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.
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Data availability
Research data are not available at this time. The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
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Acknowledgements
We thank M. Kaneko, S. Ota, and A. Enomoto for their help with the sample measurements. This study was supported by JSPS KAKENHI (grant numbers JP19K08106, JP16K10404, and JP22H00595).
Funding
This study was supported by JSPS KAKENHI (grant numbers JP19K08106, JP16K10404, and JP22H00595).
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All authors contributed to the conception and design of the study. Material preparation and data collection were performed by SS. Analysis was performed by MS and KT. The first draft of the manuscript was written by SS and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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The Ethics Committee of Tokyo Medical University Hospital granted permission to conduct a cohort study to investigate radiation pneumonitis using salivary metabolomics to treat lung cancer (SH4092).
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Shiraishi, S., Sugimoto, M. & Tokuuye, K. Salivary metabolites as novel independent predictors of radiation pneumonitis. J Cancer Res Clin Oncol 149, 17559–17566 (2023). https://doi.org/10.1007/s00432-023-05479-3
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DOI: https://doi.org/10.1007/s00432-023-05479-3