Robotic-Assisted Bronchoscopy: A Comprehensive Review of System Functions and Analysis of Outcome Data.

The past two decades have witnessed a revolutionary era for peripheral bronchoscopy. Though the initial description of radial endobronchial ultrasound can be traced back to 1992, it was not until the mid-2000s that its utilization became commonplace, primarily due to the introduction of electromagnetic navigation (EMN) bronchoscopy. While the diagnostic yield of EMN-assisted sampling has shown substantial improvement over historical fluoroscopy-assisted bronchoscopic biopsy, its diagnostic yield plateaued at around 70%. Factors contributing to this relatively low diagnostic yield include discrepancies in computed tomography to body divergence, which led to unsuccessful lesion localization and resultant unsuccessful sampling of the lesion. Furthermore, much of peripheral bronchoscopy utilized a plastic extended working channel whose tips were difficult to finely aim at potential targets. However, the recent introduction of robotic-assisted bronchoscopy, and its associated stability within the peripheral lung, has ignited optimism for its potential to significantly enhance the diagnostic performance for peripheral lesions. Moreover, some envision this technology eventually playing a pivotal role in the therapeutic delivery to lung tumors. This review aims to describe the currently available robotic-assisted bronchoscopy technologies and to discuss the existing scientific evidence supporting these.

Imaging in peripheral bronchoscopy.

PURPOSE OF REVIEW: Historically the sampling of peripheral lung lesions via bronchoscopy has suffered from inferior diagnostic outcomes relative to transthoracic needle aspiration, and neither a successful bronchoscopic navigation nor a promising radial ultrasonographic image of one's target lesion guarantees a successful biopsy. Fortunately, many of peripheral bronchoscopy's shortcomings - including an inability to detect and compensate for computed tomography (CT)-body divergence, and the absence of tool-in-lesion confirmation - are potentially remediable through the use of improved intraprocedural imaging techniques. RECENT FINDINGS: Recent advances in intraprocedural imaging, including the integration of cone beam CT, digital tomosynthesis, and augmented fluoroscopy into bronchoscopic procedures have yielded promising results. These advanced imaging modalities may improve the outcomes of peripheral bronchoscopy through the detection and correction of navigational errors, CT-body divergence, and malpositioned biopsy instruments. SUMMARY: The incorporation of advanced imaging is an essential step in the improvement of peripheral bronchoscopic procedures.

Short-term Endoscopic Outcomes of Balloon and Rigid Bronchoplasty in the Management of Benign Subglottic and Tracheal Stenosis.

BACKGROUND: Endoscopic therapies are firmly established in the management algorithm of benign subglottic and tracheal stenosis (SGTS). The optimal dilation strategy, however, has yet to be elucidated. The objective of this study was to compare the efficacy and safety of balloon versus rigid bronchoplasty in the treatment of benign SGTS. METHODS: De novo cases of benign SGTS at our institution over a 9-year period were retrospectively identified. Patients were divided into 2 groups based on the initial dilation strategy of balloon or rigid bronchoplasty. Demographics, clinical findings, concurrent interventions, lesion characteristics, and complications were analyzed. Two reviewers independently assigned an index and follow-up endoscopic stenosis grade for each case. The mean stenosis grade at follow-up in both groups was then calculated and compared. RESULTS: Sixty-three patients with benign SGTS were included. Most stenoses in the rigid (80%) and balloon (63%) bronchoplasty groups were complex ( P =0.174). In addition, 94% (59/63) of index stenoses were classified as Cotton Myer Grade 3. At follow-up, no significant difference was found in the mean stenosis grade between dilation strategies (1.97 vs. 2.2, P =0.287). Furthermore, no procedural-related complications were observed in either group. CONCLUSION: Balloon and rigid bronchoplasty are safe and effective endoscopic tools in the early management of benign SGTS. A multimodality approach centered around mucosal sparing techniques remains vitally important to the overall and likely long-term success of treating this challenging disease entity.

