Abordagem Multidisciplinar Em Hormonioterapia Neoadjuvante No Câncer De Mama: Uma Revisão

Breast cancer is the most common type of cancer and the leading cause of cancerrelated death among women worldwide. Hormone receptor-positive (HR+) tumors represent the most common form of this disease, with more than 70% of breast cancers expressing these receptors. Response and benefit to neoadjuvant chemotherapy (NCT) varies according to HR expression, with lower responses in luminal tumors as compared with hormone receptor-negative (HR-) and human epidermal growth factor receptor 2-positive (HER2+) tumors. Neoadjuvant endocrine therapy (NET) is an option for selected patients with HR+ locally advanced breast cancer. Neoadjuvant endocrine therapy has a favorable toxicity profile, and is associated with benefits such as having low cost and being more easily available even for cancer care professionals outside major urban areas or tertiary centers. These factors are particularly relevant, as 70% of breast cancer deaths occur in women from lowincome and middle-income countries. Additionally, NET is being increasingly explored, not simply to allow for less extensive surgery, but also as a scientific tool, with the use of biomarkers to predict outcomes in adjuvant trials and for the individual patient. This review details the current and most relevant evidence about NET for breast cancer as well as the future directions of this field. © 2016 by Thieme-Revinter Publicações Ltda, Rio de Janeiro, Brazil.381261562

Trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer and brain metastases: exploratory final analysis of cohort 1 from KAMILLA, a single-arm phase IIIb clinical trial

Background: Patients with brain metastases (BM) from human epidermal growth factor receptor 2 (HER2)-positive breast cancer represent a difficult-to-treat population. Trastuzumab emtansine (T-DM1) has shown potential activity in this subset of patients in small clinical series. Patients and methods: KAMILLA is an ongoing, phase IIIb study of T-DM1 in patients with HER2-positive locally advanced/metastatic breast cancer with prior HER2-targeted therapy and chemotherapy. Patients received T-DM1 3.6 mg/kg every 3 weeks (intravenously) until unacceptable toxicity, withdrawal of consent, or disease progression. Tumor response and clinical outcomes in patients with baseline BM were evaluated in this post hoc, exploratory analysis. The main outcome measures were best overall response rate (complete response + partial response) and clinical benefit rate (complete response + partial response + stable disease lasting =6 months) by RECIST v1.1 criteria, progression-free survival, overall survival, and safety. Results: Of 2002 treated patients, 398 had baseline BM. In 126 patients with measurable BM, the best overall response rate and clinical benefit rate were 21.4% [95% confidence interval (CI) 14.6–29.6] and 42.9% (95% CI 34.1–52.0), respectively. A reduction in the sum of the major diameters of BM =30% occurred in 42.9% (95% CI 34.1–52.0), including 49.3% (95% CI 36.9–61.8) of 67 patients without prior radiotherapy to BM. In the 398 patients with baseline BM, median progression-free survival and overall survival were 5.5 (95% CI 5.3–5.6) months and 18.9 (95% CI 17.1–21.3) months, respectively. The adverse event profile was broadly similar in patients with and without baseline BM, although nervous system adverse events were more common in patients with [208 (52.3%)] versus without [701 (43.7%)] baseline BM. Conclusion: This exploratory analysis of patients with HER2-positive metastatic breast cancer and BM enrolled in a prospective clinical trial shows that T-DM1 is active and well-tolerated in this population. T-DM1 should be explored further in this setting

International nosocomial infection control consortium (INICC) report, data summary of 36 countries, for 2004-2009

