Can the mean linear energy transfer of organs be directly related to patient toxicities for current head and neck cancer intensity-modulated proton therapy practice?

Highlights: • Relating organ LET to head and neck toxicity not feasible for current practice. • Does not contradict previous evidence for increased RBE for high LET. • Lack of variation in LET causes high required sample size. • Other methods to investigate RBE and LET in clinical practice are suggested. The relative biological effectiveness (RBE) of proton therapy is predicted to vary with the dose-weighted average linear energy transfer (LET_d). However, RBE values may substantially vary for different clinical endpoints. Therefore, the aim of this study was to assess the feasibility of relating mean D⋅LET_d parameters to patient toxicity for HNC patients treated with proton therapy.