In the KATHERINE study (NCT01772472), patients with residual invasive early breast cancer (EBC) after neoadjuvant chemotherapy (NACT) plus human epidermal growth factor receptor 2 (HER2)-targeted ...therapy had a 50% reduction in risk of recurrence or death with adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab. Here, we present additional exploratory safety and efficacy analyses.
KATHERINE enrolled HER2-positive EBC patients with residual invasive disease in the breast/axilla at surgery after NACT containing a taxane (± anthracycline, ± platinum) and trastuzumab (± pertuzumab). Patients were randomized to adjuvant T-DM1 (n = 743) or trastuzumab (n = 743) for 14 cycles. The primary endpoint was invasive disease-free survival (IDFS).
The incidence of peripheral neuropathy (PN) was similar regardless of neoadjuvant taxane type. Irrespective of treatment arm, baseline PN was associated with longer PN duration (median, 105-109 days longer) and lower resolution rate (∼65% versus ∼82%). Prior platinum therapy was associated with more grade 3-4 thrombocytopenia in the T-DM1 arm (13.5% versus 3.8%), but there was no grade ≥3 hemorrhage in these patients. Risk of recurrence or death was decreased with T-DM1 versus trastuzumab in patients who received anthracycline-based NACT hazard ratio (HR) = 0.51; 95% confidence interval (CI): 0.38-0.67, non-anthracycline-based NACT (HR = 0.43; 95% CI: 0.22-0.82), presented with cT1, cN0 tumors (0 versus 6 IDFS events), or had particularly high-risk tumors (HRs ranged from 0.43 to 0.72). The central nervous system (CNS) was more often the site of first recurrence in the T-DM1 arm (5.9% versus 4.3%), but T-DM1 was not associated with a difference in overall risk of CNS recurrence.
T-DM1 provides clinical benefit across patient subgroups, including small tumors and particularly high-risk tumors and does not increase the overall risk of CNS recurrence. NACT type had a minimal impact on safety.
•Baseline PN was associated with longer on-study PN and a lower resolution rate in both study arms.•Prior platinum was associated with more grade 3-4 thrombocytopenia with T-DM1, but not with more grade ≥3 hemorrhage.•IDFS benefit with T-DM1 versus trastuzumab was similar irrespective of neoadjuvant therapy containing anthracyclines.•T-DM1 was not associated with an increased overall risk of CNS recurrence.•The T-DM1 IDFS benefit was maintained in high-risk tumors defined by operable status, nodal involvement, and HR status.
Neoadjuvant systemic therapy (NAST) provides the unique opportunity to assess response to treatment after months rather than years of follow-up. However, significant variability exists in methods of ...pathologic assessment of response to NAST, and thus its interpretation for subsequent clinical decisions. Our international multidisciplinary working group was convened by the Breast International Group-North American Breast Cancer Group (BIG-NABCG) collaboration and tasked to recommend practical methods for standardized evaluation of the post-NAST surgical breast cancer specimen for clinical trials that promote accurate and reliable designation of pathologic complete response (pCR) and meaningful characterization of residual disease. Recommendations include multidisciplinary communication; clinical marking of the tumor site (clips); and radiologic, photographic, or pictorial imaging of the sliced specimen, to map the tissue sections and reconcile macroscopic and microscopic findings. The information required to define pCR (ypT0/is ypN0 or ypT0 yp N0), residual ypT and ypN stage using the current AJCC/UICC system, and the Residual Cancer Burden system were recommended for quantification of residual disease in clinical trials.
We carried out a prospective clinical study to evaluate the impact of the Recurrence Score (RS) on treatment decisions in early breast cancer (EBC).
A total of 379 eligible women with estrogen ...receptor positive (ER+), HER2-negative EBC and 0–3 positive lymph nodes were enrolled. Treatment recommendations, patients' decisional conflict, physicians' confidence before and after knowledge of the RS and actual treatment data were recorded.
Of the 366 assessable patients 244 were node negative (N0) and 122 node positive (N+). Treatment recommendations changed in 33% of all patients (N0 30%, N+ 39%). In 38% of all patients (N0 39%, N+ 37%) with an initial recommendation for chemoendocrine therapy, the post-RS recommendation changed to endocrine therapy, in 25% (N0 22%, N+ 39%) with an initial recommendation for endocrine therapy only to combined chemoendocrine therapy, respectively. A patients' decisional conflict score improved by 6% (P = 0.028) and physicians' confidence increased in 45% (P < 0.001) of all cases. Overall, 33% (N0 29%, N+ 38%) of fewer patients actually received chemotherapy as compared with patients recommended chemotherapy pre-test. Using the test was cost-saving versus current clinical practice.
