Association between salivary cytokine levels and chemoradiotherapy-induced toxicities in head and neck cancer patients.

5555 Background: Mucositis is a common complication of chemoradiotherapy (CTRT) for head and neck cancer (HNC), linked to a balance between pro- and anti-inflammation serum cytokines. No study has yet addressed the role of salivary cytokines in influencing toxicity severity. Methods: Twenty consecutive stage III (15%) and IV (85%) HNC patients (pts) were treated with radiotherapy (64-70 Gy) plus cisplatin (n=15), carboplatin (n=4) or cetuximab (n=1). Primary tumor site was oral cavity (15%), oropharynx (55%), nasopharynx (15%), larynx or hypopharynx (15%). Unstimulated saliva samples were collected according to standardized protocols before CTRT, during (3rd, 5th and 7th weeks) and two weeks after; concomitantly, mucositis grade (WHO classification), weight loss and need for feeding tube were evaluated. The salivary levels of 11 different cytokines (IFNγ, IL1β, IL2, IL4, IL5, IL6, IL8, IL10, IL12p70, TNFα and TNFβ) were analysed both in pts and in healthy donors (HD, n=10) by optimized bead-based multiplex immunoassay. The cytokine change during treatment was calculated as the difference between the mean of individual values and the baseline value. The Wilcoxon rank sum test was used for between-groups comparisons. Results: At baseline, no difference in cytokine levels was observed in pts as compared with HD, except IL8. A significant and progressive increase of IL1β, IL6, IL8, TNFα and IL10 levels was observed during treatment, with high levels persisting two weeks after treatment for all cytokines but IL1β. Significant association was shown between IL6 increase and G3/4 mucositis (p=0.009) or feeding tube need (p=0.04). The same trend was observed for TNFα. Interestingly, IL8 increase appeared to be specifically linked to weight loss (>10%, p=0.003). In contrast, baseline cytokine salivary levels were not predictive of treatment-induced toxicities. Conclusions: The increase of IL6, IL8 and TNFα salivary levels occurring in HNC patients with CTRT seems to be directly associated with mucositis severity, feeding tube prevalence and weight loss. Cytokines may represent a potential new target for preventive and/or therapeutic intervention.