Bragg-peak FLASH Biological Optimization Enables Enhanced Normal Tissue Sparing and Dose Escalation for Ocular Stereotactic Body Radiation Therapy.

Objective: To evaluate proton Bragg peak FLASH for ocular treatments to enhance normal tissue sparing and enable dose escalation via FLASH biological optimization(FBO). Approach: The FLASH-sparing factors for normal tissues were derived from the literature in modeling the phenomenological FLASH normal tissue sparing effect. Using the single-energy BP-FLASH technique(SEBP-FLASH), an in-house treatment planning system was implemented with the FLASH FBO module. Ten consecutive ocular patients who were treated using conventional dose rate intensity-modulated proton therapy(CONV-IMPT) to 50Gy in 5 fractions were replanned using the FLASH technique. The dose metrics for the OARs were compared using the two different techniques. The fraction dose was then intentionally escalated from 10 to 12Gy through FBO to assess whether the plans still met clinical constraints. Main results: In the FLASH regimen without FBO(50Gy/5 fractions), all ipsilateral OAR dosimetric metrics met clinical objectives with safe margins. While the clinical CONV-IMPT approach demonstrated slightly better dosimetric performance than SEBP-FLASH plans, the incorporation of FBO improved all OAR dose metrics beyond those of CONV- IMPT, except for the mean dose to the cornea (no difference). When the target dose was increased from 50 to 60Gy using FBO, all OARs remained within clinical limits. The mean and maximum doses to the cornea increased from 11.7 to 15.4Gy and from 22.8 to 23.6Gy, respectively, when transitioning from 50Gy CONV- IMPT to 60Gy FBO. However, in the 60Gy FBO plans, the maximum doses were reduced for the eye (102.0% to 87.0%), optic nerves (98.7% to 74.0%), retina (100.5% to 81.8%), lacrimal gland (84.9% to 73.2%), and conjunctiva (91% to 72.3%). Significance: SEBP-FLASH achieves plan quality comparable to CONV-IMPT using 50 Gy/5 fractions and enables dose escalation via FLASH FBO while meeting clinical standards, potentially improving tumor control with acceptable toxicity.