Resource Use and Costs of Indwelling Pleural Catheters vs Pleurodesis for Malignant Pleural Effusions: A Population-based Study.

RATIONALE: Malignant pleural effusions (MPE) are associated with significant health service use and healthcare costs, but the current evidence is limited. OBJECTIVES: To compare 12-month post-procedure: (1) health service utilization, and (2) healthcare costs following indwelling pleural catheter (IPC) insertion with at-home drainage performed by homecare nursing services, versus in-hospital chemical pleurodesis. METHODS: We performed a retrospective population-based study on a cohort of adults with MPE who underwent IPC insertion or chemical pleurodesis between January 1, 2015 and December 31, 2019 using provincial health administrative data (Ontario, Canada). Patients were followed from the procedure date until death or until 12-month post-procedure. Inverse probability of treatment weighting (IPTW) was performed to adjust for imbalances in baseline characteristics. Differences in length of stay (LOS), readmissions, emergency department visits, home care visits, and healthcare costs were estimated using weighted regression analysis. RESULTS: Of 5,752 included individuals, 4432 (77%) underwent IPC insertion and 1320 (23%) had pleurodesis. In the weighted sample, individuals who received an IPC had fewer inpatient days (12.4 days vs 16 days, standardized mean difference 0.229), but a higher proportion of subsequent admissions for empyema (2.7% vs 1.1%, p=0.0002) compared to those undergoing pleurodesis. IPC individuals received more hours of nursing home care (41 hours vs 21.1 hours, standardized mean difference 0.671) but overall had lower average healthcare costs ($40,179 vs $46,640 per patient, standardized mean difference 0.177) than those receiving pleurodesis. CONCLUSIONS: IPCs with home nursing drainage are associated with reduced health resource use compared to pleurodesis in adults with MPE even after controlling for important baseline and clinical characteristics. Given that both procedures have similar health outcomes, our findings support the ongoing promotion of IPCs to increase outpatient management of patients with MPEs. Primary source of funding: TOHAMO Innovation Fund grant.

Patient perspectives on the use of indwelling pleural catheters in malignant pleural effusions.

BACKGROUND: Indwelling pleural catheters are an effective treatment option for patients with malignant pleural effusions. Despite their popularity, there remains a paucity of data on the patient experience and key patient-centred outcomes. OBJECTIVE: To investigate the experience of patients receiving an indwelling pleural catheter to better inform and identify potential areas for improvement in care. METHODS: This was a multicentre survey study at three academic, tertiary-care centres in Canada. Patients with a diagnosis of malignant pleural effusion who had an indwelling pleural catheter inserted were included. An adapted questionnaire specific to indwelling pleural catheters was used with responses recorded on a 4-point Likert scale. Patients completed the questionnaire in-person or by phone at 2-week and 3-month follow-up appointments. RESULTS: A total of 105 patients were enrolled in the study with 84 patients included in the final analysis. At the 2-week follow-up, patient-reported improvements in dyspnoea and quality of life from indwelling pleural catheter were high at 93% and 87%, respectively. The predominant issues identified were discomfort at time of insertion (58%), itching (49%), difficulty with sleeping (39%), discomfort with home drainage (36%) and the pleural catheter reminding patients of their disease (63%). Avoiding hospitalisation for the management of dyspnoea was important to 95% of patients. Findings were similar at 3 months. CONCLUSIONS: Indwelling pleural catheters are an effective intervention to directly improve dyspnoea and quality of life but have important disadvantages for some; clinicians and patients should be aware of these when making an informed decision regarding treatment.

Outcomes for Malignant Pleural Effusions Because of Melanoma Treated With Indwelling Pleural Catheters.

