The RESCUE Study: Survival and Functional Outcomes Following Salvage Surgery for RESidual or reCurrent sqUamous cEll Carcinoma of the Head and Neck

Study Overview
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Brief Summary
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The RESCUE study is a combined retrospective and prospective multicentre cohort study investigating the survival and functional outcomes in patients undergoing salvage surgery for recurrent, residual, and new primary head and neck squamous cell carcinoma (SCC). Additionally, the RESCUE study will contain an exploratory molecular analysis of consenting patients to assess the relationship between cancer genomics, previous radiotherapy, and recurrence in head and neck cancer.

Detailed Description
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The RESCUE study is a combined retrospective and prospective multicentre cohort study investigating the survival and functional outcomes in patients undergoing salvage surgery for recurrent, residual, and new primary head and neck squamous cell carcinoma (SCC). Additionally, the RESCUE study will contain an exploratory molecular analysis of consenting patients to assess the relationship between cancer genomics, previous radiotherapy, and recurrence in head and neck cancer. The aim of this study is to determine the survival, functional and quality of life outcomes of patients undergoing all salvage surgery for recurrent, residual and new primary head and neck SCC, and to establish the genetic architecture and clonal evolution H&N SCC after previous treatment for radiotherapy cancer.

Official Title
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The RESCUE Study: Survival and Functional Outcomes Following Salvage Surgery for RESidual or reCurrent sqUamous cEll Carcinoma of the Head and Neck

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Genetic: Molecular Analyses


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged over 18 Previous H&N SCC treated with radiotherapy with or without chemotherapy Local or regionally recurrent, residual, or new primary SCC of the oropharynx, oral cavity, larynx, and hypopharynx Ability to give informed consent for biological sample collection (molecular analysis study only) Exclusion Criteria: Nasopharyngeal and cutaneous SCC of the H&N Thyroid, salivary gland, and non-squamous cell H&N cancers Presence of distant metastasis (M1) or surgically inoperable T4b tumours