The results of a surveillance study conducted by the International Nosocomial Infection Control Consortium (INICC) from January 2004 through December 2009 in 422 intensive care units (ICUs) of 36 countries in Latin America, Asia, Africa, and Europe are reported. During the 6-year study period, using Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN; formerly the National Nosocomial Infection Surveillance system [NNIS]) definitions for device-associated health care-associated infections, we gathered prospective data from 313,008 patients hospitalized in the consortium's ICUs for an aggregate of 2,194,897 ICU bed-days. Despite the fact that the use of devices in the developing countries' ICUs was remarkably similar to that reported in US ICUs in the CDC's NHSN, rates of device-associated nosocomial infection were significantly higher in the ICUs of the INICC hospitals; the pooled rate of central line-associated bloodstream infection in the INICC ICUs of 6.8 per 1,000 central line-days was more than 3-fold higher than the 2.0 per 1,000 central line-days reported in comparable US ICUs. The overall rate of ventilator-associated pneumonia also was far higher (15.8 vs 3.3 per 1,000 ventilator-days), as was the rate of catheter-associated urinary tract infection (6.3 vs. 3.3 per 1,000 catheter-days). Notably, the frequencies of resistance of Pseudomonas aeruginosa isolates to imipenem (47.2% vs 23.0%), Klebsiella pneumoniae isolates to ceftazidime (76.3% vs 27.1%), Escherichia coli isolates to ceftazidime (66.7% vs 8.1%), Staphylococcus aureus isolates to methicillin (84.4% vs 56.8%), were also higher in the consortium's ICUs, and the crude unadjusted excess mortalities of device-related infections ranged from 7.3% (for catheter-associated urinary tract infection) to 15.2% (for ventilator-associated pneumonia). Copyright © 2012 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved

Left Ventricular Sphericity (Sphericity Index) In the Dog

Heart disease imposes adaptation phenomena which lead to the modification of the cardiac geometry. The degree of heart change from its normal form has clinical and hemodynamic significance. The more the heart tends to the spherical shape, the worse is the prognosis. The sphericity index allows a quantitative assessment of the degree of sphericity has reached the diseased heart. In this study the authors determined the normal value of the sphericity index by two techniques in 91 dogs. The value obtained for the sphericity index by dividing axes was 1.58 and for the case of division of areas of 1.45. In both cases, significant differences (p <0.05) between males and females were obtained. The sphericity index is an indicator of worsening to the heart and to prognosis, since the processes of higher incidence in canine cardiology, the endocardiosis of mitral valve and dilated cardiomyopathies, both promote volume overload that leads inexorably to left ventricular sphericityFil: Buzzano, O.O. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Hospital Escuela de Medicina Veterinaria. Unidad de Cardiología. Buenos Aires, ArgentinaFil: Barrios, R.J. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Hospital Escuela de Medicina Veterinaria. Unidad de Cardiología. Buenos Aires, ArgentinaFil: Almagro, M.V. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Hospital Escuela de Medicina Veterinaria. Unidad de Cardiología. Buenos Aires, ArgentinaFil: Lightowler, C.H. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Hospital Escuela de Medicina Veterinaria. Unidad de Cardiología. Buenos Aires, ArgentinaLas enfermedades cardíacas imponen fenómenos de adaptación que llevan a la modificación de la geometría cardíaca. El grado con que el corazón se aparta de su forma normal, tiene significado clínico y hemodinámico. Cuanto más tiende el corazón a la forma esférica, peor es el pronóstico de la enfermedad desencadenante. El índice de esfericidad permite una evaluación cuantitativa del grado de esfericidad que ha alcanzado el corazón enfermo. En el presente estudio se determinó el valor normal del índice de esfericidad por dos técnicas en 91 caninos. El valor obtenido para el índice de esfericidad por la técnica de la división de los ejes fue de 1,58 y para el caso de la división de las áreas determinadas por planimetría de 1,45. En ambos casos se encontraron diferencias significativas (p<0,05) entre machos y hembras. Cabe destacar la importancia del índice de esfericidad tanto como indicador de agravamiento cardíaco y pronóstico, dado que los procesos de mayor incidencia en cardiología canina, las endocardiosis valvulares, principalmente la endocardiosis mitral y las\ncardiomiopatías, principalmente las dilatadas, cursan todas con sobrecarga de volumen que lleva inexorablemente la geometría ventricular izquierda hacia la esfericidad