BACKGROUND: Indwelling pleural catheters (IPCs) reduce dyspnea and improve quality of life in patients with malignant pleural effusions (MPEs). Data on outcomes of MPEs secondary to metastatic melanoma managed with IPCs are scarce. We aimed to evaluate outcomes of patients receiving IPCs for MPEs secondary to melanoma compared with other malignancies. METHODS: We identified patients from our prospectively collected database of all patients who had an IPC insertion for MPEs at our tertiary care center for melanoma between May 2006 and November 2018 and for nonmelanoma between May 2006 and June 2013. Chart reviews were conducted to obtain patient demographics, catheter complications, time of IPC removal or death, x-ray imaging, and pleural fluid characteristics. RESULTS: We identified 27 MPEs because of melanoma and 1114 because of nonmelanoma malignancies treated with IPC. The most frequent complication was pleural fluid loculation requiring fibrinolytics which was significantly higher in the melanoma (14.8%) compared with the nonmelanoma group (3.8%; P =0.02). Cumulative incidence functions for catheter removal ( P =0.8) or death with catheter in situ ( P =0.3) were not significant between melanoma and nonmelanoma groups in competing risk analysis. Baseline radiographic pleural effusion scores were similar, but became significantly higher (increased pleural opacity) in the melanoma group at time points following IPC insertion ( P <0.05). CONCLUSION: MPEs because of melanoma had a higher rate of loculations requiring fibrinolytics and less radiographic improvement after IPC insertion suggesting this patient subgroup has a more complicated pleural space which may be less responsive to drainage.

Diagnostic sensitivity of pleural fluid cytology in malignant pleural effusions: systematic review and meta-analysis.

BACKGROUND: Pleural fluid cytology is an important diagnostic test used for the investigation of pleural effusions. There is considerable variability in the reported sensitivity for the diagnosis of malignant pleural effusions (MPE) in the literature. OBJECTIVE: The purpose of this review is to determine the diagnostic sensitivity of pleural fluid cytology for MPE, both overall and by tumour type, to better inform the decision-making process when investigating pleural effusions. DATA SOURCES: A literature search of EMBASE and MEDLINE was performed by four reviewers. Articles satisfying inclusion criteria were evaluated for bias using the QUADAS-2 tool. DATA EXTRACTION: For quantitative analysis, we performed a metaanalysis using a binary random-effects model to determine pooled sensitivity. Subgroup analysis was performed based on primary cancer site and meta-regression by year of publication. SYNTHESIS: Thirty-six studies with 6057 patients with MPE were included in the meta-analysis. The overall diagnostic sensitivity of pleural fluid cytology for MPE was 58.2% (95% CI 52.5% to 63.9%; range 20.5%-86.0%). There was substantial heterogeneity present among studies (I2 95.5%). For primary thoracic malignancies, sensitivity was highest in lung adenocarcinoma (83.6%; 95% CI 77.7% to 89.6%) and lowest in lung squamous cell carcinoma (24.2%; 95% CI 17.0% to 31.5%) and mesothelioma (28.9%; 95% CI 16.2% to 41.5%). For malignancies with extrathoracic origin, sensitivity was high for ovarian cancer (85.2%; 95% CI 74.2% to 96.1%) and modest for breast cancer (65.3%; 95% CI 49.8% to 80.8%). CONCLUSIONS: Pleural fluid cytology has an overall sensitivity of 58.2% for the diagnosis of MPE. Clinicians should be aware of the high variability in diagnostic sensitivity by primary tumour type as well as the potential reasons for false-negative cytology results.PROSPERO registration numberCRD42021231473.

Use of a Novel, Shortened, Indwelling Pleural Catheter (PleurX) for the Ambulatory Management of Malignant Pleural Effusion: A Single Center Experience.

BACKGROUND: Indwelling pleural catheters are frequently used for the treatment of malignant pleural effusion. The PleurX catheter (Becton, Dickinson and Company) is a commonly used indwelling pleural catheter across Canada. The traditional PleurX catheter is designed with a long segment of tubing outside of the patient's chest, making insertion, drainage, and dressing changes awkward. Our clinic developed a novel, shortened, PleurX catheter that is easier to handle. METHODS: We conducted retrospective chart review for all patients treated with a shortened PleurX catheter at our center from December 2015 to May 2019 and demographics, clinical information, and complications were recorded retrospectively. A survey was designed and distributed to nurses experienced with the use of both catheters to elicit a preference between the short and long catheter. RESULTS: We analyzed data from 503 catheters placed in 491 patients. The most frequently encountered complications were loculation requiring fibrinolytic (2.4%), catheter dislodgement (1.2%), and pleural infection (0.6%). Of nurses surveyed, 74% preferred using the shortened PleurX catheter. CONCLUSION: Complication rates of the novel, shortened PleurX catheter are low. Further research is needed to better determine the optimal catheter length for ambulatory management of malignant pleural effusion.

