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

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.

Elevated MicroRNA-33 in Sarcoidosis and a Carbon Nanotube Model of Chronic Granulomatous Disease.

We established a murine model of multiwall carbon nanotube (MWCNT)-induced chronic granulomatous disease, which resembles human sarcoidosis pathology. At 60 days after oropharyngeal MWCNT instillation, bronchoalveolar lavage (BAL) cells from wild-type mice exhibit an M1 phenotype with elevated proinflammatory cytokines and reduced peroxisome proliferator-activated receptor γ (PPARγ)-characteristics also present in human sarcoidosis. Based upon MWCNT-associated PPARγ deficiency, we hypothesized that the PPARγ target gene, ATP-binding cassette (ABC) G1, a lipid transporter with antiinflammatory properties, might also be repressed. Results after MWCNT instillation indicated significantly repressed ABCG1, but, surprisingly, lipid transporter ABCA1 was also repressed, suggesting a possible second pathway. Exploration of potential regulators revealed that microRNA (miR)-33, a lipid transporter regulator, was strikingly elevated (13.9 fold) in BAL cells from MWCNT-instilled mice but not sham control mice. Elevated miR-33 was also detected in murine granulomatous lung tissue. In vitro studies confirmed that lentivirus-miR-33 overexpression repressed both ABCA1 and ABCG1 (but not PPARγ) in cultured murine alveolar macrophages. BAL cells of patients with sarcoidosis also displayed elevated miR-33 together with reduced ABCA1 and ABCG1 messenger RNA and protein compared with healthy control subjects. Moreover, miR-33 was elevated within sarcoidosis granulomatous tissue. The findings suggest that alveolar macrophage miR-33 is up-regulated by proinflammatory cytokines and may perpetuate chronic inflammatory granulomatous disease by repressing antiinflammatory functions of ABCA1 and ABCG1 lipid transporters. The results also suggest two possible pathways for transporter dysregulation in granulomatous disease-one associated with intrinsic PPARγ status and the other with miR-33 up-regulation triggered by environmental challenges, such as MWCNT.

The Impact of Electromagnetic Navigational Bronchoscopy on a Multidisciplinary Thoracic Oncology Program.

BACKGROUND: The Leo W. Jenkins Cancer Clinic has adopted a programmatic, multidisciplinary approach to thoracic tumors, which has involved the implementation of new therapeutic and diagnostic approaches. In 2012 we began using electromagnetic navigational bronchoscopy (ENB) as a new diagnostic tool. ENB uses a guidance system that combines CT imaging with magnetic field-guided spatial information to allow tissue sampling or placement of fiducial markers to guide radiation therapy. METHODS: The numbers of early-stage (I and II) and late-stage (III and IV) lung cancers were compared before and after the introduction of ENB. We also examined the number of cases of fiducial marker placement using bronchoscopy versus interventional radiology before and after ENB was introduced. Fisher's exact test was used to compare the early- versus late-stage lung cancers found at diagnosis pre- and post-ENB introduction, fiducial marker placements using interventional radiology versus bronchoscopy pre- and post-ENB introduction, and pneumothorax rates. RESULTS: More early-stage cancers were diagnosed after ENB introduction (67 of 286 cases vs 116 of 290; P<.0001). Bronchoscopy was also used more frequently to place fiducial markers post-ENB (53 of 86 pre-ENB vs 105 of 117 post-ENB; P<.0001) and had a lower pneumothorax rate (4% vs 22%) than fiducial placement in interventional radiology (P<.001). CONCLUSIONS: The addition of ENB to a multidisciplinary thoracic oncology program may permit the diagnosis of lung cancer at an earlier stage and offers the ability to safely place fiducial markers for therapeutic purposes, such as radiation therapy, within the same procedure, potentially improving safety and decreasing time to treatment.

Design of a prospective, multicenter, global, cohort study of electromagnetic navigation bronchoscopy.

BACKGROUND: Electromagnetic navigation bronchoscopy (ENB) procedures allow physicians to access peripheral lung lesions beyond the reach of conventional bronchoscopy. However, published research is primarily limited to small, single-center studies using previous-generation ENB software. The impact of user experience, patient factors, and lesion/procedural characteristics remains largely unexplored in a large, multicenter study. METHODS/DESIGN: NAVIGATE (Clinical Evaluation of superDimension™ Navigation System for Electromagnetic Navigation Bronchoscopy) is a prospective, multicenter, global, cohort study. The study aims to enroll up to 2,500 consecutive subjects presenting for evaluation of lung lesions utilizing the ENB procedure at up to 75 clinical sites in the United States, Europe, and Asia. Subjects will be assessed at baseline, at the time of procedure, and at 1, 12, and 24 months post-procedure. The pre-test probability of malignancy will be determined for peripheral lung nodules. Endpoints include procedure-related adverse events, including pneumothorax, bronchopulmonary hemorrhage, and respiratory failure, as well as quality of life, and subject satisfaction. Diagnostic yield and accuracy, repeat biopsy rate, tissue adequacy for genetic testing, and stage at diagnosis will be reported for biopsy procedures. Complementary technologies, such as fluoroscopy and endobronchial ultrasound, will be explored. Success rates of fiducial marker placement, dye marking, and lymph node biopsies will be captured when applicable. Subgroup analyses based on geography, demographics, investigator experience, and lesion and procedure characteristics are planned. DISCUSSION: Study enrollment began in April 2015. As of February 19, 2016, 500 subjects had been enrolled at 23 clinical sites with enrollment ongoing. NAVIGATE will be the largest prospective, multicenter clinical study on ENB procedures to date and will provide real-world experience data on the utility of the ENB procedure in a broad range of clinical scenarios. TRIAL REGISTRATION: ClinicalTrials.gov NCT02410837 . Registered 31 March 2015.

Do we measure pleural fluid pH correctly?

PURPOSE OF REVIEW: This review analyzes the current literature available on appropriate measurement of pleural fluid pH and currently used methods of measurement. RECENT FINDINGS: Current literature continues to support the superiority of blood gas analyzers (BGAs) in the accurate measurement of pleural fluid pH. Despite the compelling evidence, roughly 30-50% of the laboratories across the United States continue to use inaccurate methods for pleural fluid pH measurement. Nearly 40% of pulmonologists were incorrect in believing their laboratory uses BGA for the analysis of pleural fluid pH. SUMMARY: It is apparent that the clinical utility of pleural fluid pH is often undermined by its inappropriate measurement. Physicians must be made aware of their laboratory's method of measurement if pleural fluid pH is to be used in the evaluation of pleural diseases. If pleural fluid pH measurement is not done accurately, then other pleural fluid characteristics may be used to aid the clinician.

Chronic obstructive pulmonary disease: epidemiology, management, and impact on North Carolina.

Chronic obstructive pulmonary disease (COPD) affects millions of people worldwide, resulting in morbidity, mortality, and substantial utilization of health care resources. This review focuses on the epidemiology of COPD, management strategies, and the health and economic impact of this condition in North Carolina.

Assessing a biomarker's ability to reduce invasive procedures in patients with benign lung nodules: Results from the ORACLE study.

A blood-based integrated classifier (IC) has been clinically validated to improve accuracy in assessing probability of cancer risk (pCA) for pulmonary nodules (PN). This study evaluated the clinical utility of this biomarker for its ability to reduce invasive procedures in patients with pre-test pCA ≤ 50%. This was a propensity score matching (PSM) cohort study comparing patients in the ORACLE prospective, multicenter, observational registry to control patients treated with usual care. This study enrolled patients meeting the intended use criteria for IC testing: pCA ≤ 50%, age ≥40 years, nodule diameter 8-30 mm, and no history of lung cancer and/or active cancer (except for non-melanomatous skin cancer) within 5 years. The primary aim of this study was to evaluate invasive procedure use on benign PNs of registry patients as compared to control patients. A total of 280 IC tested, and 278 control patients met eligibility and analysis criteria and 197 were in each group after PSM (IC and control groups). Patients in the IC group were 74% less likely to undergo an invasive procedure as compared to the control group (absolute difference 14%, p <0.001) indicating that for every 7 patients tested, one unnecessary invasive procedure was avoided. Invasive procedure reduction corresponded to a reduction in risk classification, with 71 patients (36%) in the IC group classified as low risk (pCA < 5%). The proportion of IC group patients with malignant PNs sent to surveillance were not statistically different than the control group, 7.5% vs 3.5% for the IC vs. control groups, respectively (absolute difference 3.91%, p 0.075). The IC for patients with a newly discovered PN has demonstrated valuable clinical utility in a real-world setting. Use of this biomarker can change physicians' practice and reduce invasive procedures in patients with benign pulmonary nodules. Trial registration: Clinical trial registration: ClinicalTrials.gov NCT03766958.

