Role of prostaglandin pathways in radiotherapy-induced mucositis.

Abstract

e20509 Background: Pathways associated with proinflammatory molecules are upregulated in oral mucositis. Lalla (Support Care Cancer 18:95, 2010) found an association between mucositis pain scores, tissue COX-1, and salivary prostaglandins in 4 patients receiving dose-dense chemotherapy. We investigated whether similar changes would be seen with radiotherapy (XRT)-induced mucositis. Methods: Patients receiving XRT including the oropharynx were evaluated at 4 time points, before XRT, midway through XRT, end of XRT, and 1 month after XRT. Subjective report of pain and objective mucositis scores were recorded. Patients also provided a 5-minute stimulated saliva specimen at each time point collected on ice with a protease inhibitor cocktail. Proteins were estimated using a Bradford assay. Prostaglandins were measured using ELISA assays. Results: 8 evaluable patients entered the study, including 7 male/1 female, median age 60 (range 48-66), primary site (oropharynx 1, unknown primary 1, base of tongue 3, tonsil 1, tongue 1, supraglottis 1), median XRT 7000 rads (range 6000-7200 rads), concomitant chemotherapy (cisplatin 7, none 1), histology (squamous 7, mucoepidermoid 1). Pain and mucositis scores increased during XRT and improved at 1 month after XRT. No increase in COX-2 levels was seen. Salivary PGD2, PGE2, and PGF2 increased from baseline with the greatest increase 1 month after XRT. There was a significant time effect for PGF2 (p=0.028) and marginal time effects for PGD2 (p=0.107) and PGE2 (p=0.069). Conclusions: Increased salivary prostaglandins are seen during and after XRT-induced oral mucositis, suggesting a role for proinflammatory mediators and providing a possible therapeutic target. Clinical trial information: NCT01252498. [Table: see text]