Purpose: Treatment planning strategies that minimize end-of-range uncertainties associated with high linear energy transfer (LET) in proton therapy are needed. We replanned clinical cases to assess changes in LET and compromises to dose.
Methods: Four patients were chosen to represent various brain tumor shapes, locations, and proximity to the brainstem. Treatment plans were developed for each patient by changing one of the following factors from the clinical plan and re-optimizing: optimization method (i.e., single field versus multi field), spot restrictions at end range, beam orientation, number of beams, and scenario-based robust optimization parameters. Including the original clinical plans, a total of 28 unique treatment plans were used to calculate dose and dose-weighted LET (LETd) using TOPAS Monte Carlo code. Dose distributions with a constant RBE of 1.1 were assessed to judge clinical feasibility of the plan. Volume of LETd exceeding 6 keV/micron in regions receiving greater than 80% of the prescription dose, defined as a high-risk volume, mean LETd, and dose-times-LETd were used to assess changes in potential biological implications.
Results: Clinically acceptable plans were achieved for all strategies in 3 of 4 patients. Planning strategies inconsistently affected the high-risk volume (range = 0.3 to 8.1cc) and dose-times-LETd distribution in normal brain. Mean LETd in brainstem was higher in the modified plans by an average of 1.1 and 1.9 keV/micron when adding a third beam or decreasing the intersection angle between beams, respectively. The maximum change in the brainstem among all other techniques was 0.3 keV/micron.
Conclusion: Forward-based strategies to mitigate LETd hotspots are patient dependent, but generally possible in a way that does not compromise dose distribution quality. Beam geometry is a greater predictor for undesirable LETd placement than optimization parameters or restricted spot placement. We recommend the use of two parallel-opposed fields in the treatment of cranial targets.