Electromagnetic navigation bronchoscopy to access lung lesions in 1,000 subjects: first results of the prospective, multicenter NAVIGATE study
- Sandeep J. Khandhar†1,
- Mark R. Bowling2,
- Javier Flandes3,
- Thomas R. Gildea4,
- Kristin L. Hood5,
- William S. Krimsky6,
- Douglas J. Minnich7, 14,
- Septimiu D. Murgu8,
- Michael Pritchett9,
- Eric M. Toloza10, 11,
- Momen M. Wahidi12,
- Jennifer J. Wolvers5,
- Erik E. Folch†13Email author and
- for the NAVIGATE Study Investigators
© The Author(s). 2017
Received: 25 January 2017
Accepted: 28 March 2017
Published: 11 April 2017
Electromagnetic navigation bronchoscopy (ENB) is an image-guided, minimally invasive approach that uses a flexible catheter to access pulmonary lesions.
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.
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.
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.
ClinicalTrials.gov NCT02410837. Registered 31 March 2015.
KeywordsImage-Guided Biopsy Lung Cancer Lung Neoplasms Neoplasm Staging Solitary Pulmonary Nodule
Guidelines for lung nodule evaluation recommend the least invasive approach given each patient’s clinical presentation . Utilization of electromagnetic navigation bronchoscopy (ENB) has increased over the past ten years as a minimally invasive approach to complement traditional bronchoscopy, endobronchial ultrasound (EBUS), and image-guided transthoracic biopsy. Selection of the most appropriate diagnostic modality based on patient comorbidities and lesion location is critical to provide the fastest, safest, and most complete diagnosis possible.
Seventeen published studies of ENB use have been summarized in three recent meta-analyses [2–4]. Pneumothorax is the most common complication, occurring in approximately 3% of patients , lower than the pooled 20% rate reported for transthoracic needle biopsy . However, published studies have typically been small, single-center, retrospective, and mostly conducted by expert users. The safety, usage profile, and clinical utility of ENB in a large, prospective, multicenter, generalizable population is unknown. The pragmatic design  of NAVIGATE maximizes patient eligibility, usual care settings, flexibility of adherence, and a relevant primary outcome for clinical practice. The detailed prospective collection of data also minimizes retrospective bias and allows future multivariate analyses to provide more meaningful information on the variable utilization of this technology into real-world practice and its impact on measurable outcomes, such as diagnostic yield and risk. Furthermore, a heterogeneous dataset will be instructive for the design of potential comparative studies with respect to operator training, subject inclusion criteria, data to be collected, definitions, and expected complication rates.
The primary objectives of this protocol-specified 1,000-subject, 1-month interim analysis of the NAVIGATE study  are to present the preliminary safety, clinical usage patterns, and performance of ENB in a large, unrestricted, generalizable population across diverse practice settings. The interim data will provide an early look at typical patient and lesion characteristics and procedural standard-of-care, generating questions for future NAVIGATE analyses and new clinical studies. Enrollment and continued follow-up are ongoing.
NAVIGATE is a prospective, multicenter, global, single-arm, cohort study in subjects undergoing ENB procedures. Enrollment of up to 1,500 subjects is planned at 37 sites in the United States and Europe. Subjects evaluations occur at baseline (within 30 days of the procedure), on the procedure day, and at 1 month, 12 months, and 24 months post-procedure. This manuscript describes the results of a prespecified 1-month interim analysis of the first 1,000 subjects enrolled at 29 sites in the United States and Europe. Enrollment and 12- and 24-month follow-up are ongoing. Brief methods are included below. A full list of study assessments and definitions is included in Additional files 1 and 2. The study design has been published .
Inclusion criteria are intentionally broad to ensure external validity. All consecutive, consented adult patients, who are not pregnant or nursing, and who are candidates for an elective ENB procedure based on physician discretion per recommended guidelines and institutional standard-of-care, are eligible. A maximum of 75 subjects is allowed per site. All investigators must have prior ENB experience. Investigators without extensive experience may enroll a maximum of five “roll-in” cases, which are excluded from this interim analysis. Roll-in cases will be included in the 1-year and 2-year analyses of the full enrollment when a more complete evaluation of the impact of user experience on diagnostic yield and other outcomes can be conducted.
All ENB procedures use the superDimension™ navigation system [8, 9] version 6.0 or higher (Medtronic, Minneapolis, MN) per product instructions and institutional standard practice. All complementary tools and procedures, including choice of catheter and biopsy tools, order of biopsy tool use, and strategy for staging and diagnostic bronchoscopy were performed at clinician discretion and were captured prospectively for data analysis.
The primary endpoint is pneumothorax related to the ENB index procedure rated Grade ≥2 according to the validated Common Terminology Criteria for Adverse Events (CTCAE) scale [7, 10], as adjudicated by an independent medical monitor. Pneumothorax was protocol-specified as the primary endpoint because it is applicable to all ENB procedures, including lung lesion biopsy, lymph node biopsy, fiducial placement, and pleural dye marking. Major secondary endpoints were all ENB-related pneumothorax, bronchopulmonary hemorrhage, and respiratory failure. Other secondary endpoints reported at 1 month were subject self-reported satisfaction with the procedure; adequacy of samples for molecular testing and mutation type; accurate fiducial placement as assessed by follow-up imaging; and success rate of pleural dye marking demonstrated by surgical resection .
Diagnostic yield of the ENB index procedure will be calculated at the 12- and 24-month follow-up as the proportion of subjects with a definitive diagnosis (final pathology of the ENB-aided sample). One-month follow-up in this interim analysis is not sufficient to calculate the true negative rate or diagnostic yield. All lung nodules evaluated during the ENB index procedure will be followed for confirmation. Sensitivity, specificity, negative predictive value, and positive predictive value will be published beginning with the 12-month follow-up.
No sample size calculations were conducted for this single-arm, observational study. Analyses were performed using SAS® Version 9.4 (SAS Inc., Cary, NC). Data are summarized by descriptive statistics, including frequency distributions and cross-tabulations for discrete variables and mean, standard deviation, median, minimum, and maximum values for continuous variables. At least 10% of the data are verified against source files by the sponsor using risk-based monitoring.
Subject demographics (all primary cohort subjects)
N = 1000 Subjects
Age at consent (years)
67.7 ± 11.3 (1000) [69.0] (21.0–93.0)
Black or African American
American Indian or Alaska Native
Native Hawaiian or Other Pacific Islander
Unable To Report
Hispanic or Latino Ethnicity
Tobacco History (Current or Former)
FEV1 (% of predicted)
74.8 ± 25.6 (332) [75.5] (20.0–140.0)
0.9 ± 0.2 (331) [0.9] (0.3–1.9)
DLCO (% of predicted)
66.4 ± 24.9 (225) [66.0] (6.0–141.0)
Prior Invasive Lung Proceduresa
Transthoracic Needle Aspiration
Personal History of Cancer
Family History of Cancer
Subject taking Antithrombotic Medicationsc
General procedural characteristics (all primary cohort subjects)
N = 1000 Procedures
ENB Software Version
Radial EBUS used During ENB Procedurea
Cone Beam CT used
Total Procedure Time (Bronchoscope In/Out), min
52.0 (36.0 [35.0–71.0])
ENB Procedure Time (Locatable Guide In/Out), minb
25.0 (27.0 [14.0–41.0])
Adverse events related to the ENB index procedure or devices (1 Month Follow-up)a
N = 1000 Subjects
CTCAE Grade 2 or Higher
CTCAE Grade 2 and Higher
Respiratory Failure, CTCAE Grade 4 or Higher
Death (anesthesia-related respiratory failure 9 days post-ENB)b
Lung lesion biopsies
Lung lesion characteristics (subjects undergoing ENB- aided biopsy)
N = 1129 Lesions in 964 Subjects
Pre-test probability of malignancy (physician estimation)
67.1 ± 26.5 (790) [75.0] (0.0–100.0)
Pre-test probability of malignancy (Swenson’s equation)a
61.6 ± 29.4 (789) [67.1] (2.9–100.0)
Average Lung Lesion Size, mm
Mean ± SD (N)
23.6 ± 14.4 (1129)
Median, Range (min-max)
Interquartile Range (Q1-Q3)
< 20 mm
≥ 20 mm
Right Upper Lobe
Right Middle Lobe
Right Lower Lobe
Left Upper Lobe
Left Lower Lobe
Peripheral third of lung on CT
Middle third of lung on CT
Proximal third of lung on CT
Lesion Visible on Fluoroscopy
Ground Glass Lesions (Suzuki Class 1 or 2) 
Spiculated Lesion Border
Bronchus Sign Present on CT
Lesion PET Positive (≥2.5 standard uptake value)
Procedural characteristics in lung lesion biopsy cases
N = 1129 Lesions in 964 Subjects
Navigation Success (per lesion)a
Navigation Success (per subject)a
Number of Lesions Biopsied (per subject)
1.2 ± 0.5 (964) [1.0] (1.0–5.0)
Biopsy Tools Used During ENB Index Procedureb
Needle-Tipped Cytology Brush
Triple Needle-Tipped Cytology Brush
GenCut™ Core Biopsy Tool
Bronchoalveolar Lavage or Washing
Rapid on-site evaluation (ROSE) usedc
Molecular/genetic testing attemptedd
Molecular/genetic testing successful
Molecular/genetic testing not attemptedd
Not Standard Practice
Pathology result aided by the index ENB procedurea
N = 910 subjects with navigation complete and tissue sample obtained
Non-Small Cell Lung Cancer (NSCLC)
Small Cell Carcinoma
Metastatic Carcinoma of Extrathoracic Origin
Malignant Cells (unable to characterize)
Site-Reported Non-Malignant or Inconclusive Results
Normal Lung Tissue/Bronchial Epithelium
Interstitial Lung Disease
Based on site-reported assessments of the ENB-aided final pathology sample, tissue was interpreted as non-malignant in 372/910 (40.9%) subjects (Table 6). An additional 121/910 (13.3%) were interpreted as inconclusive. Longer follow-up is required to confirm true versus false negatives and calculate diagnostic yield. At this time, the true prevalence of malignancy in the patient population is unknown.
Fiducial placement and pleural dye marking
A total of 417 fiducial markers were placed in 210 subjects. Subjective operator assessment of accurate fiducial placement was 208/210 (99.0%) and fiducial markers were still present at follow-up imaging in 192/205 (93.7%). In subjects undergoing fiducial marker placement, ENB-related adverse events included eight pneumothoraces CTCAE Grade ≥2 (3.8%), three respiratory failures CTCAE Grade ≥4 (1.4%), and one bronchopulmonary hemorrhage Grade 1. Pleural dye marking was conducted in 17 subjects, of which 15 (88.2%) were considered adequate for surgical resection.
Lung cancer causes one quarter of all cancer deaths, representing a significant public health problem . While the incidence has declined in concert with decreased smoking prevalence, survival rates have improved little over the past 50–60 years, largely due to a high proportion of late-stage diagnoses with a 5-year survival rate of only 4% . Earlier-stage diagnoses will lead to more meaningful improvements in survival and will require modalities that allow the accurate sampling of smaller, more peripheral lung lesions. The National Lung Screening Trial  and screening coverage in select high-risk patients  has been projected to increase low-dose CT utilization by over ten million procedures annually . However, an extremely high percentage (96%) of false positive screening results [13, 16] and the risk of unnecessary procedures requires the judicious use of minimally invasive options and a careful balance of the risk-to-benefit ratio for further diagnosis and management .
