Moving Beyond a Generic Rbe: Experimental Validation of GSM2 for Clinical Proton Therapy
Abstract
Purpose
Proton therapy plans are optimized by relating the delivered dose to an equivalent photon dose using the Relative Biological Effectiveness (RBE). Clinically, a constant RBE of 1.1 is assumed, despite evidence that RBE varies along the proton beam path. Accurately accounting for this variability in treatment planning requires a robust RBE model. The Generalized Stochastic Microdosimetric Model (GSM2) predicts cell survival fraction (SF) and RBE based on microdosimetric principles. This study evaluates the accuracy of GSM2 by comparing predicted SF and RBE with experimental measurements and established RBE models.
Methods
In-vitro experiments were conducted at two clinical proton beams, at the University of Miami and MD-Anderson using osteosarcoma, pancreatic, and lung cancer cells. Cells received doses of radiation at increasing depths along the beam’s path, corresponding to different radiation qualities. To vary the doses, a PMMA wedge with six sections of different thicknesses was placed in front of the cell plate. Following irradiation, the SF was calculated for each section. RBE was evaluated using the SF from 250 kVp reference x-rays. Microdosimetry experiments were conducted to measure the radiation quality received by the cells, recorded spectra were input into GSM2 to predict SF and RBE.
Results
Results from the H460 cells show good agreement between model predictions and experimental values. The model predicted RBEs of 1.27, 1.19, and 0.95 in the distal region, Bragg peak, and at beam entry, respectively, compared with experimental values of 1.35, 1.13, and 0.93. Overall, the model outperformed established approaches such as the Saturation Corrected Microdosimetric Kinetic Model (SC-MKM), which predicted RBEs of 1.12, 1.08, and 1.02 at the same positions.
Conclusion
Our study supports the potential of GSM2 as a robust model for predicting variable RBE in clinical settings, paving the way for more personalized and biologically optimized proton therapy treatment plans.