About the speaker: I am an Associate Professor in the Emory University School of Medicine and a lead proton physicist at the Emory Proton Therapy Center. I am a member of the Therapy Medical Physics Committee of American Board of Radiology (ABR) and a fellow of the American Association of Physicists in Medicine (AAPM). As an expert on Monte Carlo (MC) methods and proton radiotherapy, I previously chaired the NRG workgroup for the application of MC methods in clinical trials and currently chair the NRG workgroup for stereotactic body proton therapy/ I am the physics co-chair of a newly approved NCI Phase 3 clinical trial “Phase III Prospective Randomized Trial of Primary Lung Tumor Stereotactic Body Radiation Therapy Followed by Concurrent Mediastinal Chemoradiation for Locally-Advanced Nonsmall Cell Lung Cancer” NRG-LU 008.  I also chair of the AAPM task group TG349 to validate MC methods in commercial treatment planning systems.  I have >80 peer-reviewed journal papers with H-index of 27 (Scopus). I am also the author of 2 AAPM task group reports, 1 PTCOG lung committee consensus paper and 1 NRG MC Workgroup paper.

Abstract: A recently proposed Integrated Biological Optimization Intensity-Modulated Proton Therapy (IBO-IMPT) framework allows simultaneous optimization of dose, dose rate, and linear energy transfer (LET) for proton FLASH therapy treatment planning. Such treatments have potential for lung cancer patients with tumors that are resistant to standard therapies.

Aims: We have developed simultaneous intensity and energy modulation and compensation (SIEMAC) as a solution to IBO-IMPT that simultaneously specifies the intensities of a spot map and the geometry of a filter used to modulate proton energy. Validation of dose, dose rate, and LET for ultra-high dose rate (UHDR) plans are mandated towards preclinical and clinical applications.

Methods: Iterative Monte Carlo-based algorithms for optimization of treatment plans run on a distributed computing service to simultaneously determine optimal sets of spot intensities and geometry parameters to produce biologically advantageous dose, dose rate, and LET distributions for a lung patient, mouse, and minipig. High-resolution pixelated silicon detectors and a multi-layered strip ionization chamber were used to validate dose rate and LET.

Results: SIEMAC increased dose rate coverage above 40 Gy/s to >98% while decreasing LET coverage above 4 keV/um to <10% in the lung and heart of a central lung cancer patient with similar clinical target coverage as conventional IMPT plans. Our QA measurements had gamma passing rates of >95% for dose distribution. Dose rate measurements agreed with simulation within 0.3%, and LET comparisons between experiment and simulation had Bhattacharyya distances of <1.3e-2. SIEMAC can achieve conformal FLASH with desired LET for the tumor in the mouse and the mini pig along with desired UHDR at the lung, heart, and esophagus.

 Conclusion: The experimental validation has demonstrated the clinical and preclinical feasibility of SIEMAC solution to IBO-IMPT, to generate FLASH lung treatment plans.