Medical Policy

This document addresses the use of electromagnetic navigational bronchoscopy (ENB) devices as an aid in accessing peripheral lung lesions and masses, which may be inaccessible by standard bronchoscopy. ENB has also been proposed as a means of placing fiducial markers for surgical and radiological procedures.

The U.S. Food and Drug Administration (FDA) has approved two devices:

• SuperDimension^®/Bronchus inReach^™ System (superDimension, Ltd., Herzliya, Israel; U.S. distributor: superDimension, Inc., Minneapolis, MN), which received 510(k) clearance from the U.S. Food and Drug Administration (FDA) under the classification for computed tomography (CT)/x-ray systems on March 31, 2008 (FDA, 2008).
• SpiN Drive^™ System by Veran Medical (St. Louis, MO), which also goes under the trade name: ig4^™ EndoBronchial System which received FDA clearance in December 2009.

Investigational and Not Medically Necessary:

Electromagnetic navigational bronchoscopy is considered investigational and not medically necessary for all applications.

Electromagnetic navigational bronchoscopy (ENB) is an emerging technology aimed primarily at improving the diagnostic yield of transbronchial tools used during bronchoscopy procedures to sample peripheral parenchymal lung lesions not visible through the bronchoscope. Preliminary studies have suggested that this diagnostic tool may achieve similar diagnostic yields to transthoracic biopsy of peripheral lesions with potential for less risk of pneumothorax. In addition to comparison with transthoracic biopsy, ENB is also compared to endoscopic ultrasound (EUS), another technique used during bronchoscopy for biopsy of peripheral lung lesions. It is important to note that ENB is not a real-time procedure. A CT scan is performed on one day, with a single-breath hold and the individual not moving, and on another day (or potentially later the same day) in another setting, the bronchoscopy is performed while the individual is awake and breathing with a bronchoscope placed in the airway, (which typically produces coughing and gagging to some extent). The importance of this difference is that the lesions detected on the single breath hold CT scan will not necessarily be in the same physical location as in a breathing individual during a bronchoscopy. In a retrospective review, Chen and colleagues (2015) evaluated the records of 46 individuals with pulmonary lesions who had two pre-procedure CT scans performed prior to bronchoscopy, one CT scan at full inspiration and a second CT scan at end-exhalation during tidal volume breathing. The average motion of all 85 pulmonary lesions identified was 17.6 mm with lower lobe nodules showing significantly more movement than upper lobe nodules. The authors noted that the movement on planning chest CT scans could potentially significantly affect the diagnostic yield during ENB procedures.

The ENB device is used in conjunction with standard bronchoscopy and is not FDA approved as a stand-alone surgical device/procedure. According to the U.S. FDA Center for Devices and Radiological Health (CDRH), the superDimension/Bronchus inReach System is a device that guides a bronchoscope and bronchial tool to a target in, or adjacent to, the bronchial tree on a path indicated by CT scan, and visualizes the target and the interior of the tree. The FDA-approved indications are:

For displaying images of the tracheobronchial tree to aid the physician in guiding endoscopic tools or catheters in the pulmonary tract and to enable marker placement within soft lung tissue. It does not make a diagnosis and is not an endoscopic tool. This device has not been approved for pediatric use (FDA, 2008).

According to the FDA clearance information (2008), instructions are being modified for use to include guidance and instruction for deploying radiosurgical and dye markers into soft lung tissue with the superDimension/Bronchus System. No changes are being made to the hardware or software design or to the technological characteristics of the current marketed device. According to the FDA, the superDimension/Bronchus inReach System is also marketed under the branded name, the superDimension iLogic inReach System with no change to the approved indications. In 2010, the FDA cleared the Edge^™ Catheter System (also manufactured by superDimension, Inc.) as:

An alternate catheter system for use with the superDimension iLogic inReach System. The Edge Catheter System includes modifications to the existing inReach Catheter System, procedure software, and instructions for use. The Edge Catheter and inReach Catheter systems may both be used with the superDimension iLogic inReach System. No changes are being made to the electromagnetic components or fundamental scientific technology of the iLogic inReach System (FDA, 2010).

