Distinct patterns of stomatitis with concurrent cetuximab and radiotherapy for head and neck squamous cell carcinoma

To describe the distinct patterns of severe anterior stomatitis seen with concurrent cetuximab and radiotherapy (RT) compared to chemoRT or altered fractionation RT (AFRT) and explore potential associations with clinical and dosimetric parameters. We reviewed acute toxicity data from 42 patients receiving cetuximab-RT and a matched cohort of 36 patients receiving chemoRT or AFRT. The occurrence of grade ≥3 oral toxicities was analysed with respect to clinical (age, gender, smoking/alcohol history, tumour subsite, grade of acneiform rash) and dosimetric parameters. Cetuximab-RT patients experienced higher rates of grade ≥3 cheilitis (26% vs 6%, p=0.01) and anterior stomatitis (38% vs 6%, p=0.002), despite these structures receiving low RT doses (median maximum dose to lips 9.3 Gy, anterior oral cavity 20 Gy). Multivariable analyses identified increasing severity of acneiform rash as the strongest predictor of grade ≥3 cheilitis whilst increasing RT dose was weakly correlated. A trend was observed for increasing pack years of smoking on univariate analysis only. The combination of cetuximab and low doses of RT to the anterior oral cavity has resulted in a distinctive pattern of cheilitis and anterior stomatitis in our patients. Further exploration of this phenomenon may yield additional insights into the interaction of cetuximab with RT in non-target tissues.