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ArticleClinical oral investigations2025

Salivary metabolite-based prediction of radiotherapy-induced oral mucositis and candidiasis.

Saga Ramsay, Eelis Hyvärinen, Jopi Mikkonen, Wilfredo Alejandro González-Arriagada, Tuula Salo, Márcio Ajudarte Lopes, Bina Kashyap, Arja M Kullaa

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Article in Clinical oral investigations, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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8 authors.

Saga Ramsay *Institute of Dentistry, School of Medicine, University of Eastern Finland, Kuopio campus, Yliopistonranta 8, Kuopio, FI-70210, Finland.
Eelis Hyvärinen *Institute of Dentistry, School of Medicine, University of Eastern Finland, Kuopio campus, Yliopistonranta 8, Kuopio, FI-70210, Finland.
Jopi MikkonenInstitute of Dentistry, School of Medicine, University of Eastern Finland, Kuopio campus, Yliopistonranta 8, Kuopio, FI-70210, Finland.
Wilfredo Alejandro González-ArriagadaFacultad de Odontología, Universidad de los Andes, 7620111, Santiago, Chile.
Tuula SaloDepartment of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, 00014, Finland.
Márcio Ajudarte LopesDepartment of Oral Diagnosis, School of Dentistry, State University of Campinas, Sao Paulo, CEP 13414-018, Brazil.
Bina KashyapInstitute of Dentistry, School of Medicine, University of Eastern Finland, Kuopio campus, Yliopistonranta 8, Kuopio, FI-70210, Finland.
Arja M KullaaInstitute of Dentistry, School of Medicine, University of Eastern Finland, Kuopio campus, Yliopistonranta 8, Kuopio, FI-70210, Finland. arja.kullaa@uef.fi.

Funding

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6 · The paper itself

Abstract

objectivesOral toxicities affect a high proportion of head and neck cancer (HNC) patients receiving radiotherapy, lacking reliable predictive biomarkers for incidence and severity. We investigated salivary metabolites and metabolic pathways as non-invasive predictors of radiotherapy-induced oral mucositis (OM) and candidiasis. MATERIAL AND

methodsHNC patients undergoing radiotherapy were prospectively studied. Saliva samples of 45 HNC patients and 30 controls were analysed using NMR spectroscopy, and patients were assessed for oral complications during treatment.

resultsSignificant metabolite differences were identified between patients with and without complications. An increased concentration of lactate (p < 0.000), and a reduced concentration of formate (p = 0.018) and pyruvate (p = 0.045), was found in HNC patients at risk for OM during RT. Comparison of salivary metabolites between patients at risk or not risk for candidiasis presented increases in acetate (p = 0.005), alanine (p = 0.009), proline (p = 0.002), tyrosine (p < 0.000), trimethylamine (p = 0.007) and fucose (p < 0.000), whereas the level of citrate (p = 0.008) was decreased. Of the metabolic pathways, glucose-alanine cycle and thyroid hormone synthesis, were significantly different in patients at risk for candidiasis.

conclusionsSalivary metabolomics is a promising predictive tool for radiotherapy-induced oral complications, potentially enabling early intervention and personalized supportive care. CLINICAL RELEVANCE: Elevated level of salivary lactate seems to predict the development of OM, while fucosis was a sign of candidiasis. Multicentre validation studies are needed for its clinical implementation.

Indexed as

Candidiasis, OralHead and Neck NeoplasmsRadiation InjuriesSalivaStomatitisAdultAgedBiomarkersCase-Control StudiesFemaleHumansMagnetic Resonance SpectroscopyMaleMetabolomicsMiddle AgedProspective StudiesBiomarkersCandidiasisHead and neck cancerMetabolitesNMR spectroscopyOral mucositisRadiotherapySaliva

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