a Multicentre Phase III Study of Risk-based Treatment Intensification With Hyperfractionated Radiotherapy in Head and Neck Cancer Patients

Inclusion Criteria: 1. The patient must be at least 18 years old. 2. Histologically or cytologically confirmed, previously untreated, HNSCC of the oropharynx, hypopharynx, larynx or oral cavity without distant metastases and aimed for treatment with radiotherapy (with or without concomitant chemotherapy) with curative intent. 3. The primary tumour must fulfil the following high-risk criteria: 1. For p16+ oropharyngeal cancer: Radiographic measurement of threeorthogonal diameters must render a tumour estimate of ≥30 cc. 2. For all other subsites and for p16- oropharyngeal cancer: Radiographic measurement of three orthogonal diameters must render a tumour estimate of ≥20 cc. 4. The treatment may be followed but not preceded by surgery, either as a salvage procedure or a neck dissection. An excision of a lymph node or tonsillectomy for diagnostic purposes, does not exclude the patient from participation. 5. WHO/ECOG performance status 0-2 6. The patient must be able to understand the information about the treatment and give a written informed consent to participate in the trial. Exclusion Criteria: 1. Previous radiotherapy in the head and neck region. 2. Concomitant or previous malignancies, except uncomplicated basal cell carcinoma, early (T1-2 N0) squamous cell carcinoma of the skin with follow-up time of at least one year for squamous cell carcinomas, and except other cancer with a disease-free follow-up of at least three years 3. Two or more synchronous primary HNSCC at time of diagnosis 4. Nasopharyngeal cancer 5. Sinonasal cancer 6. Co-existing disease prejudicing survival (expected survival \< three years). 7. Pregnancy or lactation 8. Psychiatric or addictive disorders or other medical conditions which in the view of the investigator might impair patient compliance