De-escalation of adjuvant radio(chemo)therapy for patients with HPV-positive head and neck squamous cell carcinoma: study protocol for a phase I trial to reduce late toxicity (DELPHI).

BACKGROUND: Patients with locally advanced head and neck squamous cell carcinoma are receiving adjuvant radio(chemo)therapy as standard of care, according to national guidelines. However, patients with human papilloma virus (HPV) driven oropharyngeal squamous cell carcinoma (OPSCC), are shown to have superior locoregional control (LRC) rates, suggesting that they are likely being overtreated. To date it is unknown, if and to which extent adjuvant radiotherapy can be safely reduced. METHODS AND DESIGN: The interventional multicentric DELPHI trial is investigating step-wise radiation dose reduction in patients with both p16-overexpressing and HPV16 DNA positive OPSCC. Depending on international clinical and histopathological risk factors, patients are being enrolled in the high-risk or intermediate-risk arm. Patients of the high-risk arm are receiving standard simultaneous chemotherapy with cisplatin. Patients with smoking history of at least 30 packyears are being treated in the observational arm. Primary endpoint of the DELPHI trial is LRC after 24 months. Secondary endpoints are acute and late toxicity, quality of life during and up to 24 months after the end of therapy as well as LRC and overall survival after 60 months. DISCUSSION: Primary aim of the DELPHI trial is to show that radiation dose reduction is safe and therefore feasible in patients with HPV-positive OPSCC. Secondary objective is to show that radiation-dose reduction leads to less late toxicity compared with standard treatment and thus improves quality of life. TRIAL REGISTRATION: The DELPHI trial is registered at clinicaltrials.gov under the identifier NCT03396718.