Role of biomarkers in lung nodule evaluation.

PURPOSE OF REVIEW: Worldwide, lung cancer is the leading cause of cancer mortality. Much of this mortality is thought to be secondary to detection in later stages, where treatment options and survivability are limited. The goals of lung nodule evaluation are to expedite the diagnosis and treatment of patients with malignant nodules and to minimize unnecessary diagnostic procedures in those with benign nodules. However, the differentiation between benign and malignant has been challenging and is further complicated by the benefits of early diagnosis competing with potential morbidity of invasive diagnostic procedures. RECENT FINDINGS: Biomarkers have the potential to improve estimates of pretest probability of malignancy in pulmonary nodules, especially in the intermediate-risk subgroup. Four biomarkers have undergone extensive validation and are available for clinical use, and we will discuss each in this review. SUMMARY: The application of biomarkers to lung cancer risk assessment has the potential to improve cancer probability assessments, which in turn can reduce unnecessary invasive testing and/or reduce delays in diagnosis and treatment.

Bronchoscopy in Patients With Known or Suspected COVID-19: Results From the Global Pandemic SARS-CoV-2 Bronchoscopy Database (GPS-BD).

BACKGROUND: Amid the Coronavirus Disease 2019 (COVID-19) pandemic, the benefits and risks of bronchoscopy remain uncertain. This study was designed to characterize bronchoscopy-related practice patterns, diagnostic yields, and adverse events involving patients with known or suspected COVID-19. METHODS: An online survey tool retrospectively queried bronchoscopists about their experiences with patients with known or suspected COVID-19 between March 20 and August 20, 2020. Collected data comprised the Global Pandemic SARS-CoV-2 Bronchoscopy Database (GPS-BD). All bronchoscopists and patients were anonymous with no direct investigator-to-respondent contact. RESULTS: Bronchoscopy procedures involving 289 patients from 26 countries were analyzed. One-half of patients had known COVID-19. Most (82%) had at least 1 pre-existing comorbidity, 80% had at least 1 organ failure, 51% were critically ill, and 37% were intubated at the time of the procedure. Bronchoscopy was performed with diagnostic intent in 166 (57%) patients, yielding a diagnosis in 86 (52%). and management changes in 80 (48%). Bronchoscopy was performed with therapeutic intent in 71 (25%) patients, mostly for secretion clearance (87%). Complications attributed to bronchoscopy or significant clinical decline within 12 hours of the procedure occurred in 24 (8%) cases, with 1 death. CONCLUSION: Results from this international database provide a widely generalizable characterization of the benefits and risks of bronchoscopy in patients with known or suspected COVID-19. Bronchoscopy in this setting has reasonable clinical benefit, with diagnosis and/or management change resulting from about half of the diagnostic cases. However, it is not without risk, especially in patients with limited physiological reserve.

Predicting Lymph Node Metastasis in Non-small Cell Lung Cancer: Prospective External and Temporal Validation of the HAL and HOMER Models.

