Extension of TOPAS for the simulation of proton radiation effects considering molecular and cellular endpoints

Abstract

The aim of this work is to extend a widely used proton Monte Carlo tool, TOPAS, towards the modeling of relative biological effect (RBE) distributions in experimental arrangements as well as patients. TOPAS provides a software core which users configure by writing parameter files to, for instance, define application specific geometries and scoring conditions. Expert users may further extend TOPAS scoring capabilities by plugging in their own additional C++ code. This structure was utilized for the implementation of eight biophysical models suited to calculate proton RBE. As far as physics parameters are concerned, four of these models are based on the proton linear energy transfer (LET), while the others are based on DNA Double Strand Break (DSB) induction and the frequency-mean specific energy, lineal energy, or delta electron generated track structure. The biological input parameters for all models are typically inferred from fits of the models to radiobiological experiments. The model structures have been implemented in a coherent way within the TOPAS architecture. Their performance was validated against measured experimental data on proton RBE in a spread-out Bragg peak using V79 Chinese Hamster cells. This work is an important step in bringing biologically optimized treatment planning for proton therapy closer to the clinical practice as it will allow researchers to refine and compare pre-defined as well as user-defined models.

A phenomenological relative biological effectiveness (RBE) model for proton therapy based on all publishedin vitrocell survival data

“…TOPAS has previously been used to simulate both LET (Giantsoudi et al 2013, Sethi et al 2014, Grassberger et al 2011) and RBE distributions (Polster et al 2015) in patient environments. For this study, two patients were selected from the MGH clinical patient database, a pediatric head and neck patient as well as a prostate patient.…”

Radiobiological issues in proton therapy

“…Many of them were incorporated into a Monte Carlo simulation system by Polster, et al and are summarized in the reference cited [16]. Some of these models are based on the use of proton LET; whereas others are based on more fundamental quantities such as DNA double strand break induction, frequency-mean specific energy, lineal energy or track structure.…”

“…These models express proton α p and β p parameters as functions of dose, LET, α x and β x . Figure 4 compares the measured H460 lung cancer cell survival data of Guan et al [4] vs. calculations using seven different models (Wilkens and Oelfke [17], Wedenberg et al [18], Carabe-Fernandez et al [19], McNamara et al [20], Chen and Ahmad [21], and RMF [16,22,23]). Although these models are more advanced in that proton RBE increases as a function of LET, they are not able to explain the high non-linearity of RBE that has been observed in pre-clinical studies at higher LET at points beyond the Bragg peak.…”

Computational models and tools

“…). This leads to another important observation: for a given mixed radiation field and its LET‐spectrum, the contributions of each particle type to the RBE‐weighted dose are not directly additive, they have to be added by particle type using a dose averaged addition . The definition of RBE is an inherently macroscopic property.…”