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Background The optimal diagnostic and staging strategy for patients with suspected lung cancer is not known. Research Question What diagnostic and staging strategies are most cost-effective for lung cancer? Study Design and Methods A decision model was developed by using a hypothetical patient with a high probability of lung cancer. Sixteen unique permutations of bronchoscopy with fluoroscopy, radial endobronchial ultrasound, electromagnetic navigation, convex endobronchial ultrasound with or without rapid-onsite evaluation (ROSE), CT-guided biopsy (CTBx), and surgery were evaluated. Outcomes included cost, complications, mortality, time to complete the evaluation, rate of undetected N2-3 disease at surgery, incremental cost-complication ratio, and willingness-to-pay thresholds. Sensitivity analyses were performed on primary outcomes. Results For a peripheral lung lesion and radiographic N0 disease, the best bronchoscopy strategy costs $1,694 more than the best CTBx strategy but resulted in fewer complications (risk difference, 14%). The additional cost of bronchoscopy to avoid one complication from a CTBx strategy was $12,037. The cost and cumulative complications of bronchoscopy strategies increased compared with CTBx strategies for small lesions. The cost and cumulative complications of bronchoscopy strategies decreased compared with CTBx strategies when a bronchus sign was present, but bronchoscopy remained more costly overall. For a central lesion and/or radiographic N1-3 disease, convex endobronchial ultrasound with ROSE followed by lung biopsy with incremental cost-effectiveness ratio, if required, was more cost-effective than any CTBx strategy across all outcomes. Strategies with ROSE were always more cost-effective than those without, irrespective of scenario. Trade-offs also exist between different bronchoscopy strategies, and optimal choices depend on the value placed on individual outcomes and willingness-to-pay. Interpretation The most cost-effective strategies depend on nodal stage, lesion location, type of peripheral bronchoscopic biopsy, and the use of ROSE. For most clinical scenarios, many strategies can be eliminated, and trade-offs between the remaining competitive strategies can be quantified.

Background Evidence-based guidelines recommend management strategies for malignant pleural effusions (MPEs) based on life expectancy. Existent risk-prediction rules do not provide precise individualized survival estimates. Research Question Can a newly developed continuous risk-prediction survival model for patients with MPE and known metastatic disease provide precise survival estimates? Study Design and Methods Single-center retrospective cohort study of patients with proven malignancy, pleural effusion, and known metastatic disease undergoing thoracentesis from 2014 through 2017. The outcome was time from thoracentesis to death. Risk factors were identified using Cox proportional hazards models. Effect-measure modification (EMM) was tested using the Mantel-Cox test and was addressed by using disease-specific models (DSMs) or interaction terms. Three DSMs and a combined model using interactions were generated. Discrimination was evaluated using Harrell’s C-statistic. Calibration was assessed by observed-minus-predicted probability graphs at specific time points. Models were validated using patients treated from 2010 through 2013. Using LENT (pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group performance score, neutrophil-to-lymphocyte ratio and tumor type) variables, we generated both discrete (LENT-D) and continuous (LENT-C) models, assessing discrete vs continuous predictors’ performances. Results The development and validation cohort included 562 and 727 patients, respectively. The Mantel-Cox test demonstrated interactions between cancer type and neutrophil to lymphocyte ratio (P Interpretation EMM is present between cancer type and other predictors; thus, DSMs outperformed the models that failed to account for this. Discrete risk-prediction models lacked enough precision to be useful for individual-level predictions.

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.

Background Systematic endobronchial ultrasound (EBUS)-guided lung cancer staging starts with hilar N3 nodes, proceeding sequentially to mediastinal N3, N2, and N1 nodes, with sampling of all enlarged nodes (size, ≥ 5 mm) by EBUS. However, procedure time is limited by patient comfort when moderate sedation is used. It is unclear if EBUS staging should start with hilar N3 nodes or whether starting with mediastinal N3 nodes suffices. Knowing the probability of hilar N3 nodes with PET-CT scan negative findings harboring occult metastasis can inform this decision. Research Question What proportion of patients with hilar N3 nodes showing negative PET-CT scan findings have malignancy by EBUS? Study Design and Methods This retrospective observational, single-center cohort study included consecutive patients with clinical-radiographic T1-3, N0-3, M0 non-small cell lung cancer undergoing systematic EBUS staging with biopsy of hilar N3 nodes with negative PET-CT scan findings. The primary outcome was the proportion of patients with malignant hilar N3 nodes showing negative PET-CT scan findings. Based on expert opinion, a threshold probability of malignancy of less than 5% was considered sufficient to skip hilar N3 nodes. We used the binomial exact test to compare the observed proportion vs threshold probability of 5%. Results Of 1,737 consecutive patients undergoing EBUS staging, 1,567 showed negative PET-CT scan findings of the hilar N3 nodes. These nodes were enlarged by EBUS and were sampled in 739 patients. Malignancy was found in the hilar N3 nodes of 5 of 739 patients (0.68%; 95% CI, 0.22%-1.57%). The proportion was significantly less than the threshold probability (P Interpretation When using moderate sedation, because time is limited, it is reasonable to start with the mediastinal N3 nodes if the hilar and mediastinal N3 nodes show negative PET scan results. Patients with positive PET scan findings of the mediastinal N3 nodes probably should undergo hilar N3 node sampling.

