Relationship between salivary inflammatory mediators and oral dryness during chemotherapy in patients with cancer: a cohort study.

PURPOSE: To evaluate the association between salivary inflammatory mediators and oral dryness during oral mucositis development in patients with cancer undergoing chemotherapy.

METHODS

This prospective cohort study (time-stratified sampling) enrolled adult patients undergoing chemotherapy or chemoradiotherapy at Niigata University Medical and Dental Hospital (November 2021-August 2023). Sample size was determined a priori from a pilot study. Oral mucosal status was graded using the World Health Organization oral toxicity scale, and oral moisture was measured (dryness < 28). Unstimulated whole saliva was analyzed for interleukins (IL)-1β, IL-6, IL-8, IL-10, IL-12p70, tumor necrosis factor (TNF), prostaglandin E2, and vascular endothelial growth factor via cytometric bead array and enzyme-linked immunosorbent assay. Clinical data included demographics, treatment, and days post-chemotherapy (0-7, 8-14, ≥ 15). TNF and IL-10 were independently associated with oral dryness; cutoffs were median levels in patients with grade 0 mucositis.

RESULTS

Among 162 patients, 56 (34.6%) had oral dryness. Dryness was associated with higher neutrophil counts (median: 3.23 vs. 3.00 × 103/µL; p = 0.04). C-reactive protein levels increased, and neutrophil counts decreased 8-14 days post-chemotherapy. Multivariate analysis showed that TNF > 4.7 pg/mL was inversely associated (OR = 0.27; 95% CI = 0.11-0.69; p = 0.0058), whereas IL-10 > 2.8 pg/mL was positively associated (OR = 3.17; 95% CI = 1.30-7.75; p = 0.011) with dryness. Sampling at 8-14 days post-chemotherapy predicted dryness (OR = 5.16; 95% CI = 1.32-20.09; p = 0.018).

CONCLUSIONS

Salivary TNF and IL-10 levels and sampling timing after CT were associated with oral dryness, suggesting temporal changes in salivary inflammatory mediators.