A novel technique for tumor localization and targeted lymphatic mapping in early-stage lung cancer

Abstract

Objective: To investigate safety and feasibility of navigational bronchoscopy (NB)-guided near-infrared (NIR) localization of small, ill-defined lung lesions and sentinel lymph nodes (SLN) for accurate staging in patients with non-small cell lung cancer (NSCLC).

Methods: Patients with known or suspected stage I NSCLC were enrolled in a prospective pilot trial for lesion localization and SLN mapping via NB-guided NIR marking. Successful localization, SLN detection rates, histopathologic status of SLN versus overall nodes, and concordance to initial clinical stage were measured. Ex vivo confirmation of NIR⁺ SLNs and adverse events were recorded.

Results: Twelve patients underwent NB-guided marking with indocyanine green of lung lesions ranging in size from 0.4 to 2.2 cm and located 0.1 to 3 cm from the pleural surface. An NIR⁺ "tattoo" was identified in all cases. Ten patients were diagnosed with NSCLC and 9 SLNs were identified in 8 of the 10 patients, resulting in an 80% SLN detection rate. SLN pathologic status was 100% sensitive and specific for overall nodal status with no false-negative results. Despite previous nodal sampling, one patient was found to have metastatic disease in the SLN alone, a 12.5% rate of disease upstaging with NIR SLN mapping. SLN were detectable for up to 3 hours, allowing time for obtaining a tissue diagnosis and surgical resection. There were no adverse events associated with NB-labeling or indocyanine green dye itself.

Conclusions: NB-guided NIR lesion localization and SLN identification was safe and feasible. This minimally invasive image-guided technique may permit the accurate localization and nodal staging of early stage lung cancers.

Keywords: lung cancer; navigational bronchoscopy; near-infrared; sentinel lymph node; tumor localization.

Figure 1. NB-guided NIR Imaging Technique

NB-guided lesion localization for NIR⁺ “tattoo”, NIR lymphatic migration, and in situ NIR⁺ SLN identification for in-depth pathologic analysis.

Figure 2. NB-guided NIR “tattoo” of lesion 2.1cm from the pleural surface

A. Navigational bronchoscopy guides the injection of 1cc of ICG. B. Axial CT image demonstrating a 1.1 cm lesion (yellow marker) that is 2.1 cm from the pleural surface (blue arrows). C. NIR⁺ “tattoo” is easily identifiable from the pleural surface nearly 4 hours after ICG injection.

Figure 3. NB-guided NIR “tattoo” and SLN identification

A.NB-guided lesion localization for transbronchial, peritumoral ICG injection B. NIR⁺ “tattoo” on pleural surface ~1hr after ICG injection (3 injections used) C. In vivo NIR⁺ level 7 SLN identification ~2hrs after ICG injection D. Axial CT of a 1.2 cm LLL lesion E. NIR⁺ ICG “tattoo” is nearly identical to a concomitant methylene blue marking (blue arrow) F. In vivo NIR⁺ level 7 SLN (white arrow) identified in situ by ICG alone with no methylene blue. G. Axial CT of 1.5 cm ill-defined, pure ground glass opacity H. In vivo NIR lymphatic track from RLL peri-tumoral “tattoo” (blue arrow) to level 11R nodal station, RUL peri-tumoral “tattoo” (white arrow) I. In vivo NIR+ level 11R SLN (white arrow)

Central picture

Level 7 NIR⁺ SLN Following NB-guided Peri-lesional “Tattoo” with Indocyanine Green