To investigate the tradeoff of esophageal treatment between real-time breath hold (BH) MR-guided radiotherapy (MRgRT), free breathing (FB) CT-based intensity modulated proton therapy (IMPT), and FB VMAT. We hypothesize that improved cardiopulmonary sparing would be achieved with BH MRgRT or FB IMPT compared to FB VMAT. We retrospectively evaluated differences in heart/lung dose and treatment plan conformality among 28 patients with distal esophageal cancer who were each treated with either IMPT (n = 10), MRgRT on an MR-guided Linac (n = 11), or VMAT (n = 7). All were prescribed 50.4 Gy/28 fractions. IMPT and VMAT patients received a 4DCT simulation scan to quantify the internal target volume margin (ITV) for respiratory motion. MRgRT patients were simulated and treated in an inspiration BH with a 3 mm CTV to PTV margin. In lieu of a PTV margin for IMPT cases, robust optimization for range and setup uncertainty was performed on iCTV (i.e., CTV with respiratory ITV). RTOG plan quality metrics were used to evaluate target coverage (TC) (PTV V100%/PTV vol), homogeneity index (HI) (PTV D2%/ D98%), high dose conformity (PITV), low dose conformity (D2cm), and gradient (R50%). For all coverage metrics, the CTV was used. Mean cardiac sparing among all patients between respective IMPT, MRgRT, and VMAT was 65.3cc, 73.0cc, and 141.5cc (V30Gy); 45.4cc, 38.5cc, and 84.7cc (V40Gy), 19.7cc, 12.5cc, 39.0cc, (V50Gy), 6.4cc, 15.0cc, 19.2cc (mean dose). Lung and liver sparing between respective IMPT, MRgRT and VMAT plans was 86.8cc, 299.7cc, and 909.0cc (lung, V20), 4.2Gy, 6.8Gy, and 15.6Gy (lung, mean dose), 3.8Gy, 19.5Gy, 16.2Gy (liver, mean dose). Homogeneity and conformity indices between IMPT, MRgRT, and VMAT were 1.6, 1.3, 1.5 (PITV), 1.1, 1.2, 1.1 (HI), 5.2, 5.2, 6.3 (R50%), and 45.3%, 56.6%, 54.1%(D2cm), respectively. CTV coverages for IMPT and MRgRT plans were 50.7, 50.5, 51.1 (D90%) and 0.99, 0.99, 0.98 (TC), respectively. Statistically significant differences in heart and lung dose are demonstrated in the Table below; no statistical difference was observed for coverage or conformality. FB IMPT and BH MRgRT both achieve significant lung and/or heart sparing compared to FB VMAT while maintaining excellent plan conformality. The varying extent of cardiopulmonary sparing achieved across these advanced radiation therapy modalities warrants prospective evaluation.Abstract 3498; TableHeart (V30)Heart (V40)Heart (V50)Heart (Mean)Lung (Mean)Lung (V20)Liver (Mean)MRgRT vs IMPTp = 0.695p = 0.602p = 0.792p = 0.0001p = 0.079p = 0.001p = 0.0001MRgRT vs VMATp = 0.048p = 0.058p = 0.053p = 0.101p = 0.0001p = 0.001p = 0.258IMPT vs VMATp = 0.031p = 0.134p = 0.218p = 0.0001p = 0.0001p = 0.0002p = 0.001 Open table in a new tab