Several current technologies can provide minimally invasive diagnostic evaluation in appropriately selected patients, although each has limitations. PET-CT is often considered the second-line diagnostic option for nodules detected on CT , but is typically not reimbursed for screening and does not provide tissue diagnosis. Conventional bronchoscopy is safe but is limited to proximal lesions and has a high non-diagnostic rate, potentially leading to unnecessary invasive procedures in 20–25% of patients, including the use of thoracoscopy for diagnostic wedge resection [19–21]. Image-guided transthoracic biopsy provides high diagnostic accuracy but at the cost of pneumothorax rates averaging 20% (range 4 to 62%)  and the need for additional procedures to diagnose and stage mediastinal lymph nodes. ENB provides a minimally invasive platform for peripheral lung lesion sampling, concurrent lymph node staging with linear EBUS, preparation for treatment via fiducial placement or localization via pleural dye marking in a single procedure.
The primary objective of this interim NAVIGATE analysis was to evaluate ENB safety. While published pneumothorax rates are low (3.1% [range 0–13%]) , most prior studies are single-center with fewer than 100 subjects [4, 7]. The current analysis demonstrates low pneumothorax, bronchopulmonary hemorrhage, and respiratory failure rates in the context of a large, diverse study cohort and a wide range of user experience levels, confirming the safety of advanced bronchoscopy for the access and sampling of all pulmonary nodules. Pneumothorax was also infrequent following fiducial placement (3.8%), in contrast to rates ranging from 22 to 67% following percutaneous fiducial marking , Despite the advanced stage of some of the enrolled subjects, there were only 23 deaths within the 1-month follow-up timeframe, further substantiating the safety of the procedure. Only one death was considered related to the ENB index procedure, due to general anesthesia in a patient with multiple comorbidities, and none were related to the ENB device or associated tools. These results suggest a highly favorable risk-to-benefit ratio for the use of ENB to aid in lung lesion biopsies, particularly given the risk profile of the patients included, with approximately 45% COPD incidence and a relatively high rate of Stage III-IV disease.
A second objective of this analysis was to explore the real-world usage patterns and clinical utility of ENB. The interim results elucidate the rates of general anesthesia use (79.7%), ROSE utilization (66.1%), and concurrent fluoroscopic (90.1%) and radial EBUS (54.3%) guidance. Of note, nearly half of ENB index procedures were conducted for multiple purposes, including 33.4% with lymph node staging (primarily EBUS-guided) and 21.0% with fiducial markers placed. Tissue adequacy for molecular genetic testing was also high (80.0%) and similar to prior studies . These results suggest that, in unrestricted practice settings, ENB is used to diagnose peripheral lung nodules and perform concurrent linear EBUS-guided mediastinal lymph node staging in a single anesthetic event, facilitating a multidisciplinary, comprehensive patient care approach.
A third objective of this interim analysis was to provide a preliminary look at ENB performance. From a patient perspective, all important follow-up cadence and treatment decisions are made within the 30-day window after the diagnostic procedure. At the 1-month time-point, ENB provided a preliminary malignant diagnosis in 45.8% of subjects, including 40.1% with lung cancer. The initial 45.8% malignancy rate in NAVIGATE is consistent with other recent ENB publications reporting malignancy rates of 35–60% [24–27], and is expectedly higher than the 3.7% positive malignancy rate seen in the National Lung Screening Trial .
One-month follow-up is not sufficient to calculate the true versus false negative rate or diagnostic yield, as the true prevalence of lung cancer in this population is unknown at this time. All non-malignant pathology findings require confirmation with longer-term follow-up or additional diagnostic procedures, depending upon the pretest probability of malignancy and in accordance with society guidelines [1, 18]. All follow-up procedures and final diagnoses will be captured and reported. Early indicators of clinical stage in NAVIGATE subjects diagnosed with lung cancer also suggest a 64% rate of Stage I-II diagnoses, which are more amenable to surgical intervention for curative intent. In this observational study with consecutive enrollment, approximately 36% of NAVIGATE subjects had Stage III-IV lung cancer. Diagnostic testing of late-stage patients in NAVIGATE may reflect not only a lack of standardization for patient selection but also the changing landscape of personalized medicine and treatment options for Stage III-IV disease. Patient selection for ENB, as well as multivariate predictors of safety and effectiveness, will be explored in future NAVIGATE analyses of the full cohort. This will include an analysis of Stage III-IV cases to explore the patient, lesion, and operator/center factors leading to the inclusion of these cases in the study.