In December 2009, a second ENB system received FDA clearance through the 510(k) process. This is marketed in the U.S. as the SpiN Drive System by Veran Medical (St. Louis, MO), which also goes under the trade name: ig4^™ EndoBronchial System. According to the 510(k) summary, the device was shown to be substantially equivalent to the inReach System for its intended use of navigating endoscopic tools, catheters, and guide wires in the pulmonary tract, and substantially equivalent to the ig4 Image Guided System in automatic 3D registration to a CT-based model of the lungs and navigation of instruments. The ig4 is an accessory for a CT system that utilizes electromagnetic tracking technology to locate and navigate endoscopically. The system incorporates a method of gating the location information in soft tissue to the individual’s respiration. The ig4 System (SpiN Drive System) is intended for:

Use in clinical interventions and for anatomical structures where CT and/or endoscopic bronchoscopy are currently used for visualizing such procedures. The system compensates for the individual’s respiratory phases. It is indicated for displaying:

• An interventional instrument such as a biopsy needle, an aspiration needle, or ablation needle on a computer monitor that also displays a CT-based model of the target organ(s);
• A CT-based model of the lungs and images of the tracheobronchial tree to aid a physician in guiding endoscopic tools, catheters or guide wires in the pulmonary tract (FDA, 2009).

Lung Biopsy

A prospective, open label, single-center pilot study was conducted at the Cleveland Clinic to determine the feasibility of ENB to sample peripheral lung lesions and mediastinal lymph nodes with standard bronchoscopic instruments and to demonstrate safety. A total of 60 non-consecutive, non-randomized subjects were enrolled from a single center. The steerable probe tip was navigated to the target lung area in all cases. The mean peripheral lesions and lymph node sizes were 22.8 ± 12.6 mm and 28.1 ± 12.8 mm, respectively. Yield was determined by results obtained during the bronchoscopy per individual. The yield per procedure was 74% and 100% for peripheral lesions and lymph nodes, respectively. A diagnosis was obtained in 80.3% of bronchoscopic procedures, and a definitive diagnosis of lung malignancy was made in 74.4% of subjects. Pneumothorax occurred in 2 subjects. The authors concluded that ENB is a safe method for sampling peripheral and mediastinal lesions with high diagnostic yield independent of lesion size and location (Gildea, 2006). A key limitation of this study is that there was no direct comparison to an appropriately selected and randomized control population.

Wilson described a retrospective review of 248 consecutive individuals who underwent electromagnetic navigation-assisted biopsy procedures. The purpose of this study was to determine the percentage of individuals who had a malignant diagnosis or a plausible nonmalignant diagnosis on the day of the procedure. The mean size of the targeted peripheral lesions and lymph nodes was 2.1 ± 1.4 standard deviations (SD) cm and 1.8 ± 0.9 (SD) cm, respectively. Mean follow-up was 6 ± 5 (SD) months. The majority of the peripheral lesions were in the upper lung lobes (51%). On the day of the procedure, 65% received a definitive malignant or plausible nonmalignant diagnosis. With additional clinical follow-up, when all inconclusive cases were treated as nondiagnostic, the yield was 70% (12 individuals [5%] with a nonmalignant diagnosis on the day of the procedure were confirmed as having no disease; 8 individuals [3%] were confirmed as having malignant disease; and 67 individuals [27%] remained inconclusive, due to lack of clinical follow-up information). The authors concluded that ENB is a safe and effective, noninvasive alternative for the diagnosis of smaller peripheral lung lesions. Its use in combination with rapid on-site cytologic evaluation may significantly increase the diagnostic yield of routine bronchoscopy. Prospective studies with longer clinical follow-up are needed, as well as studies of the impact of both ENB and rapid on-site cytologic evaluation (Wilson, 2007). A key limitation of this study is that there was no direct comparison on a per-lesion or per-subject basis to demonstrate that this technique improved the yield over standard approaches.

