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.

Clinical Presentation and Outcomes of Pregnant Women With Coronavirus Disease 2019: A Systematic Review and Meta-analysis.

BACKGROUND: Descriptions of coronavirus disease 2019 (COVID-19) have focused on the nonpregnant adult population. This study aims to describe the clinical characteristics and perinatal outcomes of COVID-19 in pregnancy. METHODS: We searched databases from December 2019 to 30 April 2020. Eligible studies reported clinical characteristics, radiological findings, and/or laboratory testing of pregnant women during infection. Data were pooled across studies using a random-effects model. RESULTS: Twenty-four studies (136 women) were included. The most common symptoms were fever (62.9%) and cough (36.8%). Laboratory findings included elevated C-reactive protein (57%) and lymphocytopenia (50%). Ground-glass opacity was the most common radiological finding (81.7%). Preterm birth rate was 37.7% and cesarean delivery rate was 76%. There was 1 maternal death. There were 2 fetal COVID-19 cases. CONCLUSIONS: The clinical picture in pregnant women with COVID-19 did not differ from the nonpregnant population; however, the rate of preterm birth and cesarean delivery are considerably higher than international averages.

A Prediction Model to Help with Oncologic Mediastinal Evaluation for Radiation: HOMER.

Rationale: When stereotactic ablative radiotherapy is an option for patients with non-small cell lung cancer (NSCLC), distinguishing between N0, N1, and N2 or N3 (N2|3) disease is important.Objectives: To develop a prediction model for estimating the probability of N0, N1, and N2|3 disease.Methods: Consecutive patients with clinical-radiographic stage T1 to T3, N0 to N3, and M0 NSCLC who underwent endobronchial ultrasound-guided staging from a single center were included. Multivariate ordinal logistic regression analysis was used to predict the presence of N0, N1, or N2|3 disease. Temporal validation used consecutive patients from 3 years later at the same center. External validation used three other hospitals.Measurements and Main Results: In the model development cohort (n = 633), younger age, central location, adenocarcinoma, and higher positron emission tomography-computed tomography nodal stage were associated with a higher probability of having advanced nodal disease. Areas under the receiver operating characteristic curve (AUCs) were 0.84 and 0.86 for predicting N1 or higher (vs. N0) disease and N2|3 (vs. N0 or N1) disease, respectively. Model fit was acceptable (Hosmer-Lemeshow, P = 0.960; Brier score, 0.36). In the temporal validation cohort (n = 473), AUCs were 0.86 and 0.88. Model fit was acceptable (Hosmer-Lemeshow, P = 0.172; Brier score, 0.30). In the external validation cohort (n = 722), AUCs were 0.86 and 0.88 but required calibration (Hosmer-Lemeshow, P < 0.001; Brier score, 0.38). Calibration using the general calibration method resulted in acceptable model fit (Hosmer-Lemeshow, P = 0.094; Brier score, 0.34).Conclusions: This prediction model can estimate the probability of N0, N1, and N2|3 disease in patients with NSCLC. The model has the potential to facilitate decision-making in patients with NSCLC when stereotactic ablative radiotherapy is an option.

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.

Advances in the management of malignant pleural effusion.

PURPOSE OF REVIEW: The current review describes the latest evidence in the management of malignant pleural effusions (MPE). RECENT FINDINGS: Daily drainage of indwelling pleural catheters achieved auto-pleurodesis at a higher rate compared with every-other-day drainage [0.47 vs. 0.24; difference in proportion of 0.23; 95% confidence interval (CI) 0.08-0.38; P = 0.003]. In patients with MPE undergoing talc pleurodesis, a large multicenter randomized clinical trial found that pain control with opiates vs. nonsteroidal anti-inflammatory drugs (NSAID) group were not significantly different (mean visual analog scale of 23.8 vs. 22.1 mm, respectively, adjusted difference -1.5 mm; 95% CI 1.3-3.4; P = 0.40). NSAID use was found to be noninferior to opiates with respect to the rate of pleurodesis failure at 3-month follow-up (prespecified noninferiority margin 15%, failure rates 20% opiates vs. 23% NSAIDS, respectively, difference -3%, 95% CI -10% to ∞; P = 0.004 for noninferiority). Talc remains the most effective sclerosing agent based on multiple systematic reviews and meta-analyses. SUMMARY: More prospective studies are needed to determine the optimal frequency of indwelling pleural catheters drainage. NSAIDS can be used for pain control and do not adversely impact the chance of successful pleurodesis.

Recent advances in diagnostic bronchoscopy.

The field of diagnostic bronchoscopy has been revolutionized in the last decade primarily with the advent of endobronchial ultrasound (EBUS) but also with the addition of multiple different techniques for "guided-bronchoscopy". These advances have had a substantial impact in the management of lung cancer with bronchoscopy now providing both diagnosis and mediastinal staging in a single procedure. EBUS has, in fact, become the first choice for staging of the mediastinum over cervical mediastinoscopy (CM). Although EBUS is now a well-established technique, there are continuous efforts from the scientific community to improve its diagnostic performance, and these will be reviewed in this manuscript. The term "guided-bronchoscopy" was recently coined to describe a myriad of techniques that guide our bronchoscopes or bronchoscopic tools into the periphery of the lungs in addition to our conventional fluoroscopy. Electromagnetic and non-electromagnetic navigation, thin and ultrathin scopes, as well as radial-probe EBUS have collectively increased our yield for smaller peripheral lung lesions and continue to evolve. Despite this improved diagnostic yield, there is still ample room for improvement and newer techniques are under way. With new therapies available for patients with interstitial lung disease, achieving a specific histologic diagnosis is now of paramount importance. Given the high morbidity and mortality of surgical biopsies, bronchoscopic cryobiopsy is being rapidly adopted as a safer and effective alternative, and it is likely going to play a major role in the management of these diseases in the near future. This manuscript we will focus on recent advances in EBUS, guided-bronchoscopy, and the use of cryobiopsy.

Early results of chemotherapy with retroperitoneal lymph node dissection for isolated retroperitoneal recurrence of upper urinary tract urothelial carcinoma after nephroureterectomy.

PURPOSE: Retroperitoneal lymph nodes are a recognized site of relapse in patients undergoing nephroureterectomy (NU) for high grade upper tract urothelial carcinoma (UC). Retrospective studies suggest that retroperitoneal lymph node dissection (RPLND) may be curative at the time of NU for high grade upper tract UC. We hypothesized that chemotherapy followed by RPLND may successfully salvage select patients with isolated retroperitoneal relapse of upper tract UC following prior NU. MATERIALS AND METHODS: We identified four patients with metastatic UC isolated to the subdiaphragmatic retroperitoneal lymph nodes after NU for upper tract UC. These patients had either a stable response or a complete response to chemotherapy and subsequently underwent a complete full bilateral template RPLND. Our primary study endpoints were disease-specific survival and recurrence-free survival. RESULTS: There was no perioperative mortality or long lasting surgery related sequelae in any patient. Two patients had no pathologic evidence of viable cancer at RPLND and are disease-free at 56 and 74 months from surgery. Two patients had evidence of active residual disease and subsequently developed distant disease at 2 months and 32 months after surgery. Both of these patients died of progressive disease at 3 months and 42 months following RPLND. The 5 year DSS and RFS rates were 50% and 50%. CONCLUSIONS: Chemotherapy followed by RPLND for isolated retroperitoneal recurrence after NU for upper tract UC urothelial carcinoma is a feasible and safe treatment that may be potentially therapeutic in select patients.