Anatomy and geometry In the congenital subaortic stenosis in boxer dogs #

The authors studied the anatomy and geometry of the left ventricle in 45 boxer dogs suffering congenital subaortic stenosis through of measurement of left ventricular systolic and diastolic diameters, the left ventricular systolic and diastolic thickness of the free wall and interventricular septum and the evaluation of the Relative Wall Thickness. All patients included in this study presented, as indication of the presence of the disease, a systolic murmur, degree 1/6 or 2/6, with maximal intensity in the aortic focus. The measures for the left ventricular diameters, septum and free wall were normal for the corresponding body weight. The mean value of the Relative Wall Thickness obtained in the present study was 0,439 ± 0,06 value considered normal in dogs. This fact indicates that in these patients the presence of the congenital subaortic stenosis did not caused anatomical or geometric adaptation of the left ventricle.Fil: Barrios, R.J. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Hospital Escuela. Unidad de Cardiología. Buenos Aires, ArgentinaFil: Casalonga, O. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Hospital Escuela. Unidad de Cardiología. Buenos Aires, ArgentinaFil: Ditollo, B. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Hospital Escuela. Unidad de Cardiología. Buenos Aires, ArgentinaFil: Bartolomeo, M. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Hospital Escuela. Unidad de Cardiología. Buenos Aires, ArgentinaFil: Lightowler, C.H. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Hospital Escuela. Unidad de Cardiología. Buenos Aires, ArgentinaLos autores estudiaron la anatomía y geometría del ventrículo izquierdo en 45 perros bóxer afectados por estenosis subaórtica congénita por medio de la evaluación de los diámetros sistólico y diastólico del ventrículo izquierdo, de los espesores sistólico y diastólico de la pared libre del ventrículo izquierdo y del septum interventricular y del espesor parietal relativo. Todos los pacientes incluidos en el presente estudio presentaban como indicio de la existencia de la enfermedad un soplo, grado 1/6 o 2/6, sistólico con epicentro en el foco aórtico. Las medidas de los diámetros sistólico y diastólico y de los espesores sistólico y diastólico de la pared libre del ventrículo izquierdo y del septum interventricular fueron normales para el correspondiente rango de peso corporal. El valor promedio del espesor parietal relativo obtenido en el presente estudio fue de 0,439 ± 0,06, valor considerado normal en perros. Ambos aspectos indican que en los pacientes estudiados el padecimiento de la estenosis subaórtica congénita no provocó adaptaciones anatómicas ni geométricas del ventrículo izquierdo

Randomized phase II study of carboplatin and paclitaxel with either linifanib or placebo for advanced nonsquamous non–small-cell lung cancer

Purpose: Linifanib, a potent, selective inhibitor of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptors, has single-agent activity in non–small-cell lung cancer (NSCLC). We evaluated linifanib with carboplatin and paclitaxel as first-line therapy of advanced nonsquamous NSCLC. Patients and Methods: Patients with stage IIIB/IV nonsquamous NSCLC were randomly assigned to 3-week cycles of carboplatin (area under the curve 6) and paclitaxel (200 mg/m2) with daily placebo (arm A), linifanib 7.5 mg (arm B), or linifanib 12.5 mg (arm C). The primary end point was progression-free survival (PFS); secondary efficacy end points included overall survival (OS) and objective response rate. Results: One hundred thirty-eight patients were randomly assigned (median age, 61 years; 57% men; 84% smokers). Median PFS times were 5.4 months (95% CI, 4.2 to 5.7 months) in arm A (n = 47), 8.3 months (95% CI, 4.2 to 10.8 months) in arm B (n = 44), and 7.3 months (95% CI, 4.6 to 10.8 months) in arm C (n = 47). Hazard ratios (HRs) for PFS were 0.51 for arm B versus A (P = .022) and 0.64 for arm C versus A (P = .118). Median OS times were 11.3, 11.4, and 13.0 months in arms A, B, and C, respectively. HRs for OS were 1.08 for arm B versus A (P = .779) and 0.88 for arm C versus A (P = .650). Both linifanib doses were associated with increased toxicity, including a higher incidence of adverse events known to be associated with VEGF/PDGF inhibition. Baseline plasma carcinoembryonic antigen/cytokeratin 19 fragments biomarker signature was associated with PFS improvement and a trend toward OS improvement with linifanib 12.5 mg. Conclusion: Addition of linifanib to chemotherapy significantly improved PFS (arm B), with a modest trend for survival benefit (arm C) and increased toxicity reflective of known VEGF/PDGF inhibitory effects.Suresh S. Ramalingam, Mikhail Shtivelband, Ross A. Soo, Carlos H. Barrios, Anatoly Makhson, José G.M. Segalla, Kenneth B. Pittman, Petr Kolman, Jose R. Pereira, Gordan Srkalovic, Chandra P. Belani, Rita Axelrod, Taofeek K. Owonikoko, Qin Qin, Jiang Qian, Evelyn M. McKeegan, Viswanath Devanarayan, Mark D. McKee, Justin L. Ricker, Dawn M. Carlson, Vera A. Gorbunov