Effect of Needle Size on Diagnosis of Sarcoidosis with Endobronchial Ultrasound-guided Transbronchial Needle Aspiration: Systematic Review and Meta-Analysis.

Background: Sarcoidosis is a multisystem disease characterized by noncaseating granulomatous inflammation that most commonly involves the lungs. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has become an invaluable tool in the assessment of patients with mediastinal and/or hilar lymphadenopathy. Objective: It has been hypothesized that use of the larger 19-gauge (G) needle with EBUS-TBNA improves diagnostic sensitivity in sarcoidosis. However, it is unclear whether the existing literature supports this supposition. Data Sources: A literature search of Embase and Medline was performed by two reviewers. Included articles were evaluated for bias using the QUADAS-2 tool. Data Extraction: For quantitative analysis, we performed a meta-analysis using a binary random-effects model to determine pooled sensitivity. Subgroup analysis was performed based on needle size, use of rapid on-site evaluation (ROSE), study design, and prevalence of sarcoidosis in study group. Synthesis: Sixty-five studies with a total of 4,242 patients were included in the meta-analysis. Overall pooled sensitivity for diagnosis of sarcoidosis was 83.99% (95% confidence interval [CI], 81.22-86.53) among all studies. The 19G subgroup had a significantly higher sensitivity (93.73%; 95% CI, 89.72-97.74%; I2 = 0.00%; P < 0.01) compared with the 21G subgroup (84.61%; 95% CI, 78.80-90.42%; I2 = 69.83%), 22G subgroup (84.07%; 95% CI, 80.90-87.24%; I2 = 85.21%) or unspecified 21G/22G subgroup (78.85%; 95% CI, 70.81-86.90%; I2 = 84.47%). There were no significant differences with use of ROSE or prevalence of sarcoidosis or by study design. Conclusions: The use of 19G needles during EBUS-TBNA had the highest diagnostic sensitivity based on available studies. Further randomized controlled trials using 19G needles should be considered in patients with suspected sarcoidosis.

Three Decades of Malignant Pleural Mesothelioma: An Academic Center Experience.

BACKGROUND: Malignant pleural mesothelioma (MPM) remains a challenging disease to manage. In the past few decades, extrapleural pneumonectomy (EPP), pemetrexed-based chemotherapy, and indwelling pleural catheters were introduced to MPM care with variable levels of efficacy and evidence. PATIENTS AND METHODS: This was a retrospective review of patients diagnosed with MPM between January 1991 and March 2019. The primary outcome was overall survival (OS). Data were examined by decade to assess trends in MPM demographics, management, and OS. A subgroup analysis was then conducted to examine the impact of EPP, pemetrexed, and indwelling pleural catheters on OS. RESULTS: The study included 337 patients; 309 patients had died at last follow-up (91.7%). Median age at diagnosis and the proportion of female patients increased from 65.8 years (interquartile range [IQR], 57.1-73.7) and 11.6% female from 1991 to 1999 to 75 years (IQR, 68.1-80.6) and 20.5% female from 2010 to 2019. Median OS was largely unchanged in the three study periods: 9.0 months (95% confidence interval [CI], 6.9-12.7) in the 1991-1999 cohort, 9.3 months (95% CI, 7.6-13.2) in the 2000-2009 cohort, and 10.1 months (95% CI, 7.9-13.6) in the 2010-2019 cohort. Controlling for a number of demographic and prognostic factors, EPP (hazard ratio [HR] = 0.50; 95% CI, 0.3-0.9; P = .02), pemetrexed-based chemotherapy (HR = 0.59; 95% CI, 0.40-0.87; P = .007), and indwelling pleural catheters (HR = 0.3; 95% CI, 0.13-0.71; P = .006) were each associated with improvements in OS. CONCLUSION: Despite the small incremental improvements in survival shown by the three interventions we examined, prognosis remains guarded for MPM patients. Better modalities of management are needed.

