Project Grant R44CA268466

ULTRA-FAST IMAGING FOR THE SAFE DELIVERY OF ELECTRON FLASH RADIATION THERAPY - ABSTRACT RADIATION THERAPY IS A SUPPLEMENTARY CURATIVE TREATMENT USED ADJUVANT WITH MOST SURGERY AND CHEMOTHERAPY, BEING DELIVERED TO NEARLY 1 OUT OF EVERY 4 PEOPLE IN THEIR LIFETIME. WHILE IMAGE GUIDANCE AND CONFORMAL PLANNING REDUCED THE DOSE TO HEALTHY TISSUE, THERE IS STILL A SUBSTANTIAL RISK OF TISSUE DAMAGE THAT SETS THE UPPER LIMIT OF DOSE DEPOSITED TO THE TUMOR. RECENTLY THE MINIMIZATION OF HEALTHY TISSUE DAMAGE WAS DEMONSTRATED TO OCCUR WHEN ULTRA-HIGH DOSE RATES (UHDR) WERE USED FOR IRRADIATION, KNOWN AS THE FLASH EFFECT. UHDR ARE DEFINED AS A COMPLEX SET OF HIGH AVERAGE DOSE RATES (>40 GY/S), INSTANTANEOUS DOSE RATES (>106 GY/S), TOTAL DOSE VALUES (>8GY) AND TEMPORAL PULSE STRUCTURES. FLASH PROMISES A REDUCTION IN NORMAL TISSUE TOXICITY BY 20-50% AND OUR CLINICAL SITE PARTNER DARTMOUTH-HITCHCOCK, HAS BEEN THE FIRST TO DEMONSTRATE ROUTINE WEEKLY DELIVERY OF FLASH ON A CLINICALLY USED LINAC. THIS MODIFICATION SHOWS ENORMOUS TRANSLATIONAL POTENTIAL TO DELIVER ELECTRON FLASH (EFLASH) IN ANY RADIOTHERAPY CENTER USING EXISTING SYSTEMS. HOWEVER, WHILE MOST RESEARCH IN THE FIELD IS FOCUSED ON ELUCIDATING THE RADIOBIOLOGICAL MECHANISMS OF FLASH, WORK TOWARDS MITIGATING THE RISKS OF FLASH IS LARGELY UNTOUCHED, YET WILL BE PIVOTAL FOR WIDER CLINICAL IMPLEMENTATION. NEW TECHNIQUES FOR DETECTION MONITORING OF RADIATION NEED TO BE DEVELOPED DUE TO THE MILLISECOND TIMESCALES AT WHICH FLASH OPERATES WHICH MAKE TRADITIONAL METHODS UNSUITABLE. IN THIS PROJECT, WE HAVE LEVERAGED OUR CAMERA PLATFORM, BEAMSITE, THE WORLD'S FIRST VIDEO SYSTEM FOR RADIOTHERAPY, NOW FDA CLEARED AND IN USE CLINICALLY, TO DEVELOPED BEAMSITE-ULTRA, SPECIFICALLY FOR IMAGING FLASH. IN OUR PHASE I GRANT, WE SUCCESSFULLY DEMONSTRATED THE ABILITY TO IMAGE AT THE HIGH FRAME RATES AND TRANSFER SPEEDS NECESSARY TO CAPTURE A SINGLE BEAM PULSE ENERGY IN PHANTOMS AND ON TISSUE. IN THIS PHASE II, WE WILL ADVANCE BEAMSITE-ULTRA AS A ROBUST, MANUFACTURABLE, AND FDA CLEARABLE COMMERCIAL SYSTEM. WE WILL QUANTIFY BOTH SPATIAL AND TEMPORAL PULSE STRUCTURES, DEMONSTRATE BEAM-ON AND GATING-OFF POTENTIAL OF THE SYSTEM, AND ESTABLISH THE CAPABILITIES IN BOTH PROTON AND ELECTRON FLASH CLINICAL SETTINGS. THE WORK INCLUDES AN EXTENSIVE TEAM OF INDUSTRY AND ACADEMIC MEDICINE COLLEAGUES, USING THE EFLASH RESOURCES AT DARTMOUTH-HITCHCOCK MEDICAL CENTER AND THE PROTON TREATMENT FACILITIES AT THE UNIVERSITY OF KANSAS MEDICAL CENTER.