The final objective of this preliminary analysis was to generate questions for future NAVIGATE analyses and comparative studies. Unexpected observations included a high percentage of lesions without a CT bronchus sign (52%) and a relatively low proportion of subjects in whom genetic testing was attempted (28%). While current guidelines recommend genetic testing for only late-stage disease, there is extensive variation between institutions. Tissue requirements for comprehensive molecular testing and the practice of personalized medicine will continue to evolve. Future analyses will describe molecular genetic evaluation in the NAVIGATE cohort in more detail. Other future questions include multivariate predictors of safety and diagnostic yield, factors affecting the need for concurrent radial EBUS or other fluoroscopic guidance, usage patterns of fiducial and pleural dye marking, success rates of various biopsy tools, and cost effectiveness. In this way, NAVIGATE will help to set the benchmark for the ideal ENB patient, and define the procedural techniques contributing to enhanced performance. Whether ENB truly enables a shift to an earlier stage diagnosis, and the impact on long-term patient survival, healthcare utilization, and costs, will also be topics for future NAVIGATE analyses.
This is a nonrandomized, single-arm analysis of 1-month interim results. Longer-term follow-up is required to determine the accuracy of ENB-aided diagnoses, and calculate diagnostic yield. Follow-up through 24 months is in progress. This analysis also evaluates only one navigational bronchoscopy system; other systems are currently available for clinical use.
This early look at the NAVIGATE results provides information about usage patterns and utility of ENB in a large, unrestricted, generalizable population across diverse practice settings. In the first 1,000 subjects enrolled, 1-month follow-up demonstrates low adverse event rates among a heterogeneous cohort. Continued enrollment and follow-up will demonstrate the negative predictive value and delineate the patient, lesion, and procedural characteristics contributing to diagnostic yield. This preliminary analysis generates questions to be explored in future controlled clinical studies. Further follow-up will also help define objective endpoints to guide future population-based guidelines for intervention.
Common Terminology Criteria for Adverse Events
Electromagnetic navigation bronchoscopy
Transthoracic needle aspiration
The study is sponsored and funded by Medtronic (Minneapolis, MN). Medical writing support was provided by Kristin L. Hood PhD, a full-time employee of Medtronic and coauthor on this paper. The authors wish to thank Haiying Lin (Medtronic) for biostatistics support. The authors also wish to thank the investigators and staff of all participating clinical sites (see Additional file 3).
The study is sponsored and funded by Medtronic (Minneapolis, MN), which contributed to the study design, data collection, and data analysis, and assisted with manuscript writing. The lead authors (EF and SK) had full access to all study data and final responsibility for the decision to submit for publication.
Availability of data and materials
The NAVIGATE dataset will be made publicly available on ClinicalTrials.gov (NCT02410837) after the completion of study enrollment and follow-up. The interim data on which this paper is based are available from the corresponding author on reasonable request.
All authors made substantial contributions to all aspects of the study conduct and manuscript development beginning with the initial study conception, including study design (SJK, MRB, TRG, KLH, WSK, SDM, MP, EMT, MMW, EEF), data acquisition (MRB, JF, TRG, WSK, DJM, SDM, MP, MMW), data analysis (SJK, KLH, JJW, EEF), data interpretation (SJK, MRB, TRG, SDM, MMW, EEF), manuscript writing (SJK, KLH, EEF), critical revisions (all authors), final approval of the manuscript for submission (all authors); and agreement to be accountable for the accuracy and integrity of the work (all authors).
