Assessment of Advanced Diagnostic Bronchoscopy Outcomes for Peripheral Lung Lesions: A Delphi Consensus Definition of Diagnostic Yield and Recommendations for Patient-centered Study Designs. An Official American Thoracic Society/American College of Chest Physicians Research Statement.

Background: Advanced diagnostic bronchoscopy targeting the lung periphery has developed at an accelerated pace over the last two decades, whereas evidence to support introduction of innovative technologies has been variable and deficient. A major gap relates to variable reporting of diagnostic yield, in addition to limited comparative studies. Objectives: To develop a research framework to standardize the evaluation of advanced diagnostic bronchoscopy techniques for peripheral lung lesions. Specifically, we aimed for consensus on a robust definition of diagnostic yield, and we propose potential study designs at various stages of technology development. Methods: Panel members were selected for their diverse expertise. Workgroup meetings were conducted in virtual or hybrid format. The cochairs subsequently developed summary statements, with voting proceeding according to a modified Delphi process. The statement was cosponsored by the American Thoracic Society and the American College of Chest Physicians. Results: Consensus was reached on 15 statements on the definition of diagnostic outcomes and study designs. A strict definition of diagnostic yield should be used, and studies should be reported according to the STARD (Standards for Reporting Diagnostic Accuracy Studies) guidelines. Clinical or radiographic follow-up may be incorporated into the reference standard definition but should not be used to calculate diagnostic yield from the procedural encounter. Methodologically robust comparative studies, with incorporation of patient-reported outcomes, are needed to adequately assess and validate minimally invasive diagnostic technologies targeting the lung periphery. Conclusions: This American Thoracic Society/American College of Chest Physicians statement aims to provide a research framework that allows greater standardization of device validation efforts through clearly defined diagnostic outcomes and robust study designs. High-quality studies, both industry and publicly funded, can support subsequent health economic analyses and guide implementation decisions in various healthcare settings.

EBUS versus EUS-B for diagnosing sarcoidosis: The International Sarcoidosis Assessment (ISA) randomized clinical trial.

BACKGROUND AND OBJECTIVE: Endosonography with intrathoracic nodal sampling is proposed as the single test with the highest granuloma detection rate in suspected sarcoidosis stage I/II. However, most studies have been performed in limited geographical regions. Studies suggest that oesophageal endosonographic nodal sampling has higher diagnostic yield than endobronchial endosonographic nodal sampling, but a head-to-head comparison of both routes has never been performed. METHODS: Global (14 hospitals, nine countries, four continents) randomized clinical trial was conducted in consecutive patients with suspected sarcoidosis stage I/II presenting between May 2015 and August 2017. Using an endobronchial ultrasound (EBUS) scope, patients were randomized to EBUS or endoscopic ultrasound (EUS)-B-guided nodal sampling, and to 22- or 25-G ProCore needle aspiration (2 × 2 factorial design). Granuloma detection rate was the primary study endpoint. Final diagnosis was based on cytology/pathology outcomes and clinical/radiological follow-up at 6 months. RESULTS: A total of 358 patients were randomized: 185 patients to EBUS-transbronchial needle aspiration (EBUS-TBNA) and 173 to EUS-B-fine-needle aspiration (FNA). Final diagnosis was sarcoidosis in 306 patients (86%). Granuloma detection rate was 70% (130/185; 95% CI, 63-76) for EBUS-TBNA and 68% (118/173; 95% CI, 61-75) for EUS-B-FNA (p = 0.67). Sensitivity for diagnosing sarcoidosis was 78% (129/165; 95% CI, 71-84) for EBUS-TBNA and 82% (115/141; 95% CI, 74-87) for EUS-B-FNA (p = 0.46). There was no significant difference between the two needle types in granuloma detection rate or sensitivity. CONCLUSION: Granuloma detection rate of mediastinal/hilar nodes by endosonography in patients with suspected sarcoidosis stage I/II is high and similar for EBUS and EUS-B. These findings imply that both diagnostic tests can be safely and universally used in suspected sarcoidosis patients.

Adequate tumour cellularity is essential for accurate PD-L1 immunohistochemistry assessment on cytology cell-block specimens.

