Sentinel lymph node biopsy for clinically node‑negative, high‑risk cutaneous squamous cell carcinoma of the head and neck

Phase 2 Pragmatic Trial Investigating Sentinel Lymph Node Biopsy (SLNB) Efficacy and Safety in Patients With Clinically Node-Negative (cN0), High-Risk Cutaneous Squamous Cell Carcinoma (cSCC) of the Head and Neck

This trial will test whether adding a sentinel lymph node biopsy (SLNB) to surgery helps adults with clinically node‑negative, high‑risk cutaneous squamous cell carcinoma of the head and neck remain disease‑free for two years.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of California, Davis (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Sacramento, California)
• Trial ID: NCT06990737 on ClinicalTrials.gov

What this trial studies

This is a single‑site, phase 2 pragmatic trial enrolling adults with high‑risk, clinically node‑negative head and neck cutaneous squamous cell carcinoma who are candidates for surgery and SLNB. Participants undergo preoperative lymphoscintigraphy and intraoperative sentinel lymph node excision per standard practice, with possible re‑resection of the primary tumor and lymphadenectomy if nodes are positive. Definitive adjuvant therapies (such as radiation or chemoradiation) are given according to standard of care after surgery, and only pre‑specified adverse events are collected for the protocol. The primary endpoint is two‑year disease‑free survival compared to a historical 50% control, analyzed by Kaplan‑Meier methods and a one‑sided log‑rank test.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed, high‑risk head and neck cSCC who are clinically node‑negative by CT, have Zubrod performance status 0–2, and are candidates for surgical resection with SLNB.

Not a fit: Patients with clinical or radiologic evidence of regional or distant metastases, other active cancers, or those who are not surgical candidates are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, SLNB could find hidden lymph node spread earlier and allow targeted lymphadenectomy and adjuvant therapy, potentially improving two‑year disease‑free survival.

How similar studies have performed: Smaller prospective and retrospective series have shown SLNB can detect occult nodal metastases in high‑risk cSCC, but randomized evidence of a survival benefit is limited.

Eligibility criteria

Inclusion Criteria:

1. Must have histologically and/or biochemically confirmed head and neck cSCC
2. Must have head and neck cSCC categorized as high risk:

   1. Location in the ear or the lip,
   2. Diameter greater than 2 cm,
   3. Depth greater than 4 mm,
   4. Perineural invasion,
   5. Poorly differentiated, and/or
   6. Recurrent disease
3. Lymph-node negative (cN0) status confirmed by computed tomography (CT) imaging.
4. Candidate for surgical intervention with sentinel lymph node biopsy (SLNB) and potential lymphadenectomy for treatment of cSCC.
5. Zubrod Performance Status 0-2
6. Age ≥18 years at time of consent.
7. Provision of signed and dated informed consent form.
8. Stated willingness to comply with all study procedures and availability for the duration of the study.

Exclusion Criteria:

1. Other active cancers.
2. Definitive clinical or radiologic evidence of regional (cervical) and/or distant metastatic disease.
3. 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.
4. Diagnosis of head and neck mucosal SCC.
5. Prior systemic chemotherapy for head and neck mucosal SCC; note that prior chemotherapy for a different cancer is allowable.
6. Prior radiotherapy to the head and neck that would result in overlap of radiation therapy fields.
7. Patient with severe, active co-morbidity that would preclude a lymphadenectomy.
8. Pregnant or breast-feeding persons.
9. 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. Prior surgery for confirmation of tumor pathology is permitted. Note: Borderline suspicious nodes that are ≥1 cm with radiographic finding suggestive of NOT malignant should be biopsied using U/S-guided fine-needle aspirate (FNA) biopsy.
10. Underlying or documented history of hematologic malignancy (e.g., chronic lymphocytic leukemia) or other active disease capable of causing lymphadenopathy (sarcoidosis or untreated mycobacterial infection).
11. Actively receiving systemic cytotoxic chemotherapy, immunosuppressive, anti-monocyte, or immunomodulatory therapy.
12. Currently participating in another investigational therapeutic trial.

Where this trial is running

Sacramento, California

• University of California, Davis — Sacramento, California, United States (Recruiting)

Study contacts

• Principal investigator: Andrew Birkeland, MD — University of California, Davis
• Study coordinator: Selina Laqui

Conditions Cutaneous Squamous Cell Carcinoma of the Head and Neck; Clinically Node-Negative; High-Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck