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.

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.

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.

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.

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.

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.

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.

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.

Electromagnetic Navigation Bronchoscopy for Peripheral Pulmonary Lesions: One-Year Results of the Prospective, Multicenter NAVIGATE Study.

INTRODUCTION: Electromagnetic navigation bronchoscopy (ENB) is a minimally invasive technology that guides endoscopic tools to pulmonary lesions. ENB has been evaluated primarily in small, single-center studies; thus, the diagnostic yield in a generalizable setting is unknown. METHODS: NAVIGATE is a prospective, multicenter, cohort study that evaluated ENB using the superDimension navigation system (Medtronic, Minneapolis, Minnesota). In this United States cohort analysis, 1215 consecutive subjects were enrolled at 29 academic and community sites from April 2015 to August 2016. RESULTS: The median lesion size was 20.0 mm. Fluoroscopy was used in 91% of cases (lesions visible in 60%) and radial endobronchial ultrasound in 57%. The median ENB planning time was 5 minutes; the ENB-specific procedure time was 25 minutes. Among 1157 subjects undergoing ENB-guided biopsy, 94% (1092 of 1157) had navigation completed and tissue obtained. Follow-up was completed in 99% of subjects at 1 month and 80% at 12 months. The 12-month diagnostic yield was 73%. Pathology results of the ENB-aided tissue samples showed malignancy in 44% (484 of 1092). Sensitivity, specificity, positive predictive value, and negative predictive value for malignancy were 69%, 100%, 100%, and 56%, respectively. ENB-related Common Terminology Criteria for Adverse Events grade 2 or higher pneumothoraces (requiring admission or chest tube placement) occurred in 2.9%. The ENB-related Common Terminology Criteria for Adverse Events grade 2 or higher bronchopulmonary hemorrhage and grade 4 or higher respiratory failure rates were 1.5% and 0.7%, respectively. CONCLUSIONS: NAVIGATE shows that an ENB-aided diagnosis can be obtained in approximately three-quarters of evaluable patients across a generalizable cohort based on prospective 12-month follow-up in a pragmatic setting with a low procedural complication rate.

Malignancy in the tracheal bronchus: A case series and review of the literature.

BACKGROUND/AIMS: The tracheal bronchus is a rare congenital abnormality with incidence reported in a range of 0.1%-2%. Infrequently, malignancy has been reported as occurring in the tracheal bronchus. In order to ascertain a relationship between malignancy and the tracheal bronchus, we performed a literature review and present a case series. METHODS: We reviewed 21 case reports of malignancy occurring in the tracheal bronchus. CONCLUSION: Although the number of cases is limited, it appears that bronchoscopy is the most frequently utilized diagnostic tool. Surgery portends the best clinical results even in higher stages of malignancy. Squamous cell carcinoma is the most common type of malignancy to occur in the tracheal bronchus.

Response criteria in solid tumors (PERCIST/RECIST) and SUVmax in early-stage non-small cell lung cancer patients treated with stereotactic body radiotherapy.

BACKGROUND: The purpose of this study was to evaluate the prognostic impact of Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) and Response Evaluation Criteria in Solid Tumors (RECIST) and of pre- and post-treatment maximum Standard Uptake Value (SUVmax) in regards to survival and tumor control for patients treated for early-stage non-small cell lung cancer (ES-NSCLC) with stereotactic body radiotherapy (SBRT). METHODS: This is a retrospective review of patients with ES-NSCLC treated at our institution using SBRT. Lobar, locoregional, and distant failures were evaluated based on PERCIST/RECIST and clinical course. Univariate analysis of the Kaplan-Meier curves for overall survival (OS), progression free survival (PFS), lobar control (LC), locoregional control (LRC), and distant control (DC) was conducted using the log-rank test. Pre- and post-treatment SUVmax were evaluated using cutoffs of < 5 and ≥ 5, < 4 and ≥ 4, and < 3 and ≥ 3. ∆SUVmax was also evaluated at various cutoffs. Cox regression analysis was conducted to evaluate survival outcomes based on age, gender, pre-treatment gross tumor volume (GTV), longest tumor dimension on imaging, and Charlson Comorbidity Index (CCI). RESULTS: This study included 95 patients (53 female, 42 male), median age 75. Lung SBRT was delivered in 3-5 fractions to a total of 48-60 Gy, with a BEDα/ß = 10Gy of at least 100 Gy. Median OS and PFS from the end of SBRT was 15.4 and 11.9 months, respectively. On univariate analysis, PERCIST/RECIST response correlated with PFS (p = 0.039), LC (p = 0.007), and LRC (p = 0.015) but not OS (p = 0.21) or DC (p = 0.94). Pre-treatment SUVmax and post-treatment SUVmax with cutoff values of < 5 and ≥ 5, < 4 and ≥ 4, and < 3 and ≥ 3 did not predict for OS, PFS, LC, LRC, or DC. ∆SUVmax did not predict for OS, PFS, LC, LRC, or DC. On multivariate analysis, pre-treatment GTV ≥ 30 cm3 was significantly associated with worse survival outcomes when accounting for other confounding variables. CONCLUSIONS: PERCIST/RECIST response is associated with improved LC and PFS in patients treated for ES-NSCLC with SBRT. In contrast, pre- and post-treatment SUVmax is not predictive of disease control or survival.

Therapeutic bronchoscopy in the era of genotype directed lung cancer management.

