Linear energy transfer optimization in proton therapy of sinonasal cancer

Background Variations in relative biological effectiveness (RBE) and linear energy transfer (LET) in proton therapy may contribute to unexpected side effects in organs of interest (OOIs). This study assessed the feasibility of LET optimization in intensity-modulated proton therapy (IMPT) for sinonasal cancer, aiming to reduce dose-averaged LET (LET d ). Materials and methods Robust optimized IMPT reference plans (Ref) were created for 16 patients ( clinical target volume (CTV) doses: 64–70 Gy[RBE 1.1 ]) assuming a fixed RBE = 1.1, 2 mm setup and 3.5% range uncertainties. LET optimized plans (LETopt) were generated from Ref plans using identical dose guidance, with additional LET d objectives (LET d < 3 keV/μm at ≥30 Gy[RBE 1.1 ]) to the brainstem, chiasm and optic nerves. Plans were compared in terms of CTV coverage , OOI dose (RBE 1.1 ), mean LET d (LET dmean ) and variable RBE-weighted doses (RBE VAR ). Results All Ref and LETopt plans met the CTV dose criteria. The median LET dmean across the patients was reduced in the chiasm (3.1 vs 2.3 keV/μm, P = 0.009), right optic nerve (3.1 vs 2.5 keV/μm, P = 0.016), and left optic nerve (2.7 vs 2.7 keV/μm, P = 0.023). RBE VAR doses (D 0.03cm3 ) to OOIs were also significantly decreased, achieving patient-specific reductions from >56 Gy (RBE VAR ) to below the 54 Gy (RBE VAR ) threshold in the brainstem, chiasm, and optic nerves. Conclusions LET optimization significantly reduced LET dmean and RBE VAR doses to critical OOIs without compromising CTV coverage. However, its effectiveness was patient specific, with notable variability in RBE VAR D 0.03cm3 doses across models, underscoring the need for individualized assessment.