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"Development of a Flash Radiotherapy Platform: Characterization, safety, and delivery validation"

Abstract

Radiotherapy treatments are intended to produce the best therapeutic ratio by minimizing effects to normal tissue with maximum achievable tumor control. Ultra-high dose-rate (UHDR, >40Gy/s mean) FLASH radiotherapy can improve this ratio as studies suggest there is reduced normal tissue toxicity, while providing new patient motion management strategies with reduced delivery time (<1s). The renewed interest in the modality lead to investigations on the underlying normal tissue sparing mechanisms and large animals including humans but is faced with two gaps:

1. Lack of UHDR delivery technology for widespread implementation
2. Shortage of UHDR appropriate dosimetry and quality assurance (QA) tools for planning and confirming treatments

We hypothesize modifying current delivery and QA technology can consistently and accurately deliver prescribed dose under UHDR conditions with minimal changes to the clinical workflow for potentially increased accessibility. A readily available clinical LINAC was modified for UHDR electron beam delivery (>300Gy/s) at the isocenter with current clinical accessories and geometry. A team of clinical and research professionals identified methods to mitigate potential errors during FLASH delivery including surface guidance, checklists, and QA automation via failure mode and effects analysis (FMEA). Prior dosimetry technology utilized for UHDR beams was assessed for implementation considering dose linearity, dose rate independence, temporal resolution, and spatial resolution, indicating optical imaging methods viable for FLASH dosimetry. Imaging Cherenkov emission and radioluminescence demonstrated full field dose distribution at single-pulse millimeter resolution. In vivo Cherenkov emission surface profiles were monitored with improved signal-to-noise ratio via an intensified camera and spectral suppression of ambient light. A diode EDGE detector characterized UHDR dose and dose rate at sub-millisecond resolution. A beam model of the modified LINAC was validated and implemented into a commercial clinical treatment planning software (TPS).

While this unique irradiation platform established ongoing investigations into the FLASH mechanism and large animal treatments in one institution, the identified dosimetry requirements, accessibility to conversion methods, and open-source beam model can catalyze studies in other clinics. Delivery and dosimetry can be further improved by identifying errors via an open access FMEA survey, resolving delivered temporal pulse structure, and ensuring pulse to pulse consistency.

Thesis Committee

• Rongxiao Zhang, PhD (Chair)
• Brian Pogue, PhD
• Petr Bruza, PhD
• David Gladstone, PhD
• Kristoffer Petersson, PhD

Contact

For more information, contact Theresa Fuller at theresa.d.fuller@dartmouth.edu.