BACKGROUND: Two models, the Help with the Assessment of Adenopathy in Lung cancer (HAL) and Help with Oncologic Mediastinal Evaluation for Radiation (HOMER), were recently developed to estimate the probability of nodal disease in patients with non-small cell lung cancer (NSCLC) as determined by endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA). The objective of this study was to prospectively externally validate both models at multiple centers. RESEARCH QUESTION: Are the HAL and HOMER models valid across multiple centers? STUDY DESIGN AND METHODS: This multicenter prospective observational cohort study enrolled consecutive patients with PET-CT clinical-radiographic stages T1-3, N0-3, M0 NSCLC undergoing EBUS-TBNA staging. HOMER was used to predict the probability of N0 vs N1 vs N2 or N3 (N2|3) disease, and HAL was used to predict the probability of N2|3 (vs N0 or N1) disease. Model discrimination was assessed using the area under the receiver operating characteristics curve (ROC-AUC), and calibration was assessed using the Brier score, calibration plots, and the Hosmer-Lemeshow test. RESULTS: Thirteen centers enrolled 1,799 patients. HAL and HOMER demonstrated good discrimination: HAL ROC-AUC = 0.873 (95%CI, 0.856-0.891) and HOMER ROC-AUC = 0.837 (95%CI, 0.814-0.859) for predicting N1 disease or higher (N1|2|3) and 0.876 (95%CI, 0.855-0.897) for predicting N2|3 disease. Brier scores were 0.117 and 0.349, respectively. Calibration plots demonstrated good calibration for both models. For HAL, the difference between forecast and observed probability of N2|3 disease was +0.012; for HOMER, the difference for N1|2|3 was -0.018 and for N2|3 was +0.002. The Hosmer-Lemeshow test was significant for both models (P = .034 and .002), indicating a small but statistically significant calibration error. INTERPRETATION: HAL and HOMER demonstrated good discrimination and calibration in multiple centers. Although calibration error was present, the magnitude of the error is small, such that the models are informative.

The Impact of Biopsy Tool Choice and Rapid On-Site Evaluation on Diagnostic Accuracy for Malignant Lesions in the Prospective: Multicenter NAVIGATE Study.

BACKGROUND: The diagnostic yield of electromagnetic navigation bronchoscopy (ENB) is impacted by biopsy tool strategy and rapid on-site evaluation (ROSE) use. This analysis evaluates usage patterns, accuracy, and safety of tool strategy and ROSE in a multicenter study. METHODS: NAVIGATE (NCT02410837) evaluates ENB using the superDimension navigation system (versions 6.3 to 7.1). The 1-year analysis included 1215 prospectively enrolled subjects at 29 United States sites. Included herein are 416 subjects who underwent ENB-aided biopsy of a single lung lesion positive for malignancy at 1 year. Use of a restricted number of tools (only biopsy forceps, standard cytology brush, and/or bronchoalveolar lavage) was compared with an extensive multimodal strategy (biopsy forceps, cytology brush, aspirating needle, triple needle cytology brush, needle-tipped cytology brush, core biopsy system, and bronchoalveolar lavage). RESULTS: Of malignant cases, 86.8% (361/416) of true positive diagnoses were obtained using extensive multimodal strategies. ROSE was used in 300/416 cases. The finding of malignancy by ROSE reduced the total number of tools used. A malignant ROSE call was obtained in 71% (212/300), most (88.7%; 188/212) by the first tool used (49.5% with aspirating needle, 20.2% with cytology brush, 17.0% with forceps). True positive rates were highest for the biopsy forceps (86.9%) and aspirating needle (86.6%). Use of extensive tool strategies did not increase the rates of pneumothorax (5.5% restricted, 2.8% extensive) or bronchopulmonary hemorrhage (3.6% restricted, 1.1% extensive). CONCLUSION: These results suggest that extensive biopsy tool strategies, including the aspirating needle, may provide higher true positive rates for detecting lung cancer without increasing complications.

Robotic Bronchoscopy for Peripheral Pulmonary Lesions: A Multicenter Pilot and Feasibility Study (BENEFIT).

