Determining a Dosimetric Correlate for Acute Esophagitis in Patients with Advanced Non-small Cell Lung Cancer Treated with Intensity Modulated Radiation Therapy (IMRT)

Abstract

Acute radiation esophagitis is a common complication in the treatment of lung malignancies which can lead to treatment interruption and undesirable morbidity. We report our experience treating locally-advanced non-small cell lung cancers using chemoradiotherapy via IMRT and the associated acute treatment-related toxicities, and we determined potential dosimetric parameters predictive for acute esophagitis. This retrospective, multi-site study assessed 37 Stage IA-IV lung cancer patients who received IMRT. All patients were scanned during free breathing using coached retrospective 4D-CT and 21 had phase-based gated treatment delivery. A median dose of 70.0 Gy (range: 50 - 81.9 Gy) over 35 fractions (range 25 - 39 fractions) was delivered to the tumor using inhomogeneity correction. The esophagus was contoured and the mean dose and the volume of esophagus receiving 30, 50, 60 and 70 Gy (V30, V50, V60, V70, respectively) was calculated for each patient. Patients were graded for acute and chronic toxicities using the CTCAE 3.0 and logistic regression was performed to test associations between dosimetric parameters and esophageal toxicity. All simulated patients completed their course of chemoradiotherapy treatment. Twenty-eight patients (76%) received radiation treatment with concurrent chemotherapy. The most common acute toxicities were nausea, esophagitis, and fatigue observed in 11, 26, and 18 patients respectively. Only 3 patients (8%) developed Grade 3 radiation pneumonitis confirmed clinical and radiographically and required treatment with oral steroids. Acute Grade 1, 2 and 3 nausea was observed in 5, 4 and 2 patients; acute Grade 1, 2 and 3 esophagitis was observed in 8, 17 and 1 patients and acute Grade 1, 2 and 3 fatigue was observed in 9, 7 and 2 patients, respectively. Patients who experienced any esophagitis had a mean dose in excess of 28.7 Gy to the esophagus (Odds ratio: 1.09, 95% confidence interval: 1.02 - 1.18, p = 0.01). Univariate logistic regression correlated acute Grade ≥2 esophagitis with V60 (p = 0.045) and mean esophageal dose (p = 0.049). We did not identify significant differences in acute esophagitis between patients receiving concurrent chemotherapy and radiation versus those receiving radiation alone (p = 0.058). We were not able to correlate any parameters with late/chronic esophagitis. The mean dose to the esophagus and the volume of esophagus receiving higher doses of irradiation, but not chemotherapy, are associated with the development of esophagitis. Maintaining a mean doses to the esophagus below 28.7 Gy and restricting the volume of esophagus receiving 60 Gy or more can help to minimize treatment associated esophagitis.