Evaluation of Electromagnetic Navigational Bronchoscopy Using Tomosynthesis-Assisted Visualization, Intraprocedural Positional Correction and Continuous Guidance for Evaluation of Peripheral Pulmonary Nodules.

BACKGROUND: Electromagnetic navigational bronchoscopy (ENB) has been shown to have variable diagnostic accuracy for the assessment of peripheral pulmonary nodules. This may be because of discrepancies between the preplanned computed tomography of chest target lesion location versus actual target location (computed tomography-to-body divergence), and the lack of a continuous navigational image. The ILLUMISITE (Medtronic, Minneapolis, MN) is a newly developed ENB platform that utilizes tomosynthesis, an imaging technology that can visualize the target location using fluoroscopy (F-ENB). This new system also allows for intraprocedural positional correction and continuous navigation guidance during sampling to overcome these limitations and improve diagnostic yield. We report our first experience in a single center, single proceduralist using this new technology. METHODS: We conducted a retrospective, single center, single operator study reviewing 72 consecutive patients (78 nodules) over a 3-month period. We investigated the overall diagnostic yield and diagnostic yield by nodule location, size, and sedation type using this new F-ENB system. RESULTS: The overall diagnostic yield was 87% and pnemothoraces occurred in 2/78 procedures. We did not find any statistically significant difference when comparing pulmonary nodule location, size or sedation method utilized ( P =0.231, 0.338, and 0.112, respectively). Sixty-nine percent of the pulmonary nodules biopsied were 2 to 3 cm in size. The average distance corrected after tomosynthesis visualization was 15.4 mm (0.4 to 29.8 mm). CONCLUSION: We report our initial experience with the ILLUMISITE system using fluoroscopic tomosynthesis-assisted visualization with continuous navigational guidance at our institution. This new technology allows the operator to correct for better target lesion alignment and real time positional correction and may improve diagnostic yields with minimal complications for evaluation of peripheral pulmonary nodules.

Clinical Factors That Affect Fiducial Tracking in Robotic SABR for Lung Tumors.

Purpose: SABR is a treatment option for patients with lung tumors that employs fiducials to track tumors during the breathing cycle. Currently, there is a paucity of data on how relative fiducial location and patient clinical characteristics affect fiducial tracking and clinical outcomes. This study aimed to identify factors that reduce the number of fiducials tracked with respiratory motion management during SABR. Methods and Materials: An institutional review board-approved retrospective review was performed of patients receiving robotic SABR for lung tumors at our institution from 2016 to 2019. Clinical data including demographics, medical history, treatment data, and follow-up were collected. Fiducial geometries were obtained with Velocity contouring software and MATLAB. Mann-Whitney U, χ2, and t tests were completed using MedCalc. Results: A total of 73 patients with 77 treatments were identified. The χ2 analysis revealed that chronic obstructive pulmonary disease was associated with having 3 or more fiducials tracked (P = .034). Tumors in lower lobes were associated with higher rates of uncertainty errors (P = .015). The number of fiducials tracked had no effect on local tumor control or overall survival, with a median of 36 months of follow-up. A total of 28 treatments had fiducial centroid data available for geometric analysis. The most common tracking errors were rigid body error (RBE; 57%) and spacing errors (36.4%). Spacing errors had a shorter average minimum interfiducial distance than nonspacing errors (1.0 cm vs 1.7 cm, respectively; P = .017). RBE treatments had a longer average maximum distance than non-RBE treatments (4.0 cm vs 3.0 cm; P = .022). Conclusions: Greater motion in lower lobes can contribute to certain tracking errors that prevent more fiducials from being tracked. Maintaining interfiducial distance between experimentally determined guidelines may limit spacing errors and RBEs, the 2 most common tracking errors. An increased number of patients in a data set may result in stronger correlations between patient and tumor factors and outcomes.

