A dedicated MKM-based radiobiological model for secondary cancer estimation in charged particle radiotherapy: An application in lymphomas and breast proton therapy.

Abstract

To introduce a new model formalism for the assessment of secondary cancer (SC) risk after proton therapy, accounting explicitly for the specific radiation quality of the beam, and to present results of a first application to two patient cohorts. A dedicated adaptation of the microdosimetric kinetic model (MKM) model was combined with the Schneider model for excess absolute risk (EAR) calculation, extending its applicability from reference photon radiation to charged particles with different values of linear energy transfer. Plans for proton treatment of Lymphoma and Breast targets were recalculated with a Monte Carlo tool (TOPAS) to obtain voxel-by-voxel radiation quality distributions. To feed the model for computing an RBE for the specific endpoint of radiation-induced mutations, this information was joined with epidemiology-based parameterization to compute the EAR for the different patients, organs, and for different tentative α/β values of the involved tissues. A non-negligible impact of the explicit integration of RBE in the proposed model, as compared to estimates without (i.e. plain Schneider approach) is evident in all evaluated cases, with a strong impact of the α/β value for mutation induction. Lower levels of α/β ratio correlate with larger effects of the LET correction. Accounting for the specific radiation quality of proton beams impacts EAR estimation, providing a more comprehensive picture in terms of SC risk prediction. Our analysis confirmed, however, that overall SC risk associated with modern proton treatments is not dramatically larger than that achievable by pure physical dose-based estimates for the most probable α/β values.