Study Comparing Limited and Extensive Neck Surgery in Oral Cancer Patients With Neck Spread

Official title

Extent of Neck Treatment in Clinically N1 Oral Cancer: A Randomized Controlled Trial

Overview

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

• Procedure Selective Neck Dissection (Levels I-IV)
  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.
• Procedure Modified 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 his

Primary outcome measures

• Regional Recurrence-Free Survival (RRFS) [Time frame: 3 years after surgery]

Secondary outcome measures (7)

• Overall Survival (OS) [Time frame: Up to 3 years after surgery]
• Disease-Free Survival (DFS) [Time frame: Up to 3 years after surgery]
• Level-wise Cervical Lymph Node Metastasis [Time frame: At the time of surgery (histopathological examination)]
• Nodal Yield [Time frame: At the time of surgery]
• Shoulder Function assesment [Time frame: Preoperatively; 1 month; 3 months; 6 months, 1 and 2 year]
• Postoperative Surgical Morbidity [Time frame: Within 30 days after surgery]
• Shoulder function assesment with Shoulder pain and disability index [Time frame: Preoperatively; 1 week; 1 month; 3 months; 6 months; 1 year; and 2 years after surgery]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

India · 1 center

• Kolhapur Cancer Centre — Kolhāpur

Publications

• Pantvaidya GH, Pal P, Vaidya AD, Pai PS, D'Cruz AK. Prospective study of 583 neck dissections in oral cancers: implications for clinical practice. Head Neck. 2014 Oct;36(10):1503-7. doi: 10.1002/hed.23494. Epub 2014 Jan 13. PMID 23996343
• Liang L, Zhang T, Kong Q, Liang J, Liao G. A meta-analysis on selective versus comprehensive neck dissection in oral squamous cell carcinoma patients with clinically node-positive neck. Oral Oncol. 2015 Dec;51(12):1076-81. doi: 10.1016/j.oraloncology.2015.10.005. Epub 2015 Oct 23. PMID 26500065
• Hashmi SS, Abbas A, Bukhari A, Saeed J, Shafqat A, Siddique AH, Buksh AR, Murtaza G. Selective Neck Dissection for Node-Positive Oral Cavity Squamous Cell Carcinoma: A Retrospective Cohort Study. Int Arch Otorhinolaryngol. 2022 Feb 22;26(4):e630-e635. doi: 10.1055/s-0041-1741437. eCollection 2022 Oct. PMID 36405475
• Shin YS, Koh YW, Kim SH, Choi EC. Selective neck dissection for clinically node-positive oral cavity squamous cell carcinoma. Yonsei Med J. 2013 Jan 1;54(1):139-44. doi: 10.3349/ymj.2013.54.1.139. PMID 23225810

Identifiers

NCT: NCT07717307 · ExteNTN1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