Nivolumab and Ipilimumab as Maintenance Therapy in Extensive-Disease Small-Cell Lung Cancer: CheckMate 451.

In extensive-disease small-cell lung cancer (ED-SCLC), response rates to first-line platinum-based chemotherapy are robust, but responses lack durability. CheckMate 451, a double-blind phase III trial, evaluated nivolumab plus ipilimumab and nivolumab monotherapy as maintenance therapy following first-line chemotherapy for ED-SCLC. Patients with ED-SCLC, Eastern Cooperative Oncology Group performance status 0-1, and no progression after ≤ 4 cycles of first-line chemotherapy were randomly assigned (1:1:1) to nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks for 12 weeks followed by nivolumab 240 mg once every 2 weeks, nivolumab 240 mg once every 2 weeks, or placebo for ≤ 2 years or until progression or unacceptable toxicity. Primary end point was overall survival (OS) with nivolumab plus ipilimumab versus placebo. Secondary end points were hierarchically tested. Overall, 834 patients were randomly assigned. The minimum follow-up was 8.9 months. OS was not significantly prolonged with nivolumab plus ipilimumab versus placebo (hazard ratio [HR], 0.92; 95% CI, 0.75 to 1.12; P = .37; median, 9.2 v 9.6 months). The HR for OS with nivolumab versus placebo was 0.84 (95% CI, 0.69 to 1.02); the median OS for nivolumab was 10.4 months. Progression-free survival HRs versus placebo were 0.72 for nivolumab plus ipilimumab (95% CI, 0.60 to 0.87) and 0.67 for nivolumab (95% CI, 0.56 to 0.81). A trend toward OS benefit with nivolumab plus ipilimumab was observed in patients with tumor mutational burden ≥ 13 mutations per megabase. Rates of grade 3-4 treatment-related adverse events were nivolumab plus ipilimumab (52.2%), nivolumab (11.5%), and placebo (8.4%). Maintenance therapy with nivolumab plus ipilimumab did not prolong OS for patients with ED-SCLC who did not progress on first-line chemotherapy. There were no new safety signals

Atezolizumab versus chemotherapy in advanced or metastatic NSCLC with high blood-based tumor mutational burden: primary analysis of BFAST cohort C randomized phase 3 trial.

Tumor mutational burden (TMB) is being explored as a predictive biomarker for cancer immunotherapy outcomes in non-small cell lung cancer. BFAST (NCT03178552)-an open-label, global, multicohort trial-evaluated the safety and efficacy of first-line targeted therapies or immunotherapy in patients with unresectable Stage IIIB or IV advanced or metastatic non-small cell lung cancer who were selected for biomarker status using blood-based targeted next-generation sequencing. In the Phase 3 cohort C evaluating blood-based (b)TMB as a biomarker of atezolizumab efficacy, patients with bTMB of ≥10 (N = 471) were randomized 1:1 to receive atezolizumab or platinum-based chemotherapy per local standard of care. Cohort C did not meet its primary endpoint of investigator-assessed progression-free survival in the population with bTMB of ≥16 (hazard ratio, 0.77; 95% confidence interval: 0.59, 1.00; P = 0.053). Adverse events leading to treatment withdrawal occurred in 10% of patients in the atezolizumab arm and 20% in the chemotherapy arm. Adverse events of special interest occurred in 42% of patients in the atezolizumab arm and 26% in the chemotherapy arm. A prespecified exploratory analysis compared the bTMB clinical trial assay with the FoundationOne Liquid Companion Diagnostic assay and showed high concordance between assays. Additional exploration of bTMB to identify optimal cutoffs, confounding factors, assay improvements or cooperative biomarkers is warranted