Prolonged survival of patients receiving trastuzumab beyond disease progression for HER2 overexpressing metastatic breast cancer (MBC)

Background: The aim of this retrospective analysis was to evaluate the impact of trastuzumab-based regimens on the survival of patients with HER2-overexpressing metastatic breast cancer (MBC). The study specifically focussed on the influence of the continuation of trastuzumab-based treatment despite tumor progression on survival. Patients and Methods: Patients with HER2 overexpressing MBC were included in this retrospective analysis. HER2 overexpression was determined by the immunohistochemical staining score (DAKO Hercep Test (TM)). Trastuzumab was applied at a loading dose of 4 mg/kg and a maintenance dose of 2 mg/kg. Results: Among 136 HER2 overexpressing patients (DAKO score 3+), 66 patients received first-line trastuzumab, 47 patients received trastuzumab as second-line therapy and 23 patients received trastuzumab beyond disease progression. There was no significant difference regarding the duration of trastuzumab-based treatment (first-line: 29.5 weeks vs. second-line: 25 weeks). Moreover, there was no difference in the response rate (first-line: 37.9% vs. second-line: 35.7%) or the median survival (p = 0.47 log rank). Patients who received >= 2 trastuzumab-based regimens for MBC survived significantly longer compared to those who had received only 1 regimen (>= 2 regimens: 62.4 months vs. 1 regimen: 38.5 months; p = 0.01 log rank). Conclusions: Trastuzumab is highly effective in the treatment of HER2 overexpressing MBC. Compared to historical controls, overall survival appears to be markedly prolonged, particularly in patients who received sequential trastuzumab-based treatment beyond disease progression

Subject preferences of fifth-grade children.

Thesis (Ed.M.)--Boston University N.B.:Pages 155 and 309 are missing from original thesis

Infused Therapy and Survival in Older Patients Diagnosed with Metastatic Breast Cancer who Received Trastuzumab

We used Surveillance, Epidemiology, and End Results-Medicare data (2000-2006) to describe treatment and survival in women diagnosed with metastatic breast cancer (MBC) who received trastuzumab. There were 610 patients with a mean age of 74 years. Overall, 32% received trastuzumab alone and 47% received trastuzumab plus a taxane. In multivariate analysis, trastuzumab plus chemotherapy was associated with a lower adjusted cancer mortality rate (Hazard Ratio [HR] 0.54; 95% Confidence Interval [CI] 0.39-0.74; p < .001) than trastuzumab alone among patients who received trastuzumab as part of first-line therapy. Adding chemotherapy to first-line trastuzumab for metastatic breast cancer is associated with improved cancer survival

Autonomous Formation Flight: Project Overview

Objectives: a) Map the vortex effects; b) Formation Auto-Pilot Requirements. Two NASA F/A-18 aircraft in formation: a) NASA 845 Systems Research Aircraft; b) NASA 847 Support Aircraft. Flight Conditions: M = 0.56, 25000 feet (Subsonic condition); b) M = 0.86, 36000 feet (Transonic condition). Nose-To-Tail (N2T) Distances: 20, 55, 110 and 190 feet. Lessons learned: a) Controllable flight in vortex is possible with pilot feedback (displays); b) Position hold at best C(sub D), is attainable; c) Best drag location is close to max rolling moment; e) Drag reductions demonstrated up to 22% (WFE up to 20%); f) Induced drag results compare favorably with simple prediction model; g) "Sweet Spot" (lateral & vertical area > 25%) is larger than predicted; h) Larger wing overlaps result in sign reversals in roll, yaw; i) As predicted, favorable effects degrade gradually with increased nose-to-tail distances after peaking at 3 span lengths aft; and j) Demonstrated - over 100 N mi (>15%) range improvement and 650 lbs (14%) fuel savings on actual simulated F/A-18 cruise mission

An incremental modular technique for checking LTL-X properties on Petri nets

Model-checking is a powerful and widespread technique for the verification of finite state concurrent systems. However, the main hindrance for wider application of this technique is the well-known state explosion problem. Modular verification is a promising natural approach to tackle this problem. It is based on the "divide and conquer" principle and aims at deducing the properties of the system from those of its components analysed in isolation. Unfortunately, several issues make the use of modular verification techniques difficult in practice. First, deciding how to partition the system into components is not trivial and can have a significant impact on the resources needed for verification. Second, when model-checking a component in isolation, how should the environment of this component be described? In this paper, we address these problems in the framework of model-checking LTL\X action-based properties on Petri nets. We propose an incremental and modular verification approach where the system model is partitioned according to the actions occurring in the property to be verified and where the environment of a component is taken into account using the linear place invariants of the system

