Andreja Radevic, Joaquin Austerlitz, Ashtyn McAdoo, Kyrionna Golliday, Takeshi Takahashi, Mitra Mehrad, Adam J. Rosenberg, Barbara A. Murphy, Eben Rosenthal, Michael C. Topf
BACKGROUND: Neoadjuvant chemoimmunotherapy is being explored in locally advanced head and neck squamous cell carcinoma (HNSCC), yet the spatial patterns of pathologic response and clinical implications remain poorly characterized. METHODS: A 79-year-old female with recurrent left oral tongue SCC (PD-L122C3 Combined Positive Score 90) who underwent prior resection and free flap reconstruction received neoadjuvant pembrolizumab, paclitaxel, and carboplatin followed by definitive surgical resection with intraoperative positron emission tomography/computed tomography (PET/CT) imaging. RESULTS: Final histopathology revealed two discrete foci of residual poorly differentiated SCC, measuring 1.8 and 0.5 cm, separated by an 8 mm intervening bridge of inflammation without viable tumor. Intraoperative PET/CT with 3D specimen mapping confirmed the spatial relationship between residual foci and intervening treatment effect. CONCLUSIONS: Pathologic response to neoadjuvant chemoimmunotherapy in HNSCC can manifest as a multifocal regression pattern. Intraoperative real-time approaches to assessing treatment response warrant further investigation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06915454.