Does variable RBE affect toxicity risks for mediastinal lymphoma patients? NTCP-based evaluation after proton therapy treatment

Introduction: Mediastinal lymphoma (ML) is a solid malignancy affecting young patients. Modern combined treatments allow obtaining good survival probability, together with a long life expectancy, and therefore with the need to minimize treatment-related toxicities. We quantified the expected toxicity risk for different organs and endpoints in ML patients treated with intensity-modulated proton therapy (IMPT) at our centre, accounting also for uncertainties related to variable RBE. Methods: Treatment plans for ten ML patients were recalculated with a TOPAS-based Monte Carlo code, thus retrieving information on LET and allowing the estimation of variable RBE. Published NTCP models were adopted to calculate the toxicity risk for hypothyroidism, heart valve defects, coronary heart disease and lung fibrosis. NTCP was calculated assuming both constant (i.e. 1.1) and variable RBE. The uncertainty associated with individual radiosensitivity was estimated by random sampling α/β values before RBE evaluation. Results: Variable RBE had a minor impact on hypothyroidism risk for 7 patients, while it led to significant increase for the remaining three (+24% risk maximum increase). Lung fibrosis was slightly affected by variable RBE, with a maximum increase of ≅ 1%. This was similar for heart valve dysfunction, with the exception of one patient showing an about 10% risk increase, which could be explained by means of large heart volume and D1 increase. Discussion: The use of NTCP models allows for identifying those patients associated with a higher toxicity risk. For those patients, it might be worth including variable RBE in plan evaluation.