Tract metastasis in patients with long-term pleural catheter-computed tomography diagnosis and longitudinal assessment.

OBJECTIVES: Long-term indwelling pleural catheters (IPC), used for the management of malignant pleural mesothelioma (MPM), may lead to catheter tract metastasis (CTM). While computed tomography (CT) is valuable for diagnosis, no studies have assessed CT manifestations of CTM. Our goal is to describe the incidence, CT appearances, and temporal evolution of CTM in MPM. METHODS: A retrospective review of CT of 90 consecutive patients with MPM and IPC. In patients with CTM, a longitudinal assessment was performed for CT appearance at diagnosis and over time, interval from insertion to diagnosis and rate of progression. RESULTS: The incidence of CTM was 26% (23/90), in 22 men (54-83 years, mean 73 years). CTM manifested with focal lesion (3 to 60 mm, mean 25 mm) in the subcutaneous tissue at the insertion site. Abnormalities of sub-adjacent skin and fat stranding were present in 16/24 (66%) and 11/24 (46%), respectively, enlargement of chest wall musculature in 11/24 (46%), and dilated subcutaneous vessels in 4/24 (17%) patients. On follow-up, 53% had enlargement of focal lesion. The average rate of progression was 3.5 mm/month, compared to 0.79 mm/month for pleural thickening (p = 0.03). The time between IPC insertion and CTM diagnosis varied from 58 to 1375 days (median 408 days); 83% occurred after IPC removal. Reporting radiologists described focal abnormality at the insertion site in only 9/23 (39%) patients. CONCLUSIONS: CTM is commonly overlooked and underreported by radiologists. CT invariably demonstrates focal subcutaneous lesion in the procedure tract, most commonly after IPC removal. Ancillary findings, notably serratus or latissimus dorsi muscle enlargement, are novel finding that can assist in CT detection and diagnosis. KEY POINTS: • Catheter tract metastasis (CTM), resulting from indwelling pleural catheter to manage malignant pleural mesothelioma, invariably manifested on CT as a focal subcutaneous lesion at the site of insertion, more commonly after catheter removal. • Ipsilateral muscle enlargement is a newly described CT finding that can assist in the detection and diagnosis. • Catheter tract metastasis was commonly overlooked by radiologists, reported in only 39% of cases.

Early Readmission to Hospital in Patients With Cancer With Malignant Pleural Effusions: Analysis of the Nationwide Readmissions Database.

BACKGROUND: Hospital readmissions are costly to health-care systems and represent a measure of quality care. Patients with cancer with malignant pleural effusions (MPEs) are at high risk for rehospitalization; however, risk factors for readmissions in this population are not well described. Understanding the incidence and risk factors for readmission could facilitate the development of a readmission reduction strategy in this patient population. METHODS: We conducted a retrospective cohort study using the Nationwide Readmissions Database (NRD) (2014 sample) to determine the proportion of all-cause, unplanned, 30-day readmissions to hospital among patients with MPEs. Survey weighting methods that accounted for the NRD sampling design were used to generate nationally representative estimates. We used multivariable logistic regression to determine predictors of early readmission. RESULTS: There were 27,900 unplanned readmissions after 108,824 index hospitalizations for MPEs, a rate of 25.6% (95% CI, 25.0%-26.3%). The mortality rate during readmission to hospital was 17.3% (n = 4,840; 95% CI, 16.6%-18.1%). Mean cost per readmission was $15,452 ± $415, with total aggregate costs of > $400 million. Predictors of early readmission included having Medicaid insurance status, treatment with thoracentesis only, and discharge to a care facility or home health care. CONCLUSIONS: One in four patients with cancer and MPEs are readmitted to hospital within 30 days of discharge, and nearly one in five die during the readmission. Nondefinitive management with thoracentesis led to more readmissions. A further understanding of factors that drive preventable readmissions could significantly improve quality of care in this population.