Financial disclosures related to the submitted work: SJK, MRB, TRG, WSK, SDM, EMT, MMW, and EEF serve on the Clinical Advisory Board for Medtronic and received travel funds and fees for participation; SJK, JF, DJM, SDM, and EEF serve on the NAVIGATE Steering Committee and have received fees for participation; KLH and JJW are full-time employees and stockholders of Medtronic, MMW received consulting fees from Medtronic. Financial disclosures outside the submitted work: MRB and MP received consulting fees from Medtronic; KLH is a stockholder of Boston Scientific; WSK is a part-time employee of Medtronic (employment began after study enrollment was complete) and has received consulting fees from Medtronic with intellectual property rights; SDM received consulting fees from Boston Scientific, Olympus, Concordia, and Auris Robotics; EMT received travel funds and honoraria from Medtronic as a member of their Speakers’ Bureau; EEF is on the Scientific Advisory board for Boston Scientific and the Education Advisory Board for Olympus.
Consent for publication
Not applicable. This paper presents aggregate data.
Ethics approval and consent to participate
This study is being conducted in accordance with the Declaration of Helsinki and all local regulatory requirements. The protocol was approved by the institutional review board of all participating clinical sites (see Additional file 4), and all subjects provided written informed consent prior to participation.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- 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 evidence-based clinical practice guidelines. Chest. 2013;143:e142S–65.View ArticlePubMedGoogle Scholar
- Gex G, Pralong JA, Combescure C, Seijo L, Rochat T, Soccal PM. Diagnostic yield and safety of electromagnetic navigation bronchoscopy for lung nodules: a systematic review and meta-analysis. Respiration. 2014;87:165–76.View ArticlePubMedGoogle Scholar
- Wang Memoli JS, Nietert PJ, Silvestri GA. Meta-analysis of guided bronchoscopy for the evaluation of the pulmonary nodule. Chest. 2012;142:385–93.View ArticlePubMedGoogle Scholar
- Zhang W, Chen S, Dong X, Lei P. Meta-analysis of the diagnostic yield and safety of electromagnetic navigation bronchoscopy for lung nodules. J Thorac Dis. 2015;7:799–809.PubMedPubMed CentralGoogle Scholar
- DiBardino DM, Yarmus LB, Semaan RW. Transthoracic needle biopsy of the lung. J Thorac Dis. 2015;7:S304–16.PubMedPubMed CentralGoogle Scholar
- Ford I, Norrie J. Pragmatic Trials. N Engl J Med. 2016;375:454–63.View ArticlePubMedGoogle Scholar
- Folch EE, Bowling MR, Gildea TR, Hood KL, Murgu SD, Toloza EM, et al. Design of a prospective, multicenter, global, cohort study of electromagnetic navigation bronchoscopy. BMC Pulm Med. 2016;16:60.View ArticlePubMedPubMed CentralGoogle Scholar
- Reynisson PJ, Leira HO, Hernes TN, Hofstad EF, Scali M, Sorger H, et al. Navigated bronchoscopy: a technical review. J Bronchology Interv Pulmonol. 2014;21:242–64.View ArticlePubMedGoogle Scholar
- Seijo L. Electromagnetic navigation bronchoscopy: clinical utility in the diagnosis of lung cancer. Lung Cancer. 2016;7:111–8.PubMedPubMed CentralGoogle Scholar
- National Cancer Institute, Cancer Therapy Evaluation Program, United States Department of Health and Human Services, National Institutes of Health. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40. Accessed 16 Dec 2016.
- Hari DM, Leung AM, Lee JH, Sim MS, Vuong B, Chiu CG, et al. AJCC Cancer Staging Manual 7th edition criteria for colon cancer: do the complex modifications improve prognostic assessment? J Am Coll Surg. 2013;217:181–90.View ArticlePubMedPubMed CentralGoogle Scholar
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30.View ArticlePubMedGoogle Scholar
- Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395–409.View ArticlePubMedGoogle Scholar
- Centers for Medicare & Medicaid Services, United States Department of Health and Human Services. Decision Memo for Screening for Lung Cancer with Low Dose Computed Tomography (LDCT) (CAG-00439 N, 5 Feb 2015). https://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=274. Accessed 16 Dec 2016.