In a systematic review and meta-analysis, Gex and colleagues (2014) included a total of 15 trials with 1033 lung nodules in 971 individuals. Successful navigation to the peripheral lung nodule was achieved 97.4% of the time, with a definitive diagnosis reported in 64.9% of the cases. The overall diagnostic accuracy was 73.9% and the sensitivity for lung cancer was 71.1%. However the negative predictive value for cancer was only 52.1% and the overall negative predictive value was suboptimal at 78.5%. The authors noted several limitations related to this review. The methodological quality of the studies, as evaluated by the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) scores, was poor. None of the studies compared ENB to the gold standard, surgical resection. In addition, there were inconsistencies in the reported outcomes between studies such as the definition of diagnostic yield, which in several studies includes more favorable outcomes such as diagnostic or malignancy status accuracy.

The authors noted that ENB’s performance, compared to CT-guided transthoracic needle biopsies, seems slightly inferior and further adequately powered prospective studies are needed.

A recent study by Ost and colleagues (2016) compared several methods used to obtain samples and diagnose peripheral lung nodules and masses. This retrospective study used data obtained from the American College of Chest Physicians (ACCP) Quality Improvement Registry, Evaluation, and Education (AQuIRE) program, which included 15 centers and 581 individuals. Overall, the bronchoscopy procedures were considered diagnostic (specific diagnosis of either benign or malignancy was made) in 53.7% of the peripheral lesions (312/587). Unadjusted for other factors, the diagnostic yield of bronchoscopy alone (without radial endobronchial ultrasound [r-EBUS] or electromagnetic navigation [EMN]) was 63.7%; 57.0% with r-EBUS only; 38.5% with EMN only; and 47.1% with EMN plus r-EBUS. These lower diagnostic yields remained even after adjusting for size, location, transbronchial needle aspiration use or tobacco use. The authors contrast these results with those higher yield results reported in previous small, retrospective studies, suggesting that EMN does not perform as well outside the research setting. This study also addressed lung cancer sensitivity. The overall sensitivity for lung cancer was 60-74%. The minimum and maximum ranges were lower in those procedures which utilized EMN versus those procedures which did not (54%-69% versus 68%-79% respectively). The authors noted that there is little difference in sensitivity between best case sensitivity scenario with EMN and the worst case scenario without EMN. This may be due to limitations with this study, including the retrospective design with limited ability to use surgical resection as the diagnostic gold standard. This study does not support that EMN is superior to bronchoscopy and highlights the need for further comparator studies.

In a 2015 meta-analysis, Zhang and colleagues evaluated the overall diagnostic yield and accuracy of ENB-based targeted biopsies in detecting peripheral lesions. This meta-analysis included 17 studies with a total of 1106 individuals with peripheral lung lesions. In the 15 studies which reported true positive (TP) and true negative (TN) data, the sensitivity ranged from 50%-100% with a pooled sensitivity of 82% (95% confidence interval [CI], 78-85%). The pooled specificity of this population was reported at 100%. The positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were reported as 18.67 (95% CI, 9.04-38.55), 0.22 (95% CI, 0.15-0.32) and 97.36 (95% CI, 43.75-216.69) respectively. There were several limitations associated with this meta-analysis. There was significant statistical heterogeneity found with the sensitivity and NLR outcomes. The authors of the study noted that the methodological quality of the studies was poor. None of the studies included a comparison to the current gold standard procedure of surgery. In addition, selection bias may have been a factor as it was not clear whether the participants were representative of the population which would be suitable ENB-candidates in the clinical setting.

