NRG Oncology Trial of Sentinel Lymph Node Biopsy for Patients with Early-Stage Oral Cavity Cancer Re-opens to Phase III (NRG-HN006)

11/12/2025

NRG Oncology recently reactivated the NRG-HN006 trial comparing sentinel lymph node (SLN) biopsy to elective neck dissection (END) for patients with early-stage oral cavity cancer. This trial completed phase II accrual in December 2024 and has since met the criteria to advance to the phase III portion of the trial.

Patients enrolled on NRG-HN006 received a PET/CT scan, and patients who were considered node negative following the scan were then randomized by clinical and radiographic T-category and Zubrod Performance Status. Patients who were considered node positive went off study, but their pathology was recorded in a prospective registry to evaluate the PET/CT scan performance. Following stratification, patients were randomized to receive either SLN biopsy or END.

The phase III portion of this study aims to accrue 425 additional patients for a total of 686 patients on this study (including the 261 patients randomized during phase II). The Phase III co-primary objectives for this study are (i) to determine if patient-reported neck and shoulder function is superior 6 months following SLN biopsy compared to END and (ii) to determine if disease-free survival is non-inferior when using SLN biopsy compared to END.

“When treated with END because of a 20-30% risk of occult nodal metastasis, many of these patients experience long-term side effects from this treatment, because of the need for more extensive surgery in the neck following the resection of the primary oral cavity tumor. There is increased risk for significant morbidity, including muscle weakness caused by spinal accessory nerve damage and other impairments to a patient’s quality of life,” stated Stephen Y. Lai, MD, PhD, FACS, of the Department of Head and Neck Surgery at the University of Texas MD Anderson Cancer Center. “It is incredibly important to determine if SLN biopsies can help inform the decision-making process on which patients could benefit from additional neck dissection and those who do not need it.”

This study has multiple secondary objectives, including measuring and comparing patterns of failure, overall survival, toxicity, longitudinal patient-reported neck and shoulder function and related quality of life, length of hospitalization, post-operative drain placement, and operative morbidity, and nodal metastasis rates between treatment arms. The trial will also assess the pathologic false omission rate for the SLN biopsy arm and compare the diagnostic performance of planar only versus SPECT/CT plus planar for SLN mapping.

More Information:

Learn more about this trial on ClinicalTrials.gov

Protocol documents and materials are located on the CTSU website.

A patient study webpage for this trial is available at NRGOncology.org/HN006