Elevation in Exhaled Nitric Oxide Predicts for Radiation Pneumonitis

Purpose: Radiation pneumonitis is a major toxicity after thoracic radiotherapy (RT), with no method available to accurately predict the individual risk. This was a prospective study to evaluate exhaled nitric oxide as a predictive biomarker for radiation pneumonitis in esophageal cancer patients. Patients and Methods: A total of 34 patients prescribed neoadjuvant chemoradiotherapy for esophageal cancer were enrolled in the present trial. Each patient underwent respiratory surveys and exhaled nitric oxide (NO) measurements before, at the end of, and 1 to 2 months after completing RT. Pneumonitis toxicity was scored using the Common Terminology Criteria for Adverse Events, version 4.0. The demographics, dosimetric factors, and exhaled NO levels were evaluated for correlation with symptomatic patients (scores ≥2). Results: Of the 34 patients, 28 were evaluable. All had received 50.4 Gy RT with concurrent chemotherapy. The pneumonitis toxicity score was Grade 3 for 1, Grade 2 for 3, Grade 1 for 7, and Grade 0 for 17. The dosimetric factors were not predictive of symptoms. The mean exhaled NO level measured before, at completion, and at restaging was 17.3 ± 8.5 (range, 5.5–36.7), 16.0 ± 14.2 (range, 5.8–67.7), and 14.7 ± 6.2 (range, 5.5–28.0) parts per billion, respectively. The ratio of exhaled NO at the end of RT vs. before treatment was 3.4 (range, 1.7–6.7) for the symptomatic and 0.8 (range, 0.3–1.3) for the asymptomatic (p = .0017) patients. The elevation in exhaled NO preceded the peak symptoms by 33 days (range, 21–50). The interval to peak symptoms was inversely related to the exhaled NO elevation. Conclusions: Elevations in exhaled NO at the end of RT was found to predict for radiation pneumonitis symptoms.