Open IPO and QA platform for conformal flash proton therapy

Emory University received a $158,899 Project Grant from the National Cancer Institute under the Cancer Treatment Research program (CFDA 93.395) awarded June 20, 2025, with completion targeted for May 31, 2027. This award supports the development of an innovative Simultaneous Intensity Energy Modulation and Compensation (SIEMAC) optimization platform and integrated quality assurance (QA) system for conformal flash proton therapy treatment of central lung cancer. The project addresses critical clinical challenges in stereotactic body radiotherapy by combining three therapeutic advantages: zero physical dose to organs at risk beyond the Bragg peak, 50% biological effective dose reduction to organs at risk through ultra-high dose rates (40 Gy/s), and 30% increased biological effective dose with elevated linear energy transfer in tumor tissue. The deliverables include the SIEMAC optimization platform for inverse solving of intensity and energy variables, alongside a dual-component QA system integrating micro-timing/dose rate measurement with micro dosimetry/linear energy transfer assessment using Advanced Detector Technology (ADVACAM) prototype detectors and commercial strip-segmented ionization chamber arrays.

The research aims to establish clinical translation pathways for flash proton therapy while mitigating organ toxicity risks that currently limit dose escalation in central lung cancer treatment. This project represents applied research in cancer treatment methodology development within the National Institutes of Health's broader mission to develop improved cancer treatment methods through laboratory and clinical research innovations.

Abstract

Lung cancer causes about 20% of all cancer deaths making IT the most lethal cancer. For central lung cancer (CLC), even the most conformal stereotactic body radiotherapy (SBRT) treatment plans inevitably overlap with organs at risk (OARS) such as the lung, heart, esophagus, and central airways. This overlap incurs substantial physical doses to these OARS, resulting in up to a 35% risk of fatal morbidity and guarded prognosis. Conformal flash proton therapy holds great promise for toxicity reduction while maintaining tumor control, by combining the advantages of (1) zero physical dose for OAR beyond bragg peak in proton SBRT, (2) 50% biological effective dose (bed) reduction to OAR in ultra-high dose rates (UHDR), which is delivery of a hypo fraction dose at a dose rate ≥40 GY/S and (3) 30% more bed and greater immune response with more elevated linear energy transfer (let) in tumor. CLC needs all three advantages because OAR toxicities hinder physical dose escalation. Its clinic translation needs UHDR in OARS and high let in tumor but has two challenges: (1) if not optimized, elevated let in OAR can lead to an elevated OAR toxicity (2) quality assurance (QA) to ensure the micro timing structure and microspatial let, two critical factors impacting flash has not yet been developed. Our integrated physical optimization (IPO) considers dose, dose rate and let in the objective function. This grant aims to establish an innovative platform of simultaneous intensity energy modulation and compensation (SIEMAC) optimization to inversely solve the variables (intensity and energy) of the IPO objectives and a QA system that combines micro-timing/dose rate with micro dosimetry/let. Advacam protype detector and commercial 2D strip-segmented ionization chamber array (SICA) can meet the QA needs. Aim 1: SIEMAC platform for CLC conformal flash. We will compare SIEMAC optimized plans with impt plans using ten CLC patients involving different OARS (lung, heart, esophagus, and central airways). Based on our preliminary data, the criteria are a >20% reduction in OAR bed or a >20% reduction in the irradiated volume for heart at 5 GY and lung at 20 GY, relative to impt, maintaining target coverage. We will reoptimize these plans for pulsed cyclotron and synchrotron beams to evaluate the impact of pulse structures over average dose rate. Aim 2: QA platform to validate monte carlo (MC) calculated UHDR and let. We will perform MC simulation, 3D print example passive energy modulation filters for three SIEMAC optimized flash fields. We will use advacam prototype detector to measure let spectra and micro timing and SICA to measure dose rate under conformal flash. Measured dose rates should agree within 5% of SICA. Measured let spectra agreement with MC simulation should be