Linear Energy Transfer and Relative Biological Effectiveness Investigation of Various Structures for a Cohort of Proton Patients With Brain Tumors

PURPOSE: The current knowledge on biological effects associated with proton therapy is limited. Therefore, we investigated the distributions of dose, dose-averaged linear energy transfer (LET(d)), and the product between dose and LET(d) (DLET(d)) for a patient cohort treated with proton therapy. Different treatment planning system features and visualization tools were explored. METHODS AND MATERIALS: For a cohort of 24 patients with brain tumors, the LET(d), DLET(d), and dose was calculated for a fixed relative biological effectiveness value and 2 variable models: plan-based and phenomenological. Dose threshold levels of 0, 5, and 20 Gy were imposed for LET(d) visualization. The relationship between physical dose and LET(d) and the frequency of LET(d) hotspots were investigated. RESULTS: The phenomenological relative biological effectiveness model presented consistently higher dose values. For lower dose thresholds, the LET(d) distribution was steered toward higher values related to low treatment doses. Differences up to 26.0% were found according to the threshold. Maximum LET(d) values were identified in the brain, periventricular space, and ventricles. An inverse relationship between LET(d) and dose was observed. Frequency information to the domain of dose and LET(d) allowed for the identification of clusters, which steer the mean LET(d) values, and the identification of higher, but sparse, LET(d) values. CONCLUSIONS: Identifying, quantifying, and recording LET distributions in a standardized fashion is necessary, because concern exists over a link between toxicity and LET hotspots. Visualizing DLET(d) or dose × LET(d) during treatment planning could allow for clinicians to make informed decisions.