RS-guided chemotherapy decision-making resulted in a substantial modification of adjuvant chemotherapy usage in node-negative and node-positive ER+ EBC.
Quality indicators in breast cancer care Rosselli Del Turco, M; Ponti, A; Bick, U ...
European journal of cancer (1990),
09/2010, Letnik:
46, Številka:
13
Journal Article, Conference Proceeding
Recenzirano
Abstract To define a set of quality indicators that should be routinely measured and evaluated to confirm that the clinical outcome reaches the requested standards, Eusoma has organised a workshop ...during which twenty four experts from different disciplines have reviewed the international literature and selected the main process and outcome indicators available for quality assurance of breast cancer care. A review of the literature for evidence-based recommendations have been performed by the steering committee. The experts have identified the quality indicators also taking into account the usability and feasibility. For each of them it has been reported: definition, minimum and target standard, motivation for selection and level of evidence (graded according to AHRO). In overall 17 main quality indicators have been identified, respectively, 7 on diagnosis, 4 on surgery and loco-regional treatment, 2 on systemic treatment and 4 on staging, counselling, follow-up and rehabilitation. Breast Units in Europe are invited to comply with these indicators and monitor them during their periodic audit meetings.
The General Board of the Navy was a uniquely American strategic planning organization with few analogs at the time of its establishment, except perhaps the various components of the Admiralty in ...Great Britain. It existed from 1900 to 1950. Then, as now, confusion reigned over what sort of fleet to design and how to build it. The General Board served as the “balance wheel,” or nexus, for bringing together coherent strategy and fleet design. As John T. Kuehn shows, this Board was the United States' first modern general staff in peacetime. It emerged from the trends and developments of the Progressive Era of the late 19th and early 20th centuries. Its creation was very much a reflection of the reformist spirit of the times that also gave birth to the Army War College, the Army General Staff, and the Chief of Naval Operations. As such it reflected a uniquely American attempt to reconcile the primacy of civilian control with the new requirements of the modern age that seemed to dictate a more formal military and naval planning establishment and associated processes and methods. Thus its name reflected corporate America as well as longstanding naval tradition to meet challenges and problems with special, temporary boards. The General Board, however, differed from these temporary boards due to its longevity. By the 1920s it had become a permanent feature of the Navy and was regarded as the premier strategic “think tank” for advice to the Secretary of the Navy. The author highlights how this small body wielded immense influence over its organizational life that was, on balance, innovative, progressive, and productive for the security of the United States in peace and its success in war via the mechanism of its Navy. The service of the men who comprised it is little-known, but their collaborative and creative ethos should still serve as a model for the modern analogs of today like strategic initiatives groups (SIGs). Kuehn's organizational history of this body reflects the turbulence of those times as well as provides a not too “distant mirror” to understand a complexities involved in building a Navy that saw the transition from coal and sail to the nuclear powered warships.
•Developed regime-specific correlations for free convection from an isothermal cylinder for a Pr ≈ 0.7.•Developed simplified regime-specific correlations for free convection from an isothermal ...cylinder for any Pr.•Proposed a combined correlation, with a blending function, that is applicable for any Ra and Pr.•The proposed simplified correlations agree well with existing literature.
Heat transfer by buoyancy-driven convection from a heated horizontal cylinder is present in many situations. Applications occur in nuclear reactor safety, solar energy systems, computer cooling, and many heat exchangers. A number of experimental and numerical studies exist for such flow situations and often provide correlating equations to calculate the heat transfer. The existing studies, most of which are for the case where Prandtl number is approximately 0.7, show a considerable variation in their average Nusselt number predictions. Some studies have addressed the variation in Prandtl number with reasonably accurate and consistent correlations but these are often complex and cumbersome to use. To address these issues, the current paper proposes simplified sets of correlating equations using results from prior numerical and experimental studies.
