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

Overview

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.

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

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Treatment
  • Masking: Double (Participant, Outcomes Assessor)
• Study Primary Completion Date: April 2032

Detailed Description

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 1. Shoulder morbidity (key secondary endpoint) longitudinally up to 2 years 2. Disease-free survival 3. Neck nodal recurrence-free survival 4. Other side effects (chyle leak, hematoma, lymphoedema) 5. Longitudinal Quality of life up to 2 years 6. 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.

Interventions

• Procedure: Sentinel Node Biopsy
  • 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.
• Procedure: Limited Elective Neck Dissection
  • 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.

Arms, Groups and Cohorts

• Active Comparator: Sentinel node biopsy
• Experimental: Limited elective neck dissection

Clinical Trial Outcome Measures

Primary Measures

• Overall survival
  • Time Frame: 3 years
  • Defined from the date of randomization to death due to any cause

Secondary Measures

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

Participating in This Clinical Trial

Inclusion Criteria

1. Age >18 years of age 2. Biopsy-proven invasive squamous cell carcinoma involving the site tongue and buccal mucosa 3. T1 and T2 lesions as per AJCC TNM 8 edition 4. Clinicoradiologically node negative 5. Amenable to per oral excision 6. Treatment naïve 7. No other site of malignancy Exclusion Criteria:

1. Previous surgery in the head and neck region, 2. Upper alveolar or palatal lesions 3. Large heterogeneous leukoplakia or other premalignant lesions 4. Previous malignancy in the head and neck region 5. Patients requiring the free flap reconstruction

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Tata Memorial Hospital
• Collaborator
  • Tata Memorial Centre
• Provider of Information About this Clinical Study
  • Principal Investigator: Richa Vaish, Professor and Surgeon – Tata Memorial Hospital
• Overall Official(s)
  • Richa Vaish, MS, M.Ch, Principal Investigator, Tata Memorial Hospital
• Overall Contact(s)
  • Richa Vaish, MS, M.Ch, 02224177000, drvaishricha@gmail.com

References

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D'Cruz AK, Vaish R, Kapre N, Dandekar M, Gupta S, Hawaldar R, Agarwal JP, Pantvaidya G, Chaukar D, Deshmukh A, Kane S, Arya S, Ghosh-Laskar S, Chaturvedi P, Pai P, Nair S, Nair D, Badwe R; Head and Neck Disease Management Group. Elective versus Therapeutic Neck Dissection in Node-Negative Oral Cancer. N Engl J Med. 2015 Aug 6;373(6):521-9. doi: 10.1056/NEJMoa1506007. Epub 2015 May 31.

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