Perception versus reality: the measuring of pleural fluid pH in the United States.

BACKGROUND: Pleural fluid pH measured by a blood gas analyzer is the only recommended method of pH measurement to guide management for patients with parapneumonic pleural effusions. Not all hospitals use blood gas analyzers for pleural fluid pH determination and it is unknown if physicians are aware of this problem. OBJECTIVE: To determine if a discrepancy exists between the modality used for measuring pleural fluid pH and how physicians believe it is measured. METHODS: We surveyed pulmonologists randomly across the USA by e-mail inquiring how they thought pleural fluid pH was measured at their laboratory. We then independently contacted the laboratory and asked how pleural fluid pH was actually measured. RESULTS: Two hundred and sixty-seven pulmonologists completed the survey. Eighty-six percent of the pulmonologists use pleural fluid pH to manage complicated parapneumonic effusions. Forty-three percent did not recognize blood gas analyzer solely as the most accurate and validated method. Thirty-nine percent of the physicians who use pleural pH to manage effusions and believe that blood gas analyzers are the most accurate were wrong in their assumption that their laboratory was using this tool for pleural pH measurement. CONCLUSIONS: Whether it is due to inaccurate knowledge or a perception of how pleural fluid pH is tested, a significant number of pulmonologists, when treating complicated parapneumonic effusions, may be making management decisions based on erroneous information.

NAVIGATE 24-Month Results: Electromagnetic Navigation Bronchoscopy for Pulmonary Lesions at 37 Centers in Europe and the United States.

INTRODUCTION: Electromagnetic navigation bronchoscopy (ENB) is a minimally invasive, image-guided approach to access lung lesions for biopsy or localization for treatment. However, no studies have reported prospective 24-month follow-up from a large, multinational, generalizable cohort. This study evaluated ENB safety, diagnostic yield, and usage patterns in an unrestricted, real-world observational design. METHODS: The NAVIGATE single-arm, pragmatic cohort study (NCT02410837) enrolled subjects at 37 academic and community sites in seven countries with prospective 24-month follow-up. Subjects underwent ENB using the superDimension navigation system versions 6.3 to 7.1. The prespecified primary end point was procedure-related pneumothorax requiring intervention or hospitalization. RESULTS: A total of 1388 subjects were enrolled for lung lesion biopsy (1329; 95.7%), fiducial marker placement (272; 19.6%), dye marking (23; 1.7%), or lymph node biopsy (36; 2.6%). Concurrent endobronchial ultrasound-guided staging occurred in 456 subjects. General anesthesia (78.2% overall, 56.6% Europe, 81.4% United States), radial endobronchial ultrasound (50.6%, 4.0%, 57.4%), fluoroscopy (85.0%, 41.7%, 91.0%), and rapid on-site evaluation use (61.7%, 17.3%, 68.5%) differed between regions. Pneumothorax and bronchopulmonary hemorrhage occurred in 4.7% and 2.7% of subjects, respectively (3.2% [primary end point] and 1.7% requiring intervention or hospitalization). Respiratory failure occurred in 0.6%. The diagnostic yield was 67.8% (range: 61.9%-70.7%; 55.2% Europe, 69.8% United States). Sensitivity for malignancy was 62.6%. Lung cancer clinical stage was I to II in 64.7% (55.3% Europe, 65.8% United States). CONCLUSIONS: Despite a heterogeneous cohort and regional differences in procedural techniques, ENB demonstrates low complications and a 67.8% diagnostic yield while allowing biopsy, staging, fiducial placement, and dye marking in a single procedure.

Current management of salicylate-induced pulmonary edema.

