Can exhaled nitric oxide (FeNO) predict radiotherapy-induced lung toxicity in lung cancer patients?

A strong increase in FeNO after radiotherapy (RT) for lung cancer may predict RT-induced lung toxicity. We aimed to describe the time-course of FeNO till 7.5 months after 3D conformal RT, and assess the relationships between FeNO variations and respiratory symptoms, CT scan changes or dosimetric parameters. FeNO was measured before RT, and 4, 5, 6, 10 weeks, 4 and 7.5 months after the beginning of RT. Results: Most of the 65 patients were males (74%), had squamous cell carcinoma (48%), and stage III disease (72%). 41 patients had sequential chemo-RT, 20 had concurrent RT and chemotherapy, and 4 had only RT. Eleven patients (17%) complained of respiratory symptoms after RT. Mean FeNO was a little lower before RT (14.3 (7.2) ppb) than at 7.5 months (18.2 (12.5) ppb, + 30% (8%), p<0.05). Between 4-10 weeks, 51-61% of patients showed non-significant changes in FeNO (< 5 ppb), whereas 13-18% showed increased FeNO compared to pre-RT values. Mean changes in FeNO were not different in patients with or without respiratory symptoms. Three patients (5%) had a >2-fold increase in FeNO, at 4 and 5 weeks. All three showed radiation-pneumonitis images at 3-4 months but only two had respiratory symptoms. The sensitivity and specificity of FeNO for the diagnosis of RT-induced symptoms were 18% and 84% for a >5 ppb increase, and 18% and 98% for a >2-fold increase. There was no correlation between dosimetric parameters and changes in FeNO. There was no correlation between absolute values or variations in FeNO and CT scan changes after RT. Conclusion: Serial FeNO measurements during RT cannot separate patients who will develop or stay free of radiation pneumonitis with sufficient accuracy.