Lessons and Opportunities for Biomarker-Driven Radiation Personalization in Head and Neck Cancer

Head and neck cancer is notoriously challenging to treat in part because it constitutes an anatomically and biologically diverse group of cancers with heterogeneous prognoses. While treatment can be associated with significant late toxicities, recurrence is often difficult to salvage with poor survival rates and functional morbidity.^1,2 Thus, achieving tumor control and cure at the initial diagnosis is the highest priority. Given the differing outcome expectations (even within a specific sub-site like oropharyngeal carcinoma), there has been growing interest in personalizing treatment: de-escalation in selected cancers to decrease the risk of late toxicity without compromising oncologic outcomes, and intensification for more aggressive cancers to improve oncologic outcomes without causing undue toxicity. This risk stratification is increasingly accomplished using biomarkers, which can represent molecular, clinicopathologic, and/or radiologic data. In this review, we will focus on biomarker-driven radiotherapy dose personalization with emphasis on oropharyngeal and nasopharyngeal carcinoma. This radiation personalization is largely performed on the population level by identifying patients with good prognosis via traditional clinicopathologic factors, although there are emerging studies supporting inter-tumor and intra-tumor level personalization via imaging and molecular biomarkers.