AIM:To analyze the clinical and dosimetric predictive factors for radiation-induced esophageal injury in patients with non-small-cell lung cancer (NSCLC) during threedimensional conformal radiotherapy (3D-CRT). METHODS:We retrospectively analyzed 208 consecutive patients (146 men and 62 women) with NSCLC treated with 3D-CRT. The median age of the patients was 64 years (range 35-87 years). The clinical and treatment parameters including gender, age, performance status, sequential chemotherapy, concurrent chemotherapy, presence of carinal or subcarinal lymph nodes, pretreatment weight loss, mean dose to the entire esophagus, maximal point dose to the esophagus, and percentage of volume of esophagus receiving >55 Gy were studied. Clinical and dosimetric factors for radiation-induced acute and late grade 3-5 esophageal injury were analyzed according to Radiation Therapy Oncology Group (RTOG) criteria. RESULTS:Twenty-five (12%) of the two hundred and eight patients developed acute or late grade 3-5 esophageal injury. Among them, nine patients had both acute and late grade 3-5 esophageal injury, two died of late esophageal perforation. Concurrent chemotherapy and maximal point dose to the esophagus ≥60 Gy were significantly associated with the risk of grade 3-5 esophageal injury. Fifty-four (26%) of the two hundred and eight patients received concurrent chemotherapy. Among them, 25 (46%) developed grade 3-5 esophageal injury (P = 0.0001<0.01). However, no grade 3-5 esophageal injury occurred in patients who received a maximal point dose to the esophagus <60 Gy (P = 0.0001<0.01). CONCLUSION:Concurrent chemotherapy and the maximal esophageal point dose ≥60 Gy are significantly associated with the risk of grade 3-5 esophageal injury in patients with NSCLC treated with 3D-CRT. INTRODUCTIONRadiotherapy (RT) can achieve good results in the treatment of non-small-cell lung cancer (NSCLC). The key is how to monitor the dose to critical normal tissues such as the heart, normal lung, and esophagus. Several factors can minimize the dose of RT to the esophagus, including proximity of the esophagus to midline tumors or mediastinal adenopathy, proximity of the esophagus to higher priority organs such as spinal cord and heart and relative paucity of information on the clinical and dosimetric predictors of radiation-induced esophageal injury.Clinicians familiar with RT planning are often forced to evaluate multiple plans that produce equivalent coverage of the target with variable sparing of critical structures. By our experience, the esophageal dose is not critically considered because the clinical and dosimetric variables predicting esophageal injury are not well characterized. The purpose of this investigation was to analyze the incidence of acute and late grade 3-5 esophageal injury in patients with NSCLC during three-dimensional conformal radiotherapy (3D-CRT) combined with or without chemotherapy (sequential or concurrent).