Clinical Predictors of Successful and Earlier Removal of Indwelling Pleural Catheters in Benign Pleural Effusions.

BACKGROUND: Indwelling pleural catheters (IPCs) are an emerging therapy for persistent benign pleural effusions. IPCs may achieve pleurodesis and be removed. OBJECTIVES: We aimed to identify factors associated with higher pleurodesis rates and earlier IPC removal in benign pleural effusions. METHODS: We reviewed a database of IPCs inserted for nonmalignant pleural effusions in the period August 2007 to June 2017 in patients who underwent medical thoracoscopy (MT). Clinical, radiologic, and pleural fluid data were recorded. Logistic regression and Cox proportional hazards were used to assess the rate of and time to pleurodesis. RESULTS: 304 IPCs were reviewed. 52 were excluded from the pleurodesis analysis due to removal for another reason, or because of an eventual diagnosis of malignant disease. The overall pleurodesis rate was 74%, and median time to pleurodesis was 42 (IQR 18-93) days. Variables with increased pleurodesis rates in multivariate analysis include Eastern Cooperative Oncology Group performance status score of ≤2 (odds ratio [OR] 4.22, 95% confidence interval [CI] 1.75-10.16) and MT (OR 5.27, 95% CI 2.74-10.11). No variables were associated with reduced pleurodesis rates in multivariate analysis. Variables that predicted earlier removal in multivariate analysis included secondary pleural infection (hazard ratio [HR] 14.19, 95% CI 4.11-48.91), % eosinophils (HR 1.03, 95% CI 1.01-1.05), and connective tissue disease (HR 2.59, 95% CI 1.20-5.57). Variables that predicted delayed removal include pleural effusion above the hilum (HR 0.54, 95% CI 0.34-0.85), liver failure (HR 0.31, 95% CI 0.16-0.60), and heart failure (HR 0.32, 95% CI 0.20-0.52). CONCLUSIONS: IPCs are safe in benign effusions. Clinicians should consider numerous factors when predicting the rate of and time to pleurodesis.

Catheter Tract Metastasis in Mesothelioma Patients with Indwelling Pleural Catheters: A Retrospective Cohort Study.

BACKGROUND: Use of indwelling pleural catheters (IPCs) for the management of symptomatic pleural effusions in patients with mesothelioma has increased in popularity. An important concern with this approach is the potential for the development of catheter tract metastasis (CTM). OBJECTIVES: To determine the incidence of IPC-related CTM in patients with malignant pleural mesothelioma (MPM). METHODS: In this single-center retrospective cohort study, patients with biopsy-confirmed MPM who had an IPC inserted between May 2006 and July 2017 were identified from a prospectively collected database. Thoracic CT scans following IPC insertion were reviewed to assess for evidence of CTM. Patients were followed until death or last documented patient encounter with a minimum of 6-month follow-up. RESULTS: A total of 90 patients were included in the cohort. CTM was identified in 23 of 90 patients (26%). Median time from IPC insertion to CTM was 408 days (interquartile range 196-721 days). Medical thoracoscopy at the time of IPC insertion did not lead to a significantly increased odds of CTM (OR 2.30; 95% CI 0.66-7.94; p = 0.19). Incidence of CTM was not different between mesothelioma subtypes (p = 0.09). Patient-reported dyspnea scores were improved following IPC insertion in 80% of patients. CONCLUSIONS: CTM was identified in over a quarter of MPM patients when follow-up imaging was reviewed. Treating physicians should be cognizant of the possibility of CTM at the site of prior IPC.

Atezolizumab-induced sarcoid-like granulomatous reaction in a patient with urothelial cell carcinoma.

