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

Abstract

Purpose: 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. Materials and Methods: 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 (truey‒normalD) was measured under similar conditions as the cells by using a microdosimeter. Dose-averaged linear energy transfer (LETd) 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 (D6MV/Dp) that results in 50% (RBE0.5) and 10% (RBE0.1) cell survival, and survival after 2 Gy (RBE2Gy). Results: 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 truey‒normalD and LETd. Conclusion: Proton RBE was found to depend on mean proton energy, survival end point, and cell type. Changes in both truey‒normalD and LETd 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.

Exploring the advantages of intensity-modulated proton therapy: experimental validation of biological effects using two different beam intensity-modulation patterns

“…LET d is usually calculated using Monte Carlo particle tracking methods or analytical methods 12,[14][15][16][17] . The results of recent experiments have shown the increasing trend of RBE along the path of mono-energetic proton beams: slowly increasing in the entrance, but sharply increasing in the Bragg peak region [18][19][20][21] , which is similar to the spatial variation trend of LET d 12 . Therefore, it is believed that LET d may serve as a quantity connecting physical characteristics of beams and the biological effects in the biological samples.…”

Exploration and application of phenomenological RBE models for proton therapy

“…Some recent articles have included experiments and analysis of wide and narrow spectra with the same LETd value (Chaudhary et al 2014, Howard et al 2018, Grün et al 2019, Dahle et al 2017, however, all of these only give an illustration of the spectra.…”

Physical and biological impacts of collimator‐scattered protons in spot‐scanning proton therapy

“…The protons lose energy when hitting the collimator, and their linear energy transfer (LET) increases accordingly. A higher proton LET generates a greater biological effect, as observed in both in vivo and in vitro experiments and even in the clinical outcome . In the previously mentioned study, van Luijk et al estimated the increase of the biological damage based on a simple assumption that the protons with energy above 40 MeV have a relative biological effectiveness (RBE) of 1, while for those below 40 MeV have RBE of 1.2.…”