This study is being done to answer the following question: Does stereotactic body radiation therapy (SBRT) provide better cancer control compared to standard radiation therapy (RT) for those with advanced head and neck cancer?

Stereotactic body radiation therapy, or SBRT, is a cancer treatment that more precisely delivers radiation to the tumour area with less radiation going to unaffected areas around the tumour. It uses fewer treatments of higher doses compared to standard radiation therapy.

This study is being done to find out if this approach is better than the usual approach for advanced head and neck cancer. The usual approach is defined as care most people get for advanced head and neck cancer.

Inclusion Criteria:

• Histologically confirmed mucosal squamous cell carcinoma (SCC) of the head and neck arising from at least one of the following sites: oro/hypopharynx, oral cavity, supraglottic larynx, maxillary sinus, nasal cavity, or unknown primary
• Stages TX or T0-T4/N0-N3
• Must be considered unfit for curative intent RT as determined by the treating oncologist(s)
• Geriatric 8 score <14
• Patient must be ≥18 years of age
• Staging CT or MRI of the head and neck within 8 weeks prior to randomization
• Chest CT or x-ray. PET CT is permitted if CT is of diagnostic quality.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-3
• Participants of childbearing potential must have agreed to use a highly effective contraceptive method during protocol therapy.
• Patients with a prior malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational treatment are eligible for this trial.

Exclusion Criteria:

• Patients with nasopharyngeal carcinoma.
• Prior systemic therapy (including immunotherapy).
• Prior radiotherapy to the head and neck excluding superficial radiotherapy for head and neck skin cancer that does not overlap with current protocol treatment.
• Prior head and neck cancer excluding skin cancer.
• Patients with tumour locations/at risk of SBRT toxicity, including glottic/subglottic larynx, T4 hypopharynx, post-cricoid, cervical esophagus, circumferential pharyngeal involvement, extension/proximity to brain/optic structures, any single tumour mass >8 cm (in one dimension).
• > 2 nodal levels (Level 1a/b not counted); retropharyngeal lymph nodes (where the closest edge is < 2cm from the closest edge of CTV (primary or nodal) will not be considered as a different level). Note: a single lymph node mass that spans 2 levels will be considered as 1 level.
• Gross tumour poorly visualized on CT/MRI.
• Definitive radiological or clinically evident distant metastases.
• Scleroderma/CREST syndrome.