2246 - Advancing Pancreatic Cancer Treatment with Bragg Peak Proton FLASH Radiotherapy: Escalating Target Dose through Biological Optimization of the FLASH Effect

C. Cheng¹, X. Zhao², I. J. Choi², Y. Zhang¹, S. Hasan², A. M. Chhabra², C. B. Simone II², H. Lin², and M. Kang²; ¹Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, ²New York Proton Center, New York, NY

Purpose/Objective(s): Delivering adequate doses to the target while sparing surrounding radiosensitive organs presents a challenge for unresectable pancreatic cancer. Planning Bragg peak proton FLASH therapy has yet to be studied but can allow for precise delivery of ablative doses to the target area while maintaining an ultra-high dose rate, potentially offering additional protection to adjacent organs-at-risk (OARs) through the FLASH-sparing effect. Through a combined optimization of target coverage and FLASH dose ratios of OARs based on a phenomenological FLASH-sparing modeling, toxicities may be reduced. We hypothesize that the innovative Bragg peak FLASH technique can escalate the target dose, improve tumor control while maintain acceptable expected toxicity levels. Materials/

Methods: Phenomenological FLASH-sparing modeling for different types of tissues sourced from existing literature was applied to simulate the FLASH-sparing effect. We used an in-house treatment planning system incorporating a FLASH biological optimization (FBO) module using the single-energy Bragg peak technique. Seven consecutive pancreatic cancer patients previously treated with conventional proton pencil beam scanning (CONV-IMPT) were reoptimized, with the target dose intentionally escalated from 40 Gy to 50 Gy in 5 fractions with both methods. Dose metrics for OARs according to AGITG and TROG guidelines were compared.
Results: Table 1 illustrates the doses to major OARs of a 40 Gy in 5 fractions regimen. The stomach, duodenum, and bowel are similar between CONV-IMPT and Bragg peak proton FLASH. The D0.5cc for the stomach, duodenum, and small bowel are 30.3 Gy, 32.6 Gy, and 14.2 Gy respectively, for clinical plans and 32.4 Gy, 38.8 Gy, and 3.9 Gy for Bragg peak plans. Escalating the target dose to 50 Gy without FBO leads to D0.5cc exceeding constraints, at 39.1 Gy for stomach, 48.5 Gy for stomach PRV, 44.7 Gy for duodenum, and 49.3 Gy for duodenum PRV. Conversely, with FBO, all D0.5cc values for OARs meet constraints.
Conclusion: With innovative Bragg peak technique, incorporating FBO elevates the target dose, improves tumor control while potentially achieving reduced toxicities. Abstract 2246 - Table 1: Plan Compliance with the Australasian Gastrointestinal Trials Group (AGITG) and Trans-Tasman Radiation Oncology Group (TROG) Guidelines for Pancreatic SBRT 40 Gy in 5 fractions.

		Clinical CONV-IMPT	Bragg peak RBE dose		Bragg peak with FBO
Prescriptions		8 Gy*5	8 Gy*5	10 Gy*5	8 Gy*5	10 Gy*5
ROIs	Constraints
CTV	D95=100%	100.0	100.0	100.0	100.0	100.0
	D0.5cc<130%	103.0	109.3	113.4	109.3	113.4
Duodenum	D0.5cc<33Gy	32.6	38.8	44.7	32.7	33.9
	V30<5cc	4.0	14.0	19.4	1.9	3.9
Stomach	D0.5cc<33Gy	30.3	32.4	39.1	25.2	30.0
Duodenum PRV	D0.5cc<38Gy	38.0	41.0	49.3	33.4	37.1
Stomach PRV	D0.5cc<38Gy	37.6	38.3	48.5	29.9	36.4
Spinal cord+5mm	D0.5cc<20Gy	16.8	17.4	22.3	13.6	16.4
Combined kidneys	V12<25%	25.0	18.6	33.1	8.2	15.8