Treatment-related Acute Esophagitis For Patients With Locoregionally Advanced Non–Small Cell Lung Cancer Treated With Involved-field Radiotherapy and Concurrent Chemotherapy

PURPOSE: To explore the incidence and risk factors for treatment-related acute esophagitis associated with involved-field radiation therapy (RT) delivered concurrently with chemotherapy for patients with locoregionally advanced non-small cell lung cancer. MATERIALS AND METHODS: Forty-nine consecutive patients diagnosed with locoregionally advanced non-small cell lung cancer were treated using involved-field RT. Radiotherapy target volumes included the primary lung tumor and involved mediastinal lymphadenopathy as defined on imaging studies including computed tomography of the chest and fluorodeoxyglucose-positron emission tomography/computed tomography. The patients were treated to a median total dose of 63 Gy (range, 55.8 to 74 Gy) using daily fractions of 1.8 or 2.0 Gy. No elective radiotherapy of mediastinal lymph nodes was used. Concurrent platinum-based chemotherapy was delivered to all patients. Treatment-related toxicity was evaluated during the course of RT and subsequent follow-up visits. RESULTS: Thirty-one (63%) patients were female and 18 (37%) were male. Median age at the time of diagnosis was 68 years (range, 36 to 83 y). Thirty-one patients (63%) developed treatment-related acute esophagitis: 24 patients (49%) grade 2 and 7 (14%) patients grade 3 esophagitis, with the peak occurring during the seventh week of radiotherapy. No grade ≥ 4 esophagitis was seen in this cohort. Eighteen patients (37%) did not develop radiation-induced esophagitis associated with their course of chemoradiotherapy. In the univariate analysis, age at the time of diagnosis, radiation dose per fraction, and total volume of the esophagus were significantly associated with the risk of acute esophagitis. Increasing age reduced the risk of acute esophagitis (odds ratio [OR] for 10-y increase = 0.40) as did increasing total esophagus volume (OR for 10-U increase = 0.27). Dose per fraction of 1.8 Gy was associated with lower risk of acute esophagitis when compared with dose per fraction of 2 Gy (OR = 0.19). Marginal associations were observed for all of the volume variables. Higher volume variable values had a nonsignificant association with an increase in risk of acute esophagitis. However, only the total volume of the esophagus (P = 0.0032) and larger dose per fraction (2 vs. 1.8 Gy) (P = 0.011) remained significantly associated with higher risk of developing grade ≥ 2 acute esophagitis in the multivariate analysis. CONCLUSIONS: Higher risk of grade ≥ 2 treatment-related esophagitis was associated with lower total esophageal volume and higher radiotherapy dose per fraction and should be taken into consideration during patient treatment planning. Inclusion of total esophageal volume and dose per fraction into future clinical protocols may further help our understanding of treatment-related esophagitis and enable the development of novel preventative approaches.