To assess and localize hypoxic tumor subregions both at baseline and during the second week of radiotherapy. And to hypothesize that an intensified IMRT regimen may ensure higher local response rates compared to the standard IMRT approach.

A randomized, prospective, phase II study conducted with the aim of evaluating whether the strategy of overdosing hypoxic sub-regions of the primary tumor is associated with better local control compared to standard chemoradiotherapy for squamous cell carcinomas of the head and neck.

To evaluate whether side effects are influenced by the MRT approach. To search for initial (pre-treatment) hypoxic regions during treatment (at the 10th fraction of RT) in terms of volume and location. And finally to determine the prevalence and importance of pre-treatment hypoxic sub-regions and correlate the results with both clinical (primary site and tumor volume) and pathological (VEGF, EGFR and HIF-α expression in the primary tumor) characteristics.

Inclusion Criteria:

• histologically confirmed squamous cell carcinoma of the oropharynx, hypopharynx, or larynx;
• AJCC stage III or IV (cT2-4 N0-3 M0);
• specific informed consent.

Exclusion Criteria:

• Documented allergy to radiological contrast media or inability to receive contrast media due to concomitant pathology (e.g. renal);
• inability to receive radiotherapy (e.g. previous radiotherapy in the same region) and/or chemotherapy (inadequate bone marrow and/or liver and/or renal function);
• incomplete acquisition of MRI images;
• performance status 2 or more according to Zubrod;
• Previous invasive neoplasm (except skin cancer), except for neoplasms controlled for at least three years; non-invasive tumors (e.g. carcinoma in situ of the breast) are admitted even if diagnosed and treated in a period less than 3 years prior; patients with simultaneous or bilateral primary tumors are excluded;
• alcohol or drug abuse;
• legal incapacity or limited legal capacity;
• concomitant treatment with investigational drugs or participation in another clinical trial with use of investigational drugs within 30 days prior to screening for the study;
• documented hypersensitivity to study drugs or any of their excipients;
• pregnancy and/or breastfeeding.