Salicylate-induced pulmonary edema (SIPE) can occur in both acute and chronic users of aspirin or salicylate products. The medical history, especially when it reveals the use of salicylates, is critical when considering this diagnosis. Unfortunately, the neurologic and systemic effects of salicylate toxicity may hinder the ability to obtain a reliable medical history. SIPE should be considered in patients who present with pulmonary edema and neurological changes, anion-gap metabolic acidosis, or possible sepsis. Some patients may be treated for "pseudosepsis" or other conditions, thereby delaying the diagnosis of salicylate intoxication. Misdiagnosis and possibly delayed diagnosis of SIPE can lead to a significant increase in morbidity and mortality. Serum and urine alkalinization by administration of intravenous sodium bicarbonate are commonly utilized therapeutic strategies. Finally, hemodialysis is a therapy which should be considered early in the course of treatment. The objective of this review was to emphasize the importance of rapid diagnosis and appropriate treatment in patients with SIPE, and summarize the current literature as it relates to the adult population.

Standardized Definitions of Bleeding After Transbronchial Lung Biopsy: A Delphi Consensus Statement From the Nashville Working Group.

BACKGROUND: Transbronchial lung biopsies are commonly performed for a variety of indications. Although generally well tolerated, complications such as bleeding do occur. Description of bleeding severity is crucial both clinically and in research trials; to date, there is no validated scale that is widely accepted for this purpose. Can a simple, reproducible tool for categorizing the severity of bleeding after transbronchial biopsy be created? METHODS: Using the modified Delphi method, an international group of bronchoscopists sought to create a new scale tailored to assess bleeding severity among patients undergoing flexible bronchoscopy with transbronchial lung biopsies. Cessation criteria were specified a priori and included reaching > 80% consensus among the experts or three rounds, whichever occurred first. RESULTS: Thirty-six expert bronchoscopists from eight countries, both in academic and community practice settings, participated in the creation of the scale. After the live meeting, two iterations were made. The second and final scale was vetted by all 36 participants, with a weighted average of 4.47/5; 53% were satisfied, and 47% were very satisfied. The panel reached a consensus and proposes the Nashville Bleeding Scale. CONCLUSIONS: The use of a simplified airway bleeding scale that can be applied at bedside is an important, necessary tool for categorizing the severity of bleeding. Uniformity in reporting clinically significant airway bleeding during bronchoscopic procedures will improve the quality of the information derived and could lead to standardization of management. In addition to transbronchial biopsies, this scale could also be applied to other bronchoscopic procedures, such as endobronchial biopsy or endobronchial ultrasound-guided needle aspiration.

Perceptions vs. reality: measuring of pleural fluid pH in North Carolina.

BACKGROUND: Pleural fluid pH anaerobically handled and measured by a blood gas analyzer (BGA) is used to define a pleural space infection as complicated and predict the life expectancy of patients with malignant pleural effusions. Pleural fluid pH can also be measured by other less accurate methods. It is unknown whether physicians who use pleural fluid pH measurements are aware of the method used by their laboratories. METHODS: We surveyed 90 pulmonary physicians in North Carolina about their use of pleural fluid pH and their hospital laboratory's approach (pH indicator stick, pH meter, or BGA). We then contacted their hospital laboratories to determine the actual method of pH measurement. RESULTS: Twenty-eight (31%) pulmonologists in 11 North Carolina hospitals responded on their use of pleural fluid pH. Of the 20 pulmonologists who order pleural fluid pH, 90% reported that their hospital measures pleural fluid pH via BGA, but the majority (72%) were inaccurate. Only two of 11 hospitals reported that they measure pleural fluid pH with a BGA. CONCLUSION: Almost two-thirds of the chest physicians that order pleural fluid pH to help manage pleural effusions were using information that is not substantiated by the literature and, despite previous reports, hospitals still use suboptimal methods to measure pleural fluid pH. Further information is needed concerning the barriers to physicians and laboratory practices concerning the use of BGA for the measurement of pleural fluid pH.

Malignant pleural effusion and cancer of unknown primary site: a review of literature.

