Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Background: Carcinomas of unknown primary represent up to 5% of all head and neck squamous cell carcinoma (HNSCC) and are now mostly associated with human papillomavirus oropharyngeal squamous cell carcinoma (SCC). Identification of the primary tumor anatomic subsite allows for more targeted radiotherapy, which is associated with reduced side effects, morbidities, and long-term sequelae.
Methods: This is an ongoing prospective, single-institution, clinical trial, utilizing an antibody-labeled PET scan for detection of unknown primary HNSCC from July 2023 to present (NCT05747625). The investigational anti-EGFR monoclonal antibody, panitumumab, labeled with 89-Zirconium (IND163929) is utilized. Patients with biopsy-proven SCC in a cervical lymph node without an identifiable primary tumor on physical exam or imaging (including 18F-FDG PET and contrasted CT neck), are considered eligible and approached for the study. Drug infusion occurs with a loading dose of unlabeled panitumumab, followed by 89Zr-panitumumab, and PET scan 48-72 hours later. PET images are analyzed by two nuclear medicine radiologists independently and conflicts reconciled via in-person discussion. Final 89Zr-panitumumab PET imaging results, and potential primary tumor localization, is compared to surgical biopsy results and imaging results from contrasted CT neck and 18F-FDG-PET. The sensitivity, specificity, and diagnostic accuracy of 89Zr-panitumumab-PET will be compared to 18F-FDG-PET, and for both modalities together.
Results: To date, three unknown primary patients have enrolled in the study. In two patients, the 89Zr-panitumumab-PET identified a primary tumor that was not appreciated on 18F-FDG-PET. This included one patient with a 0.9 mm HPV-positive SCC in the left glossotonsillar sulcus, which was not appreciated on 18F-FDG-PET. This patient had previously undergone left base of tongue and tonsil biopsies, with negative results, but following the 89Zr-panitumumab-PET, underwent transoral robotic surgery (TORS), where the primary tumor was identified on final surgical pathology. The second patient had a 1 cm Epstein Barr Virus (EBV)-positive nasopharyngeal SCC, with an associated intra-parotid lymph node, both of which were not appreciated on 18F-FDG-PET, and both were subsequently biopsy-proven EBV-positive SCC. The third patient had an avid base of tongue lesion with 89Zr-panitumumab-PET. This area had previously been biopsied to be negative, and patient elected to undergo definitive chemoradiation for treatment, and did not receive any further biopsies or TORS. Further patient recruitment is ongoing, and current analysis evaluating sensitivity, specificity, and diagnostic accuracy of the two PET imaging modalities in comparison and in conjunction.
Conclusion: Targeted molecular imaging with 89Zr-panitumumab-PET scanning is an innovative approach with high potential for a non-invasive method of primary tumor detection in head and neck carcinomas of unknown primary, with a large potential impact on treatment.