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1<br>Participants with previous diagnosis of H&N SCC treated with radiotherapy. Recurrent, residual, or new primary SCC of the oropharynx, oral cavity, larynx, and hypopharynx treated with salvage surgery | Genetic: Molecular Analyses<br>* Nucleic acid extraction, protein analysis. Tumour tissue, blood and saliva samples collected.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ascertain the 2-year disease-free survival post salvage surgery | Ascertain the 2-year disease-free survival post salvage surgery for recurrent/ residual/ new primary head and neck SCC (split cohort of prospective and retrospective patients) | Study duration is 3 years to include 1 year recruitment period. Active follow-up for patients is up to 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Define the 2- and 5-year overall and disease specific survival in retrospectively identified patients | Define the 2- and 5-year overall and disease specific survival in retrospectively identified patients undergoing salvage surgery for recurrent/ residual/ new primary head and neck SCC | Study duration is 3 years to include 1 year recruitment period. Active follow-up for prospective patients is up to 2 years. Follow-up for retrospective patients is up to 5 years. | 
| Define the 2 year overall and disease specific survival in prospectively identified patients | Define the 2 year overall and disease specific survival in prospectively identified patients undergoing salvage surgery for recurrent/ residual/ new primary head and neck SCC | Study duration is 3 years to include 1 year recruitment period. Active follow-up for patients is up to 2 years. | 
| Report on gross functional outcomes by documenting rates of gastrostomy and tracheostomy dependence at 1-year post-salvage surgery. | Report on gross functional outcomes by documenting rates of gastrostomy and tracheostomy dependence at 1-year post-salvage surgery. | Study duration is 3 years with up to 2 years follow-up in prospective and up to 5 years follow-up in retrospective patients. Functional outcomes will be measured from the date of surgery. | 
| For the prospective cohort assess the overall quality-of-life outcomes pre-operatively and at 6- and 12-months post-surgery using validated questionnaires. | For the prospective cohort assess the overall quality-of-life outcomes at pre-operatively and at 6- and 12-months post-surgery using validated University of Washington Quality of Life questionnaire. | University of Washing Quality of life questionnaire distributed pre-operatively, 6 months and 12 months. | 
| For the prospective cohort assess the swallow-related quality-of-life outcomes at pre-operatively and at 6- and 12-months post-surgery using validated questionnaires. | For the prospective cohort assess the swallow-related quality-of-life outcomes pre-operatively and at 6- and 12-months post-surgery using validated questionnaires. | MD Anderson Dysphagia Inventory distributed pre-operatively, 6 months and 12 months. | 
| Estimate the rates of close and involved surgical margins across all surgical salvage procedures | Estimate the rates of close and involved surgical margins across all surgical salvage procedures | Through study completion, expected duration of 3 years | 
| Determine the impact of close and involved margins on overall survival outcomes | Determine the impact of close and involved margins on overall survival outcomes | Through study completion, expected duration of 3 years | 
| Determine the impact of close and involved margins on disease-free survival outcomes | Determine the impact of close and involved margins on disease-free survival outcomes | Through study completion, expected duration of 3 years | 
| Determine the impact of close and involved margins on disease-specific survival outcomes | Determine the impact of close and involved margins on disease-specific survival outcomes | Through study completion, expected duration of 3 years | 
| Establish the rates of super-selective, selective and modified/ radical salvage neck dissection in clinically N0 and N+ necks | Establish the rates of super-selective, selective and modified/ radical salvage neck dissection in clinically N0 and N+ necks | Through study completion, expected duration of 3 years | 
| Ascertain how the extent of salvage neck dissection influences overall survival outcomes. | Ascertain how the extent of salvage neck dissection influences overall survival outcomes. | Through study completion, expected duration of 3 years | 
| Ascertain how the extent of salvage neck dissection influences disease-free survival outcomes. | Ascertain how the extent of salvage neck dissection influences disease-free survival outcomes. | Through study completion, expected duration of 3 years | 
| Ascertain how the extent of salvage neck dissection influences disease-specific survival outcomes. | Ascertain how the extent of salvage neck dissection influences disease-specific survival outcomes. | Through study completion, expected duration of 3 years | 
| Estimate the rate of occult nodal metastasis in clinically N0 necks with locally recurrent disease | Estimate the rate of occult nodal metastasis in clinically N0 necks with locally recurrent disease | Through study completion, expected duration of 3 years | 
| Describe the impact of neck dissection on overall survival outcomes in patients with clinically N0 necks with and without subsequent occult nodal disease | Describe the impact of neck dissection on overall survival outcomes in patients with clinically N0 necks with and without subsequent occult nodal disease | Through study completion, expected duration of 3 years | 
| Describe the impact of neck dissection on disease-free survival outcomes in patients with clinically N0 necks with and without subsequent occult nodal disease | Describe the impact of neck dissection on disease-free survival outcomes in patients with clinically N0 necks with and without subsequent occult nodal disease | Through study completion, expected duration of 3 years | 
| Describe the impact of neck dissection on disease-specific survival outcomes in patients with clinically N0 necks with and without subsequent occult nodal disease | Describe the impact of neck dissection on disease-specific survival outcomes in patients with clinically N0 necks with and without subsequent occult nodal disease | Through study completion, expected duration of 3 years | 
| Using multi-variate analysis, establish the clinical prognostic indicators of overall, disease free and disease specific survival. | Establish the clinical prognostic indicators of positive survival and functional outcomes | Through study completion, expected duration of 3 years | 
| Using multi-variate analysis, establish the clinical prognostic indicators 12 month tracheostomy and gastrostomy dependence. | Establish the clinical prognostic indicators of functional outcomes | Through study completion, expected duration of 3 years | 
| Compare the DNA genetic and epigenetic changes in residual, recurrent, and new primary head and neck squamous cell carcinoma with primary tumour and germline DNA samples. | Assess the molecular makeup of head and neck tumours that have not responded to radiotherapy treatment, or which recur having previously responded. | Through study completion, expected duration of 3 years |