Identification of Metastatic Nodal Disease in a Phase 1 Dose-Escalation Trial of Intraoperative Sentinel Lymph Node Mapping in Non–small Cell Lung Cancer Using Near-Infrared Imaging

Abstract

Objectives Early stage non-small cell lung cancer (NSCLC) has a high recurrence rate and poor 5-yearsurvival, particularly if lymph nodes are involved. Our objective was to perform a dose escalationstudy to assess safety and feasibility of intraoperative near-infrared (NIR) fluorescence imaging toidentify the first tumor draining lymph nodes, i.e. sentinel lymph nodes (SLN) in NSCLCpatients.

Methods A dose escalation Phase I clinical trial assessing real-time NIR imaging followingperitumoral injection of 3.8 – 2500 μg indocyanine green (ICG) was initiated inpatients with suspected stage I/II NSCLC. Visualization of lymphatic migration, SLN identification,and adverse events were recorded.

Results Thirty eight patients underwent ICG injection and NIR imaging via thoracotomy(n=18) or thoracoscopic imaging (n=20). SLN identification increased with ICG dosewith <25% SLN detected in dose cohorts ≤600ug vs 89% success at≥1000 μg. Twenty six NIR+ SLNs were identified in fifteenpatients, with seven NIR+ SLNs (six patients) harboring metastatic disease onhistologic analysis. Metastatic nodal disease was never identified in patients with a histologicallynegative NIR+ SLN. No adverse reactions were noted.

Conclusion NIR-guided SLN identification with ICG was safe and feasible in this initial doseescalation trial. ICG doses ≥ 1000ug yielded nearly 90% intrathoracic SLNvisualization, with presence or absence of metastatic disease in the SLN directly correlating withfinal nodal status of the lymphadenectomy specimen. Further studies are needed to optimize imagingparameters and confirm sensitivity and specificity of SLN mapping in NSCLC using this promisingimaging technique.