Malignant pleural effusions (MPE) are most frequently (50-65%) noted from lung and breast cancers. They are commonly unilateral and are reflective of poorer prognosis. Cancer of unknown primary (CUP) account for 4-5% of all invasive cancers. These are metastatic tumors in which the primary is unknown despite an extensive medical evaluation. About 11% of MPE are from CUP. These MPEs present a clinical dilemma to physicians as there is a paucity of literature on their management and no consensus or guideline statement. This paper provides an overview of MPE from CUP in regard to diagnosis, prognosis, and treatment options. A selective search was performed in Medline and PubMed, with the keywords "Malignant pleural effusion" and "Cancer of unknown primary" up to December 2018. A review of literature would suggest that a thoracentesis is the first step in all cases but additional work up such as thoracoscopy & pleural biopsies is frequently warranted. With advances in immunohistochemical staining and biomarker development, MPE with CUP maybe profiled in a similar manner as lung cancer. Similarly, liquid biopsy or identification of circulating tumor cell free DNA may have a role in the work up of CUP in the future. There is some experience in managing these patients with gene directed therapies and immune checkpoint inhibitors, however, with mixed results. Given the poor prognosis associated with MPE from CUP, symptom alleviating measures such as indwelling pleural catheters should be part of the management strategy.

A novel diagnostic approach for Pneumocystis jirovecii pneumonia using fine-needle aspiration, electromagnetic navigational bronchoscopy and rapid on-site evaluation.

Cavitary lung lesions are common in patients with human immunodeficiency virus infections. Both atypical infections and thoracic malignancies can manifest as a cavitary pulmonary lesion. Standard bronchoscopy is commonly used to evaluate these abnormalities but is limited in its ability to fully assess for cancer and infection. Bronchoalveolar lavage samples are likely to aid in the diagnosis of infection but are less useful in the evaluation of malignancy. In addition, many of these pulmonary lesions are located in the periphery of the lung and are not accessible for tissue sampling by standard bronchoscopy. We present a unique presentation of Pneumocystis jirovecii pneumonia and discuss the utility of electromagnetic navigational bronchoscopy in the evaluation of immunocompromised patients with peripheral cavitary lung lesion.

Longitudinal monitoring for the emergence of epidermal growth factor C797S resistance mutations in non-small cell lung cancer using blood-based droplet digital PCR.

Validation of assays for the C797S mutation as a biomarker for osimertinib resistance is promising in guiding treatment decision-making for multidrug resistant non-small cell lung cancer. A newly developed droplet digital PCR (ddPCR) assay was used to retrospectively evaluate the emergence of the C797S mutation in six remnant plasma samples in this case report. It was found that the detected emergence of C797S clearly correlated with clinical signs of treatment resistance. Had these data been available to aid treatment selection in real time, there would have been hope for recaptured disease response and control instead of treatment cessation. The results of this study show that highly sensitive ddPCR methods can be used for the monitoring of emergent epidermal growth factor somatic variant mutations in circulation.

Pleural dye marking of lung nodules by electromagnetic navigation bronchoscopy.

INTRODUCTION: Electromagnetic navigation bronchoscopy (ENB)-guided pleural dye marking is useful to localize small peripheral pulmonary nodules for sublobar resection. OBJECTIVE: To report findings on the use of ENB-guided dye marking among participants in the NAVIGATE study. METHODS: NAVIGATE is a prospective, multicentre, global and observational cohort study of ENB use in patients with lung lesions. The current subgroup report is a prespecified 1-month interim analysis of ENB-guided pleural dye marking in the NAVIGATE United States cohort. RESULTS: The full United States cohort includes 1215 subjects from 29 sites (April 2015 to August 2016). Among those, 23 subjects (24 lesions) from seven sites underwent dye marking in preparation for surgical resection. ENB was conducted for dye marking alone in nine subjects while 14 underwent dye marking concurrent with lung lesion biopsy, lymph node biopsy and/or fiducial marker placement. The median nodule size was 10 mm (range 4-22) and 83.3% were <20 mm in diameter. Most lesions (95.5%) were located in the peripheral third of the lung, at a median of 3.0 mm from the pleura. The median ENB-specific procedure time was 11.5 minutes (range 4-38). The median time from dye marking to resection was 0.5 hours (range 0.3-24). Dye marking was adequate for surgical resection in 91.3%. Surgical biopsies were malignant in 75% (18/24). CONCLUSION: In this study, ENB-guided dye marking to localize lung lesions for surgery was safe, accurate and versatile. More information is needed about surgical practice patterns and the utility of localization procedures.

