Serum citrulline as a prognostic marker in patients with oropharyngeal carcinoma treated with chemoradiotherapy.

Introduction: Oropharyngeal carcinoma (OPC) represents one of the most rapidly increasing head and neck cancers worldwide, with prognosis strongly influenced by human papillomavirus (HPV) infection. Given the clinical significance, there is a strong demand to evaluate novel biomarkers to monitor treatment outcomes. Therefore, we conducted a study to assess the prognostic value of citrulline, a well- established marker of enterocyte injury, in patients undergoing OPC treatment. Material and methods: We reanalysed a cohort of patients with OPC recruited across three tertiary oncology centres in Poland. All patients were treated with intensity-modulated radiotherapy, with concurrent chemotherapy. Serum citrulline levels were measured prior to treatment using a dedicated ELISA kit. The associations between pre-treatment citrulline levels, clinical characteristics, and patient survival outcomes were evaluated. Results: A total of 64 patients treated with chemoradiotherapy (CRT) were included. The baseline citrulline level showed no significant association with clinical characteristics. In univariable Cox regression, tumour size, along with induction chemotherapy, were significantly associated with poorer overall survival (OS) and progression- free survival (PFS). In contrast, the baseline citrulline level was not predictive in univariate analysis. In the subgroup analysis of patients with positive HPV status, both the larger tumour size and higher citrulline level were significantly associated with poorer OS and PFS. Conclusions: Baseline citrulline demonstrated prognostic value for OS and PFS in HPV-positive patients treated with CRT. These findings suggest a potential role for citrulline as a biomarker of treatment-related vulnerability in OPC and warrant further validation in larger, independent cohorts.