Background Despite the many advances in peripheral bronchoscopy, its diagnostic yield remains suboptimal. With the use of cone-beam CT imaging we have found atelectasis mimicking lung tumors or obscuring them when using radial-probe endobronchial ultrasound (RP-EBUS), but its incidence remains unknown. Research Question What are the incidence, anatomic location, and risk factors for developing atelectasis during bronchoscopy under general anesthesia? Study Design and Methods We performed a prospective observational study in which patients undergoing peripheral bronchoscopy under general anesthesia were subject to an atelectasis survey carried out by RP-EBUS under fluoroscopic guidance. The following dependent segments were evaluated: right bronchus 2 (RB2), RB6, RB9, and RB10; and left bronchus 2 (LB2), LB6, LB9, and LB10. Images were categorized either as aerated lung (“snowstorm” pattern) or as having a nonaerated/atelectatic pattern. Categorization was performed by three independent readers. Results Fifty-seven patients were enrolled. The overall intraclass correlation agreement among readers was 0.82 (95% CI, 0.71-0.89). Median time from anesthesia induction to atelectasis survey was 33 min (range, 3-94 min). Fifty-one patients (89%; 95% CI, 78%-96%) had atelectasis in at least one of the eight evaluated segments, 45 patients (79%) had atelectasis in at least three, 41 patients (72%) had atelectasis in at least four, 33 patients (58%) had atelectasis in at least five, and 18 patients (32%) had atelectasis in at least six segments. Right and left B6, B9, and B10 segments showed atelectasis in > 50% of patients. BMI and time to atelectasis survey were associated with increased odds of having more atelectatic segments (BMI: OR, 1.13 per unit change; 95% CI, 1.034-1.235; P = .007; time to survey: OR, 1.064 per minute; 95% CI, 1.025-1.105; P = .001). Interpretation The incidence of atelectasis developing during bronchoscopy under general anesthesia in dependent lung zones is high, and the number of atelectatic segments is greater with higher BMI and with longer time under anesthesia. Clinical Trial Registration ClinicalTrials.gov ; No.: NCT03523689; URL: www.clinicaltrials.gov .

Background The management of recurrent pleural effusions remains a challenging issue for clinicians. Advances in management have led to increased use of indwelling tunneled pleural catheters (IPC) because of their effectiveness and ease of outpatient placement. However, with the increase in IPC placement there have also been increasing reports of complications, including infections. Currently there is minimal guidance in IPC-related management issues after placement. Research Question Our objective was to formulate clinical consensus statements related to perioperative and long-term IPC catheter management based on a modified Delphi process from experts in pleural disease management. Study Design and Methods Expert panel members used a modified Delphi process to reach consensus on common perioperative and long-term management options related to IPC use. Members were identified from multiple countries, specialties, and practice settings. A series of meetings and anonymous online surveys were completed. Responses were used to formulate consensus statements among panel experts, using a modified Delphi process. Consensus was defined a priori as greater than 80% agreement among panel constituents. Results A total of 25 physicians participated in this project. The following topics were addressed during the process: definition of an IPC infection, management of IPC-related infectious complications, interventions to prevent IPC infections, IPC-related obstruction/malfunction management, assessment of IPC removal, and instructions regarding IPC management by patients and caregivers. Strong consensus was obtained on 36 statements. No consensus was obtained on 29 statements. Interpretation The management of recurrent pleural disease with IPC remains complex and challenging. This statement offers statements for care in numerous areas related to IPC management based on expert consensus and identifies areas that lack consensus. Further studies related to long-term management of IPC are warranted.

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 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.

