2411 - Optimizing Dose Escalation for Lung Cancer Reirradiation: Integrating Conformal Bragg Peak FLASH Radiotherapy with FLASH Biological Optimization

B. Selvaraj¹, X. Zhao¹, C. Cheng², D. Meng³, I. J. Choi^1,4, H. Zhai¹, F. Yu¹, J. R. Rembish¹, H. Lin^1,5, M. Kang¹, and C. B. Simone II^1,4; ¹New York Proton Center, New York, NY, ²Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, ³Peking University, Beijing, China, ⁴Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ⁵Memorial Sloan Kettering Cancer Center, New York, NY

Purpose/Objective(s): The reirradiation of recurrent lung cancers following definitive radiotherapy (RT) doses presents significant challenges due to the heightened risk of toxicities of the surrounding organs-at-risk (OARs) heart, lungs, spinal cord, and esophagus. We hypothesized that the novel Bragg peak FLASH technique (BP-FLASH) may provide enhanced protection for these OARs, thus allowing for higher treatment doses aimed at curative outcomes. Materials/

Methods: A model quantifying FLASH effectiveness was created based on existing biological evidence. In the design of FLASH plans for recurrent lung patients, a FLASH-sparing biological optimization (FBO) approach was integrated into the inverse treatment planning optimization. This process took into account the doses from prior RT during the optimization of FLASH planning, focusing on optimizing the FLASH ratio (V40Gy/s) to OARs that had received significant RT doses in the initial treatment. Ten consecutive lung cancer patients, previously treated with conventional proton pencil beam scanning (PBS)(CONV-PBS) reirradiation were selected for FBO. Three distinct reirradiation regimens were employed, consisting of doses of 40Gy, 50Gy, and 60Gy delivered in 5 fractions, which equate to EQD2 (equivalent doses in 2 Gy per fraction) of 60, 83.3, and 110 Gy, respectively. The EQD2 values for both CONV-PBS and BP-FLASH plans were determined, combined with the doses from previous radiotherapy, and a comprehensive analysis of all dose metrics was conducted.
Results: For the combined dose (prior-RT plus reirradiation), all BP-FLASH FBO plans targeting up to 60Gy (equivalent to 110Gy in EQD2) adhered to clinical guidelines and showed comparatively lower total dose metrics than the CONV-PBS 50Gy plan (equivalent to 83.3Gy EQD2). This decrease was noted in key OARs, with comparisons of BP-FLASH-EQD2-110Gy with CONV-PBS-83.3Gy showing: for the esophagus-V60, 6.8±7.1% versus 11.4±9.0%(p=0.07); for lung-V20, 17.0±11.9% versus 16.9±11.8%(p=0.38); for heart-V40, 6.0±5.8% versus 6.4±5.8%(p=0.07); and for spinal cord maximum dose, 30.8±15.7Gy versus 34.0±17.3Gy(p=0.24).
Conclusion: The FBO approaches utilizing BP-FLASH enable an escalation of the target dose to 60Gy while adhering to acceptable dose constraints. Integrating BP-FLASH with FBO presents a viable option for effective curative treatments in lung reirradiation.