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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Pilot Study Integrating Transoral Robotic Surgery, Histopathologic Localization, and Tailored De-Intensification of Radiotherapy for Unknown Primary and Small Oropharyngeal Head and Neck Squamous Cell Carcinoma(FIND Trial)

Conditions
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Head and Neck Squamous Cell Carcinoma

Intervention / Treatment
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* Other: da Vinci Surgical System Model IS4000


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: There will only be a single group of participants in this study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: da Vinci Surgical System Model IS4000<br>Transoral robotic surgery, followed by tailored radiotherapy | Other: da Vinci Surgical System Model IS4000<br>* tailored radiotherapy regimen following transoral robotic surgery<br>* Other names: tailored radiotherapy regimen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of the rate of out-of-field failures following treatment | The primary outcome for the study is to determine the rate of out-of-field failures following treatment as determined by use of morphologic imaging (contrast enhanced CT or MRI of the head) and confirmed by biopsy. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (AE) monitoring | To determine the profile of TORS related complications and Surgical Adverse Events within 30 days of surgery using National Cancer Institute Common Terminology Criteria (CTC) for Adverse Events (NCI CTC-AE v 4.0) | 2 years | 
| Determination of proportions of occult oropharyngeal cancers identified | To determine the proportion of patients with occult oropharyngeal cancers identified | 2 years | 
| Location of primary tumours identified through enumeration of patients in each identified site group | To determine the location of primary tumours identified through enumeration of patients in each identified site group. The study data will be sorted by location of primary tumour and the proportions for each location calculated | 2 years | 
| Determination of the proportion of patients with completely resected primary tumours | To determine the location of primary tumours identified, the proportion of patients with primary oropharyngeal carcinomas completely resected (with negative margins), and the proportion of patients amenable to de-intensification treatment (ie, patients who receive no radiotherapy to the primary site and/or unilateral neck radiotherapy). | 2 years | 
| Determination of the proportion of patients patients amenable to de-intensification treatment | Determination of the proportion of patients patients amenable to de-intensification treatment | 2 years | 
| Exploration of expert rated swallowing impairment | To explore expert rated swallowing impairment on video fluoroscopic swallow studies (VFSS) using the Modified Barium Swallow Impairment (MBS-Imp)instrument tool 2 years | 2 years | 
| Exploration of patient reported swallowing related quality of life | To explore patient reported swallowing related quality of life using the MD Anderson Dysphagia Inventory (MDADI) | 2 years | 
| Exploration of speech and swallowing performance status | To explore observer rated speech and swallowing using the Performance Status Scale for Head and Neck (PSS-HN) instrument | 2 years | 
| Exploration of patient reported neck impairment | To explore patient reported neck impairment using the Neck Dissection Impairment Index (NDII) instrument | 2 years | 
| Determination of patterns of failure by location | To determine patterns of failure by location (local, regional, distant) as determined by CT/MRI of the Head and Neck and/or biopsy. | 2 years | 
| Rates of survival after treatment | To determine rates of survival at 2 years | 2 years |