Salivary Cytokine Levels and Oral Mucositis in Head and Neck Cancer Patients Treated With Chemotherapy and Radiation Therapy

• Published in: International journal of radiation oncology, biology, physics Vol. 96; no. 5; pp. 959 - 966
• Main Authors: Bossi, Paolo, MD, Bergamini, Cristiana, MD, Miceli, Rosalba, PhD, Cova, Agata, MLS, Orlandi, Ester, MD, Resteghini, Carlo, MD, Locati, Laura, MD, Alfieri, Salvatore, MD, Imbimbo, Martina, MD, Granata, Roberta, MD, Mariani, Luigi, PhD, Iacovelli, Nicola Alessandro, MD, Huber, Veronica, MD, Cavallo, Anna, MSc, Licitra, Lisa, MD, Rivoltini, Licia, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2016
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Area Under Curve; Carboplatin - administration & dosage; Carcinoma - therapy; Carcinoma, Squamous Cell - therapy; Cetuximab - administration & dosage; Chemoradiotherapy - adverse effects; CHEMOTHERAPY; Cisplatin - administration & dosage; Cytokines - analysis; Dose Fractionation; Fluorouracil - administration & dosage; HEAD; Head and Neck Neoplasms - therapy; Hematology, Oncology and Palliative Medicine; Humans; Hypopharyngeal Neoplasms - therapy; Interleukin-1beta - analysis; Interleukin-6 - analysis; Laryngeal Neoplasms - therapy; LYMPHOKINES; Mouth Neoplasms - therapy; Nasopharyngeal Neoplasms - therapy; NECK; NEOPLASMS; Oropharyngeal Neoplasms - therapy; PATIENTS; Prospective Studies; RADIATION HAZARDS; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; Radiotherapy, Intensity-Modulated - methods; Saliva - chemistry; Severity of Illness Index; Stomatitis - etiology; Stomatitis - metabolism; Taxoids - administration & dosage; Time Factors; Tumor Necrosis Factor-alpha - analysis
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2016.08.047

Purpose We assessed the presence of salivary cytokines, their modulation during chemoradiation therapy (CTRT), and their association with oral mucositis severity in patients with head and neck cancer (HNC). Methods and Materials The present prospective observational study enrolled 55 patients with locally advanced HNC requiring CTRT. We also studied 10 healthy volunteers and 10 patients with other cancers. The salivary levels of 13 cytokines were analyzed. We constructed a cytokine predictive score of oral mucositis severity. Results The baseline salivary cytokine levels were not associated with the severity of treatment-induced oral mucositis. The cytokine levels overall increased during treatment, especially in patients with worse mucositis. In particular, on univariable analysis, an increase of interleukin (IL)-1β (area under the curve [AUC] 0.733; P =.009), IL-6 (AUC 0.746; P =.005), and tumor necrosis factor-α (AUC 0.710; P =.005) at the third week of treatment was significantly associated with the development of severe oral mucositis. On multivariable analysis, the predictive score based on the IL-1β and IL-6 changes from baseline to week 3 was an early strong predictor of higher grade oral mucositis. Conclusions The treatment of HNC patients with concurrent CTRT induces a significant increase in the salivary levels of IL-1β, IL-6, and tumor necrosis factor-α, all positively associated with the severity of mucosal toxicity. A greater increase of IL-1β and IL-6 3 weeks after treatment initiation is predictive of worse oral mucositis, representing a potential tool for the early identification of patients at risk.