Author: Alexei V. Chvetsov, Pavitra Ramesh, Alexei V. Trofimov 👨🔬
Affiliation: Massachusetts General Hospital, University of Washington 🌍
Purpose: To investigate the effect of dose and depth dependence of relative biological effectiveness (RBE) on hypofractionated proton therapy for ocular melanoma using equivalent uniform RBE-weighted dose (EUDRBE).
Methods: The EUDRBE was formulated in this study to compare the integrated cell survival between radiotherapy modalities with nonuniform distributions of physical dose and RBE. There are several competing parameters that may affect the EUDRBE in hypofractionated proton therapy. First, the relatively short proton ranges are comparable to small tumor widths and shallow positioning of ocular treatments. Secondly, EUDRBE is sensitive to fractionation as a result of the dual radiation action theory, which states that higher LET radiation increases the linear component (α) of radiation damage, while the quadratic component (β) remains unchanged. These two changes were incorporated in the calculation of EUDRBE for cell line Mel 202 under several fractionation schedules.
Results: Our simulations for our model problem show that EUDRBE increases with the fraction of the tumor receiving distal edge high RBE, and that EUDRBE decreases with increasing dose per fraction. The combined effect of these two processes predicts that the EUDRBE is 8-10% larger than the physical dose for fractionation schedule 5 x 10 Gy (RBE). A slightly lower increase in the EUDRBE by 6-8% is observed for the fractionated schedules 5 x 14 Gy (RBE) and 4 x 15 Gy (RBE).
Conclusion: The increase in the RBE at the end of the proton range counteracts the decrease in the RBE for higher fractional proton dose, thus producing EUDRBE that is comparable to the clinically used uniform value of RBE=1.1. The calculated of EUDRBE highlights the importance of fractionation schedule and depth dependence of RBE and may impact tumor control. Lastly, this research can be applied to other tumors treated with hypofractionated modalities using high RBE.