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. Materials/Methods: 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 Z 10), MRgRT on an MR-guided Linac (n Z 11), or VMAT (n Z 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. Results: Mean cardiac sparing among all patients between respective

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death as a competing risk. Univariable associations were analyzed using Cox proportional hazards regression. Radiation statistics were calculated using Monte Carlo dosimetry. Results: There were 146 patients included. Patient demographics and presenting tumor features are described in Table 1. Patients were treated with 125 I plaque radiotherapy at median dose 65 Gy (IQR: 65-65 Gy) to depth of 5 mm, with additional transpupillary thermotherapy (TTT) at the time of plaque removal in 140 (95.9%) cases. Median follow-up was 6.7 years (IQR: 2.7-9.3 years). At final follow-up, median logMAR visual acuity was 1.1 (IQR: 0.4-2.0) with Snellen acuity 20/15-20/40 (20%), 20/ 50-20/160 (26%), and 20/200 or worse (54%). Radiation complications were as follows: cystoid macular edema in 54 (38%), radiation maculopathy in 71 (50%), non-proliferative radiation retinopathy in 53 (38%), proliferative radiation retinopathy in 20 (14%), and radiation papillopathy in 53 (38%). There were 11 patients who required subsequent pan-retinal laser photocoagulation (8%). Radiation dose did not appear to impact radiation maculopathy or retinopathy, but radiation papillopathy was significantly associated with point dose, maximum dose, and mean dose to the optic disc (p < 0.05). Local tumor control was achieved in 145 (99.3%) patients with recurrence in 1 (0.7%) patient 6.5 years after plaque. The 5year cumulative incidence of distant metastasis was 7.2% with 5-year overall survival of 96.2%. Conclusion: Low dose 125 I plaque radiotherapy with TTT provided high rates of local tumor control. Radiation maculopathy, retinopathy, and papillopathy were still observed even with reduced radiation apex dose. Future studies are warranted to determine rates of tumor control and ocular toxicity in low dose brachytherapy without TTT.

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