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Temporal lobe necrosis (TLN) is a potential late effect after radiotherapy for skull base head and neck cancer (HNC). Several photon-derived dose constraints and normal tissue complication probability (NTCP) models have been proposed, however variation in relative biological effectiveness (RBE) may challenge the applicability of these dose constraints and models in proton therapy. The purpose of this study was therefore to investigate the influence of RBE variations on risk estimates of TLN after Intensity-Modulated Proton Therapy for HNC. Seventy-five temporal lobes from 45 previously treated patients were included in the analysis. Sixteen temporal lobes had radiation associated Magnetic Resonance image changes (TLIC) suspected to be early signs of TLN. Fixed (RWD Fix ) and variable RBE-weighed doses (RWD Var ) were calculated using RBE = 1.1 and two RBE models, respectively. RWD Fix  and RWD Var  for temporal lobes were compared using Friedman’s test. Based on RWD Fix , six NTCP models were fitted and internally validated through bootstrapping. Estimated probabilities from RWD Fix  and RWD Var  were compared using paired Wilcoxon test. Seven dose constraints were evaluated separately for RWD Fix  and RWD Var  by calculating the observed proportion of TLIC in temporal lobes meeting the specific dose constraints. RWD Var  were significantly higher than RWD Fix  ( p  &lt; 0.01). NTCP model performance was good (AUC:0.79-0.84). The median difference in estimated probability between RWD Fix  and RWD Var  ranged between 5.3% and 20.0% points ( p  &lt; 0.01), with V 60GyRBE  and D Max  at the smallest and largest differences, respectively. The proportion of TLIC was higher for RWD Fix  (4.0%–13.1%) versus RWD Var  (1.3%–5.3%). For V 65GyRBE  ≤ 0.03 cc the proportion of TLIC was less than 5% for both RWD Fix  and RWD Var. NTCP estimates were significantly influenced by RBE variations. D max  as model predictor resulted in the largest deviations in risk estimates between RWD Fix  and RWD Var . V 65GyRBE  ≤ 0.03 cc was the most consistent dose constraint for RWD Fix  and RWD Var.

acta oncologica

Impact of RBE variations on risk estimates of temporal lobe necrosis in patients treated with intensity-modulated proton therapy for head and neck cancer