In 2017, Khandar and colleagues published the interim, 1-month results of the NAVIGATE study, a prospective, single arm, multicenter study of individuals who underwent ENB. Participants included individuals undergoing ENB procedures for lung lesion biopsy (n=964), fiducial marker placement (n=210), pleural dye marking (n=17), and/or lymph node biopsy (n=334). The majority of the lesions were in the peripheral/middle lung thirds (92.7%). The primary endpoint was index ENB-related pneumothorax rated grade ≥ 2, as it is applicable to all ENB procedures. At the 12- and 24-month follow-ups, the diagnostic yield of the index ENB procedure will be calculated as the proportion of individuals with a definitive diagnosis. One month follow-up data was obtained on 93.3% of the first 1000 primary cohort participants. Pneumothorax of grade ≥ 2 related to the ENB procedure was reported in 3.2% (32/1000) of the group. Pneumothorax of any grade was reported in 4.9% (49/1000) of the cases. There were 23 individuals who died by the 1-month follow-up, no deaths were considered to be related to the ENB device. Tissue biopsy was successful in 94.4% (910/1000) in those individuals who were diagnosed with primary lung adenocarcinoma or non-small-cell lung cancer NOS and molecular genetic testing was attempted; there was adequate tissue in 56/70 (80%). The onsite pathology sample assessments reported non-malignancy in 372/910 (40.9%) cases, malignancy in 45.8% (417/910) cases and inconclusive results in an additional 13.3% (121/910). Fiducial markers were placed in 210 individuals with operators reporting accurate placement in 208/210 (99.0%) cases. A total of eight (3.8%) grade ≥ 2 pneumothoraces were reported. The authors noted that a 1-month interim analysis is not a sufficient amount of time to calculate a true negative yield or the diagnostic yield. While the results suggest ENB might be a safe alternative for a certain population, further follow-up is needed to determine impact on long-term survival and “will help to set the benchmark for the ideal ENB patient, and define the procedural techniques contributing to enhanced performance” (Khandhar, 2017).

In 2019, the 1 year results of the NAVIGATE study were reported by Folch and colleagues. The purpose of 12- month follow-up was to determine the true diagnosis (malignant or nonmalignant). The study defined initial negative results as results that were diagnostic of a nonmalignant condition or indeterminate results. At 12 months post-procedure, cases reporting subsequent diagnostic tests confirming a nonmalignant diagnosis or without lesion progression on radiographic follow-up were considered true-negative. Cases categorized as false-negative included those cases in which follow-up diagnostics revealed malignancy, lesion growth was noted on repeat diagnostic testing, death due to lung cancer within 12 months, treatment without a confirmed diagnosis or new diagnoses of cancer in the lung from any site. A total of 1215 individuals underwent an ENB aided procedure. A 12-month follow-up was completed on 80.3% (976/1215) of the participants. In those individuals who underwent lung lesion biopsy (n=1157), tissue was obtained in 94.4% of the cases (n=1092). Malignancy was diagnosed in 44.3% (484/1092) of the cases and was negative in 55.7% (608/1092) of the cases. At 12 months, the diagnostic yield was 72.9%. Sensitivity for malignancy was 68.8% (range: 59.9%-68.8%); the reported negative predictive value (NPV) was 56.3% (range: 46.7%-63.8%). The specificity and positive predictive value (PPV) were reported as 100% and the NPV was calculated at 56%. Further evaluation at 24 months will be performed and a recalculation of the indexes will be performed at that time. While the study evaluates a large population, the accuracy of these diagnostic indicators is limited by the significant loss to follow-up of approximately 20%.

Bhatt and associates (2018) reported on the results of a retrospective study of individuals who underwent tissue sampling of lung nodules via guidance by ENB (n=146) or CT (n=149). The modality used was based on the anticipated yield which was determined by multiple factors including comorbidities such as regional emphysema, location of nodules and the need for concomitant lymph node staging. The lesions in both groups were predominantly peripherally located (2 or less centimeters (cm) from the pleura). The diagnostic yield and complication rates for each procedure were evaluated and compared. The diagnostic yield reported in the CT group was significantly better than the diagnostic yield in the ENB group (86.0% versus 66.0%; p<0.001 respectively). The rate of major complications, defined as symptomatic hemorrhage or pneumothorax requiring chest tube or hospital admission were not significantly different between the CT and ENB groups. In addition, the authors noted that the intra-procedural time was lower in the CT guided group compared to the ENB group. The authors concluded that CT transthoracic biopsy could be considered the preferred approach when feasible.

The 2013 American College of Chest Physicians Evidence Based Guidelines includes a recommendation for electromagnetic navigation guidance:

In patients with peripheral lung lesions difficult to reach with conventional bronchoscopy, electromagnetic navigation guidance is recommended if the equipment and the expertise are available (Grade 1C).

