Transoral Robotic Surgery and Tailored Radiotherapy in Unknown Primary and Small Squamous Cell Head and Neck Cancer

The purpose of this study is to evaluate the use of Transoral Robotic Surgery (TORS) to identify small oropharyngeal carcinomas. Findings from this study will be used to better determine which patients may be suitable for more targeted radiotherapy that would lead to a reduction in the total amount of radiotherapy needed as part of their treatment. Reducing the amount of radiotherapy received has been found to reduce the risk of late complications and toxicity to the patient.The pathologic findings will then be used to determine patients who may be candidates for de-intensification of radiotherapy.

Patients who present with carcinomas of unknown primary site (CUP) of the head and neck represent a challenging problem for clinicians both from a diagnostic and therapeutic perspective. Traditional techniques for identification of primary tumors involved a Positron Emission Tomography scan (PET)/ computerized tomography scan(CT) followed by examination under anesthesia with biopsies of the nasopharynx, tongue base, piriform sinuses in conjunction with a tonsillectomy may identify as many as 44% of primary tumors, the remaining unidentified tumors are treated with mucosal irradiation to all high risk mucosal sites. The addition of a lingual tonsillectomy with Transoral Robotic Surgery (TORS) may identify almost 70% of primary tumours that have otherwise escaped initial identification at this timepoint,. Historically, for those whose primary would not be discovered at the PET/CT, the discovery would have been made later during follow up visits.

The investigators propose to integrate Transoral Robotic Surgery into the diagnostic evaluation of participants presenting with metastatic squamous cell carcinoma to the neck of unknown primary origin. The investigators will localize small hidden oropharyngeal carcinomas, determine their laterality, and based on the laterality of the tumour, laterality of neck nodes, and completeness of resection, will offer reduced radiotherapy to the primary site and/or to the neck (de-intensification)to the participant. The investigators hypothesize that this approach to unknown primary carcinomas will be both safe and effective.

Eligibility Criteria:
Inclusion Criteria:

* Age \>= 18
* Metastatic squamous cell carcinoma (T0,N1-3,M0) to at least one regional lymph node of the neck (includes N1-N3) based on fine needle aspiration (FNA) biopsy, core biopsy, excisional biopsy, or neck dissection
* Ability to understand and willing to sign a written informed consent document
* Women of child-producing potential must agree to use effective contraceptive methods prior to study entry, during study participation, and for at least 30 days after the last administration of study medication.

Exclusion Criteria:

* Evidence of a nasopharyngeal carcinoma by one or more of the following methods: endoscopic examination, imaging, positive nasopharyngeal biopsy or core lymph node biopsy staining for Epstein Barr Encoded RNA (EBER) by In Situ Hybridization.
* Prior non-cutaneous head and neck squamous cell carcinoma
* Prior head and neck radiotherapy
* History of neck dissection - contralateral to the side of the nodal disease
* Presence of lymphadenopathy on CT unlikely to originate from a primary oropharyngeal carcinoma (i.e., parotid, isolated low (level IV/low level V)
* Radiologically abnormal/enlarged retropharyngeal adenopathy.
* Poor performance status (ECOG status 3 - 5)
* Severe comorbidity or uncontrolled inter-current illness (i.e., unstable angina or heart failure in last 6 months, myocardial infarction in last 6 months, chronic obstructive pulmonary disease with exacerbations necessitating hospitalization or emergency room visit in the past 3 months, history of pneumonia in the past 3 months, use of home oxygen, uncorrectable coagulopathy)
* Not a surgical candidate
* Pregnancy