OBJECTIVES: PD-L1 immunohistochemistry (IHC) is an essential predictive biomarker for patients with non-small cell lung cancer (NSCLC), required to inform treatment decisions regarding anti-PD-1 immune checkpoint inhibitor therapy. This study aims to investigate the concordance between PD-L1 IHC assessed on NSCLC cytology and histology specimens and to determine the impactce of tumour cellularity. METHODS: Matched cytology and histology NSCLC specimens were retrieved from the archives of the Royal Melbourne Hospital and the Royal Prince Alfred Hospital. PD-L1 IHC was performed concurrently on both specimens at the Peter MacCallum Cancer Centre using the SP263 assay kit on the Ventana Benchmark Ultra staining platform and scored by two experienced pathologists. RESULTS: Overall agreement between matched cytology and histology specimens was good (intraclass correlation coefficient = 0.653, n = 58); however, markedly increased when the analysis was limited to cell-blocks with >100 tumour cells (intraclass correlation coefficient = 0.957, n = 29). Specificity at both 1% and 50% cut-offs was high regardless of cellularity; however, sensitivity decreased in samples with <100 tumour cells. CONCLUSIONS: PD-L1 IHC on cytology cell-block specimens in NSCLC is an acceptable alternative to histological specimens, provided adequate tumour cells are present. Clinicians and pathologists should be mindful of the risk of false negative PD-L1 IHC in samples with low tumour cellularity, to avoid excluding patients from potentially beneficial treatment.

Utility of Endobronchial Ultrasound in Assessment of Intrathoracic Lesions in Paediatric Patients.

INTRODUCTION: In adults, linear endobronchial ultrasound (EBUS) is the preferred modality to sample intrathoracic adenopathy and radial EBUS is a useful tool to biopsy peripheral pulmonary nodules. Utility in children is less well known. OBJECTIVES: The objective of this study was to review the EBUS experience of two specialist centres to better define the current role of EBUS in paediatric practice. METHODS: A retrospective record review of EBUS procedures undertaken in patients aged 0-17 years at the Royal Children's Hospital (Melbourne, Australia) and Thoraxklinik (Heidelberg, Germany) was performed. Data extracted included patient demographics, clinical presentation, bronchoscope (size and model), EBUS technique used, pathologic results, need for further invasive investigation, and complications. RESULTS: Between 2008 and 2017, ten EBUS procedures were performed (6 linear EBUS and 4 radial EBUS). No complications were reported. Linear EBUS was performed on subjects who were between 4 and 15 years old, with a 100% diagnostic yield. Radial EBUS was non-diagnostic in three cases of non-malignant disease. In one case, it was used successfully for imaging alone. CONCLUSION: Both linear and radial EBUS are safe and feasible in children. Diagnostic yield of linear EBUS was 100%. Radial EBUS did not demonstrate utility, likely reflecting the pathologies of underlying parenchymal masses in paediatric populations.

Assessment of Bronchoscopic Dexterity and Procedural Competency in a Low-fidelity Simulation Model.

BACKGROUND: Assessment of competency in bronchoscopy has traditionally been undertaken in clinical settings, however, recent recognition of increased procedural complications and learner anxiety have led to interest in simulation-based competency assessment. The aim of this study was to determine if low-fidelity simulation-based assessment allows discrimination of competency based on prior experience between bronchoscopists. METHODS: Forty-four participants were allocated to 3 groups based on prior bronchoscopic experience [novices (n=31) with no prior experience, intermediates (n=7) with prior experience of 5 to 10 bronchoscopies, and expert bronchoscopists (n=6) with minimum 200 prior bronchoscopies performed]. Participants performed bronchoscopy in a 3D-printed anatomic airway model and were assessed according to time required to navigate to a target bronchus. Bronchoscopic dexterity was measured using a modified version of the validated Bronchoscopy Skills and Tasks Assessment Tool. RESULTS: Competency based on successful navigation to a target bronchus differed significantly between each group [experts, 12/12 (100%); intermediates, 9/14 (64%); novices, 19/62 (31%); P<0.001]. Bronchoscopic dexterity as measured by modified Bronchoscopy Skills and Tasks Assessment Tool also differed significantly between groups with experts achieving consistently higher scores compared with other 2 groups [median (interquartile range) scores: novices, 3.5 (2.5 to 5); intermediate, 5 (4.5 to 7); experts, 8 (7.5 to 8); P<0.0.001). CONCLUSIONS: Multiple measures demonstrate that low-fidelity simulation-based assessment may reliably discriminate between different levels of skill in performing bronchoscopic navigation and airway inspection. Procedural dexterity of trainees may be assessed in a 0-risk simulation environment.

Practical Assessment of Bronchoscopically Inserted Fiducial Markers for Image Guidance in Stereotactic Lung Radiotherapy.