This recommendation is based on low quality evidence; higher quality evidence may impact confidence in this recommendation and may even change the estimate itself. Ost and colleagues (2016) noted that much of the data was obtained at centers of excellence with a carefully selected study population; it is uncertain how representative this study population is of the general population.

Fiducial Marker Placement or Pleural Dye Marking of Lung Nodule

Fiducial markers (FM) are used as a means of motion management during gated stereotactic body radiation therapy (SBRT) for the treatment of non-small cell lung cancer. FMs can also be used as a visualization aid during surgery with or without pleural dye marking. FMs allow the operator to confirm correct positioning on the target center and to facilitate accuracy of high-dose radiation treatments to small targets and targets in close proximity organs. FMs are placed percutaneously with image guidance or through video bronchoscope. ENB has been proposed as an alternative method of FM placement that may result in fewer complications (Bowling, 2019).

Bowling and associates (2019) reviewed the safety and accuracy outcomes of ENB-guided FM placement in the participants of the NAVIGATE trial who underwent FM placement with the superDimension™ navigation system. The NAVIGATE trial, a prospective, multicenter, observational cohort study of ENB using the superDimension™ navigation system, included 258 adults who underwent elective FM placement. Concurrent procedures included FM placement and lung biopsy, FM placement and dye marking, FM placement alone and FM placement and dye marking and biopsy. The median overall procedure time was 57 minutes and 31 minutes for the ENB procedure; general anesthesia was used in 68.2% (176/258) of the cases. An average of 2.2 ± 1.7 FMs were placed in each session. A placement accuracy of 99.2% was based on subjective operator assessment, which authors admit may not be the most clinically appropriate indicator for SBRT success. When confirmed during follow-up imaging, 94.1% of the markers remained in place. Complication rates were reported as procedure-related pneumothorax rate 5.4% (14/258) overall, grade 2 or higher pneumothorax rate 3.1% (8/258) and respiratory failure rate 1.6% (4/258). Similar to the studies regarding ENB for biopsy, this study lacks a comparator group using an established means of FM placement.

Using data from the NAVIGATE trial, Bowling and colleagues (2019a) reported on the 1 month interim analysis of 23 individuals who underwent pleural dye marking prior to lung resection. The objective of the study was to evaluate usage patterns, techniques and performance. Dye marking was conducted alone or concurrently with lesion or lymph node biopsy and/or FM placement. Fluoroscopy was used in all cases, EBUS was used in 4/23 cases. Following dye marking, surgical resection was attempted in all cases and the surgeon considered pleural dye marking adequate in 21/23 cases (91.3%). The authors note, “The combined method of ENB, fluoroscopy and radial EBUS may be advantageous when indicated and available.” It is unclear what additional benefit ENB provides during pleural dye marking.

Summary

There have been a number of prospective and retrospective studies evaluating the outcomes of ENB-guided lesion biopsy, (Bhatt, 2018; Bolton, 2014; Bolton, 2018; Krimsky, 2013; Loo, 2014; Nabavizadeh, 2014; Odronic, 2014; Ozgul, 2016). While the NAVIGATE study attempts to provide a real world, practical design, the results of the study are limited by the absence of a protocolized approach (Thiboutot, 2019). There remains a lack of studies that include head-to-head comparisons of ENB with established biopsy techniques; the impact on care management and clinical outcomes is also unclear at the present time. In addition, there is a paucity of  literature to support the use of ENB to place surgical or radiological markers (Bolton, 2015; Bolton, 2017; Nabavizadeh, 2014; Schroeder, 2010).