A 61-year-old woman with locally advanced, high-grade urothelial cell carcinoma was treated with the anti-programmed death-ligand 1 antibody atezolizumab. She initially received neoadjuvant chemotherapy and surgery that led to clinical and radiographic remission at the time of atezolizumab initiation. Within 3 months she developed new mediastinal and hilar lymphadenopathy as well as pulmonary nodules in a pattern characteristic of pulmonary sarcoidosis. Mediastinal lymph node biopsy by endobronchial ultrasound demonstrated noncaseating granulomas without evidence of malignancy or infection. Within 4 weeks of initiation of prednisone and cessation of atezolizumab there was marked reduction in intrathoracic lymphadenopathy and perilymphatic nodules. This is the first reported case of atezolizumab-induced sarcoid-like granulomatous reaction.

Effect of Chemotherapy on Removal of Indwelling Pleural Catheters in Breast Cancer Patients with Malignant Pleural Effusions.

BACKGROUND: Indwelling pleural catheters (IPC) are commonly used in the management of malignant pleural effusions (MPE). The effect of systemic chemotherapy on IPC removal has not been reported previously. OBJECTIVES: The purpose of this study is to identify the effect of chemotherapy on the removal of IPCs in breast cancer patients with MPEs. METHODS: In this retrospective cohort study at an academic tertiary-care center, patients with breast cancer and MPE who received an IPC between 2006 and 2016 were identified from a prospectively collected database. Patient chemotherapy data were obtained, as well estrogen receptor (ER) and human epidermal growth factor receptor-2 status at the time of diagnosis. Patients receiving chemotherapy while their IPC was in situ were compared to those who did not. The primary outcome was time to IPC removal. All patients were followed until IPC removal or death. RESULTS: A total of 207 patients and 216 IPCs were included in the analysis. There was no difference in time to IPC removal between the chemotherapy and no-chemotherapy groups (HR 0.73, 95% CI 0.50-1.07, p = 0.10) or rate of IPC removal (OR 1.16, 95% CI 0.68-1.98, p = 0.59). The risk of IPC infection was not different between patients who received chemotherapy and those who did not (RR 0.57, 95% CI 0.06-5.39, p = 0.48). CONCLUSIONS: Treatment with chemotherapy with an IPC in situ was not associated with a reduced time to IPC removal in our breast cancer population. IPC insertion in patients receiving chemotherapy is safe and not associated with an increased risk of infection.

Clinical predictors of successful and earlier pleurodesis with a tunnelled pleural catheter in malignant pleural effusion: a cohort study.

BACKGROUND: Tunnelled pleural catheters used to treat malignant pleural effusions may achieve pleurodesis. We aimed to identify factors associated with higher pleurodesis rates and earlier catheter removal. METHODS: We retrospectively reviewed a prospective database of tunnelled pleural catheters inserted consecutively between May 2006 and June 2013 for confirmed malignant pleural effusion. The cohort included patients who underwent medical thoracoscopy. Clinical, radiologic and pleural fluid data were recorded. We used logistic regression and Cox regression to assess rates of and days to pleurodesis, respectively. RESULTS: We analyzed data for 1071 tunnelled pleural catheters in 956 patients. Increased rates of pleurodesis were associated with lymphoma (odds ratio [OR] 3.49, 95% confidence interval [CI] 1.93-6.33), ovarian cancer (OR 2.93, 95% CI 1.68-5.11), Eastern Cooperative Oncology Group Scale of Performance Status grade 2 or less (OR 2.79, 95% CI 1.79-4.34), medical thoracoscopy (OR 2.21, 95% CI 1.28-3.85), protein level (OR 1.03, 95% CI 1.01-1.06), albumin level (OR 1.07, 95% CI 1.03-1.12) and percent eosinophils (OR 1.04, 95% CI 1.00-1.07). Reduced rates of pleurodesis were associated with gastrointestinal cancers (OR 0.41, 95% CI 0.19-0.87), hydropneumothorax on the postdrainage chest radiograph (OR 0.62, 95% CI 0.41-0.94) and percent other cells on cell count (OR 0.98, 95% CI 0.97-0.99). Earlier pleurodesis was associated with ovarian cancer (hazard ratio [HR] 1.48, 95% CI 1.06-2.08), medical thoracoscopy (HR 1.45, 95% CI 1.10-1.92), protein level (HR 1.03, 95% CI 1.01-1.04) and percent eosinophils (HR 1.02, 95% CI 1.00-1.04). Delayed pleurodesis was associated with breast cancer (HR 0.61, 95% CI 0.46-0.81), hydropneumothorax with 80% or less lung expansion (HR 0.55, 95% CI 0.38-0.80) and percent other cells (HR 0.99, 95% CI 0.98-1.00). INTERPRETATION: Clinicians should consider numerous factors to predict the probability of and timing to pleurodesis with tunnelled pleural catheters.