The optimal diagnostic and staging strategy for patients with suspected lung cancer is not known.What diagnostic and staging strategies are most cost-effective for lung cancer?A decision model was developed by using a hypothetical patient with a high probability of lung cancer. Sixteen unique permutations of bronchoscopy with fluoroscopy, radial endobronchial ultrasound, electromagnetic navigation, convex endobronchial ultrasound with or without rapid-onsite evaluation (ROSE), CT-guided biopsy (CTBx), and surgery were evaluated. Outcomes included cost, complications, mortality, time to complete the evaluation, rate of undetected N2-3 disease at surgery, incremental cost-complication ratio, and willingness-to-pay thresholds. Sensitivity analyses were performed on primary outcomes.For a peripheral lung lesion and radiographic N0 disease, the best bronchoscopy strategy costs $1,694 more than the best CTBx strategy but resulted in fewer complications (risk difference, 14%). The additional cost of bronchoscopy to avoid one complication from a CTBx strategy was $12,037. The cost and cumulative complications of bronchoscopy strategies increased compared with CTBx strategies for small lesions. The cost and cumulative complications of bronchoscopy strategies decreased compared with CTBx strategies when a bronchus sign was present, but bronchoscopy remained more costly overall. For a central lesion and/or radiographic N1-3 disease, convex endobronchial ultrasound with ROSE followed by lung biopsy with incremental cost-effectiveness ratio, if required, was more cost-effective than any CTBx strategy across all outcomes. Strategies with ROSE were always more cost-effective than those without, irrespective of scenario. Trade-offs also exist between different bronchoscopy strategies, and optimal choices depend on the value placed on individual outcomes and willingness-to-pay.The most cost-effective strategies depend on nodal stage, lesion location, type of peripheral bronchoscopic biopsy, and the use of ROSE. For most clinical scenarios, many strategies can be eliminated, and trade-offs between the remaining competitive strategies can be quantified.

BACKGROUND: Evidence-based guidelines recommend management strategies for malignant pleural effusions (MPEs) based on life expectancy. Existent risk-prediction rules do not provide precise individualized survival estimates. RESEARCH QUESTION: Can a newly developed continuous risk-prediction survival model for patients with MPE and known metastatic disease provide precise survival estimates? STUDY DESIGN AND METHODS: Single-center retrospective cohort study of patients with proven malignancy, pleural effusion, and known metastatic disease undergoing thoracentesis from 2014 through 2017. The outcome was time from thoracentesis to death. Risk factors were identified using Cox proportional hazards models. Effect-measure modification (EMM) was tested using the Mantel-Cox test and was addressed by using disease-specific models (DSMs) or interaction terms. Three DSMs and a combined model using interactions were generated. Discrimination was evaluated using Harrell’s C-statistic. Calibration was assessed by observed-minus-predicted probability graphs at specific time points. Models were validated using patients treated from 2010 through 2013. Using LENT (pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group performance score, neutrophil-to-lymphocyte ratio and tumor type) variables, we generated both discrete (LENT-D) and continuous (LENT-C) models, assessing discrete vs continuous predictors’ performances. RESULTS: The development and validation cohort included 562 and 727 patients, respectively. The Mantel-Cox test demonstrated interactions between cancer type and neutrophil to lymphocyte ratio (P < .0001), pleural fluid lactate dehydrogenase (P = .029), and bilateral effusion (P = .002). DSMs for lung, breast, and hematologic malignancies showed C-statistics of 0.72, 0.72, and 0.62, respectively; the combined model’s C-statistics was 0.67. LENT-D (C-statistic, 0.60) and LENT-C (C-statistic, 0.65) models underperformed. INTERPRETATION: EMM is present between cancer type and other predictors; thus, DSMs outperformed the models that failed to account for this. Discrete risk-prediction models lacked enough precision to be useful for individual-level predictions.

