Electromagnetic navigation bronchoscopy to access lung lesions in 1,000 subjects: first results of the prospective, multicenter NAVIGATE study

Abstract

Background: Electromagnetic navigation bronchoscopy (ENB) is an image-guided, minimally invasive approach that uses a flexible catheter to access pulmonary lesions.

Methods: NAVIGATE is a prospective, multicenter study of the superDimension™ navigation system. A prespecified 1-month interim analysis of the first 1,000 primary cohort subjects enrolled at 29 sites in the United States and Europe is described. Enrollment and 24-month follow-up are ongoing.

Results: ENB index procedures were conducted for lung lesion biopsy (n = 964), fiducial marker placement (n = 210), pleural dye marking (n = 17), and/or lymph node biopsy (n = 334; primarily endobronchial ultrasound-guided). Lesions were in the peripheral/middle lung thirds in 92.7%, 49.7% were <20 mm, and 48.4% had a bronchus sign. Radial EBUS was used in 54.3% (543/1,000 subjects) and general anesthesia in 79.7% (797/1,000). Among the 964 subjects (1,129 lesions) undergoing lung lesion biopsy, navigation was completed and tissue was obtained in 94.4% (910/964). Based on final pathology results, ENB-aided samples were read as malignant in 417/910 (45.8%) subjects and non-malignant in 372/910 (40.9%) subjects. An additional 121/910 (13.3%) were read as inconclusive. One-month follow-up in this interim analysis is not sufficient to calculate the true negative rate or diagnostic yield. Tissue adequacy for genetic testing was 80.0% (56 of 70 lesions sent for testing). The ENB-related pneumothorax rate was 4.9% (49/1,000) overall and 3.2% (32/1,000) CTCAE Grade ≥2 (primary endpoint). The ENB-related Grade ≥2 bronchopulmonary hemorrhage and Grade ≥4 respiratory failure rates were 1.0 and 0.6%, respectively.

Conclusions: One-month results of the first 1,000 subjects enrolled demonstrate low adverse event rates in a generalizable population across diverse practice settings. Continued enrollment and follow-up are required to calculate the true negative rate and delineate the patient, lesion, and procedural factors contributing to diagnostic yield.

Trial registration: ClinicalTrials.gov NCT02410837 . Registered 31 March 2015.

Keywords: Image-Guided Biopsy; Lung Cancer; Lung Neoplasms; Neoplasm Staging; Solitary Pulmonary Nodule.

Fig. 1

Flow Diagram. As of June 27, 2016, 1,000 primary cohort subjects had been enrolled into the NAVIGATE study and comprise the first protocol-specified interim analysis of the 1-month results. The primary cohort is defined per protocol as those subjects who undergo an ENB index procedure minus roll-in subjects [7]. One-month follow-up is complete in 933/1,000 subjects (93.3%)

Fig. 2

Reasons for Conducting ENB on a Per Subject Basis. The NAVIGATE ENB index procedure could be conducted for more than one purpose in the same anesthetic event, including lung lesion biopsy, fiducial marker placement, pleural dye marking, or lymph node biopsy. Not drawn to scale. Not shown in graph: ENB-guided fiducial marker placement plus lymph node biopsy (n = 10); ENB-guided fiducial marker placement plus lymph node biopsy plus ENB-guided pleural dye marking (n = 0)

Fig. 3

Lung Cancer Clinical Stage at Diagnosis in Subjects with Primary Lung Cancer (365 subjects with 395 lesions). Not shown in graph: One subject had a diagnosis of Stage 0