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Sentinel lymph node biopsy versus standard neck dissection for early-stage oral cavity cancer

Randomized Phase II/III Trial of Sentinel Lymph Node Biopsy Versus Elective Neck Dissection for Early-Stage Oral Cavity Cancer

Phase2; Phase3 Interventional NRG Oncology · NCT04333537

This trial tests whether removing only the sentinel lymph nodes instead of doing a full neck dissection helps people with early-stage oral cavity cancer have better neck and shoulder function while keeping cancer control the same.

Quick facts

PhasePhase2; Phase3
Study typeInterventional
Enrollment686 (estimated)
Ages18 Years and up
SexAll
SponsorNRG Oncology Academic / other
Drugs / interventionschemotherapy, radiation
Locations106 sites (Birmingham, Alabama and 105 other locations)
Trial IDNCT04333537 on ClinicalTrials.gov

What this trial studies

This randomized phase II/III trial compares sentinel lymph node (SLN) biopsy to elective neck dissection (END) in patients with early-stage (cT1-2N0M0) oral cavity squamous cell carcinoma. Patients undergo preoperative imaging and SLN mapping with an imaging agent when assigned to the SLN arm, and surgeons remove either mapped sentinel nodes or perform a standard neck dissection per randomization. The phase II component focuses on patient-reported neck and shoulder function at 6 months using the Neck Dissection Impairment Index (NDII), and the phase III component tests non-inferiority for disease-free survival while also measuring quality of life, complications, and survival. Secondary endpoints include patterns of failure, overall survival, treatment toxicity, length of stay, drain use, and longitudinal patient-reported outcomes.

Who should consider this trial

Good fit: Ideal candidates are people with pathologically confirmed early-stage (T1-2N0M0) oral cavity squamous cell carcinoma who are medically fit for surgery and have completed the required diagnostic imaging.

Not a fit: Patients with clinically or radiographically node-positive disease, more advanced tumors, or prior head and neck treatments are unlikely to benefit from the SLN approach in this trial.

Why it matters

Potential benefit: If successful, patients could experience less neck and shoulder dysfunction, shorter recovery, and fewer surgical complications while maintaining the same cancer control.

How similar studies have performed: Previous single-center and multicenter studies have shown promising accuracy and reduced morbidity with SLN biopsy in early oral cavity cancers, but definitive phase III data are limited.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* PRIOR TO STEP 1 REGISTRATION INCLUSION:
* Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma (SCC) of the oral cavity, including the oral (mobile) tongue, floor of mouth (FOM), mucosal lip, buccal mucosa, lower alveolar ridge, upper alveolar ridge, retromolar gingiva (retromolar trigone; RMT), or hard palate prior to registration
* Appropriate stage for study entry (T1-2N0M0; American Joint Committee on Cancer \[AJCC\] 8th edition \[ed.\]) based on the following diagnostic workup:

  * History/physical examination within 42 days prior to registration
  * Imaging of head and neck within 42 days prior to registration

    * PET/CT scan or contrast neck CT scan, or gadolinium-enhanced neck magnetic resonance imaging (MRI) or lateral and central neck ultrasound; diagnostic quality CT is preferred and highly recommended as part of the PET/CT when possible
  * Imaging of chest within 42 days prior to registration

    * Chest x-ray, CT chest scan (with or without contrast), or PET/CT (with or without contrast)
* Surgical assessment within 42 days prior to registration. Patient must be a candidate for surgical intervention with sentinel lymph node (SLN) biopsy and potential completion neck dissection (CND) or elective neck dissection (END)

  * Surgical resection of the primary tumor will occur through a transoral approach with anticipation of resection free margins
* Age \>= 18
* Zubrod performance status 0-2 within 42 days prior to registration
* For women of child-bearing potential, negative serum or urine pregnancy test within 42 days prior to registration
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
* Only patients who are able to read and understand English or French are eligible to participate as the mandatory patient reported NDII tool is only available in these languages
* PRIOR TO STEP 2 RANDOMIZATION:
* FDG PET/CT required prior to step 2. Note: FDG PET/CT done prior to step 1 can be submitted for central review

  * PET/CT node negative patients, determined by central read, will proceed to randomization. PET/CT node positive patients will go off study, but will be entered in a registry and data will be collected to record the pathological outcome of neck nodes for diagnostic imaging assessment and future clinical trial development

    * NOTE: All FDG PET/CT scans must be performed on an American College of Radiology (ACR) accredited scanner (or similar accrediting organization)
* The patient must complete NDII prior to step 2 registration

Exclusion Criteria:

* PRIOR TO STEP 1 REGISTRATION EXCLUSION:
* Definitive clinical or radiologic evidence of regional (cervical) and/or distant metastatic disease
* Prior non-head and neck invasive malignancy (except non-melanomatous skin cancer, including effectively treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or cervix) unless disease free for ≥ 2 years
* Diagnosis of head and neck SCC in the oropharynx, nasopharynx, hypopharynx, and larynx
* Unable or unwilling to complete NDII (baseline only)
* Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for different cancer(s) is allowable
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* Severe, active co-morbidity that would preclude an elective or completion neck dissection
* Pregnancy and breast-feeding mothers
* Incomplete resection of oral cavity lesion with a positive margin; however, an excisional biopsy is permitted
* Prior surgery involving the lateral neck, including neck dissection or gross injury to the neck that would preclude surgical dissection for this trial. Prior thyroid and central neck surgery is permissible; biopsy is permitted. Note: Borderline suspicious nodes that are \>= 1 cm with radiographic finding suggestive of NOT malignant should be biopsied using ultrasound (U/S)-guided fine-needle aspiration (FNA) biopsy
* Underlying or documented history of hematologic malignancy (e.g., chronic lymphocytic leukemia \[CLL\]) or other active disease capable of causing lymphadenopathy (e.g., sarcoidosis or untreated mycobacterial infection)
* Actively receiving systemic cytotoxic chemotherapy, immunosuppressive, anti-monocyte or immunomodulatory therapy
* Currently participating in another investigational therapeutic trial

Where this trial is running

Birmingham, Alabama and 105 other locations

+56 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Buccal Mucosa Squamous Cell CarcinomaFloor of Mouth Squamous Cell CarcinomaGingival Squamous Cell CarcinomaHard Palate Squamous Cell CarcinomaLip Squamous Cell CarcinomaLower Alveolar Ridge Squamous Cell CarcinomaOral Cavity Squamous Cell CarcinomaRetromolar Trigone Squamous Cell Carcinoma
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.