Detection of Lymph Node Metastases of Well-Differentiated Thyroid Cancer using Fluorescence-Guided Surgery with Bevacizumab-IRDye800CW

Introduction The incidence of thyroid carcinoma is rising, primarily due to the overdiagnosis of indolent papillary thyroid cancer (PTC). Despite its favourable prognosis, central lymph node metastases are common and associated with worse outcomes. Prophylactic central lymph node dissection (CLND) may reduce recurrence but carries risks such as recurrent laryngeal nerve injury and hypoparathyroidism without improving survival. Therefore, real-time intraoperative methods are needed to enable selective CLND and thereby reduce unnecessary surgical morbidity. This study evaluates the feasibility of bevacizumab-IRDye800CW, a Vascular Endothelial Growth Factor (VEGF)-A-targeting fluorescent tracer, to differentiate metastatic from healthy lymph nodes in thyroid cancer surgery. Methods This single-centre, non-randomized phase I feasibility and dose-finding study included patients with well-differentiated thyroid carcinoma undergoing lymph node dissection. Bevacizumab-IRDye800CW (4.5, 10, or 25 mg) was administered two to four days preoperatively with three patients per dose level. Near-infrared fluorescence imaging was performed intraoperatively and ex vivo on resected specimens. Mean fluorescence intensities (FI mean ) of metastatic and healthy lymph nodes were compared. An interim analysis determined the optimal dose, which was subsequently expanded to ten patients. Results Sixteen patients with PTC were included. In vivo imaging in the 10mg and 25mg cohort ( n = 6) did not distinguish metastatic lymph nodes from surrounding tissue and was therefore discontinued after interim analysis. Ex vivo , the 10 mg dose showed the highest contrast between metastatic and healthy lymph nodes (LN+/LN− ratio 3.5 versus 3.1 and 3.2 for 4.5 and 25 mg, respectively) and was selected for expansion. After expansion, 133 metastatic and 239 healthy lymph nodes were analysed in the 10mg group. FI mean was significantly higher in metastatic than healthy nodes (28.7 versus 8.9 × 10 -4 a.u.; p < 0.001). Conclusion Fluorescence-guided imaging with bevacizumab-IRDye800CW is feasible for ex vivo detection of lymph node metastases in PTC, with optimal performance at 10 mg. Intraoperative in vivo imaging was not sufficient, but the observed ex vivo contrast suggests potential for intraoperative back-table assessment pending further validation.