Simple SummaryWhile pre-operative radiation did not improve abdominal recurrence-free survival for retroperitoneal sarcoma in the randomized STRASS trial, it did reduce rates of local recurrence. However, the risk of toxicity was substantial and the time to surgery was prolonged. A combination of hypofractionation and proton therapy may reduce delays from the initiation of radiation to surgery and limit the dose to surrounding organs at risk. We conducted a dosimetric comparison of the pre-operative ultra-hypofractionated intensity-modulated photon radiotherapy and proton therapy using a five-fraction regimen of 25 Gy radiobiological equivalent (GyE) to the clinical target volume and 30 GyE to the margin-at-risk (radiobiological effective dose 1.1). Proton therapy maintained target coverage while significantly reducing the dose to adjacent organs at risk and the integral dose compared to photons. Further investigation is warranted to validate these dosimetric findings and potential clinical benefit. A prospective trial treating retroperitoneal sarcoma with pre-operative ultra-hypofractionated proton therapy at our institution is currently being pursued.AbstractBackground: While pre-operative radiation did not improve abdominal recurrence-free survival for retroperitoneal sarcoma (RPS) in the randomized STRASS trial, it did reduce rates of local recurrence. However, the risk of toxicity was substantial and the time to surgery was prolonged. A combination of hypofractionation and proton therapy may reduce delays from the initiation of radiation to surgery and limit the dose to surrounding organs at risk (OARs). We conducted a dosimetric comparison of the pre-operative ultra-hypofractionated intensity-modulated photon (IMRT) and proton radiotherapy (IMPT). Methods: Pre-operative IMRT and IMPT plans were generated on 10 RPS patients. The prescription was 25 Gy radiobiological equivalents (GyEs) (radiobiological effective dose of 1.1) to the clinical target volume and 30 GyEs to the margin at risk, all in five fractions. Comparisons were made using student T-tests. Results: The following endpoints were significantly lower with IMPT than with IMRT: mean doses to liver, bone, and all genitourinary and gastrointestinal OARs; bowel, kidney, and bone V5–V20; stomach V15; liver V5; maximum doses to stomach, spinal canal, and body; and whole-body integral dose. Conclusions: IMPT maintained target coverage while significantly reducing the dose to adjacent OARs and integral dose compared to IMRT. A prospective trial treating RPS with pre-operative ultra-hypofractionated IMPT at our institution is currently being pursued.