BACKGROUND: The diagnosis of peripheral pulmonary lesions (PPL) continues to present clinical challenges. Despite extensive experience with guided bronchoscopy, the diagnostic yield has not improved significantly. Robotic-assisted bronchoscopic platforms have been developed potentially to improve the diagnostic yield for PPL. Presently, limited data exist that evaluate the performance of robotic systems in live human subjects. RESEARCH QUESTION: What is the safety and feasibility of robotic-assisted bronchoscopy in patients with PPLs? STUDY DESIGN AND METHODS: This was a prospective, multicenter pilot and feasibility study that used a robotic bronchoscopic system with a mother-daughter configuration in patients with PPL 1 to 5 cm in size. The primary end points were successful lesion localization with the use of radial probe endobronchial ultrasound (R-EBUS) imaging and incidence of procedure related adverse events. Robotic bronchoscopy was performed in patients with the use of direct visualization, electromagnetic navigation, and fluoroscopy. After the use of R-EBUS imaging, transbronchial needle aspiration was performed. Rapid on-site evaluation (ROSE) was used on all cases. Transbronchial needle aspiration alone was sufficient when ROSE was diagnostic; when ROSE was not diagnostic, transbronchial biopsy was performed with the use of the robotic platform, followed by conventional guided bronchoscopic approaches at the discretion of the investigator. RESULTS: Fifty-five patients were enrolled at five centers. One patient withdrew consent, which left 54 patients for data analysis. Median lesion size was 23 mm (interquartile range, 15 to 29 mm). R-EBUS images were available in 53 of 54 cases. Lesion localization was successful in 51 of 53 patients (96.2%). Pneumothorax was reported in two of 54 of the cases (3.7%); tube thoracostomy was required in one of the cases (1.9 %). No additional adverse events occurred. INTERPRETATION: This is the first, prospective, multicenter study of robotic bronchoscopy in patients with PPLs. Successful lesion localization was achieved in 96.2% of cases, with an adverse event rate comparable with conventional bronchoscopic procedures. Additional large prospective studies are warranted to evaluate procedure characteristics, such as diagnostic yield. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03727425; URL: www.clinicaltrials.gov.

Augmented Fluoroscopy: A New and Novel Navigation Platform for Peripheral Bronchoscopy.

BACKGROUND: The diagnosis of lung nodules continues to be a challenge. Confirmed diagnosis allows appropriate treatment for cancers and allows avoidance of more invasive procedures for proven noncancers. Currently, available lung biopsy technologies each have their own limitations, which affect the ability to successfully navigate to a suspicious nodule and to collect a diagnostic sample. Additional advancements in endobronchial navigation, localization, and guided biopsy are needed to obtain higher rates of definitive diagnosis for lung nodules. METHODS: This is a prospective, multicenter study that assessed the localization success rate and diagnostic yield of bronchoscopies guided only by the LungVision platform. Physicians navigated to pulmonary nodules according to a proposed pathway and verified nodule location using radial endobronchial ultrasound before the biopsy. RESULTS: Fifty-five patients were enrolled in the study. Two patients had >1 nodule that was evaluated on the day of the procedure. During bronchoscopy, the nodule localization success rate was 93%. The overall diagnostic yield measured the day of the procedure, based on the immediate rapid on-site pathology report, was 75.4%. CONCLUSION: LungVision provides reliable navigation and ability to biopsy pulmonary nodules with an acceptable success rate. The platform demonstrates a high localization rate of pulmonary nodules.

Navigational bronchoscopy: a guide through history, current use, and developing technology.

The peripheral pulmonary nodule offers unique challenges to the clinician, especially in regards to diagnostic approach. Quite often the etiology of the nodule is spurious, though the specter of malignancy drives accurate classification of the nodule. Diagnostic approaches range in degrees of invasiveness, accuracy, and morbidity. Bronchoscopic access to these nodules had been plagued by low reported yields, especially in fluoroscopically invisible nodules. Navigational bronchoscopy, however, allowed more accurate access to peripheral nodules while maintaining a low morbidity, and thus reshaped the historic diagnostic algorithms. Though navigational bronchoscopy was initially associated with electromagnetic navigation, newer approaches to navigation and new technologies provide enthusiasm that yield can improve. In this article we will provide a historical approach to navigational bronchoscopy, from its origins to its current state, and we will discuss developing technology and its potential role in the evolving paradigm of the peripheral nodule biopsy.

Bronchoscopic lung volume reduction with valves: What should the internist know?