Improved respiratory motion tracking through a novel fiducial marker placement guidance system during electromagnetic navigational bronchoscopy (ENB).

BACKGROUND: Stereotactic ablative radiotherapy (SABR) is a treatment option for patients with early stage non-small cell lung cancer (NSCLC) and recurrent or oligometastatic disease who are not surgical candidates. Due to the continuous motion of tumors within the lungs, implementing a strategy to track the target lesion is crucial. One method is to place fiducial markers which the robotic SABR system is able to track during treatment. However, placing these markers in a manner that maximizes tracking efficacy can be challenging. Using a novel fiducial placement guidance system (FPGS) during fiducial deployment may offer a way to improve the quantity of fiducials tracked by the robotic SABR system. METHOD: This was an institutional, retrospective review identifying all patients who received robotic SABR for lung tumors from May 2015 until January 2017. The FPGS was instituted in May 2016. The median number of fiducials tracked and the rate of complication was compared between patients whose fiducials were placed using FPGS versus those that were not. RESULTS: A total of 128 patients with 147 treated lung lesions were identified. Of the lesions that utilized FPGS (n = 44), 28 had 2 tracked fiducials (63.6%), 14 had 3 (31.8%) and 2 had 4 (4.6%). Of the lesions treated without FPGS (n = 103), 5 had 1 tracked fiducial (4.9%), 91 had 2 (88.4%), 6 had 3 (5.8%), and 2 had 4 (1.9%). A significant improvement in the median number of fiducials tracked per fraction was observed for the lesions with fiducials placed using FPGS on Wilcoxon rank sum test (p < 0.001). The rate of complication was low and not statistically different between cohorts (p = 0.44). CONCLUSIONS: The FPGS can be used during the deployment of fiducial markers and may increase the number of fiducials tracked. TRIAL REGISTRATION: An exemption for this retrospective review was granted by the East Carolina University IRB under UMCIRB 15-001726.

Fiducial marker placement with electromagnetic navigation bronchoscopy: a subgroup analysis of the prospective, multicenter NAVIGATE study.

BACKGROUND: Fiducial markers (FMs) help direct stereotactic body radiation therapy (SBRT) and localization for surgical resection in lung cancer management. We report the safety, accuracy, and practice patterns of FM placement utilizing electromagnetic navigation bronchoscopy (ENB). METHODS: NAVIGATE is a global, prospective, multicenter, observational cohort study of ENB using the superDimension™ navigation system. This prospectively collected subgroup analysis presents the patient demographics, procedural characteristics, and 1-month outcomes in patients undergoing ENB-guided FM placement. Follow up through 24 months is ongoing. RESULTS: Two-hundred fifty-eight patients from 21 centers in the United States were included. General anesthesia was used in 68.2%. Lesion location was confirmed by radial endobronchial ultrasound in 34.5% of procedures. The median ENB procedure time was 31.0 min. Concurrent lung lesion biopsy was conducted in 82.6% (213/258) of patients. A mean of 2.2 ± 1.7 FMs (median 1.0 FMs) were placed per patient and 99.2% were accurately positioned based on subjective operator assessment. Follow-up imaging showed that 94.1% (239/254) of markers remained in place. The procedure-related pneumothorax rate was 5.4% (14/258) overall and 3.1% (8/258) grade ⩾ 2 based on the Common Terminology Criteria for Adverse Events scale. The procedure-related grade ⩾ 4 respiratory failure rate was 1.6% (4/258). There were no bronchopulmonary hemorrhages. CONCLUSION: ENB is an accurate and versatile tool to place FMs for SBRT and localization for surgical resection with low complication rates. The ability to perform a biopsy safely in the same procedure can also increase efficiency. The impact of practice pattern variations on therapeutic effectiveness requires further study. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02410837.