PET-Guided Modeling of Mucosal Boron Heterogeneity Improves Dose-Toxicity Prediction in BNCT

Purpose To evaluate whether mucosal boron heterogeneity measured using fluoro-boronophenylalanine positron emission tomography ( 18 F-BPA PET) improves the prediction of oral mucositis in boron neutron capture therapy (BNCT), and to establish an imaging-guided framework for normal tissue complication probability (NTCP) modeling. Methods and Materials This retrospective study analyzed 45 BNCT treatment sessions for head and neck cancer. Pre-treatment 18 F-BPA PET was used to quantify PET-derived mucosal uptake and to derive an uptake-defined mucosal region using a tissue-to-blood ratio (TBR) threshold of 1.8. Four mucosal dose-calculation workflows were compared: (1) the Finnish workflow and (2) the Japanese workflow—both delineating mucosa anatomically and assuming uniform boron concentration implemented via a fixed TBR; (3) anatomical mucosa and (4) uptake-defined mucosa with heterogeneous boron distribution derived from PET-derived uptake heterogeneity. Biological (Gy-equivalent) and physical (Gy) subvolume dose metrics, including dose to the hottest 0.05 cubic centimeters (D 0.05cc ), were evaluated for correlation with mucositis severity, discrimination of grade ≥ 2 toxicity, and suitability for NTCP modeling. Results 18 F-BPA PET demonstrated pronounced functional heterogeneity across the mucosa. Among all evaluated metrics, only the uptake-defined biological D 0.05cc showed a significant monotonic association with toxicity and fulfilled all NTCP validity criteria, yielding the highest discriminative performance (area under the curve 0.765 ± 0.025) and physiologically plausible TD 10 –TD 90 thresholds (4.85–12.84 Gy-equivalent). In contrast, Finnish and Japanese anatomical maximum-dose metrics, based on uniform-boron assumptions, showed no meaningful correlation with clinical outcomes. Conclusions Functional PET imaging reveals clinically important mucosal heterogeneity that influences BNCT toxicity. The uptake-defined biological D 0.05cc demonstrated superior prediction of oral mucositis and may provide a promising hypothesis-generating framework for developing patient-specific mucosal dose constraints, pending prospective validation.