Abstract
Simple SummaryThis study attempts to answer a novel and clinically relevant question of the value of Bragg-peak-based FLASH planning for lung tumors. Most existing studies and literature are limited to using transmission proton beams at ultra-high dose rates, resulting in unnecessary irradiation exposure to normal tissues beyond the target volume. By combining a new hardware design (universal range shifter and range compensator) and an inverse planning system, the novel Bragg peak method makes the Bragg-peak-based FLASH planning possible. The treatment planning study and dosimetry comparison between single-energy proton Bragg peak beams and transmission proton beams demonstrated superior performances in OAR sparing and comparable FLASH dose rate of the Bragg peak FLASH. Beam angle optimization can further improve Bragg peak FLASH dosimetry performance while maintaining the similar 3D FLASH dose rate coverage for OARs.Purpose: While transmission proton beams have been demonstrated to achieve ultra-high dose rate FLASH therapy delivery, they are unable to spare normal tissues distal to the target. This study aims to compare FLASH treatment planning using single energy Bragg peak proton beams versus transmission proton beams in lung tumors and to evaluate Bragg peak plan optimization, characterize plan quality, and quantify organ-at-risk (OAR) sparing. Materials and Methods: Both Bragg peak and transmission plans were optimized using an in-house platform for 10 consecutive lung patients previously treated with proton stereotactic body radiation therapy (SBRT). To bring the dose rate up to the FLASH-RT threshold, Bragg peak plans with a minimum MU/spot of 1200 and transmission plans with a minimum MU/spot of 400 were developed. Two common prescriptions, 34 Gy in 1 fraction and 54 Gy in 3 fractions, were studied with the same beam arrangement for both Bragg peak and transmission plans (n = 40 plans). RTOG 0915 dosimetry metrics and dose rate metrics based on different dose rate calculations, including average dose rate (ADR), dose-averaged dose rate (DADR), and dose threshold dose rate (DTDR), were investigated. We then evaluated the effect of beam angular optimization on the Bragg peak plans to explore the potential for superior OAR sparing. Results: Bragg peak plans significantly reduced doses to several OAR dose parameters, including lung V7.4Gy and V7Gy by 32.0% (p < 0.01) and 30.4% (p < 0.01) for 34Gy/fx plans, respectively; and by 40.8% (p < 0.01) and 41.2% (p < 0.01) for 18Gy/fx plans, respectively, compared with transmission plans. Bragg peak plans have ~3% less in DADR and ~10% differences in mean OARs in DTDR and DADR relative to transmission plans due to the larger portion of lower dose regions of Bragg peak plans. With angular optimization, optimized Bragg peak plans can further reduce the lung V7Gy by 20.7% (p < 0.01) and V7.4Gy by 19.7% (p < 0.01) compared with Bragg peak plans without angular optimization while achieving a similar 3D dose rate distribution. Conclusion: The single-energy Bragg peak plans achieve superior dosimetry performances in OARs to transmission plans with comparable dose rate performances for lung cancer FLASH therapy. Beam angle optimization can further improve the OAR dosimetry parameters with similar 3D FLASH dose rate coverage.
Highlights
FLASH radiation therapy (RT), characterized by an ultra-high dose rate of >40 Gy/s, has the potential to offer superior normal tissue sparing while retaining similar tumor control to conventional dose rate RT [1,2,3,4]
To achieve acceptable plan quality and ultra-high dose rates for the Bragg peak plans, we developed a novel method for spot map and dose rate optimization through inverse intensity-modulated proton therapy (IMPT) planning
For the dose rate results (Figure 6f) that we found in most OARs, the V40Gy/s associated with beam angular optimization are comparable to those without optimization for all dose rate calculations, and the dose rate differences are less than 5%
Summary
FLASH radiation therapy (RT), characterized by an ultra-high dose rate of >40 Gy/s, has the potential to offer superior normal tissue sparing while retaining similar tumor control to conventional dose rate RT [1,2,3,4]. Several pioneering pre-clinical studies have corroborated the FLASH effect using electron beams in mice models with lung [3], brain [1,5,6], and mini-pig and cat patients [7]. FLASH RT using proton beams has been implemented using scattering systems, showing promising pre-clinical treatment outcomes [9,10,11]. Pencil beam scanning (PBS), the most advanced proton beam delivery technique, is capable of achieving extraordinary dose conformity by steering narrow proton beamlets with scanning magnets. Major proton vendors have upgraded their PBS proton systems, which are capable of delivering ultra-high nozzle beam currents to reach FLASH dose rates [12,13,14,15]. The first FLASH clinical trial has been activated using a proton accelerator [16,17]
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