In 2020, lung cancer will be diagnosed in approximately 228,820 individuals in the United States and will cause an estimated 135,720 deaths (ACS, 2020). Lung cancer screening is recommended in individuals considered at high risk (NCCN, 2019). Over 25% of the computed tomography (CT) scans in the high-risk population will be abnormal. While early detection is integral to improved outcomes, false positive results can result in over-diagnosis, increased testing (including invasive testing),the potential for less risk of pneumothorax. In addition to comparison with transthoracic biopsy, ENB is also compared to endoscopic ultrasound (EUS), another technique used during bronchoscopy for biopsy of peripheral lung lesions. It is important to note that ENB is not a real-time procedure. A CT scan is performed on one day, with a single-breath hold and the individual not moving, and on another day (or potentially later the same day) in another setting, the bronchoscopy is performed while the individual is awake and breathing with a bronchoscope placed in the airway, (which typically produces coughing and gagging to some extent). The importance of this difference is that the lesions detected on the single breath hold CT scan will not necessarily be in the same physical location as in a breathing individual during a bronchoscopy.

Further description from the manufacturer of the superDimension/Bronchus inReach System states (superDimension, Inc., 2008):

…The system is used as an adjunct to standard bronchoscopy. It provides a three-dimensional roadmap of the lungs generated from standard CT images taken of the lung prior to the procedure. Once the physician creates the plan and maps the individual’s lungs, the inReach System’s disposable guide catheter is used with standard bronchoscopic tools to reach the targeted lesion. The catheter’s tip contains an electromagnetic location sensor that allows its location to be overlaid in real time on the pre-generated CT roadmap of the lungs. The physician can steer the catheter 360 degrees to reach distant locations in the bronchial tree.

Pre-procedure computed tomography (CT) is converted to 3-dimensional (3-D) and "virtual" bronchoscopy formats. Landmarks, including the target lesion(s), are identified on the images. Bronchoscopy is then performed with the individual lying on an electromagnetic board; actual landmarks are compared to the image landmarks, and a steerable probe with a sensor at the tip, whose location is monitored by the electromagnetic field linked to the 3-D CT images, is navigated to the target lesion. Sampling tools (brushes, forceps, etc.) are then passed through an extended work catheter placed at the site of the lesion.

Bronchoscopy: An endoscopic test that utilizes either a rigid or flexible scope, in order to visualize and collect samples (washing, brushing, biopsy, culture, etc.) from the endobronchial tubes/branches of the respiratory system.

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Investigational and Not Medically Necessary:

Peer Reviewed Publications:

