Investigating Dependencies of Relative Biological Effectiveness for Proton Therapy in Cancer Cells

Relative biological effectiveness (RBE) accounts for the differences in biological effect from different radiation types. The RBE for proton therapy remains uncertain, as it has been shown to vary from the clinically used value of 1.1. In this work we investigated the RBE of protons and correlated the biological differences with the underlying physical quantities.

Three cell lines were irradiated (CHO, Chinese hamster ovary; A549, human lung adenocarcinoma; and T98, human glioma) and assessed for cell survival by using clonogenic assay. Cells were irradiated with 71- and 160-MeV protons at depths along the Bragg curve and 6-MV photons to various doses. The dose-averaged lineal energy ( ${\stackrel{‒}{y}}_D$ ) was measured under similar conditions as the cells by using a microdosimeter. Dose-averaged linear energy transfer (LET_d) was also calculated by using Monte Carlo (MC) simulations. Survival data were fit by using the linear quadratic model. The RBE values were calculated by comparing the physical dose (D_6MV/D_p) that results in 50% (RBE_0.5) and 10% (RBE_0.1) cell survival, and survival after 2 Gy (RBE_2Gy).

Proton RBE values ranged from 0.89 to 2.40. The RBE for all 3 cell lines increased with decreasing proton energy and was higher at 50% survival than at 10% survival. Additionally, both A549 and T98 cells generally had higher RBE values relative to the CHO cells, indicating a greater biological response to protons. An increase in RBE corresponded with an increase in ${\stackrel{‒}{y}}_D$ and LET_d.

Proton RBE was found to depend on mean proton energy, survival end point, and cell type. Changes in both ${\stackrel{‒}{y}}_D$ and LET_d were also found to impact proton RBE values, but consideration of the energy spectrum may provide additional information. The RBE values in this study vary greatly, indicating the clinical value of 1.1 may not be suitable in all cases.