INTRODUCTION: Stereotactic radiotherapy is a high-dose precision technique necessitating accurate target visualization through either cone beam computed tomography (CBCT) or planar imaging with implanted fiducial markers. We have investigated the properties for image guidance using fiducial markers implanted through minimally invasive bronchoscopy. METHODS: Two fiducial marker types were implanted endobronchially in 10 patients undergoing radical radiation treatment for non-small cell lung cancer (eight using Visicoil linear fiducial markers [IBA Dosimetry GmbH, Schwarzenbruck Germany] and two using superDimension and superLock two-band markers [Covidien Inc., Minneapolis, MN]). Patients underwent four-dimensional computed tomography imaging for treatment planning and after completion of treatment to investigate marker movement. As part of the image guidance assessment, megavolt electronic portal images (EPIs) were acquired in addition to kilovolt planar and CBCT (Varian Medical Systems, Palo Alto, CA) images. RESULTS: In two of 10 patients (both receiving Visicoil markers), marker migration was observed before treatment. In patients with stable markers, both types were clearly visible in planar kilovolt imaging; however, in EPIs the markers could be detected only in selected beam directions in which bony interference was minimal. Diagnostic computed tomography scanning was able to demonstrate the markers with clarity, but significant starring artifacts were observed in CBCT. This was particularly problematic in patients with some lateral component of tumor motion during breathing. CONCLUSIONS: The potential for fiducial migration must be considered and investigated if bronchoscopic implantation of fiducial markers is performed. The choice of marker is a compromise between trying to minimize CBCT artifacts while enabling visualization in EPI imaging, which is an ideal tool to verify gated radiotherapy delivery.

Development and Assessment of a Low-Cost 3D-printed Airway Model for Bronchoscopy Simulation Training.

We report upon the techniques used to create a plastic 3-dimensional-printed bronchoscopy trainer from an actual patient computed tomography scan. The formatting methods to create the printable file, using free open access software, are outlined. The resulting high anatomic fidelity part-task trainer is described, as well as experienced bronchoscopists' perception of its realism and utility as a training tool. A discussion of the current state of knowledge about the role of simulation in bronchoscopy training, as well as the potential contribution of this device, is presented.

Radial probe EBUS versus CT-guided needle biopsy for evaluation of peripheral pulmonary lesions: an economic analysis.

Selection of the optimal procedure for minimally invasive diagnosis of peripheral pulmonary lesions (PPLs) may be based on clinical factors; however, selection of diagnostic strategy may also be influenced by cost. Economic analysis of minimally invasive diagnosis of PPL has not been performed previously. Decision-tree analysis was applied to compare downstream costs of endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) with computed tomography-guided percutaneous needle biopsy (CT-PNB). Calculations were based on real costs derived from patient data. Sensitivity analyses and probabilistic sensitivity analysis were undertaken to identify the more cost-beneficial approach for varying input parameter values. Cost-effectiveness calculations were based on estimated disutility, according to the wait-trade-off technique. For base-case analysis, initial evaluation with CT-PNB was cost-beneficial (AU$2,724 versus EBUS-TBLB AU$2,748). The variable which exerted the most influence on cost-benefit outcomes was the cost of managing complications. CT-PNB remained the more cost-effective procedure at base-case parameters, although thresholds were identified during sensitivity analysis where EBUS-TBLB became more cost-effective. The costs of EBUS-TBLB and CT-PNB to evaluate PPL appear to be equivalent, but specific clinical-radiologic factors known to influence procedural outcomes will influence cost-benefit outcomes. Further evaluation of patient preferences and their influence on cost-effectiveness are required.

Cost-benefit of minimally invasive staging of non-small cell lung cancer: a decision tree sensitivity analysis.

BACKGROUND: Accurate staging of non-small cell lung cancer (NSCLC) is critical for optimal management. Minimally invasive pathologic assessment of mediastinal lymphadenopathy is increasingly being performed. The cost-benefit (minimization of health care costs) of such approaches, in comparison with traditional surgical methods, is yet to be established. METHODS: Decision-tree analysis was applied to compare downstream costs of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), conventional TBNA, and surgical mediastinoscopy. Calculations were based on real costs derived from actual patient data at a major teaching hospital in Melbourne, Australia. One- and two-way sensitivity analyses were undertaken to account for potential variation in input parameter values. RESULTS: For the base-case analysis, initial evaluation with EBUS-TBNA (with negative results being surgically confirmed) was the most cost-beneficial approach (AU$2961) in comparison with EBUS-TBNA (negative results not surgically confirmed) ($3344), conventional TBNA ($3754), and mediastinoscopy ($8859). The sensitivity of EBUS-TBNA for detecting disease had the largest impact on cost, whereas the prevalence of mediastinal lymph node metastases determined whether surgical confirmation of negative EBUS-TBNA results remained cost-beneficial. CONCLUSIONS: Our study confirms that minimally invasive staging of NSCLC is cost-beneficial in comparison with traditional surgical techniques. EBUS-TBNA was the most cost-beneficial approach for mediastinal staging of patients with NSCLC across all studied parameters.