Eric Abel (United States of America)
Varian Medical Systems FLASHAuthor Of 2 Presentations
Treatment Planning And Dose-Rate Distributions For Conventionally Fractionated Head And Neck Cancer Using Uhdr Transmission Beam Proton Therapy
Abstract
Background and Aims
Transmission beam (TB) proton therapy (PT) uses single, high energy beams with Bragg-peak behind the target, sharp penumbras and simplified planning/delivery. TB facilitates ultra-high dose-rates (UHDRs, e.g. ≥40Gy/s), which is a requirement for the FLASH-effect. FLASH may also require a dose threshold, but this remains uncertain and UHDR-distribution investigation is of interest for head-and-neck cancer treatment.
Methods
We investigated (1) plan quality for conventionally-fractionated head-and-neck cancer treatment using spot-scanning proton TBs, intensity-modulated PT (IMPT) and photon volumetric-modulated arc therapy (VMAT); (2) UHDR-metrics. VMAT, 3-field IMPT and 10-field TB-plans, delivering 70/54.25Gy in 35 fractions to boost/elective volumes, were compared (n=10 patients). To increase spot peak dose-rates (SPDRs), TB-plans were split into three subplans, with varying spot monitor units and different gantry currents.
Results
Despite the lack of Bragg-peak advantages, average TB-plan OAR-sparing was comparable to IMPT: mean oral cavity/body dose were 4.1/2.5Gy higher than IMPT (9.3/2.0Gy lower than VMAT); most other OAR (salivary glands, larynx, pharynx) mean doses differed by <2Gy (2.0-12.1Gy lower than VMAT). Average percentage of dose delivered at UHDRs was 46%/12% for split/non-split TB-plans and mean dose-averaged dose-rate 46/21Gy/s. Average total beam-on irradiation time was 1.9/3.8s for split/non-split plans and overall time including scanning 8.9/7.6s.
Conclusions
Conventionally-fractionated proton TB-plans achieved comparable OAR-sparing to IMPT and better than VMAT, with total beam-on irradiation times <10s. Splitting TB-plans increased the UHDR, demonstrating the advantage of gantry current variation per spot. If a FLASH-effect can be demonstrated at conventional dose/fraction, this would further improve plan quality and TB-protons would be a suitable delivery system.
FLASH PROTON PENCIL BEAM SCANNING IRRADIATION USING A CLINICAL GANTRY DIMINISHES RADIATION INDUCED SKIN AND SOFT TISSUE TOXICITY IN MICE
Abstract
Background and Aims
Radiation induced skin and soft tissue toxicity remains a complication even for targeted proton pencil beam scanning (PBS) therapy. In this study, we determined the feasibility and benefit of Flash PBS therapy on these toxicities in mice.
Methods
A uniform dose of 35 Gy (toxicity study) or 15 Gy (tumor control study) was delivered to the right hind leg of mice at 1 Gy/s (Conv), 57 Gy/s (FLASH60) and 115 Gy/s (FLASH115) using the plateau region of a 250MeV proton beam. Acute radiation effects were quantified by measurements of TGF-β1 in the plasma and skin and by skin toxicity scoring. Delayed irradiation response was defined by hind leg contracture and plasma levels of 13 cytokines (CXCL1, CXCL10, Eotaxin, IL1-beta, IL-6, MCP-1, Mip1alpha, TNF-alpha, TNF-beta, VEGF, G-CSF, GM-CSF and TGF-β1). Tumor control was quantified in vivo using MOC1 and MOC2 murine oral squamous cell carcinoma (OSCC) cells transplanted into the flank of immunocompetent mice.
Results
Plasma and skin levels of TGF-β1, skin toxicity and leg contracture were significantly decreased in FLASH compared to Conv groups. Maximal FLASH effect was already observed at 60 Gy/s. Plasma levels of CXCL1, GM-CSF, G-CSF and IL-6 were significantly different between FLASH and Con PBS treated animals. FLASH and Conv PBS had similar efficacy on MOC1 and MOC2 tumor growth in vivo.
Conclusions
FLASH PBS radiation can be delivered to mice at dose rates up to 115 Gy/s in a clinical gantry and can improve radiation induced skin and soft tissue toxicity while remaining isoefficient in delaying OSCC growth.