Traditional therapies for emphysema such as bronchodilators and anti-inflammatory drugs have limited value due to permanent structural changes in the emphysematous lung that result in hyperinflation. Surgical lung volume reduction partially corrects hyperinflation by removing emphysematous lung and is an option in selected patients, but it carries a risk of morbidity and death. Valve therapy is a less-invasive option that involves bronchoscopic implantation of 1-way valves in emphysematous lung segments to allow air flow and mucus clearance in the direction of central airways. The authors review the rationale, evidence, and applications of valve therapy.

Role of Endobronchial Ultrasound-guided Transbronchial Needle Aspiration in the Diagnosis and Management of Mediastinal Cyst.

BACKGROUND: Foregut cysts account for >50% of cystic lesions in the mediastinum, of which bronchogenic cysts are most common. Surgical resection is the most definitive approach for its diagnosis and treatment. A recent systematic review, however, suggests that endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has a role in the management of bronchogenic cyst. We report our experience with EBUS-TBNA in the diagnosis and management of bronchogenic cysts. METHODS: Medical records of patients with evidence of mediastinal cysts who underwent EBUS-TBNA between 2008 and 2016 were reviewed.The primary aims of this study were to assess EBUS-TBNA diagnostic yield of peri-bronchial cysts and their specific type/origin and to determine its short-term and long-term drainage efficacy. RESULTS: A total of 26 patients met the inclusion criteria. The cytopathology diagnosis was compatible with bronchogenic cyst in 4 cases, pleural-pericardial cyst in 3 cases, and 19 were indeterminate cysts. Successful long-term treatment occurred in 5.5% of the subjects. One patient developed inflammatory pericarditis after EBUS-TBNA. CONCLUSION: Diagnostic and therapeutic yield of EBUS-TBNA for mediastinal cysts is limited and surgical resection remains the treatment of choice.

The Impact of Gravity vs Suction-driven Therapeutic Thoracentesis on Pressure-related Complications: The GRAVITAS Multicenter Randomized Controlled Trial.

BACKGROUND: Thoracentesis can be accomplished by active aspiration or drainage with gravity. This trial investigated whether gravity drainage could protect against negative pressure-related complications such as chest discomfort, re-expansion pulmonary edema, or pneumothorax compared with active aspiration. METHODS: This prospective, multicenter, single-blind, randomized controlled trial allocated patients with large free-flowing effusions estimated ≥ 500 mL 1:1 to undergo active aspiration or gravity drainage. Patients rated chest discomfort on 100-mm visual analog scales prior to, during, and following drainage. Thoracentesis was halted at complete evacuation or for persistent chest discomfort, intractable cough, or other complication. The primary outcome was overall procedural chest discomfort scored 5 min following the procedure. Secondary outcomes included measures of discomfort and breathlessness through 48 h postprocedure. RESULTS: A total of 142 patients were randomized to undergo treatment, with 140 in the final analysis. Groups did not differ for the primary outcome (mean visual analog scale score difference, 5.3 mm; 95% CI, -2.4 to 13.0; P = .17). Secondary outcomes of discomfort and dyspnea did not differ between groups. Comparable volumes were drained in both groups, but the procedure duration was significantly longer in the gravity arm (mean difference, 7.4 min; 95% CI, 10.2 to 4.6; P < .001). There were no serious complications. CONCLUSIONS: Thoracentesis via active aspiration and gravity drainage are both safe and result in comparable levels of procedural comfort and dyspnea improvement. Active aspiration requires less total procedural time. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03591952; URL: www.clinicaltrials.gov.

Predictors of Response to Endobronchial Coil Therapy in Patients With Advanced Emphysema.

