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"Towards clinical translation of flash radiotherapy: comprehensive prediction and validation for accurate treatment delivery"

Abstract

Over 12 million new cancer cases are reported per year worldwide and radiotherapy treats nearly 50% of all cancers and contributes to 40% of curative treatments. Radiotherapy treatments are delivered and intended to produce the best therapeutic ratio by lowering effects to normal tissue with maximum achievable tumor control. Ultra-high dose-rate (UHDR, >40Gy/s) FLASH radiotherapy can potentially improve this therapeutic ratio as studies suggest there is reduced normal tissue toxicity. Reduced treatment delivery time (<1s) allows new patient motion management strategies, with decreased margin and reduced delivery uncertainty. Recent resurgence and investigations into this modality with studies on the underlying normal tissue sparing mechanisms and treating large mammals including humans are faced with two gaps:

1. Lack of UHDR delivery technology for widespread implementation.
2. Shortage of UHDR appropriate dosimeters for planning and confirming treatments.

Prior studies sought to address these shortcomings with minimal changes to current clinical setting and treatment delivery workflow. Methods for modifying a readily available clinical LINAC were developed and implemented for UHDR electron beam delivery (>300Gy/s) at the isocenter with current clinical accessories and geometry. A beam model of the modified LINAC was implemented into a commercial clinical treatment planning software (TPS) and validated. Preliminary study on imaging Cherenkov and scintillation under UHDR conditions demonstrated dose-rate independence and full field dose distribution at single pulse millimeter resolution.

The proposal aims will focus on further developing the dosimetry and delivery technologies for future clinical implementations. We hypothesize Cherenkov emission-based imaging can provide full field in vivo surface dose at UHDR. Cherenkov emission will be compared to standard dosimeters and TPS planned dose for tissue phantoms along with a cohort of pigs, mice, and dogs. Efficacy of electron FLASH intensity modulation will be explored via TPS for dose rate effects and improving normal tissue sparing while incorporating differential response from the FLASH effect (including retrospective evaluation by incorporating a TCP/NTCP, tumor control and normal tissue complications probability, model for a patient cohort with electron treated lesions). Methodology for commissioning a FLASH irradiator will be developed for human treatment including beam stability, end-to-end dosimetry, and complex treatment verifications.

Thesis Committee

• Brian W. Pogue, PhD (Chair)
• Petr Bruza, PhD
• Rongxiao Zhang, PhD
• Kristoffer Petersson, PhD

Contact

For more information, contact Daryl Laware at daryl.a.laware@dartmouth.edu.