Participant selection for lung cancer screening by risk modelling (the Pan-Canadian Early Detection of Lung Cancer [PanCan] study): a single-arm, prospective study.

BACKGROUND: Results from retrospective studies indicate that selecting individuals for low-dose CT lung cancer screening on the basis of a highly predictive risk model is superior to using criteria similar to those used in the National Lung Screening Trial (NLST; age, pack-year, and smoking quit-time). We designed the Pan-Canadian Early Detection of Lung Cancer (PanCan) study to assess the efficacy of a risk prediction model to select candidates for lung cancer screening, with the aim of determining whether this approach could better detect patients with early, potentially curable, lung cancer. METHODS: We did this single-arm, prospective study in eight centres across Canada. We recruited participants aged 50-75 years, who had smoked at some point in their life (ever-smokers), and who did not have a self-reported history of lung cancer. Participants had at least a 2% 6-year risk of lung cancer as estimated by the PanCan model, a precursor to the validated PLCOm2012 model. Risk variables in the model were age, smoking duration, pack-years, family history of lung cancer, education level, body-mass index, chest x-ray in the past 3 years, and history of chronic obstructive pulmonary disease. Individuals were screened with low-dose CT at baseline (T0), and at 1 (T1) and 4 (T4) years post-baseline. The primary outcome of the study was incidence of lung cancer. This study is registered with ClinicalTrials.gov, number NCT00751660. FINDINGS: 7059 queries came into the study coordinating centre and were screened for PanCan risk. 15 were duplicates, so 7044 participants were considered for enrolment. Between Sept 24, 2008, and Dec 17, 2010, we recruited and enrolled 2537 eligible ever-smokers. After a median follow-up of 5·5 years (IQR 3·2-6·1), 172 lung cancers were diagnosed in 164 individuals (cumulative incidence 0·065 [95% CI 0·055-0·075], incidence rate 138·1 per 10 000 person-years [117·8-160·9]). There were ten interval lung cancers (6% of lung cancers and 6% of individuals with cancer): one diagnosed between T0 and T1, and nine between T1 and T4. Cumulative incidence was significantly higher than that observed in NLST (4·0%; p<0·0001). Compared with 593 (57%) of 1040 lung cancers observed in NLST, 133 (77%) of 172 lung cancers in the PanCan Study were early stage (I or II; p<0·0001). INTERPRETATION: The PanCan model was effective in identifying individuals who were subsequently diagnosed with early, potentially curable, lung cancer. The incidence of cancers detected and the proportion of early stage cancers in the screened population was higher than observed in previous studies. This approach should be considered for adoption in lung cancer screening programmes. FUNDING: Terry Fox Research Institute and Canadian Partnership Against Cancer.

Safety and Performance Characteristics of Outpatient Medical Thoracoscopy and Indwelling Pleural Catheter Insertion for Evaluation and Diagnosis of Pleural Disease at a Tertiary Center in Canada.

BACKGROUND: Many centers performing medical thoracoscopy (MT) to diagnose pleural disease will insert a chest tube and admit patients to hospital after the procedure, which is inconvenient for patients and contributes to healthcare costs. We report the data on the safety, outcomes, and performance characteristics of outpatient MT with indwelling pleural catheter (IPC) insertion in a large Canadian cohort. METHODS: This retrospective cohort study reviewed patients who underwent outpatient MT and IPC insertion under conscious sedation. Patients without complications were discharged the same day. We report the data on safety, outcomes, and performance characteristics of our program. RESULTS: Outpatient MT and IPC insertion was performed on 218 patients. 99.1% of patients were safely discharged the same day. There was no procedure associated mortality. Pleural malignancy (59.6%) and nonspecific pleuritis (29.4%) were the most common pathologies. Pleural nodularity detected endoscopically was excellent at predicting malignancy with a positive predictive value of 92.5% and is more frequently detected endoscopically when compared to CT scan (p < 0.001). CONCLUSIONS: In the setting of a comprehensive pleural disease program, outpatient MT can be safely performed and is an alternative to an inpatient surgical approach for undiagnosed pleural effusions.

