPAS were performed to model proton minibeam arrangements with 70 and 150 MeV monoenergetic beams. We investigated the impact of multiple collimator configurations (a total of 108) on PVDR: collimator thickness (3.25 and 6.35 cm), hole diameter (1-3 mm), center-to-center (c-t-c) distances (2-12 mm), and air gaps (5, 10, and 15 cm) between the collimator and water phantom. For each configuration, 3D dose and LET distributions were scored in water phantom, which were subsequently used for RBE calculation using the McNamara model with a/ß ratios of 3 and 10 Gy representing 'normal tissue' and 'tumor' responses, respectively. PVDR values were analyzed at two critical regions: at the Bragg peak depth in water (representing the 'tumor' region) and in the proximal plateau region before the Bragg peak (representing 'normal tissue') for each corresponding energy.
Results: Our comprehensive analysis revealed significant differences between physical and biological PVDRs across various configurations. PVDRRBE was consistently lower than PVDRPHYS, with reductions of 6-26% for 70 MeV beams and 1-17% for 150 MeV beams. The most pronounced differences were observed at shallow depths, smaller air gaps and larger c-t-c distances. To exemplify, for 70 MeV beams, the magnitude of PVDR reduction varied systematically with depth, c-t-c distance, and air gap: it diminished by 5-8% from shallow (1 cm) to deeper (3 cm) locations, intensified by 8-12% with c-t-c distance changing from 4 mm to 8 mm, and decreased by 9-10% when air gap increased from 5 cm to 15 cm.
Conclusion: The significant variations between PVDRPHYS and PVDRRBE across different beam energies, depths, and collimator configurations demonstrate that conventional PVDR calculations based solely on physical dose may not fully represent the biological impact of proton SFRT. These findings highlight the importance of incorporating radiobiological considerations when evaluating and optimizing proton minibeam therapy, potentially leading to more biologically informed treatment planning approaches.