A Novel Inverse Algorithm To Solve the Integrated Optimization of Dose, Dose Rate, and Linear Energy Transfer of Proton FLASH Therapy With Sparse Filters.

Purpose: The recently proposed Integrated Physical Optimization Intensity Modulated Proton Therapy (IPO-IMPT) framework allows simultaneous optimization of dose, dose rate, and linear energy transfer (LET) for ultra-high dose rate (FLASH) treatment planning. Finding solutions to IPO-IMPT is difficult because of computational intensiveness. Nevertheless, an inverse solution that simultaneously specifies the geometry of a sparse filter and weights of a proton intensity map is desirable for both clinical and preclinical applications. Such solutions can reduce effective biologic dose to organs at risk in patients with cancer as well as reduce the number of animal irradiations needed to derive extra biologic dose models in preclinical studies.

Methods And Materials: Unlike the initial forward heuristic, this inverse IPO-IMPT solution includes simultaneous optimization of sparse range compensation, sparse range modulation, and spot intensity. The daunting computational tasks vital to this endeavor were resolved iteratively with a distributed computing framework to enable Simultaneous Intensity and Energy Modulation and Compensation (SIEMAC). SIEMAC was demonstrated on a human patient with central lung cancer and a minipig.

Results: SIEMAC simultaneously improves maps of spot intensities and patient-field-specific sparse range compensators and range modulators. For the patient with lung cancer, at our maximum nozzle current of 300 nA, dose rate coverage above 100 Gy/s increased from 57% to 96% in the lung and from 93% to 100% in the heart, and LET coverage above 4 keV/µm dropped from 68% to 9% in the lung and from 26% to <1% in the heart. For a simple minipig plan, the full-width half-maximum of the dose, dose rate, and LET distributions decreased by 30%, 1.6%, and 57%, respectively, again with similar target dose coverage, thus reducing uncertainty in these quantities for preclinical studies.

Conclusions: The inverse solution to IPO-IMPT demonstrated the capability to simultaneously modulate subspot proton energy and intensity distributions for clinical and preclinical studies.