The aim of this research project is to test the local response and the acute toxicity (which can be observed within 90 days).

Local response and acute toxicity are primary endpoints of the trial. At CNAO a proton boost is delivered on the PTV1rx (area at high risk of relapse) up to at least 70 Gy [RBE] in 2-3 Gy [RBE] per fractions for 8-15 total fractions.

PTV2 rx (area at low or intermediate risk of relapse) will be irradiated with photon IMRT up to a total dose of 50-60 Gy [RBE].

Secondary endpoints of the trial are local control, relapse free survival, overall survival, tumor specific survival, intermediate and long term toxicity.

Inclusion Criteria:

• Histologic/cytologic diagnosis of primary epithelial malignant or neuroendocrine tumour
• Inoperable tumour, locally advanced stage
• Seated in rhinopharynx, nasal and paranasal sinuses, hypopharynx, larynx, oral cavity and oropharynx
• At least one lesion measured according to the RECIST criteria
• Enrollment for irradiation with IMRT up to 50-60 Gy RBE] on the PTV1rx and PTV2 rx to be followed at CNAO with irradiation with proton boost on thePTV1rx.

Exclusion Criteria:

• Metastasis
• Previous radiotherapy
• Any metallic implants or other conditions such to prevent an adequate imaging of target volume
• Unavailability of previous IMRT first phase radiotherapy plans