This study compares the fungal growth ratio on loaded ventilation filters under various temperature, relative humidity (RH), and air flow conditions in a controlled laboratory setting. A new ...full-size commercial building ventilation filter was loaded with malt extract nutrients and conidia of Cladosporium sphaerospermum in an ASHRAE Standard 52.2 filter test facility. Small sections cut from this filter were incubated under the following conditions: constant room temperature and a high RH of 97%; sinusoidal temperature (with an amplitude of 10°C, an average of 23°C, and a period of 24 hr) and a mean RH of 97%; room temperature and step changes between 97% and 75% RH, 97% and 43% RH, and 97% and 11% RH every 12 hr. The biomass on the filter sections was measured using both an elution-culture method and by ergosterol assay immediately after loading and every 2 days up to 10 days after loading. Fungal growth was detected earlier using ergosterol content than with the elution-culture method. A student's t-test indicated that Cladosporium sphaerospermum grew better at the constant room temperature condition than at the sinusoidal temperature condition. By part-time exposure to dry environments, the fungal growth was reduced (75% and 43% RH) or even inhibited (11% RH). Additional loaded filters were installed in the wind tunnel at room temperature and an RH greater than 95% under one of two air flow test conditions: continuous air flow or air flow only 9 hr/day with a flow rate of 0.7 m
3
/s (filter media velocity 0.15 m/s). Swab tests and a tease mount method were used to detect fungal growth on the filters at day 0, 5, and 10. Fungal growth was detected for both test conditions, which indicates that when temperature and relative humidity are optimum, controlling the air flow alone cannot prevent fungal growth. In real applications where nutrients are less sufficient than in this laboratory study, fungal growth rate may be reduced under the same operating conditions.
The 100 Worst Military Disasters in History is a fascinating collection that educators, students, and historians will all find useful in helping them understand the causes and consequences of the ...most infamous military failures in history. The dynamics of military disaster are equally, if not more, important as understanding how to achieve success on the battlefield. This comprehensive book covers the complete gamut of human history as it tells the compelling stories of the worst military debacles of all time. It covers battles, campaigns, and wars, starting with the ancient Persians and Greeks and finishing with the U.S. conflicts in Afghanistan and Iraq. Not limited to land warfare, however, the book also includes a number of the most disastrous naval engagements and campaigns in world history. The 100 Worst Military Disasters in History opens with a detailed introduction illuminating the role military strategy and politics played in some of the worst battlefield failures throughout history. The entries are augmented with several engaging sidebars related to various military disasters. This eclectic collection includes coverage of many lesser known military disasters such as the Taiping Rebellion, during which 20 times more Chinese died than the number of people killed in the American Civil War.
The U.S. Navy is currently at war on behalf of the United States and its partners in the seas off the coast of Yemen. The nation’s earlier Quasi-War with France (1798–1801) shares many of the same ...attributes with this current conflict. Both involve attacks on neutral shipping and thereby the vital interests of the United States, and both were unprovoked, as the shipping under attack has not violated any international laws or sovereignty. The current conflict traces its origins to both the long-running Yemeni Civil War as well as the more recent Israel-Hamas war. It offers both insight and opportunity for the United States and its maritime partners. Insights reflect key issues involved in protecting maritime shipping in the current environment of high-technology missiles and unmanned aerial systems (UAS, a.k.a. drones), as well as in examining older concepts of sea control such as convoys. Finally, it offers the United States a graphic reminder of the importance of sea power and why the nation has a navy in the first place.
The objective of this study was to quantify body weight changes in German adult populations during the past decades.
Longitudinal analysis of seven cohort studies covering different age ranges ...between 18 and 83 years. Baseline examinations were between 1994 and 2007 and follow-up durations between 4.0 and 11.9 years. For each study, mean change in body weight per year and 10-year change in body mass index (BMI) classification were analyzed. For the middle age group of 45-64 years, meta-analysis was conducted to obtain an overall estimate for Germany.
Among men weight gain was highest in the youngest participants and decreased with advancing age. Among women weight gain was on a stable high level among those younger than 45 years and decreased at older age. Within 10 years, 30-40% of middle-aged participants with normal baseline weight became pre-obese or obese and 20-25% of those with pre-obesity at baseline became obese, whereas >80% of persons who were obese at baseline remained obese over time. The estimated average weight change in adults aged 45-64 years was 0.25 (95% confidence interval (CI): 0.18-0.33) kg/year among men and 0.24 (0.17-0.30) kg/year among women.
We could observe a moderate weight gain over the past years in German middle-aged populations of 0.25 kg/year. Obesity prevention needs to be targeted to specific subgroups in the population, especially to younger adults, who seem to be most vulnerable for gaining weight. Obesity intervention needs to be improved, as the majority of obese adults remained obese over time.
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