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Impact of range uncertainty on clinical distributions of linear energy transfer and biological effectiveness in proton therapy
Author(s) -
Hahn Christian,
Eulitz Jan,
Peters Nils,
Wohlfahrt Patrick,
Enghardt Wolfgang,
Richter Christian,
Lühr Armin
Publication year - 2020
Publication title -
medical physics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 180
eISSN - 2473-4209
pISSN - 0094-2405
DOI - 10.1002/mp.14560
Subject(s) - proton therapy , linear energy transfer , relative biological effectiveness , nuclear medicine , stopping power , dosimetry , range (aeronautics) , proton , confidence interval , radiation therapy , mathematics , irradiation , physics , computational physics , statistics , medicine , nuclear physics , materials science , optics , detector , composite material
Purpose Increased radiation response after proton irradiation, such as late radiation‐induced toxicity, is determined by high dose and elevated linear energy transfer (LET). Steep dose‐averaged LET (LET d ) gradients and elevated LET d occur at the end of proton range and might be particularly sensitive to uncertainties in range prediction. Therefore, this study quantified LET d distributions and the impact of range uncertainty in robust dose‐optimized proton treatment plans and assessed the biological effect in normal tissues and tumors of patients. Methods For each of six cancer patients (two brain, head‐and‐neck, and prostate), two nominal treatment plans were robustly dose optimized using single‐ and multi‐field optimization, respectively. For each plan, two additional scenarios with ±3.5% range deviation relative to the nominal plan were derived by global rescaling of stopping‐power ratios. Dose and LET d distributions were calculated for each scenario using the beam parameters of the corresponding nominal plan. The variability in relative biological effectiveness (RBE) and probability of late radiation‐induced brain toxicity ( P IC ) was assessed. Results The optimization technique (single‐ vs multi‐field) had a negligible impact on the LET d distributions in the clinical target volume (CTV) and in most organs at risk (OARs). LET d distributions in the CTV were rather homogeneous with arithmetic mean of LET d below 3.2 keV/µm and robust against range deviations. The RBE variability within the CTV induced by range uncertainty was small (≤0.05, 95% confidence interval). In OARs, LET d hotspots (>7 keV/µm) occurred and LET d distributions were inhomogeneous and sensitive to range deviations. LET d hotspots and the impact of range deviations were most prominent in OARs of brain tumor patients which translated in RBE values exceeding 1.1 in all brain OARs. The near‐maximum predicted P IC in healthy brain tissue of brain tumor patients was smaller than 5% and occurred adjacent to the CTV. Range deviations induced absolute differences in P IC up to 1.2%. Conclusions Robust dose optimization generates LET d distributions in the target volume robust against range deviations. The current findings support using a constant RBE within the CTV. The impact of range deviations on the considered probability of late radiation‐induced toxicity in brain tissue was limited for robust dose‐optimized treatment plans. Incorporation of LET d in robust optimization frameworks may further reduce uncertainty related to the RBE‐weighted dose estimation in normal tissues.