Increased acid sphingomyelinase levels in saliva as oral mucositis severity predictors?

Elsa Beatriz Monroy Ordonez¹Tanja Sprave^1*Andreas R Thomsen¹Henning Schäfer¹Anca-Ligia Grosu¹Verena Jendrossek²Michael Henke¹Kristian Unger³Diana Klein²

• ¹Department of Radiation Oncology, Freiburg University Medical Center, Freiburg, Germany
• ²University of Duisburg-Essen, Duisburg, Germany
• ³Faculty of Medicine, Ludwig Maximilian University of Munich, Munich, Bavaria, Germany

Radiotherapy (RT) plays a central role in multidisciplinary treatment approaches in cancer therapy overall and, in particular, as an effective primary treatment modality for patients with head and neck cancer (HNC). One of the most common acute complications of RT for HNC patients is radiationinduced oral mucositis (OM), which can lead to severe oropharyngeal pain, swallowing and speech difficulties, and weight loss, thereby eventually causing interruption of RT. Although OM varies with tumor location and treatment methods, it is overall a common occurrence. However, it is unclear in which patients this severe condition occurs. The aim of this study was to evaluate the suitability of acid sphingomyelinase (ASM) as a potential biomarker for predicting the risk of OM and to investigate the association with mucositis severity. We investigated two independent patient cohorts from consecutive prospective studies (n=187). In the first cohort, 74 out of 109 patients developed OM during RT, of which 42 patients displayed early OM at low radiation dose. Grade 3 OM developed in 50 (67.6%) patients after definitive and in 24 (32.4%) after adjuvant RT. 34 patients did not develop OM. ASM protein levels were analyzed by Western blot analysis in unstimulated saliva samples collected from respective patients at least three days before the radiotherapy started. A significant increase in ASM levels was detected in the saliva of patients who developed mucositis early. Respective findings were confirmed in a second cohort (n=78). 44 out of 78 patients developed OM, of which 21 patients displayed early OM. 53 patients did not develop OM. Elevated ASM levels were confirmed in saliva of patients who developed mucositis early, an observation that was found particularly in the saliva of HPV-negative patients. HPV-positivity was present in 32 (41,0%) patients. Overall and regression-free survival did not correlate with the incidence of mucositis nor with the HPV-status. Although there is currently limited evidence for the potential implementation of salivary biomarkers to assess their association with the severity of mucositis, the findings here show that determining ASM levels in saliva of HNC patients before starting RT could be a promising method to predict mucositis risk.