Advanced stage head and neck squamous cell carcinoma: What is next?

For most advanced stage head and neck squamous cell carcinomas (HNSCC) from the pharynx and larynx, organ preservation radiotherapy (RT) is standard of care. For advanced stage HNSCC from the oral cavity and tumor recurrences after radiotherapy, surgery is the preferred treatment. In the first part of this thesis, we evaluate clinical outcome after standard of care by retrospective analyses of patients treated in the Netherlands Cancer Institute and by systematic review and meta-analysis of literature. From these data, we must conclude that there is an urgent need for novel treatment strategies to improve clinical outcome. Over the last decade, immunotherapy has revolutionized cancer treatment. As anti-PD-(L)1 immune checkpoint blockade (ICB) results in an overall survival benefit in metastatic HNSCC, the primary objective was to evaluate ICB in the curative setting. In the second part of this thesis, we present feasibility data from two phase-I trials. First, we prove that anti-PD-L1 (avelumab) in combination with cetuximab-RT is feasible and safe in patients who are unfit for concurrent cisplatin treatment (BIR trial, NCT02938273). Second, anti-PD-1 (nivolumab) with anti-CTLA-4 (ipilimumab) prior to extensive (salvage) surgery is feasible in patients with considerable comorbidity, and results in major pathological responses within a short 5-week time frame in 50% of patients (IMCISION trial, NCT03003637). It is of great importance to find biomarkers to adequately predict treatment response. In the last part of this thesis, we present the ongoing prospective observational PECAN study. Our objective is to determine the prognostic value of circulating tumor DNA ‘liquid biopsies’ in blood and saliva during and after radiotherapy for response monitoring and as a tool for future dose (de-)escalation trials.