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Purpose We previously found that up to 75% of treatment failures after chemoradiation for unresectable esophageal cancer appear within the gross tumor volume (GTV) and that intensity-modulated [photon] radiation therapy (IMRT) may allow dose escalation to the tumor without increasing normal-tissue toxicity. Proton therapy may allow further dose escalation with even lower normal-tissue toxicity. Here we compared dosimetric parameters for photon IMRT with intensity-modulated proton therapy (IMPT) for unresectable, locally advanced distal esophageal cancer. Methods and Materials Four plans were created for each of 10 patients: IMPT delivered via anteroposterior/posteroanterior (AP/PA) beams, left posterior oblique/right posterior oblique (LPO/RPO) beams, or AP/LPO/RPO beams; and IMRT delivered with a concomitant boost to the GTV. Doses were 65.8 Gy to the GTV and 50.4 Gy to the planning target volume (PTV) in 28 fractions. Results Relative to IMRT, the IMPT (AP/PA) plan led to considerable reductions in mean lung dose (3.18 Gy vs 8.27 Gy, p<0.0001) and in lung V5, V10, and V20 (p≤0.0006) but did not reduce cardiac dose; the IMPT LPO/RPO plan also reduced the mean lung dose (4.9 Gy vs 8.2 Gy, p<0.001) as well as reducing heart doses (mean cardiac dose and cardiac V10, V20, and V30, p≤0.02) and liver doses (mean hepatic dose 5 Gy vs 14.9 Gy, p<0.0001). The IMPT AP/LPO/RPO plan led to considerable reductions in dose to the lung (p≤0.005), heart (p≤0.003), and liver (p≤0.04). Conclusions Compared with IMRT, IMPT for distal esophageal cancer can lower the dose to the heart, lung, and liver. The AP/LPO/RPO beam arrangement was optimal for sparing all three organs. The dosimetric benefits of protons will need to tailored to each patient based on their specific cardiac and pulmonary risks. IMPT for esophageal cancer will soon be investigate further in a prospective trial at our institution.

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