A Study Comparing Adaptive Biological Imaging - Voxel Intensity - Based Radiotherapy (Adaptive Dose Escalation) Versus Standard Radiotherapy for Head and Neck Cancer

• Regional (elective neck) and distant control. [ Time Frame: after 1 year ] [ Designated as safety issue: No ]
  18F-FDG-PET/CT scans will be performed.
• Topography of local and/or regional relapse. [ Time Frame: during the first year post-treatment ] [ Designated as safety issue: No ]
  18F-FDG-PET/CT scans will be performedduring the first year post-treatment time point of local and/or regional relapse
• Tumor response [ Time Frame: 3 months post-treatment ] [ Designated as safety issue: No ]
  18F-FDG-PET/CT scans will be performed
• Acute toxicity [ Time Frame: up to 12 months of follow-up ] [ Designated as safety issue: Yes ]
• Overall disease-specific, disease-free survival. [ Time Frame: at 1 year ] [ Designated as safety issue: No ]
• Late toxicity [ Time Frame: up to 12 months of follow-up ] [ Designated as safety issue: Yes ]
• Time point of local and/or regional relapse. [ Time Frame: during the first year post-treatment ] [ Designated as safety issue: No ]
  18F-FDG-PET/CT scans will be performed.

The investigators hypothesize that treatment adaptation to biological and anatomical changes, occurring during treatment, can increase the chance of cure at minimized or equal radiation-induced toxicity in head and neck cancer patients. This trial compares standard intensity-modulated radiotherapy (IMRT), using only pre-treatment planning 18F-FDG-PET/CT scans to adaptive 18F-FDG-PET-voxel intensity based IMRT or volumetric-modulated arc therapy (VMAT) using repetitive per-treatment planning 18F-FDG-PET/CT scans for head and neck cancer.

• Radiation: Adaptive dose-painting-by-numbers
  Adaptive dose escalation by dose-painting-by-numbers.
• Radiation: standard intensity-modulated radiotherapy (IMRT)
  Standard radiotherapy for head and neck cancer.

• Experimental: adaptive dose-painting-by-numbers

  This patient group will be treated by adaptive dose-painting-by-numbers, while patients in the control arm will receive standard treatment.

  Patients will have a 50 % chance of being allocated to the experimental arm and a 50 % chance of being allocated to the control arm.

  Intervention: Radiation: Adaptive dose-painting-by-numbers
• Active Comparator: standard intensity-modulated radiotherapy (IMRT)

  This patient group will be treated by standard intensity-modulated radiotherapy (IMRT), while patients in the experimental arm will receive adaptive dose-painting-by-numbers.

  Patients will have a 50 % chance of being allocated to the experimental arm and a 50 % chance of being allocated to the control arm.

  Intervention: Radiation: standard intensity-modulated radiotherapy (IMRT)

Inclusion Criteria:

• Histologically confirmed squamous cell carcinoma of oral cavity, oropharynx, hypopharynx or larynx
• Primary unresectable tumor and/or patients that refused surgery
• Stages T1-4; T3-4 N0 or T(any) N1-3 for glottic cancer
• Multidisciplinary decision of curative radiotherapy or radiochemotherapy
• Karnofsky performance status >= 70 %
• Age >= 18 years old
• Informed consent obtained, signed and dated before specific protocol procedures

Exclusion Criteria:

• High risk Human Papilloma Virus (HPV)
• Treatment combined with brachytherapy
• Prior irradiation to the head and neck region
• History of prior malignancies, except for cured non-melanoma skin cancer, curatively treated in-situ carcinoma of the cervix or other cancer curatively treated and with no evidence of disease for at least 5 years.
• Distant metastases
• Pregnant or lactating women
• Creatinine clearance (Cockcroft-Gault) =< 60 mL/min
• Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study
• Patient unlikely to comply with protocol, i.e. uncooperative attitude, inability to return for follow-up visits, and unlikely to complete the study.