The investigators aim at investigating in a prospective clinical trial whether using a Simoultaneous Integrated Boost of carbon ions treatment planning approach, improving the tumor dose conformation while lowering the unintended dose to the low-risk volume, can significantly reduce the probability of toxicity without affecting Local Control.

In photon radiotherapy, Simultaneous integrated boost (SIB)-intensity-modulated radiation therapy (IMRT) with slight hypofractionation in the HR-CTV is the current standard of care, being previously largely adopted in clinical practice and within several prospective clinical trials, with similar results in terms of toxicity and oncologic outcome.

Up to now, a simultaneous integrated boost (SIB) approach has not been fully exploited in CIRT so far. The expected benefit of a SIB planning approach in carbon ion treatment is the reduction of toxicity with respect to the sequential (SEQ) approach currently used in CNAO clinical practice, while maintaining the same local control rate. This benefit depends on the potentiality of SIB to better spare normal tissues, further enhancing the intrinsic favourable physical and radiobiological characteristics of the carbon ions.

Inclusion Criteria:

• Histologically-proven primary head and neck ACC;
• Unresectable stage or residual macroscopic disease after surgery or multiple microscopic margins after surgery;
• Patient with resectable tumor but refusing surgery
• cN0/pN0 - cN1/pN1 patients (only ipsilateral neck levels I and II)
• Absence of distant metastases or oligometastatic status (patients with ≤ 3 metastatic lung or bone lesions, excluding other sites;
• No previous radiotherapy in head and neck region;
• Karnofsky Performance Status ≥ 70;
• Age ≥ 18 years;
• Written informed consent
• Patients' ability to understand the characteristics and consequences of the clinical trial.

Exclusion Criteria:

• Local conditions contraindicating CIRT (e.g., active infection or previous history of recurrent infections in or close to the tumor site; intratumoral necrosis in strict proximity of vessels; pre-existing skin, bone or soft tissue fistula; extended mucosal involvement by the tumor; previous surgery with flap reconstruction);
• Tumour site in nasopharynx, pharynx and tongue base (where an exclusive CIRT treatment could be at high risk of toxicity);
• Tumor disease involving ≥ 50% of the palate with consequent high risks of serious anatomical damage in case of significant and rapid disease response to CIRT
• Nodal involvement > cN1/pN1 or cN1/pN1 outside ipsilateral levels I and II
• Tumor surrounding carotid artery > 180° or infiltrating the vessels
• itanium surgical implants or metal prostheses or any other condition that prevents adequate imaging to identify the target volume and may determine uncertainties in CIRT dose distribution during treatment planning
• Presence of any comorbidity deemed to impact on treatment toxicity;
• Psychic or other disorders that may prevent informed consent
• Active autoimmune disease (e.g. systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis)
• Contraindication to MRI
• Pregnancy or breastfeeding in progress