Lung cancer is the leading cause of cancer related deaths. Non-small cell lung cancer (NSCLC) accounts for ~85% of lung cancers. Our understanding of driver mutations and genotype directed therapy has revolutionized the management of advanced NSCLC. Commonly described mutations include mutations in epidermal growth factor (EGFR) & BRAF and translocations in anaplastic lymphoma kinase (ALK) & rat osteosarcoma (ROS1). Drugs directed against these translocations have significantly improved progression free survival individually and have shown a survival benefit when studied in the Lung Cancer Mutation Consortium (median survival 3.5 vs. 2.4 years compared to standard therapy). In a related yet parallel universe, the number of bronchoscopic ablative modalities available for management of cancer related airway obstruction have increased exponentially over the past decade. A wealth of literature has given us a better understanding of the technical aspects, benefits and risks associated with these procedures. While they all show benefits in terms of relieving airway obstruction, symptom control, quality of life and lung function testing, their complication rates vary based on the modality. The overall complication rate was ~4% in the AQuIRE registry. Bronchoscopic therapeutic modalities include rigid bronchoscopy with mechanical debulking, laser, thermo-coagulation [electrocautery & argon plasma coagulation (APC)], cryotherapy, endobronchial brachytherapy (EBT), photodynamic therapy (PDT), intratumoral chemotherapy (ITC) and transbronchial needle injection (TBNI) of chemotherapy. Intuitively, one would assume that the science of driver mutations would crisscross with the science of bronchoscopic ablation as they overlap in the same patient population. Sadly, this is not the case and there is a paucity of literature looking at these fields together. This results in several unanswered questions about the interplay between these two therapies.

Feasibility and Safety of the Transbronchial Access Tool for Peripheral Pulmonary Nodule and Mass.

BACKGROUND: Navigational bronchoscopy and other imaging modalities have improved the ability to evaluate pulmonary nodules/mass. Many of these lesions are located outside the bronchial airway and are difficult to access even with these devices. The Transbronchial Access Tool (Medtronic, Minneapolis, MN) allows the bronchoscopist to create a pathway from the bronchial airway, across the lung parenchyma, and into the target lesion. We are reporting the feasibility and safety of this new device. METHODS: Patients with peripheral pulmonary nodules/mass with an absence of an air bronchogram on thoracic imaging underwent a navigational bronchoscopy in a hybrid operating room under general anesthesia. A navigational system located predetermined areas in the bronchial tree to deploy the Transbronchial Access Tool, and cone beam computed tomography confirmed that the target lesion was accessed. A standard protocol was developed and followed in the last 7 patients directing cone beam computed tomography use. The ability to enter the target lesion, diagnostic yield, radiation exposure, and procedural complications were recorded. RESULTS: The Transbronchial Access Tool was used in 14 patients who underwent an electromagnetic navigational bronchoscopy-guided biopsy from September 2015 to January 2016. The overall diagnostic yield was 71% (10 of 14) and 100% (7 of 7) when the standard protocol was instituted. Access was achieved in 75% (9 of 12) of the targeted lesions, with a diagnostic yield of 66% (8 of 12). One complication, a pneumothorax, occurred. The average radiation exposure during the procedure was 4.3 mSv (range, 3 to 5 mSv), and fluoroscopic time was 17 minutes (range, 2 to 44 minutes). CONCLUSIONS: The Transbronchial Access Tool is safe and permits access to pulmonary nodules/masses with navigational bronchoscopy.

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.

Going Off Road: The First Case Reports of the Use of the Transbronchial Access Tool With Electromagnetic Navigational Bronchoscopy.

The ability to reach the peripheral pulmonary nodule/mass with bronchoscopy has improved greatly over the past several years with the use of Electromagnetic navigational bronchoscopy; however, many of these lesions are unable to be adequately sampled due to their location outside the bronchial airways. We report the first use of the transbronchial access tool that creates a pathway from the bronchial airway through the lung parenchyma into the targeted lung abnormality.

Long-Term Survival after Cardiac Surgery in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Although many patients with chronic obstructive pulmonary disease (COPD) require a prolonged length of stay (PLOS) following coronary artery bypass grafting (CABG), the impact of PLOS on long-term survival has not been examined in this population. OBJECTIVES: To determine the association between PLOS and long-term survival among COPD and non-COPD patients after CABG and to examine consequent policy and practice-based implications. METHODS: A retrospective cohort study of CABG patients was conducted between 2002 and 2011. Long-term survival was compared in patients with and without COPD and stratified by PLOS. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. RESULTS: A total of 203 patients (4.2%) had PLOS after nonemergent CABG (N = 4801). PLOS was an important independent predictor of decreased long-term survival (no COPD, no PLOS: HR = 1.0; COPD, no PLOS: adjusted HR [95% CI], 1.8 [1.5-2.1]; no COPD, PLOS: 3.3 [2.5-4.4]; COPD, PLOS: 6.0 [4.4-8.2]; PTrend < .001). CONCLUSIONS: COPD and PLOS are 2 of many factors that affect long-term mortality in postoperative CABG patients. Aggressive treatment strategies aimed at early weaning off of mechanical ventilation and prevention of reintubation among COPD patients must be considered carefully as a means to reduce length of stay after CABG. Our results also have important implications for the long-term management of these patients and strategies for containing costs over the life course of the patient.

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.