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.

Diagnostic Yield and Complications of Bronchoscopy for Peripheral Lung Lesions. Results of the AQuIRE Registry.

RATIONALE: Advanced bronchoscopy techniques such as electromagnetic navigation (EMN) have been studied in clinical trials, but there are no randomized studies comparing EMN with standard bronchoscopy. OBJECTIVES: To measure and identify the determinants of diagnostic yield for bronchoscopy in patients with peripheral lung lesions. Secondary outcomes included diagnostic yield of different sampling techniques, complications, and practice pattern variations. METHODS: We used the AQuIRE (ACCP Quality Improvement Registry, Evaluation, and Education) registry to conduct a multicenter study of consecutive patients who underwent transbronchial biopsy (TBBx) for evaluation of peripheral lesions. MEASUREMENTS AND MAIN RESULTS: Fifteen centers with 22 physicians enrolled 581 patients. Of the 581 patients, 312 (53.7%) had a diagnostic bronchoscopy. Unadjusted for other factors, the diagnostic yield was 63.7% when no radial endobronchial ultrasound (r-EBUS) and no EMN were used, 57.0% with r-EBUS alone, 38.5% with EMN alone, and 47.1% with EMN combined with r-EBUS. In multivariate analysis, peripheral transbronchial needle aspiration (TBNA), larger lesion size, nonupper lobe location, and tobacco use were associated with increased diagnostic yield, whereas EMN was associated with lower diagnostic yield. Peripheral TBNA was used in 16.4% of cases. TBNA was diagnostic, whereas TBBx was nondiagnostic in 9.5% of cases in which both were performed. Complications occurred in 13 (2.2%) patients, and pneumothorax occurred in 10 (1.7%) patients. There were significant differences between centers and physicians in terms of case selection, sampling methods, and anesthesia. Medical center diagnostic yields ranged from 33 to 73% (P = 0.16). CONCLUSIONS: Peripheral TBNA improved diagnostic yield for peripheral lesions but was underused. The diagnostic yields of EMN and r-EBUS were lower than expected, even after adjustment.

Bronchoscopic fibered confocal fluorescence microscopy image characteristics and pathologic correlations.

BACKGROUND: Fibered confocal fluorescence microscopy (FCFM) is a new imaging modality in bronchoscopy. The purpose of this study was to assess FCFM reliability, interpretation, and to make image-pathologic correlations. METHODS: Twenty-six patients underwent FCFM. A validation set was used to determine image characteristics and interobserver reliability. Each patient underwent bronchoscopy using a standardized protocol. The images were evaluated by 4 observers based on brightness, fiber thickness, and alveolar cellularity. Image characteristics showing good interobserver agreement were tested to see if they were related to smoking status. Subsequently, 18 consecutive patients underwent FCFM and biopsy to correlate images with pathology. The blinded reviewers were asked to distinguish between controls and patients with pathologically proven disease. RESULTS: Interobserver agreement for image brightness, as measured by intraclass correlation coefficients (ICCs), ranged from 0.48 to 0.92 (P<0.001) and varied by location. ICCs for image brightness were high, ranging from 0.53 to 0.99 (P<0.001). Agreement for fiber thickness was poor for respiratory bronchioles (ICC 0.12, P<0.05) and fair for alveoli (ICC range, 0.37 to 0.42, P<0.001). The intraobserver (ICC range, 0.69 to 0.91, P<0.001) and intrapatient (ICC 0.65 to 0.84, P<0.001) reliability were excellent. Computer image interpretation showed excellent agreement with humans (ICC 0.62 to 0.99, P<0.001). Smoking was inversely associated with respiratory bronchiole brightness (P<0.001). In FCFM-pathologic correlation, FCFM could distinguish normal from diseased tissue; however, specific diseases could not be distinguished from other diseases. CONCLUSION: FCFM shows a high degree of image reliability and can detect changes in the respiratory bronchioles because of smoking and other diseases, but whether it can discriminate among diseases requires additional study.

Principles of staging as applied to nonsmall cell lung cancer.

PURPOSE OF REVIEW: To review the principles of staging cancer as applied to nonsmall cell lung cancer. RECENT FINDINGS: The current staging system is under review for update. It is timely to review the principles of staging cancer to see how the nonsmall cell lung cancer staging system can be improved. Staging systems should predict prognosis, and guide therapy and research. Based on newer data the next staging system will likely incorporate more categories for tumor size and metastatic disease. Nodal staging may need to distinguish between single station N2 disease and multiple N2 station involvement, as there is some evidence that those with bulky multiple station N2 disease do worse. Histology is increasingly used to guide therapy and there are data that it can affect prognosis. SUMMARY: How we stage patients with nonsmall cell lung cancer is about to change. The most important changes are to tumor size classification and classification of metastatic disease. Better standardization of measurements for tumor staging may further improve the utility of staging.

Risk factors for osteoporosis in Alaska Native women: a cross-sectional survey.

OBJECTIVES: To estimate the prevalence of risk factors for osteoporosis in Alaska Native (AN) women and to assess the feasibility of portable bone density measurement in rural Alaska. METHODS: We conducted a cross-sectional survey of a convenience sample of 452 patients from 17 clinics in Alaska. We interviewed subjects regarding risk factors for osteoporosis and measured calcaneal bone density by ultrasound. RESULTS: Of the 452 women, 316 (70%) were Alaska Natives. Risk factors for osteoporosis were common among study participants. Total dietary calcium intake was low (mean = 306 mg/day). Current smokers [Odds Ratio (OR) = 3.9, 95% Confidence Interval (95% C.I.) 1.8, 8.4], former smokers (OR = 2.8, 95% C.I. 1.3, 6.2) and chronic users of oral steroids (OR = 4.7, 95% C.I. 1.8, 12.0) were at increased risk for low bone density. CONCLUSIONS: Reduction of cigarette smoking, increase in dietary calcium, and reduction of oral steroid use would likely decrease the prevalence of osteoporosis in AN women. A comprehensive prevention program including bone density screening is warranted in rural Alaska.