Predictive Modelling for Patient Stratification According to Treatment-related Toxicity and Survival After Chemoradiation for Head and Neck Cancer

Radiotherapy is an integral component of the current multimodality treatment approach in locally advanced head and neck cancer (HNC). There is growing evidence that more aggressive treatment regimens improve tumour control and survival. However, intensified treatment is at the expense of increased toxicity, in particular severe acute mucositis. In addition and of increasing importance, late and irreversible treatment-related side effects, including xerostomia and swallowing dysfunction, occur in a considerable proportion of patients and negatively affect quality of life. High-risk human papilloma virus (HPV), specifically HPV type-16, is implicated as the causative factor in a proportion of HNC, especially those of the oropharynx. HPV-related cancers respond well to chemoradiotherapy compared to HNC related to tobacco and alcohol. Furthermore, the incidence of HPV-related oropharyngeal cancer is rising in Western countries. Given the significant toxicity associated with concurrent chemoradiotherapy, subsets of patients could be managed differently. The first objective of the project is to develop predictive models for radiation-induced dysphagia and xerostomia in HNC patients. Clinical characteristics, treatment parameters, dose-volume effects on healthy tissues and whole-genome genetic data will be considered. The second objective of the project is to study the prognostic value of HPV status together with a panel of tumour biomarkers in oropharyngeal cancer patients. The overall aim of the project is to stratify patients according to the risks (side-effects) and benefits (survival) of cancer treatment using the developed risk models. Clustering patients into different risk categories may aid treatment decision making reducing therapy toxicity without compromising survival.