Surgery and Reducing Ionizing Radiation of the Unknown Primary

About 3% of people with head and neck cancer have cancer in their lymph nodes, but doctors are unable to find the primary tumour. This situation has become more common due to human papillomavirus (HPV), a virus linked to certain cancers. Generally, patients with HPV-related cancers have a good outlook, with around 90% surviving for at least five years. Recent advancements in medical technology, such as advanced imaging and specialized surgeries, have significantly improved doctors' ability to find these hidden tumours. These techniques can locate the primary tumour in 70-80% of cases. If the tumour remains undetected, it could be very small or potentially eliminated by the body's immune system. The best way to treat this type of cancer is still debated. Current treatment options include surgery to remove lymph nodes or radiation therapy. There is no clear agreement on which areas should receive radiation. Often, surgery is performed on one side of the throat to try and locate the tumour's origin. Researchers are exploring ways to minimize the harmful side effects of treatment. Some studies suggest that surgery alone might be sufficient for patients with small tumours in their neck, but more research is needed. Another important question is whether radiation needs to cover the entire throat area. Recent findings suggest that omitting radiation from some areas might reduce side effects such as difficulty swallowing and dry mouth. The SUPERIOR trial aims to investigate whether reducing the amount of radiation can still be effective and improve patients' quality of life. The study also examines whether surgery alone is adequate for certain patients with HPV-related cancers.

Sex

All

Minimum age

18 Years

Inclusion criteria for the Registration phase

* p16 positive PUK SCC of the neck
* Age 18 years or older
* Willing to provide informed consent
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Clinical nodal stage N1, AJCC 8th edition (i.e. clinical unilateral nodal disease, none larger than 6 cm)
* Complete clinical work-up, including CT neck, physical examination with nasopharyngoscopy, and PET/CT, with no evidence of a primary tumor. The PET/CT scan must be without focal metabolic activity concerning for a primary tumor, in the opinion of the nuclear medicine physician. Metabolic activity, particularly in the tonsils and base of the tongue which is within normal physiologic range, does not exclude participation.

Inclusion criteria for the Randomization phase

* Completed ipsilateral tonsillectomy and base of tongue mucosectomy with no evidence of a primary tumor

  o Note, patients who had a PET/CT that was initially positive, and therefore not meeting criteria in 4.10, but panendoscopy with biopsies of the fluorodeoxyglucose (FDG)-avid areas do not show malignancy, can then be enrolled and would be returned the OR for a neck dissection prior to randomization
* Ipsilateral nodal disease on pathology with no evidence of extranodal extension

Exclusion Criteria:

* Radiological or pathological extra-nodal extension
* Epstein-Barr Virus (EBV)-positive
* Clinical nodal stage (i.e. before neck dissection) N2-3, AJCC 8th edition (ie. bilateral nodes or node \>6cm)
* Pathological nodal stage (i.e. after neck dissection) pN3
* Prior history of head and neck cancer within 2 years
* Any other active invasive malignancy, except non-melanotic skin cancers, low-risk prostate cancer, and stage I-IVA papillary or follicular thyroid cancer
* Known metastatic disease
* Unable to complete QOL questionnaires
* Pregnant or lactating women

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