Citations

Purpose To provide recommendations on the appropriate use of breast tumor biomarker assay results to guide decisions on systemic therapy for metastatic breast cancer. Methods A literature search and prospectively defined study selection identified systematic reviews, meta-analyses, randomized controlled trials (RCTs), prospective–retrospective studies, and prospective comparative observational studies published from 2006 through September 2014. Results The literature search revealed 17 articles that met criteria for further review: 11 studies reporting discordances between primary tumors and metastases in expression of hormone receptors or human epidermal growth factor receptor 2 (HER2), one RCT that addressed the use of a biomarker to decide whether to change or continue a treatment regimen, and five prospective–retrospective studies that evaluated the clinical utility of biomarkers. Recommendations In patients with accessible metastases, biopsy for confirmation of disease process and retesting of estrogen receptor, progesterone receptor, and HER2 status should be offered, but evidence is lacking to determine whether changing anticancer treatment on the basis of change in receptor status affects clinical outcomes. With discordance of results between primary and metastatic tissues, the Panel consensus is to use preferentially the estrogen receptor, progesterone receptor, and HER2 status of the metastasis to direct therapy if supported by the clinical scenario and patient's goals for care. Carcinoembryonic antigen, cancer antigen 15-3, and cancer antigen 27-29 may be used as adjunctive assessments, but not alone, to contribute to decisions regarding therapy. Recommendations for tumor rebiopsy and use of circulating tumor markers are based on clinical experience and Panel informal consensus in the absence of studies designed to evaluate the clinical utility of the markers. As such, it is also reasonable for clinicians to not use these markers as adjunctive assessments.

Abstract Background & Aims Accumulating evidence indicates that micro RNA s play a role in a number of disease processes including the pathogenesis of liver fibrosis in hepatitis C infection. Our goal is to add to the accruing information regarding micro RNA deregulation in liver fibrosis to increase our understanding of the underlying mechanisms of pathology and progression. Methods We used next generation sequencing to profile all detectable micro RNA s in liver tissue and serum from patients with hepatitis C, stages F1–F4 of fibrosis. Results We found altered expression of several micro RNA s, in particular, miR‐182, miR199a‐5p, miR‐200a‐5p and miR‐183 were found to be significantly upregulated in tissue from liver biopsies of hepatitis C patients with advanced fibrosis, stage F3 and F4, when compared with liver biopsies from patients with early fibrosis, stages F1 and F2. We also found miR‐148‐5p, miR‐1260b, miR‐122‐3p and miR‐378i among the micro RNA s most significantly down‐regulated from early to advanced fibrosis of the liver. We also sequenced the serum micro RNA s; however, we were not able to detect significant changes in circulating micro RNA s associated with fibrosis stage after adjusting for multiple tests. Conclusions Adding measurements of tissue micro RNA s acquired during routine biopsies will continue to increase our knowledge of underlying mechanisms of fibrosis. Our goal is that these data, in combination with studies from other researchers and future long‐term studies, could be used to enhance the staging accuracy of liver biopsies and expand the surveillance of patients at increased risk for cancer and progression to advanced fibrosis.

Neoadjuvant treatment may result in better quality of life and functional status 1 year after diagnosis.

ObjectiveTo characterize the evolving management of vestibular schwannoma (VS) in the United States.Study DesignRetrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database.SettingSEER database.Subjects and MethodsAll patients with a diagnosis of VS were analyzed. Data were described and compared using trend analyses and univariate and multivariable logistic regression.ResultsA total of 8330 patients (average age 54.7 years, 51.9% female) were analyzed. The mean incidence was approximately 1.1 per 100,000 per year and did not vary significantly across time; however, from 2004 to 2011, there was a statistically significant decrease in tumor size category at time of diagnosis (P <. 01). Overall, 3982 patients (48%) received primary microsurgery, 1978 (24%) radiation therapy alone, and 2370 (29%) observation. Within the microsurgical cohort, 732 (18%) underwent subtotal resection, and of those, 98 (13.4%) received postoperative radiation therapy. Multivariable regression revealed that surgical treatment was more common in younger patients and larger tumor size categories (P <. 05). Management trend analysis revealed that microsurgery was used less frequently over time (P <. 0001), observation was used more frequently (P <. 0001), and the pattern of radiation therapy remained unchanged. Linear regression was used to create an equation that was applied to predict future management practices. These data predict that by 2026, half of all cases of VS will be managed initially with observation.ConclusionWhile the incidence of VS has remained steady, tumor size at time of diagnosis has decreased over time. Within the United States there has been a clear, recent evolution in management toward observation.

The recent introduction of novel anticancer therapies, including bevacizumab (BVZ) and sunitinib (SNT), is associated with an increased risk of cardiotoxicity. However, early identification of left ventricular (LV) systolic dysfunction may facilitate dose modification and avoid the development of advanced heart failure. Using a murine model of BVZ- and SNT-mediated cardiotoxicity, we investigated whether cardiac biomarkers and/or tissue velocity imaging (TVI) using echocardiography can detect early changes in cardiac function, before a decrease in LV ejection fraction is identified. A total of 75 wild-type C57Bl/6 male mice were treated with either 0.9% saline, BVZ, or SNT. Serial monitoring of blood pressure, high-sensitivity troponin I, and echocardiographic indexes were performed over a 14-day study period, after which the mice were euthanized for histological and biochemical analyses. Mice treated with either BVZ or SNT developed systemic hypertension as early as day 7, which increased by day 14. Cardiac biomarkers, specifically high-sensitivity troponin I, were not predictive of early LV systolic dysfunction. Although conventional LV ejection fraction values decreased at day 13 in mice treated with either BVZ or SNT, TVI confirmed early LV systolic dysfunction at day 8. Histological and biochemical analysis demonstrated loss of cellular integrity, increased oxidative stress, and increased cardiac apoptosis in mice treated with BVZ or SNT therapy at day 14. In a murine model of BVZ- or SNT-mediated cardiomyopathy, noninvasive assessment by TVI detected early LV systolic dysfunction before alterations in conventional echocardiographic indexes.