1. Atkins NK, Marjara J, Kaifi JT, et al. Role of Computed tomography-guided biopsies in the era of electromagnetic navigational bronchoscopy: a retrospective study of factors predicting diagnostic yield in electromagnetic navigational bronchoscopy and computed tomography biopsies. J Clin Imaging Sci. 2020; 10:33.
2. Bhatt KM, Tandon YK, Graham R, et al. Electromagnetic navigational bronchoscopy versus CT-guided percutaneous sampling of peripheral indeterminate pulmonary nodules: a cohort study. Radiology. 2018; 286(3):1052-1061.
3. Bolton WD, Richey J, Ben-Or S, et al. Electromagnetic navigational bronchoscopy: a safe and effective method for fiducial marker placement in lung cancer patients. Am Surg. 2015; 81(7):659-662.
4. Bolton WD, Cochran T, Ben-Or S, et al. Electromagnetic navigational bronchoscopy reduces the time required for localization and resection of lung nodules. Innovations (Phila). 2017; 12(5):333-337.
5. Bowling MR, Folch EE, Khandhar SJ, et al. Fiducial marker placement with electromagnetic navigation bronchoscopy: a subgroup analysis of the prospective, multicenter NAVIGATE study. Ther Adv Respir Dis. 2019; 13:1753466619841234.
6. Bowling MR, Folch EE, Khandhar SJ, et al. Pleural dye marking of lung nodules by electromagnetic navigation bronchoscopy. Clin Respir J. 2019(a); 13(11):700-707.
7. Brownback KR, Quijano F, Latham HE, Simpson SQ. Electromagnetic navigational bronchoscopy in the diagnosis of lung lesions. J Bronchology Interv Pulmonol. 2012; 19(2):91-97.
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9. Eberhardt R, Anantham D, Ernst A, et al. Multimodality bronchoscopic diagnosis of peripheral lung lesions: a randomized controlled trial. Am J Respir Crit Care Med. 2007a; 176(1):36-41.
10. Eberhardt R, Anantham D, Herth F, et al. Electromagnetic navigation diagnostic bronchoscopy in peripheral lung lesions. Chest. 2007b; 131(6):1800-1805.
11. Eberhardt R, Morgan RK, Ernst A, et al. Comparison of suction catheter versus forceps biopsy for sampling of solitary pulmonary nodules guided by electromagnetic navigational bronchoscopy. Respiration. 2010; 79(1):54-60.
12. Folch EE, Pritchett MA, Nead MA, et al.; NAVIGATE Study Investigators. Electromagnetic navigation bronchoscopy for peripheral pulmonary lesions: one-year results of the prospective, multicenter NAVIGATE study. J Thorac Oncol. 2019; 14(3):445-458.
13. Gex G, Pralong JA, Combescure C, et al. Diagnostic yield and safety of electromagnetic navigation bronchoscopy for lung nodules: a systematic review and meta-analysis. Respiration. 2014;87(2):165-176.
14. Gildea TR, Mazzone PJ, Karnak D, et al. Electromagnetic navigation diagnostic bronchoscopy: a prospective study. The Cleveland Clinic Foundation, Cleveland, OH. Am J Respir Crit Care Med. 2006; 174(9):982-989.
15. Jensen KW, Hsia DW, Seijo LM, et al. Multicenter experience with electromagnetic navigation bronchoscopy for the diagnosis of pulmonary nodules. J Bronchology Interv Pulmonol. 2012; 19(3):195-199.
16. Khandhar SJ, Bowling MR, Flandes J, et al.; NAVIGATE Study Investigators. Electromagnetic navigation bronchoscopy to access lung lesions in 1,000 subjects: first results of the prospective, multicenter NAVIGATE study. BMC Pulm Med. 2017; 17(1):59.
17. Krimsky WS, Minnich DJ, Cattaneo SM, et al. Thoracoscopic detection of occult indeterminate pulmonary nodules using bronchoscopic pleural dye marking. J Community Hosp Intern Med Perspect. 2014; 4.
18. Kupelian PA, Forbes A, Willoughby TR, et al. Implantation and stability of metallic fiducials within pulmonary lesions. Int J Radiation Oncol Biol Phys. 2007; 69(3):777-785.
19. Lamprecht B, Porsch P, Pirich C, Studnicka M. Electromagnetic navigation bronchoscopy in combination with PET-CT and rapid on-site cytopathologic examination for diagnosis of peripheral lung lesions. Lung. 2009; 187(1):55-59.
20. Lamprecht B, Porsch P, Wegleitner B, et al. Electromagnetic navigation bronchoscopy (ENB): increasing diagnostic yield. Respir Med. 2012; 106(5):710-715.
21. Loo FL, Halligan AM, Port JL, Hoda RS. The emerging technique of electromagnetic navigation bronchoscopy-guided fine-needle aspiration of peripheral lung lesions: promising results in 50 lesions. Cancer Cytopathol. 2014; 122(3):191-199.
22. Nabavizadeh N, Zhang J, Elliott DA, et al. Electromagnetic navigational bronchoscopy-guided fiducial markers for lung stereotactic body radiation therapy: analysis of safety, feasibility, and interfraction stability. J Bronchology Interv Pulmonol. 2014; 21(2):123-130.
23. Odronic SI, Gildea TR, Chute DJ. Electromagnetic navigation bronchoscopy-guided fine needle aspiration for the diagnosis of lung lesions. Diagn Cytopathol. 2014; 42(12):1045-1050.
24. Ost DE, Ernst A, Lei X, et al.; AQuIRE Bronchoscopy Registry. Diagnostic yield and complications of bronchoscopy for peripheral lung lesions: results of the AQuIRE Registry. Am J Respir Crit Care Med. 2016; 193(1):68-77.
25. Ozgul G, Cetinkaya E, Ozgul MA, et al. Efficacy and safety of electromagnetic navigation bronchoscopy with or without radial endobronchial ultrasound for peripheral lung lesions. Endosc Ultrasound. 2016; 5(3):189-195.
26. Pearlstein DP, Quinn CC, Burtis CC, et al. Electromagnetic navigation bronchoscopy performed by thoracic surgeons: one center's early success. Ann Thorac Surg. 2012; 93(3):944-949; discussion 949-950.
27. Schroeder C, Hejal R, Linden PA. Coil spring fiducial markers placed safely using navigation bronchoscopy in inoperable patients allows accurate delivery of CyberKnife stereotactic radiosurgery. J Thorac Cardiovasc Surg. 2010; 140(5):1137-1142.
28. Schwarz Y, Greif J, Becker HD, et al. Real-time electromagnetic navigation bronchoscopy to peripheral lung lesions using overlaid CT images: the first human study. Chest. 2006; 129(4):988–994.
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Government Agency, Medical Society, and Other Authoritative Publications:

1. Du Rand IA, Barber PV, Goldring J, et al. British Thoracic Society guideline for advanced diagnostic and therapeutic flexible bronchoscopy in adults. Thorax. 2011; 66(Suppl 3):iii1-21. Available at: https://thorax.bmj.com/content/66/Suppl_3/iii1. Accessed on July 17, 2020.
2. Lewis SZ, Diekemper R, Addrizzo-Harris DJ. Methodology for development of guidelines for lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013; 143(5 Suppl):41S-50S. Available at: http://journal.chestnet.org/article/S0012-3692(13)60285-8/pdf. Accessed on July 17, 2020.
3. National Clinical Practice Guidelines in Oncology^®. ^©2020 National Comprehensive Cancer Network, Inc. Lung Cancer Screening. V1.2020. May 14, 2019. For additional information, visit the NCCN website:  http://www.nccn.org/index.asp. Accessed on July 17, 2020.
4. Rivera MP, Mehta AC, Wahidi MM. Establishing the diagnosis of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines. Chest. 2013; 143(5 Suppl):e142S-165S. Available at http://journal.chestnet.org/article/S0012-3692(13)60293-7/fulltext. Accessed on July 20, 2020.
5. U.S. Food and Drug Administration. Center for Devices and Radiological Health (CDRH) 510(k) Premarket Notification Database.
   • Ig4^™ EndoBronchial. Summary of Safety and Effectiveness. No. K091934. Rockville, MD: FDA. December 2, 2009. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf9/K091934.pdf. Accessed on July 20, 2020.
   • LungPoint® Virtual Bronchoscoppppic Navigation (VBS), Summary of Safety and Effectiveness. No. K090095. Rockville, MD: FDA. March 13, 2009. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf9/K091160.pdf. Accessed on July 20, 2020.
   • superDimension^®/Bronchus inReach^TM System. Summary of Safety and Effectiveness. No. K080271. Rockville, MD: FDA. September 4, 2009. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf9/k092365.pdf . Accessed on July 20, 2020.
   • superDimension^®  i-Logic^™ inReach^® System with the Edge^™ Catheter System. Summary of Safety and Effectiveness. No. K102604. Rockville, MD: FDA. October 7, 2010. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf10/K102604.pdf. Accessed on July 20, 2020.

1. American Cancer Society (ACS).
   • Lung Cancer (Non-Small Cell). Available at: http://www.cancer.org/acs/groups/cid/documents/webcontent/003115-pdf.pdf. Accessed on July 20, 2020.
   • Key Statistics for Lung Cancer. Available at: https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html. Accessed on July 6, 2020.
2. American Lung Association. Diagnosing Lung Cancer. Available at:  http://www.lung.org/lung-health-and-diseases/lung-disease-lookup/lung-cancer/diagnosing-and-treating/how-lung-cancer-diagnosed.html. Accessed on July 20, 2020.
3. National Heart, Lung and Blood Institute. What is Bronchoscopy? Available at: https://www.nhlbi.nih.gov/health-topics/bronchoscopy. Accessed on July 20, 2020.

Electromagnetic Navigational Bronchoscopy (ENB)
ig4 EndoBronchial System
iLogic Electromagnetic Navigation Bronchoscopy
LungPoint® Virtual Bronchoscopic Navigation
SpiN Drive System
superDimension/Bronchus inReach System

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.