An Algorithmic Approach for Assessment of Mediastinal Lesions Using Conventional Transbronchial Needle Aspiration and Endoscopic Ultrasonography in a Single Procedure.

BACKGROUND: In the era of endobronchial/esophageal ultrasound (EBUS-TBNA/EUS-FNA), many centers forgo conventional transbronchial needle aspiration (C-TBNA) in favour of EBUS-TBNA/EUS-FNA despite no conclusive evidence showing better yields with EBUS-TBNA/EUS-FNA. OBJECTIVES: Assess the feasibility of an algorithmic approach for mediastinal sampling beginning with C-TBNA utilizing rapid onsite cytologic evaluation. METHODS: Descriptive analysis of 92 consecutive patients referred for adenopathy that underwent C-TBNA and subsequent EBUS-TBNA/EUS-FNA if C-TBNA was negative or nondiagnostic. RESULTS: 92 procedures were analyzed. In 50 (54.3%) of cases, C-TBNA alone was sufficient. EBUS-TBNA was performed after C-TBNA in 27 (29.3%) of cases and EUS-FNA in 33 (35.9%) of cases. The yield was 92.9% for C-TBNA, 92.5% for EBUS-TBNA, and 89.7% for EUS-FNA. There were no statistically significant differences in yields by LN station (P = 0.51), the relationship between yield and LN size (P = 0.37), or time difference in procedures following the algorithm compared to EBUS/EUS only procedures (33.7 minutes versus 32.4 minutes on average [95% CI for difference: -9.1 to 11.7], P = 0.80). CONCLUSIONS: An algorithmic approach to assess the mediastinum using C-TBNA initially is feasible without sacrificing yield or procedure times. C-TBNA was sufficient for diagnosis in 54.3% of cases and can be efficiently taught in an IP training program.

The Cost-Effectiveness of High-Risk Lung Cancer Screening and Drivers of Program Efficiency.

INTRODUCTION: Lung cancer risk prediction models have the potential to make programs more affordable; however, the economic evidence is limited. METHODS: Participants in the National Lung Cancer Screening Trial (NLST) were retrospectively identified with the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The high-risk subgroup was assessed for lung cancer incidence and demographic characteristics compared with those in the low-risk subgroup and the Pan-Canadian Early Detection of Lung Cancer Study (PanCan), which is an observational study that was high-risk-selected in Canada. A comparison of high-risk screening versus standard care was made with a decision-analytic model using data from the NLST with Canadian cost data from screening and treatment in the PanCan study. Probabilistic and deterministic sensitivity analyses were undertaken to assess uncertainty and identify drivers of program efficiency. RESULTS: Use of the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial with a threshold set at 2% over 6 years would have reduced the number of individuals who needed to be screened in the NLST by 81%. High-risk screening participants in the NLST had more adverse demographic characteristics than their counterparts in the PanCan study. High-risk screening would cost $20,724 (in 2015 Canadian dollars) per quality-adjusted life-year gained and would be considered cost-effective at a willingness-to-pay threshold of $100,000 in Canadian dollars per quality-adjusted life-year gained with a probability of 0.62. Cost-effectiveness was driven primarily by non-lung cancer outcomes. Higher noncurative drug costs or current costs for immunotherapy and targeted therapies in the United States would render lung cancer screening a cost-saving intervention. CONCLUSIONS: Non-lung cancer outcomes drive screening efficiency in diverse, tobacco-exposed populations. Use of risk selection can reduce the budget impact, and screening may even offer cost savings if noncurative treatment costs continue to rise.