- Roth JA, Sullivan SD, Goulart BH, Ravelo A, Sanderson JC, Ramsey SD. Projected Clinical, Resource Use, and Fiscal Impacts of Implementing Low-Dose Computed Tomography Lung Cancer Screening in Medicare. J Oncol Pract. 2015;11:267–72.View ArticlePubMedGoogle Scholar
- McWilliams A, Tammemagi MC, Mayo JR, Roberts H, Liu G, Soghrati K, et al. Probability of cancer in pulmonary nodules detected on first screening CT. N Engl J Med. 2013;369:910–9.View ArticlePubMedPubMed CentralGoogle Scholar
- Tanoue LT, Tanner NT, Gould MK, Silvestri GA. Lung cancer screening. Am J Respir Crit Care Med. 2015;191:19–33.View ArticlePubMedGoogle Scholar
- Gould MK, Donington J, Lynch WR, Mazzone PJ, Midthun DE, Naidich DP, et al. Evaluation of individuals with pulmonary nodules: when is it lung cancer? Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e93S–120.View ArticlePubMedPubMed CentralGoogle Scholar
- Silvestri GA, Vachani A, Whitney D, Elashoff M, Porta Smith K, Ferguson JS, et al. A Bronchial Genomic Classifier for the Diagnostic Evaluation of Lung Cancer. N Engl J Med. 2015;373:243–51.View ArticlePubMedPubMed CentralGoogle Scholar
- Detterbeck FC, Mazzone PJ, Naidich DP, Bach PB. Screening for lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e78S–92.View ArticlePubMedPubMed CentralGoogle Scholar
- Grogan EL, Weinstein JJ, Deppen SA, Putnam Jr JB, Nesbitt JC, Lambright ES, et al. Thoracic operations for pulmonary nodules are frequently not futile in patients with benign disease. J Thorac Oncol. 2011;6:1720–5.View ArticlePubMedPubMed CentralGoogle Scholar
- Hagmeyer L, Priegnitz C, Kocher M, Schilcher B, Budach W, Treml M, et al. Fiducial marker placement via conventional or electromagnetic navigation bronchoscopy (ENB): an interdisciplinary approach to the curative management of lung cancer. Clin Respir J. 2016;10:291–7.View ArticlePubMedGoogle Scholar
- Vanderlaan PA, Yamaguchi N, Folch E, Boucher DH, Kent MS, Gangadharan SP, et al. Success and failure rates of tumor genotyping techniques in routine pathological samples with non-small-cell lung cancer. Lung Cancer. 2014;84:39–44.View ArticlePubMedPubMed CentralGoogle Scholar
- 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;122:191–9.View ArticlePubMedGoogle Scholar
- Odronic SI, Gildea TR, Chute DJ. Electromagnetic navigation bronchoscopy-guided fine needle aspiration for the diagnosis of lung lesions. Diagn Cytopathol. 2014;42:1045–50.View ArticlePubMedGoogle Scholar
- Garwood SK, ClenDening P, Hevelone ND, Hood KL, Pidgeon S, Wudel LJ. Navigational bronchoscopy at a community hospital: clinical and economic outcomes. Lung Cancer Manag. 2016;5:131–40.View ArticleGoogle Scholar
- Bowling MR, Kohan MW, Walker P, Efird J, Ben OS. The effect of general anesthesia versus intravenous sedation on diagnostic yield and success in electromagnetic navigation bronchoscopy. J Bronchology Interv Pulmonol. 2015;22:5–13.View ArticlePubMedGoogle Scholar
- Suzuki K, Kusumoto M, Watanabe S, Tsuchiya R, Asamura H. Radiologic classification of small adenocarcinoma of the lung: radiologic-pathologic correlation and its prognostic impact. Ann Thorac Surg. 2006;81:413–9.View ArticlePubMedGoogle Scholar
- Swensen SJ, Silverstein MD, Ilstrup DM, Schleck CD, Edell ES. The probability of malignancy in solitary pulmonary nodules. Application to small radiologically indeterminate nodules. Arch Intern Med. 1997;157:849–55.View ArticlePubMedGoogle Scholar