BACKGROUND: The Lung Volume Reduction Coil Treatment in Patients With Emphysema (RENEW) trial reported improvements in quality of life, pulmonary function, and exercise performance following endobronchial coil treatment. OBJECTIVES: The purpose of this post hoc analysis was to identify baseline predictors, including quantitative CT measures, that identify patients most likely to significantly benefit from endobronchial coil therapy. METHODS: Quantitative CT analysis by an independent radiology laboratory and a qualitative evaluation by five blinded experts of the baseline thoracic CT imaging were performed. Univariate and multivariate logistic regression analyses were performed to elucidate characteristics associated with clinical response. RESULTS: In total, 125 patients underwent coil treatment and had evaluable 12-month follow-up results. Of these, 78 patients received treatment of lobes with the highest emphysematous destruction determined by quantitative CT analysis (quantitative visual match [QVM]+), and 47 received treatment in at least one lobe that was not the most destroyed (QVM-). From the 78 patients with QVM+ treatment, a subgroup of 50 patients (64%) was identified with baseline residual volume > 200% predicted, emphysema score > 20% low attenuation area, and absence of airway disease. In this subgroup, greater lobar residual volume reduction in the treated lobes was achieved, which was associated with significant mean ± SE improvement in FEV1 (15.2 ± 3.1%), St. George's Respiratory Questionnaire (-12 ± 2 points), and residual volume (-0.57 ± 0.13 L). DISCUSSION: This post hoc analysis found that both significant hyperinflation (residual volume ≥ 200% predicted) and CT analysis are critical for patient selection and treatment planning for endobronchial coil therapy. Quantitative CT analysis is important to identify optimal lobar treatment and to exclude patients with insufficient emphysema (< 20% low attenuation area), whereas visual assessment identifies patients with signs of airway disease associated with worse outcomes. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01608490; URL: www.clinicaltrials.gov.

Sampling Utility of the Convex Probe Endobronchial Ultrasound Visible Intrapulmonary Lesion.

BACKGROUND: The value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the mediastinal staging of lung cancer has been well established. However, data regarding its utility in the diagnosis of intrapulmonary lesions has been sparse. This study assesses the sampling utility of convex probe EBUS-visible intrapulmonary lesions not visualized by the white-light bronchoscopy. METHODS: A retrospective analysis of EBUS-TBNA of EBUS-visible intrapulmonary lesions was performed between January 2010 and March 2015. Patients with visible endobronchial lesions by white-light bronchoscopy were excluded from analysis. RESULTS: Among 108 procedures, the diagnostic yield of EBUS-TBNA for EBUS-visible intrapulmonary lesions was 87%. Following diagnoses were established: lung cancer (73/67.6%), lung metastases (10/9.2%), infection (5/4.6%), lymphoma (1/<1%), sarcoma/spindle cell sarcoma or neoplasm (3/2.8%), unspecified malignancy (1<1%), and hamartoma (1/<1%). EBUS-TBNA was nondiagnostic in 14 (13%); among these, 9 turned out to have benign disease based on additional bronchoscopy samples or other testing and/or follow-up imaging. Five were ultimately diagnosed with a malignant condition: lymphoma (1), epithelioid hemangioendothelioma (1), and non-small cell lung cancer (3). The sensitivity and the negative predicted value of EBUS-TBNA for differentiating malignancy from benign disease was 94.7% and 75%, respectively, while the accuracy for diagnosing the neoplastic disease was 95.3%. There was one major bleeding requiring bronchial artery embolization and 1 pneumothorax requiring chest tube drainage. CONCLUSION: EBUS-TBNA is safe and effective in the diagnosis of EBUS-visible intrapulmonary lesions. It should be considered as the diagnostic test of choice in patients with these lesions undergoing EBUS-TBNA for the staging of suspected lung cancer.

Clinical Success Stenting Distal Bronchi for "Lobar Salvage" in Bronchial Stenosis.

