Meeks Nicole, James Sherin, Krishnan Giri, Wodeyar Akhilesh, Tanaka Hidenori, Kasten Benjamin B, Lee Yu-Jin, Hom Marisa E, Rosenthal Eben L, Warram Jason M
Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Otolaryngology, The University of Alabama at Birmingham, Birmingham, AL, USA.
Mol Imaging Biol. 2025 Jun;27(3):333-340. doi: 10.1007/s11307-025-01996-4. Epub 2025 Mar 18.
Survival and treatment intensity in patients with head and neck squamous cell carcinoma (HNSCC) is determined by the presence of lymph node (LN) metastasis, and as a result surgical removal of potentially affected LN remains a mainstay practice. Fluorescence guided surgery (FGS) using targeted optical agents is an expanding field that shows great potential for aiding diagnosis of metastatic LN. Given variations in fluorescence background, a reference standard for regions of interest is necessary for cross patient comparison. The present study aims to determine whether tissue with native target expression can be used as a background to determine metastatic LN in patients with HNSCC infused with anti-epidermal growth factor receptor (EGFR) targeted imaging agents.
Twenty-two patients infused with panitumumab-IRDye800 or cetuximab-IRDye800 prior to surgery were included. Fluorescence imaging and analysis was performed on resected LNs (N = 843) using the submandibular glands (SMG) and skin as reference standard tissue with known EGFR antigen expression.
Sixteen patients (72.7%) had at least one positive LN on final pathology. The LN to SMG (LN/SMG) and LN to skin (LN/skin) ratios were significantly higher in metastatic LN compared to benign LN (p < 0.0001 for both). Using patient-specific ratios to determine an optimal LN/skin cutoff was the most sensitive (95.2%) and directly comparing the LN/skin ratio of all patients to determine a cutoff was the most specific (86.3%).
In HNSCC patients infused with a molecularly targeted fluorescent tracer, endogenous expression of the target antigen can be used as a reference standard to detect LN metastasis. Additionally, the performance of the background in determining metastatic LN can be improved by utilizing patient-specific reference standards.
头颈部鳞状细胞癌（HNSCC）患者的生存及治疗强度取决于淋巴结（LN）转移情况，因此手术切除潜在受累淋巴结仍是主要治疗手段。使用靶向光学剂的荧光引导手术（FGS）是一个不断发展的领域，在辅助诊断转移性淋巴结方面显示出巨大潜力。鉴于荧光背景存在差异，为了进行患者间比较，需要一个感兴趣区域的参考标准。本研究旨在确定在输注抗表皮生长因子受体（EGFR）靶向成像剂的HNSCC患者中，具有天然靶点表达的组织是否可作为背景来确定转移性淋巴结。
纳入22例术前输注帕尼单抗 - IRDye800或西妥昔单抗 - IRDye800的患者。使用已知EGFR抗原表达的下颌下腺（SMG）和皮肤作为参考标准组织，对切除的淋巴结（N = 843）进行荧光成像和分析。
16例患者（72.7%）最终病理检查至少有一个阳性淋巴结。与良性淋巴结相比，转移性淋巴结的淋巴结与下颌下腺（LN/SMG）及淋巴结与皮肤（LN/皮肤）比值显著更高（两者p均<0.0001）。使用患者特异性比值确定最佳LN/皮肤临界值最敏感（95.2%），直接比较所有患者的LN/皮肤比值以确定临界值最特异（86.3%）。
在输注分子靶向荧光示踪剂的HNSCC患者中，靶抗原的内源性表达可作为检测淋巴结转移的参考标准。此外，通过利用患者特异性参考标准，背景在确定转移性淋巴结方面的性能可得到改善。
