Abstract
PURPOSE: Radiotherapy is an integral treatment for non-small cell lung cancer (NSCLC); however, radiation-induced toxicities such as radiation pneumonitis (RP) present a considerable challenge. Herein, we aimed to evaluate the potential of salivary metabolomics as an independent risk factor for predicting RP. METHODS: This study included 62 consecutive patients with NSCLC who underwent thoracic radiotherapy at Tokyo Medical University between September 2016 and December 2018. The median age of the patients was 75 years (range: 41-89), comprising 47 (75.8%) males and 15 (24.2%) females. Patients with stage I NSCLC received 75 Gy in 30 fractions, whereas those with stage II and III NSCLC received 66 Gy in 33 fractions. Saliva samples were collected before treatment and at 2 weeks, 1 month, 3 months, and 1 year after initiating radiotherapy. Clinical RP was defined as grade 2 according to the Common Toxicity Criteria for Adverse Events. Salivary metabolomics were analyzed using capillary electrophoresis-mass spectrometry. Salivary metabolites were evaluated as potential predictors of RP. RESULTS: Clinical RP was observed in 11 patients (17.7%); no RP-related deaths were observed. Clinical RP developed at a median of 4 months (range: 2-6 months) after initiating radiotherapy. Three metabolites, butyrate, propionate, and hexanoate, collected before radiotherapy exhibited predictive ability for clinical RP. Multivariate logistic analysis indicated butyrate (P = 0.033) as a predictive factor, along with the previously known factor of lung volume irradiated with > 20 Gy (P = 0.045). CONCLUSION: Salivary metabolite butyrate was an independent risk factor for clinical RP.