BACKGROUND: Airway stents are traditionally used in central airway obstructions to maintain airway patency. Historically, distal bronchial stenting within lobar and segmental bronchi has not been amenable to stenting. In addition, there are questionable benefits to stenting small airways. The Atrium iCast stent is a polytetrafluoroethylene covered stainless steel balloon deployed stent which can be deployed through a flexible bronchoscope under direct visualization. The purpose of this study was to assess the feasibility, complications, and long-term impact of using this stent in patients with lobar bronchial stenosis either secondary to malignancy or benign etiologies. METHODS: All records of patients who had the placement of an iCast stent were reviewed over 3.5 years. For each patient the age, sex, location, histology, stent size, duration of stent placement, radiographic improvement, and complications were collected. RESULTS: A total of 122 iCast stents were deployed in 38 patients with lobar bronchial stenosis. The average age was 58 years with 50% male. The etiology included 45% malignant and 55% due to benign conditions. In total, 18.5% patients had stents placed in >1 segment. There was an average of 4 procedures per patient with a mean time to stent revision or removal of 85 days. All patients had symptomatic or radiographic improvement. Common complications included migration (10%), granulation tissue formation (5%), deployment malfunction (2%), stent dislodgement immediately after deployment (2%), mucous plugging (1%), and tumor occlusion (1%). CONCLUSION: Stenting small airways with lobar salvage is feasible and improves symptoms and radiographic outcomes.

A Prediction Model to Help with the Assessment of Adenopathy in Lung Cancer: HAL.

RATIONALE: Estimating the probability of finding N2 or N3 (prN2/3) malignant nodal disease on endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with non-small cell lung cancer (NSCLC) can facilitate the selection of subsequent management strategies. OBJECTIVES: To develop a clinical prediction model for estimating the prN2/3. METHODS: We used the AQuIRE (American College of Chest Physicians Quality Improvement Registry, Evaluation, and Education) registry to identify patients with NSCLC with clinical radiographic stage T1-3, N0-3, M0 disease that had EBUS-TBNA for staging. The dependent variable was the presence of N2 or N3 disease (vs. N0 or N1) as assessed by EBUS-TBNA. Univariate followed by multivariable logistic regression analysis was used to develop a parsimonious clinical prediction model to estimate prN2/3. External validation was performed using data from three other hospitals. MEASUREMENTS AND MAIN RESULTS: The model derivation cohort (n = 633) had a 25% prevalence of malignant N2 or N3 disease. Younger age, central location, adenocarcinoma histology, and higher positron emission tomography-computed tomography N stage were associated with a higher prN2/3. Area under the receiver operating characteristic curve was 0.85 (95% confidence interval, 0.82-0.89), model fit was acceptable (Hosmer-Lemeshow, P = 0.62; Brier score, 0.125). We externally validated the model in 722 patients. Area under the receiver operating characteristic curve was 0.88 (95% confidence interval, 0.85-0.90). Calibration using the general calibration model method resulted in acceptable goodness of fit (Hosmer-Lemeshow test, P = 0.54; Brier score, 0.132). CONCLUSIONS: Our prediction rule can be used to estimate prN2/3 in patients with NSCLC. The model has the potential to facilitate clinical decision making in the staging of NSCLC.

A Histologic Basis for the Efficacy of SBRT to the lung.

PURPOSE: Stereotactic body radiation therapy (SBRT) is the standard of care for medically inoperable patients with early-stage NSCLC. However, NSCLC is composed of several histological subtypes and the impact of this heterogeneity on SBRT treatments has yet to be established. METHODS: We analyzed 740 patients with early-stage NSCLC treated definitively with SBRT from 2003 through 2015. We calculated cumulative incidence curves using the competing risk method and identified predictors of local failure using Fine and Gray regression. RESULTS: Overall, 72 patients had a local failure, with a cumulative incidence of local failure at 3 years of 11.8%. On univariate analysis, squamous histological subtype, younger age, fewer medical comorbidities, higher body mass index, higher positron emission tomography standardized uptake value, central tumors, and lower radiation dose were associated with an increased risk for local failure. On multivariable analysis, squamous histological subtype (hazard ratio = 2.4 p = 0.008) was the strongest predictor of local failure. Patients with squamous cancers fail SBRT at a significantly higher rate than do those with adenocarcinomas or NSCLC not otherwise specified, with 3-year cumulative rates of local failure of 18.9% (95% confidence interval [CI]: 12.7-25.1), 8.7% (95% CI: 4.6-12.8), and 4.1% (95% CI: 0-9.6), respectively. CONCLUSION: Our results demonstrate an increased rate of local failure in patients with squamous cell carcinoma. Standard approaches for radiotherapy that demonstrate efficacy for a population may not achieve optimal results for individual patients. Establishing the differential dose effect of SBRT across histological groups is likely to improve efficacy and inform ongoing and future studies that aim to expand indications for SBRT.

