Integrating microdosimetric in vitro RBE models for particle therapy into TOPAS MC using the MicrOdosimetry-based modeling for RBE Assessment (MONAS) tool

TL;DR

The paper introduces MONAS, a TOPAS extension that integrates microdosimetric simulations with radiobiological models to predict cell survival and RBE in particle therapy, validated against experimental data and applied to clinical scenarios.

Contribution

MONAS is the first toolkit to combine microdosimetric spectra with multiple radiobiological models within TOPAS for RBE prediction in proton therapy.

Findings

MONAS accurately predicts dose-dependent RBE and cell survival.

The 3D RBE map shows higher RBE at the distal edge of the proton SOBP.

Validation against experimental spectra confirms the model's reliability.

Abstract

We present MONAS (MicrOdosimetry-based modelliNg for relative biological effectiveness (RBE) ASsessment) toolkit. MONAS is a TOPAS Monte Carlo extension, that combines simulations of microdosimetric distributions with radiobiological microdosimetry-based models for predicting cell survival curves and dose-dependent RBE. MONAS expands TOPAS microdosimetric extension, by including novel specific energy scorers. These spectra are used as physical input to three different formulations of the Microdosimetric Kinetic Model (MKM), and to the Generalized Stochastic Microdosimetric Model (GSM2), to predict dose-dependent cell survival fraction and RBE. MONAS predictions are then validated against experimental microdosimetric spectra and in vitro survival fraction data. We present two different applications of the code: i) the depth-RBE curve calculation from a passively scattered proton SOBP, and ii) the calculation of the 3D RBE distribution on a real head and neck patient geometry treated with protons. MONAS can estimate dose dependent RBE and cell survival curves from experimentally validated microdosimetric spectra with four clinically relevant radiobiological models. From the radiobiological characterization of a proton SOBP field, we observe the well-known trend of increasing RBE values at the distal edge of the radiation field. The 3D RBE map calculated confirmed the trend observed in the analysis of the SOBP, with the highest RBE values found in the distal edge of the target. MONAS extension offers a comprehensive microdosimetry-based framework for assessing the biological effects of particle radiation in both research and clinical environments, contributing to bridging the gap between a microdosimetric description of the radiation field and its application in proton therapy treatment with variable RBE.