Oral Cavity Squamous Cell Carcinoma
Conditions
Keywords
Oral Cavity Squamous Cell Carcinoma, Oral Cancer, Head and Neck Cancer, Neck Dissection, Modified Neck Dissection, Cervical Lymph Node Metastasis
Brief summary
Oral cavity squamous cell carcinoma (OCSCC) frequently metastasizes to cervical lymph nodes, and the extent of neck dissection remains an area of ongoing debate in patients with clinically node-positive (cN1) disease. While modified neck dissection (MND, levels I-V) is widely practiced, selective neck dissection (SND, levels I-IV) may provide equivalent oncologic outcomes with reduced surgical morbidity. However, high-quality randomized evidence comparing these approaches is lacking. The ExteNT N1 Trial is a prospective, randomized, open-label, parallel-group clinical trial designed to compare selective neck dissection (levels I-IV) with modified neck dissection (levels I-V, preserving the spinal accessory nerve, internal jugular vein, and sternocleidomastoid muscle) in patients with resectable cN1 oral cavity squamous cell carcinoma. Eligible participants will be randomized in a 1:1 ratio to either treatment arm. The primary endpoint is 3-year regional recurrence-free survival (RRFS), along with postoperative quality of life measured using the Neck Dissection Impairment Index (NDII). Secondary endpoints include overall survival, disease-free survival, level-wise nodal involvement, nodal yield, shoulder function (Constant-Murley Score, SPADI, and Arm Abduction Score), postoperative complications including chyle leak, and other surgical morbidities. This trial aims to generate level I evidence regarding the optimal extent of neck dissection for cN1 OCSCC, balancing oncologic safety with preservation of postoperative function and quality of life.
Detailed description
Cervical lymph node metastasis is the most important prognostic factor in oral cavity squamous cell carcinoma (OCSCC). Surgical management of the neck is an integral component of treatment; however, the optimal extent of neck dissection for patients with clinically node-positive (cN1) disease remains uncertain. Although modified neck dissection (levels I-V with preservation of non-lymphatic structures) has traditionally been recommended for node-positive disease, several retrospective studies have suggested that carefully selected patients with limited nodal disease may achieve comparable regional control with a less extensive selective neck dissection. Nevertheless, these studies are subject to selection bias, and no adequately powered randomized controlled trial has directly compared these surgical approaches. Dissection of lower cervical nodal levels may increase operative time and postoperative morbidity, including shoulder dysfunction, sensory deficits, chyle leak, and impairment in quality of life. Reducing the extent of neck dissection without compromising oncologic outcomes could improve postoperative functional recovery and patient-reported outcomes while maintaining regional disease control. The ExteNT N1 Trial is designed to address this evidence gap by comparing selective neck dissection (levels I-IV) with modified neck dissection (levels I-V) in patients with resectable cN1 OCSCC. In addition to evaluating oncologic outcomes, the study incorporates validated functional and quality-of-life assessments to comprehensively evaluate the impact of the two surgical strategies. Participants will receive standard treatment for the primary tumor, and adjuvant therapy will be administered according to final histopathological findings and contemporary treatment guidelines. The findings of this trial are expected to provide high-level evidence to guide the surgical management of the clinically N1 neck in OCSCC. If selective neck dissection demonstrates equivalent oncologic outcomes with lower morbidity, it may support a change in surgical practice by reducing unnecessary treatment while preserving function and quality of life.
Interventions
Selective neck dissection will include removal of cervical lymph node levels Ia, Ib, IIa, IIb, III, and IV on the ipsilateral side while preserving uninvolved non-lymphatic structures. The primary oral cavity tumor will be resected according to oncologic principles with reconstruction as required. Contralateral neck management and adjuvant therapy will be provided according to institutional protocols and final histopathological findings.
PROCEDUREModified Neck Dissection (Levels I-V)
Modified neck dissection will include removal of cervical lymph node levels Ia, Ib, IIa, IIb, III, IV, and V on the ipsilateral side while preserving the spinal accessory nerve, internal jugular vein, and sternocleidomastoid muscle whenever oncologically appropriate. The primary oral cavity tumor will be resected according to oncologic principles with reconstruction as required. Contralateral neck management and adjuvant therapy will be provided according to institutional protocols and final histopathological findings.
Sponsors
Kolhapur Cancer Centre - Cancer Centers of America
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Because of the nature of the surgical interventions, neither the participants nor the operating surgeons can be blinded to treatment allocation. However, postoperative functional assessments (e.g., shoulder function) and quality-of-life evaluations will be performed, whenever feasible, by trained assessors who are unaware of the assigned treatment arm. Data analysts will also be blinded to treatment allocation until the primary analysis is completed.
Intervention model description
Participants will be randomized in a 1:1 ratio to one of two surgical treatment arms using a computer-generated stratified permuted block randomization sequence with variable block sizes. Stratification will be based on primary tumor subsite and clinical T stage to ensure balanced allocation. This is an open-label trial because blinding of surgeons and participants is not feasible due to the nature of the surgical interventions. However, postoperative functional and quality-of-life assessments will be performed by outcome assessors who are blinded to treatment allocation whenever feasible. All analyses will follow the intention-to-treat principle.
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Histologically proven squamous cell carcinoma of oral cavity will be included * Clinical stage T1-T4, N1, M0 * cN1 neck on clinical examination and imaging (CT/MRI) * Single node which is FNAC proven without any other significant nodes. * Patients with ASA grade II and I. * Understands the protocol and able to give informed consent.
Exclusion criteria
* Recurrent cases * Multiple significant nodes * Nodes clinical/radiological with ENE * Single metastatic node at level III/IV/V * Single metastatic node with other suspicious nodes * Patients with a history of head and neck radiation therapy treatment * Previous history of any malignancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Regional Recurrence-Free Survival (RRFS) | 3 years after surgery | Regional recurrence-free survival is defined as the time from the date of definitive surgery to the first documented regional recurrence in the cervical lymph nodes or death from any cause, whichever occurs first. Regional recurrence will be confirmed by clinical examination, imaging, and histopathological evaluation whenever feasible. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to 3 years after surgery | Overall survival is defined as the time from definitive surgery until death from any cause. |
| Disease-Free Survival (DFS) | Up to 3 years after surgery | Disease-free survival is defined as the time from definitive surgery to the first documented local, regional, or distant recurrence, or death from any cause. |
| Level-wise Cervical Lymph Node Metastasis | At the time of surgery (histopathological examination) | Distribution of histopathologically confirmed metastatic lymph nodes according to cervical nodal level. |
| Nodal Yield | At the time of surgery | Total number of lymph nodes retrieved during neck dissection and confirmed by histopathological examination. |
| Shoulder Function assesment | Preoperatively; 1 month; 3 months; 6 months, 1 and 2 year | Shoulder function will be assessed using the Constant-Murley Score (0-100 points), with higher scores indicating better shoulder function. |
| Postoperative Surgical Morbidity | Within 30 days after surgery | Incidence of postoperative complications, including chyle leak, hematoma, wound infection, seroma, cranial nerve injury |
| Shoulder function assesment with Shoulder pain and disability index | Preoperatively; 1 week; 1 month; 3 months; 6 months; 1 year; and 2 years after surgery | Shoulder pain and disability will be assessed using theShoulder pain and disability index questionnaire. Scores range from 0 to 100, with higher scores indicating greater pain and disability. |
Countries
India
Contacts
CONTACTMaroti B Wadewale, MDS, FHNO
CONTACTParag J Watve, MS, FHNS
Outcome results
None listed