Sentinel Node Biopsy Versus Limited Elective Neck Dissection in Early Cancers of Oral Cavity NoDe Negative

Study Overview
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Brief Summary
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The goal of this clinical trial is to compare the survival outcomes, morbidity and cost-effectiveness of sentinel node biopsy versus limited elective neck dissection in node-negative early oral cancers. The main questions it aims to answer are: Survival outcomes Morbidity outcomes Cost-effectiveness Participants will either undergo sentinel node biopsy followed by completion neck dissection if sentinel node is reported to be metastatic (SNB) or limited elective neck dissection where level IIb will be cleared only if level IIa is metastatic (limited END). The study will compare the outcomes in the two cohorts.

Detailed Description
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Based on the current literature, we know that elective neck dissection (END) is mandatory in clinically node-negative early oral cancers. However, this leads to overtreatment and morbidity in about 55-80% of patients. The emergence of recent level I evidence makes SNB the standard of care in this setting. However, its limitation of being a two-staged procedure, steep learning curve, the burden on resources, lack of infrastructure, short-lasting decrease in morbidity and lack of cost-effectiveness data limits its wide applicability. It is our routine departmental practice of performing limited neck dissection clearing level I-III/IV sparing level IIb which is cleared only if level IIa is metastatic. It is hypothesized that limited END would limit the morbidity of shoulder dysfunction and be a more feasible and cost-effective treatment option which could be a suitable alternative to SNB in this setting without compromising the survival outcomes. With this background, we propose to embark upon a phase III RCT comparing the oncologic outcomes and morbidity of SNB versus limited END. We hypothesize that limited END would have survival outcomes non-inferior, morbidity similar to SNB with higher cost-effectiveness. Aims and objectives: Aim To compare the survival outcomes, morbidity and cost-effectiveness of SNB versus limited END in node-negative early oral cancers Primary objective 1) Overall survival Secondary objectives Shoulder morbidity (key secondary endpoint) longitudinally up to 2 years Disease-free survival Neck nodal recurrence-free survival Other side effects (chyle leak, hematoma, lymphoedema) Longitudinal Quality of life up to 2 years Cost-effective analysis Exploratory objectives Blood and tumour tissue will be collected and banked for biomarker studies. Exploratory analyses will be conducted at a later date. Efforts may be directed to identify the biomarkers to predict nodal metastasis.

Official Title
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Sentinel Node Biopsy Versus Limited Elective Neck Dissection in Early Cancers of Oral Cavity NoDe Negative (SECOND N0): Non-inferiority Phase III Trial

Conditions
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Mouth Neoplasms

Intervention / Treatment
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* Procedure: Sentinel Node Biopsy
* Procedure: Limited Elective Neck Dissection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years of age Biopsy-proven invasive squamous cell carcinoma involving the site tongue and buccal mucosa T1 and T2 lesions as per AJCC TNM 8 edition Clinicoradiologically node negative Amenable to per oral excision Treatment naïve No other site of malignancy Exclusion Criteria: Previous surgery in the head and neck region, Upper alveolar or palatal lesions Large heterogeneous leukoplakia or other premalignant lesions Previous malignancy in the head and neck region Patients requiring the free flap reconstruction

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sentinel node biopsy<br> | Procedure: Sentinel Node Biopsy<br>* The Sentinel node will be localized after injecting peritumoral nano colloid followed by dynamic lymphoscintigraphy and SPECT localization. Methylene blue or indocyanine green may be used but not mandatory as an adjunct for lymphoscintigraphy for node localization. Intraoperatively the node will be identified using a hand-held gamma probe. The sentinel node will be processed on a frozen section, histopathological processing with serial step sectioning, and immunohistochemistry. If reported as metastatic, then a single-stage or second-stage completion neck dissection will be performed.<br>|
| Experimental: Limited elective neck dissection<br> | Procedure: Limited Elective Neck Dissection<br>* Patients who are allocated to the limited END arm will undergo dissection of level I, IIa and III/IV nodes sparing level IIb. Level IIa will be subjected to a frozen section and if reported as metastatic will mandate clearance of level IIb.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Defined from the date of randomization to death due to any cause | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Shoulder morbidity | It will be assessed using the neck dissection impairment index (NDII). The range of movement of the shoulder will also be assessed using a goniometer | Longitudinally at preoperatively, 3 months, at 6 months, 12 months and 24 months of treatment | 
| Neck nodal recurrence | Defined from the date of randomization to isolated neck node recurrence or death due to any cause | 3 years | 
| Disease free survival | Defined from the date of randomization to any recurrence (local, regional or distant metastasis) and second primary in the oral cavity | 3 years | 
| Health related Quality of life | Quality of life will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) QLQ C30 and QLQ HN35 instruments | Longitudinally at preoperatively, 3 months, at 6 months, 12 months and 24 months of treatment | 
| Adverse events related to the surgical procedure and lymphedema | Details of the intra and perioperative delay including injury to critical structures, chyle leak, haemorrhage, and head and neck lymphedema | The lymphedema rating will be done at 3 months, at 6 months, 12 months and 24 months of treatment | 
| Cost effectiveness | Based on direct cost comparison | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mouth neoplasms, neck dissection, sentinel lymph node biopsy, survival, morbidity