FLASH-Enabled Proton SBRT/SRS via Simultaneous Dose and Dose Rate Optimization (SDDRO)

Abstract

<h3>Purpose/Objective(s)</h3> The availability of SBRT/SRS is often hindered by dose-limiting toxicities to organs at risk (OAR). This work investigates the clinical potential of FLASH-RT for improving high-dose sparing of OAR, to enable SBRT/SRS that could otherwise fail to meet dose constraints with CONV-RT. <h3>Materials/Methods</h3> CONV-RT (via Bragg peaks (BP)) and FLASH-RT (via transmission beams (TB)) are compared with pencil beam scanning proton therapy, i.e., CONV-RT planned with IMPT-BP, and FLASH-RT planned respectively with IMPT and SDDRO of TB. While IMPT only optimizes the dose distribution, SDDRO also optimizes the FLASH effect, i.e., to maximize the normal tissue volume receiving dose rate and dose thresholds pertinent to the FLASH effect, which was set to be 40Gy/s and 8Gy. The plan evaluation is based on the effective dose, i.e., the product of the physical dose and FLASH dose modifying factor, which was set to be 0.7 when normal tissues meet both dose rate and dose thresholds. <h3>Results</h3> CONV-RT (i.e., IMPT-BP) was compared with FLASH-RT (planned with IMPT and SDDRO respectively) for three clinical SBRT/SRS cases of lung, prostate, and brain. For fair comparison, all plans had the same clinical objectives and were after the same normalization of D95%=100% for PTV. The effective dose results are summarized in the table. (1) The CI values show that SDDRO had the best target dose conformality (note that 0.95 is optimal under D95%=100%). (2) The mean doses at PTV-10mm (10mm expansion of PTV) suggest that SDDRO had the fastest high-dose falloff for normal tissues adjacent to the target. (3) For the lung case, per RTOG 0618, the max dose constraint 27Gy for esophagus was only met by SDDRO (25Gy), not CONV-RT (35Gy) or IMPT (37Gy); the max dose constraint 30Gy for trachea and bronchus was substantially relaxed to 22Gy by SDDRO. (4) For the prostate case, SDDRO substantially decreased V32Gy to nearly 0cc. (5) For the brain case, compared to CONV-RT, SDDRO substantially decreased V12Gy from 44cc to 14cc; note that V12Gy≤15cc is required to reduce the likelihood of symptomatic radiation necrosis per HyTEC reports. <h3>Conclusion</h3> Compared to CONV-RT (i.e., IMPT-BP), FLASH-RT via SDDRO improved high-dose sparing of OAR, which can potentially enable proton SBRT/SRS that could otherwise fail to meet dose constraints, e.g., the reduction of V12Gy from 44cc to 14cc to meet V12Gy≤15cc for this case to be eligible for brain SRS.