Numerical Method for Rapid Aerostructural Design and Optimization

During early phases of wing design, analytic and low-fidelity methods are often used to identify promising design concepts. In many cases, solutions obtained using these methods provide intuition about the design space that is not easily obtained using higher-fidelity methods. This is especially true for aerostructural design. However, many analytic and low-fidelity aerostructural solutions are limited in application to wings with specific planforms and weight distributions. Here, a numerical method for minimizing induced drag with structural constraints is presented that uses approximations that apply to wings with arbitrary planforms and weight distributions. The method is applied to the NASA Ikhana airframe to show how it can be used for rapid aerostructural optimization and design-space exploration. The design space around the optimum solution is visualized, and the sensitivity of the optimum solution to changes in weight distribution, structural properties, wing loading, and taper ratio is shown. The optimum lift distribution and wing-structure weight for the Ikhana airframe are shown to be in good agreement with analytic solutions. Whereas most modern high-fidelity solvers obtain solutions in a matter of hours, all of the solutions shown here can be obtained in a matter of seconds

HER2 testing in breast cancer: Opportunities and challenges

Human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-25% of breast cancers, usually as a result of HER2 gene amplification. Positive HER2 status is considered to be an adverse prognostic factor. Recognition of the role of HER2 in breast cancer growth has led to the development of anti-HER2 directed therapy, with the humanized monoclonal antibody trastuzumab (Herceptin (R)) having been approved for the therapy of HER2-positive metastatic breast cancer. Clinical studies have further suggested that HER2 status can provide important information regarding success or failure of certain hormonal therapies or chemotherapies. As a result of these developments, there has been increasing demand to perform HER2 testing on current and archived breast cancer specimens. This article reviews the molecular background of HER2 function, activation and inhibition as well as current opinions concerning its role in chemosensitivity and interaction with estrogen receptor biology. The different tissue-based assays used to detect HER2 amplification and overexpression are discussed with respect to their advantages and disadvantages, when to test (at initial diagnosis or pre-treatment), where to test (locally or centralized) and the need for quality assurance to ensure accurate and valid testing results

Treating breast cancer through novel inhibitors of the phosphatidylinositol 3'-kinase pathway

Recent studies indicate that constitutive signaling through the phosphatidylinositol 3'-kinase (PI3K) pathway is a cause of treatment resistance in breast cancer patients. This implies that patients with tumors that exhibit aberrant PI3K signaling may benefit from targeted pathway inhibitors. The first agents to make it to the clinic are the rapamycin analogs. These compounds inhibit the downstream PI3K effector mTOR (mammalian target of rapamycin). A study presented in this issue of Breast Cancer Research suggests that recently developed inhibitors of phosphoinositide-dependent protein kinase 1, a more proximal target of the PI3K pathway, may provide an alternative route to effective PI3K pathway inhibition for breast cancer treatment

A weakness measure for GR(1) formulae

In spite of the theoretical and algorithmic developments for system synthesis in recent years, little effort has been dedicated to quantifying the quality of the specifications used for synthesis. When dealing with unrealizable specifications, finding the weakest environment assumptions that would ensure realizability is typically a desirable property; in such context the weakness of the assumptions is a major quality parameter. The question of whether one assumption is weaker than another is commonly interpreted using implication or, equivalently, language inclusion. However, this interpretation does not provide any further insight into the weakness of assumptions when implication does not hold. To our knowledge, the only measure that is capable of comparing two formulae in this case is entropy, but even it fails to provide a sufficiently refined notion of weakness in case of GR(1) formulae, a subset of linear temporal logic formulae which is of particular interest in controller synthesis. In this paper we propose a more refined measure of weakness based on the Hausdorff dimension, a concept that captures the notion of size of the omega-language satisfying a linear temporal logic formula. We identify the conditions under which this measure is guaranteed to distinguish between weaker and stronger GR(1) formulae. We evaluate our proposed weakness measure in the context of computing GR(1) assumptions refinements