Despite the many advances in peripheral bronchoscopy, its diagnostic yield remains suboptimal. With the use of cone-beam CT imaging we have found atelectasis mimicking lung tumors or obscuring them when using radial-probe endobronchial ultrasound (RP-EBUS), but its incidence remains unknown.What are the incidence, anatomic location, and risk factors for developing atelectasis during bronchoscopy under general anesthesia?We performed a prospective observational study in which patients undergoing peripheral bronchoscopy under general anesthesia were subject to an atelectasis survey carried out by RP-EBUS under fluoroscopic guidance. The following dependent segments were evaluated: right bronchus 2 (RB2), RB6, RB9, and RB10; and left bronchus 2 (LB2), LB6, LB9, and LB10. Images were categorized either as aerated lung ("snowstorm" pattern) or as having a nonaerated/atelectatic pattern. Categorization was performed by three independent readers.Fifty-seven patients were enrolled. The overall intraclass correlation agreement among readers was 0.82 (95% CI, 0.71-0.89). Median time from anesthesia induction to atelectasis survey was 33 min (range, 3-94 min). Fifty-one patients (89%; 95% CI, 78%-96%) had atelectasis in at least one of the eight evaluated segments, 45 patients (79%) had atelectasis in at least three, 41 patients (72%) had atelectasis in at least four, 33 patients (58%) had atelectasis in at least five, and 18 patients (32%) had atelectasis in at least six segments. Right and left B6, B9, and B10 segments showed atelectasis in50% of patients. BMI and time to atelectasis survey were associated with increased odds of having more atelectatic segments (BMI: OR, 1.13 per unit change; 95% CI, 1.034-1.235; P = .007; time to survey: OR, 1.064 per minute; 95% CI, 1.025-1.105; P = .001).The incidence of atelectasis developing during bronchoscopy under general anesthesia in dependent lung zones is high, and the number of atelectatic segments is greater with higher BMI and with longer time under anesthesia.ClinicalTrials.gov; No.: NCT03523689; URL: www.clinicaltrials.gov.

Background: The management of recurrent pleural effusions remains a challenging issue for clinicians. Advances in management have led to increased use of indwelling tunneled pleural catheters (IPC) because of their effectiveness and ease of outpatient placement. However, with the increase in IPC placement there have also been increasing reports of complications, including infections. Currently there is minimal guidance in IPC-related management issues after placement. Research Question: Our objective was to formulate clinical consensus statements related to perioperative and long-term IPC catheter management based on a modified Delphi process from experts in pleural disease management. Study Design and Methods: Expert panel members used a modified Delphi process to reach consensus on common perioperative and long-term management options related to IPC use. Members were identified from multiple countries, specialties, and practice settings. A series of meetings and anonymous online surveys were completed. Responses were used to formulate consensus statements among panel experts, using a modified Delphi process. Consensus was defined a priori as greater than 80% agreement among panel constituents. Results: A total of 25 physicians participated in this project. The following topics were addressed during the process: definition of an IPC infection, management of IPC-related infectious complications, interventions to prevent IPC infections, IPC-related obstruction/malfunction management, assessment of IPC removal, and instructions regarding IPC management by patients and caregivers. Strong consensus was obtained on 36 statements. No consensus was obtained on 29 statements. Interpretation: The management of recurrent pleural disease with IPC remains complex and challenging. This statement offers statements for care in numerous areas related to IPC management based on expert consensus and identifies areas that lack consensus. Further studies related to long-term management of IPC are warranted.

BACKGROUND: Thoracentesis can be accomplished by active aspiration or drainage with gravity. We investigated whether gravity drainage could protect against negative-pressure related complications, such as chest discomfort, re-expansion pulmonary edema or pneumothorax, compared to active aspiration. METHODS: This prospective, multicenter single blinded randomized controlled trial allocated patients with large free-flowing effusions estimated ≥ 500 mL 1:1 to active aspiration or gravity drainage. Patients rated chest discomfort on 100 mm visual analog scales before, during, and after 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 five minutes post-procedure. Secondary outcomes included measures of discomfort and breathlessness through 48 hours post-procedure. RESULTS: One hundred forty-two patients were randomized with 140 in the final analysis. Groups did not differ for the primary outcome (mean VAS score difference 5.3 mm, 95% CI -2.4 to 13.0, p = 0.17). Secondary outcomes of discomfort and dyspnea did not differ between groups. Comparable volumes were drained in both groups but procedure duration was significantly longer in the gravity arm (mean difference 7.4 minutes, 95% CI 10.2 to 4.6, p

Response to: 'Considering the Duration of Lung Collapse When Comparing Thoracentesis Techniques', Chest, Vol. 158, Issue 1, and 'Gravity vs Active Aspiration for Thoracentesis', Chest, Vol. 158, Issue 1, based on the initial article: 'The Impact of Gravity vs Suction-driven Therapeutic Thoracentesis on Pressure-related Complications', Chest, Vol. 157, Issue 3.

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.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.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.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.ClinicalTrials.gov; No.: NCT03591952; URL: www.clinicaltrials.gov.