Citations

An autoantibody target on brain microvascular endothelial cells in patients with neuromyelitis optica may be exploited to manipulate blood-brain barrier permeability.

Abstract This study assessed the inter-user reproducibility of Computer-Aided Nodule Assessment and Risk Yield (CANARY), a novel analytical tool that risk stratifies lung adenocarcinomas (ADCs) according to defined computed tomography (CT) structural characteristics. CANARY detects nine distinct voxel signatures in ADCs based on standard CT imaging, thereby defining nodule characteristics correlating with patient outcomes, and corresponding to invasion or lepidic growth histologically. A software user segments the borders of each ADC prior to voxel analysis, introducing potential variability into the assessment. While CANARY is a promising method, it requires validation of the analytical variability between users and prediction of accuracy in an independent cohort. To evaluate the reproducibility of CANARY analysis, three independent users who are not part of the CANARY development team segmented and analyzed 50 biopsy-confirmed primary lung ADCs from Vanderbilt University Medical Center. The CT scans of ADCs were selected retrospectively based on the following criteria: ADC-histology proven on biopsy, diagnosed between 2009-2015, less than 3cm in greatest diameter, and stages IA-IV. Users followed a standard operating procedure established at the Mayo Clinic, and were blinded to clinical characteristics and patient outcomes. Results: To measure inter-user variability of ADC voxel composition, the intraclass correlation coefficient (ICC) was calculated based upon the percentage of each voxel subtype within the whole ADC. An ICC of 1 reflects high reproducibility between users. Amongst all 50 ADCs, the average ICC for all nine voxel types was 0.828 (95% CI 0.76, 0.895). The ICC of the four voxel types associated with invasive features on CT was 0.865 (95% CI 0.805, 0.924). ICCs were also calculated using a logarithmic transformation for data normalization, generating an ICC of 0.745 (95% CI 0.663, 0.826) for all nine voxel types, and an ICC of 0.995 (95% CI 0.993, 0.997) for the four voxel types associated with invasion. Conclusions: (1) CANARY analysis of lung ADC voxel signatures appears to be reproducible amongst users, making it a reliable tool for the evaluation of ADC voxel density. (2) Correlation of invasive signatures associated with more aggressive ADCs was nearly perfect amongst users. Additional validation metrics for CANARY with larger datasets are being evaluated, including the accuracy of tumor prognostic predictions between users and analysis of ADC datasets from other institutions. Citation Format: Erica C. Nakajima, Michael P. Frankland, Tucker Johnson, Sanja L. Antic, Ronald A. Karwoski, Bennett Landman, Heidi Chen, Ronald C. Walker, Brian J. Bartholmai, Tobias Peikert, Srinivasan Rajagopalan, Pierre P. Massion, Fabien Maldonado. Assessing the reproducibility of computer-aided nodule assessment and risk yield (CANARY) method to characterize lung adenocarcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3723. doi:10.1158/1538-7445.AM2017-3723

In patients treated with macitentan (Opsumit®, Actelion Pharmaceuticals Ltd., Basel, Switzerland) for pulmonary arterial hypertension (PAH), prevention and/or effective management of treatment‐related adverse events may improve adherence. However, management of these adverse events can be challenging and the base of evidence and clinical experience for macitentan is limited. In the absence of evidence, consensus recommendations from physicians experienced in using macitentan to treat PAH may benefit patients and physicians who are using macitentan. Consensus recommendations were developed by a panel of physicians experienced with macitentan and PAH using a modified Delphi process. Over three iterations, panelists developed and refined a series of statements on the use of macitentan in PAH and rated their agreement with each statement on a Likert scale. The panel of 18 physicians participated and developed a total of 118 statements on special populations, add‐on therapy, drug–drug interactions, warnings and precautions, hospitalization and functional class, and adverse event management. The resulting consensus recommendations are intended to provide practical guidance on real‐world issues in using macitentan to treat patients with PAH.

LBA2 Background: We previously reported significant benefits in quality of life, patient satisfaction, and emergency room utilization outcomes from a large single-center randomized controlled trial comparing web-based symptom monitoring with patient-reported outcomes (PROs) vs. usual care in patients receiving chemotherapy for metastatic solid tumors (Clinicaltrials.gov: NCT00578006). We now present overall survival results from this trial. Methods: Patients receiving routine outpatient chemotherapy for metastatic solid tumors at Memorial Sloan Kettering Cancer Center were randomly assigned to self-report 12 common symptoms via tablet computers (“PRO intervention”), or to usual care. Treating physicians received symptom printouts at visits and nurses received email alerts when participants reported severe or worsening symptoms. Overall survival was tabulated based on medical records and Social Security Death Index data, estimated using the Kaplan-Meier method, and compared between arms using a log-rank test and Cox proportional hazards regression adjusting for age, sex, race, education level, and cancer type. Results: Between September 2007 and January 2011, 766 patients were randomized, with median age 61 (range 26-91), 86% white, 58% female, and 22% with less than high school education. Cancer types included genitourinary (32% of patients), gynecologic (23%), breast (19%), and lung cancer (26%). Survival results were assessed in June 2016 after a median follow up of 7 years and 517/766 (67%) of participants had died. Median overall survival in the PRO intervention arm was 5 months longer than the control arm (31.2 vs. 26.0 months, p = 0.03). In the multivariable model, results remained statistically significant with a hazard ratio of 0.832 (p = 0.04; 95% CI; 0.696, 0.995). Conclusions: Systematic symptom monitoring during outpatient chemotherapy using web-based patient-reported outcomes confers overall survival benefits. These single-center results are being further evaluated in a national multicenter implementation trial. Clinical trial information: NCT00578006.