Rapid On-Site Evaluation in Detection of Granulomas in the Mediastinal Lymph Nodes.

RATIONALE: Rapid On-Site Evaluation (ROSE) of specimens collected by endobronchial ultrasound (EBUS)-guided-transbronchial needle aspiration (TBNA) ensures sample adequacy and triages subsequent biopsy procedures. EBUS-TBNA allows sampling of lymph nodes in granulomatous diseases; however, the ability of ROSE to predict the final diagnosis in this setting has not been well characterized. OBJECTIVES: We performed a retrospective evaluation to study the utility of ROSE in the diagnosis of granulomatous diseases as well as to establish the procedure characteristics that would optimize the concordance between ROSE and final diagnosis. METHODS: Charts of patients with a cytological diagnosis of granuloma by EBUS-TBNA between June 2008 and May 2013 were reviewed. Preliminary ROSE findings and final cytological diagnosis were compared. Patient demographics and procedure variables were assessed using mean (±SD). The variables collected were considered in a logistic regression analysis using concordance as the outcome. MEASUREMENTS AND MAIN RESULTS: In our study, 255 procedures were performed to sample 625 lymph nodes that contained granulomas. An average of 2.4 (±1.2) lymph nodes were biopsied per procedure, with a mean size of 14.4 (±7.9) mm. The concordance between ROSE and the final diagnosis was 81.6%. The concordance rate was not impacted by needle size, lymph nodes size or station, number of stations biopsied, or passes per lymph node. The concordance did improve with the experience of the bronchoscopist (P < 0001). CONCLUSIONS: In this single-center study, there was a high concordance between ROSE and the final cytological diagnosis for mediastinal lymph nodes containing granulomas that were sampled by EBUS-TBNA. ROSE may serve to reduce procedure time, enhance sample triaging, and obviate the need for further invasive testing. The only variable associated with increased concordance was the experience of the operator.

Cost effectiveness of bronchial thermoplasty in patients with severe uncontrolled asthma.

RATIONALE: Based on its clinical effectiveness, bronchial thermoplasty (BT) was approved by the Food and Drug Administration in 2010 for the treatment of severe persistent asthma in patients 18 years and older whose asthma is not well-controlled with inhaled corticosteroids and long-acting beta-agonist medicines. OBJECTIVE: Assess the 10 year cost-effectiveness of BT for individuals with severe uncontrolled asthma. METHODS: Using a Markov decision analytic model, the cost-effectiveness of BT was estimated. The patient population involved a hypothetical cohort of 41-year-old patients comparing BT to usual care over a 10-year time frame. The main outcome measure was cost in 2013 dollars per additional quality adjusted life year (QALY). RESULTS: Treatment with BT resulted in 6.40 QALYs and $7512 in cost compared to 6.21 QALYs and $2054 for usual care. The incremental cost-effectiveness ratio for BT at 10 years was $29,821/QALY. At a willingness to pay per QALY of $50,000, BT continues to be cost effective unless the probability of severe asthma exacerbation drops below 0.63 exacerbation per year or the cost of BT rises above $10,384 total for all three bronchoscopic procedures needed to perform thermoplasty and to cover the entire bronchial tree (baseline = $6690). CONCLUSIONS: BT is a cost-effective treatment for asthmatics at high risk of exacerbations. Continuing to follow asthmatics treated with BT beyond 5 years will help inform longer efficacy and support its cost-effectiveness.