Statistics

Radiation

Proton

Nuclear physics

Dosimetry

Radiation therapy

Radiology

Relative biological effectiveness

Physics

Mathematics

Monte Carlo method

Medicine

Proton therapy

Nuclear medicine

Linear energy transfer

Medical Physics

The enhanced relative biological effectiveness (RBE) at the end of the proton range might increase the risk of radiation-induced toxicities. This is of special concern for intracranial treatments where several critical organs at risk (OARs) surround the tumor. In the light of this, a retrospective analysis of dose-averaged linear energy transfer (LETd ) and RBE-weighted dose (DRBE ) distributions was conducted for three clinical cases with suspected treatment-related toxicities following intracranial proton therapy. Alternative treatment strategies aiming to reduce toxicity risks are also presented.The clinical single-field optimized (SFO) plans were recalculated for 81 error scenarios with a Monte Carlo dose engine. The fractionation DRBE was 1.8 Gy (RBE) in 28 or 30 fractions assuming a constant RBE of 1.1. Two LETd - and α/β-dependent variable RBE models were used for evaluation, including a sensitivity analysis of the α/β parameter. Resulting distributions of DRBE and LETd were analyzed together with normal tissue complication probabilities (NTCPs). Subsequently, four multi-field optimized (MFO) plans, with an additional beam and/or objectives penalizing protons stopping in OARs, were created to investigate the potential reduction of LETd , DRBE , and NTCP.The two variable RBE models agreed well and predicted average RBE values around 1.3 in the toxicity volumes, resulting in an increased near-maximum DRBE of 7-11 Gy (RBE) compared to RBE = 1.1 in the nominal scenario. The corresponding NTCP estimates increased from 0.8%, 0.0%, and 3.7% (RBE = 1.1) to 15.5%, 1.8%, and 45.7% (Wedenberg RBE model) for the three patients, respectively. The MFO plans generally allowed for LETd , DRBE , and NTCP reductions in OARs, without compromising the target dose. Compared to the clinical SFO plans, the maximum reduction in the near-maximum LETd was 56%, 63%, and 72% in the OAR exhibiting the toxicity for the three patients, respectively.Although a direct causality between RBE and toxicity cannot be established here, high LETd and DRBE correlated spatially with the observed toxicities, whereas setup and range uncertainties had a minor impact. Individual factors, which might affect the patient-specific radiosensitivity, were however not included in these calculations. The MFO plans using both an additional beam and proton track-end objectives allowed the largest reductions in LETd , DRBE , and NTCP, and might be future tools for similar cases.

Spatial correlation of linear energy transfer and relative biological effectiveness with suspected treatment‐related toxicities following proton therapy for intracranial tumors