Independent validation of the PAM50-based chemo-endocrine score (CES) in hormone receptor-positive HER2-positive breast cancer treated with neoadjuvant anti-HER2-based therapy

Purpose: We do not yet have validated biomarkers to predict response and outcome within hormone receptor-positive/HER2-positive (HR+/HER2+) breast cancer. The PAM50-based chemoendocrine score (CES) predicts chemo-endocrine sensitivity in hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer. Here, we evaluate the relationship of CES with response and survival in HRþ/HER2þ breast cancer. Experimental Design: Intrinsic subtype and clinicopathologic data were obtained from seven studies in which patients were treated with HER2-targeted therapy either with endocrine therapy (ET) or with chemotherapy (CTX). CES was evaluated as a continuous variable and categorically from low to high scores [CES-C (chemo-sensitive), CES-U (uncertain), and CES-E (endocrine-sensitive)]. We first analyzed each dataset individually, and then all combined. Multivariable analyses were used to test CES association with pathologic complete response (pCR) and disease-free survival (DFS). Results: A total of 457 patients were included (112 with ET and 345 with CTX). In the combined cohort, CES-C, CES-U, and CES-E were identified in 60%, 23%, and 17% of the patients, respectively. High CES (i.e., CES-E) was associated with a lower probability of achieving pCR independently of clinical characteristics, therapy, intrinsic subtype, and study (adjusted OR ¼ 0.42; P ¼ 0.016). A total of 295 patients were analyzed for DFS with a median follow-up of 66 months. High CES was also associated with better DFS (adjusted HR, 0.174; P ¼ 0.003) independently of pCR, clinical characteristics and intrinsic subtype. In patients with residual disease, the adjusted DFS HR of CES was 0.160 (P ¼ 0.012). Conclusions: In HER2þ/HRþ breast cancer, CES is useful for predicting chemo-endocrine sensitivity and provides additional prognostication beyond intrinsic subtype and clinicopathologic characteristics

Planck early results II : The thermal performance of Planck

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Planck pre-launch status : The Planck mission

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Planck early results. II. The thermal performance of Planck

The performance of the Planck instruments in space is enabled by their low operating temperatures, 20 K for LFI and 0.1 K for HFI, achieved through a combination of passive radiative cooling and three active mechanical coolers. The scientific requirement for very broad frequency coverage led to two detector technologies with widely different temperature and cooling needs. Active coolers could satisfy these needs; a helium cryostat, as used by previous cryogenic space missions (IRAS, COBE, ISO, Spitzer, AKARI), could not. Radiative cooling is provided by three V-groove radiators and a large telescope baffle. The active coolers are a hydrogen sorption cooler (<20 K), a 4He Joule-Thomson cooler (4.7 K), and a 3He-4He dilution cooler (1.4 K and 0.1 K). The flight system was at ambient temperature at launch and cooled in space to operating conditions. The HFI bolometer plate reached 93 mK on 3 July 2009, 50 days after launch. The solar panel always faces the Sun, shadowing the rest of Planck, and operates at a mean temperature of 384 K. At the other end of the spacecraft, the telescope baffle operates at 42.3 K and the telescope primary mirror operates at 35.9 K. The temperatures of key parts of the instruments are stabilized by both active and passive methods. Temperature fluctuations are driven by changes in the distance from the Sun, sorption cooler cycling and fluctuations in gas-liquid flow, and fluctuations in cosmic ray flux on the dilution and bolometer plates. These fluctuations do not compromise the science data

Operating a full tungsten actively cooled tokamak: overview of WEST first phase of operation

WEST is an MA class superconducting, actively cooled, full tungsten (W) tokamak, designed to operate in long pulses up to 1000 s. In support of ITER operation and DEMO conceptual activities, key missions of WEST are: (i) qualification of high heat flux plasma-facing components in integrating both technological and physics aspects in relevant heat and particle exhaust conditions, particularly for the tungsten monoblocks foreseen in ITER divertor; (ii) integrated steady-state operation at high confinement, with a focus on power exhaust issues. During the phase 1 of operation (2017–2020), a set of actively cooled ITER-grade plasma facing unit prototypes was integrated into the inertially cooled W coated startup lower divertor. Up to 8.8 MW of RF power has been coupled to the plasma and divertor heat flux of up to 6 MW m−2 were reached. Long pulse operation was started, using the upper actively cooled divertor, with a discharge of about 1 min achieved. This paper gives an overview of the results achieved in phase 1. Perspectives for phase 2, operating with the full capability of the device with the complete ITER-grade actively cooled lower divertor, are also described

High heat flux testing of EU tungsten monoblock mock-ups for the ITER divertor

With the aim to assess the option to start the ITER operation with a full tungsten divertor, an R&D program was launched in order to evaluate the performances of tungsten (W) armoured plasma facing components (PFCs) under high heat flux. The F4E program consisted in the manufacturing and high heat flux (HHF) testing of W monoblock mock-ups and medium scale prototypes up to 20 MW/m2. During the test campaign, 26 W mock-ups and two medium scale prototypes manufactured by Plansee SE (Austria) and by Ansaldo Nucleare (Italy) have been tested at the FE200 (AREVA, Le Creusot, France) and ITER Divertor Test Facility (IDTF) (Efremov Institute Saint Petersburg, Russian Federation) electron beam test facilities. The high heat flux (HHF) testing program foresaw the performance of 5000 cycles at 10 MW/m2 and 300 + 700 cycles at 20 MW/m2, 10 s power on and 10 s dwell time with ITER relevant hydraulic parameters.The test results fulfilled the ITER qualification requirements, although a few items did not sustain the extended test program (additional 700 cycles at 20 MW/m2), the analysis of the results gave indications on potential improvements, in particular concerning the W material itself with the objective to remove the self-castellation of the W monoblocks and concerning the thermo-mechanical fatigue performances of the CuCrZr heat sink. In addition, some critical heat flux experiments, whose results confirmed those previously obtained were also performed

Direct measurement of total emissivities at cryogenic temperatures: Application to satellite coatings

International audienceThis paper presents a direct measurement method for optical properties of different materials at cryogenic temperatures from 20 K to 200 K. It has been developed within the framework of the design of Planck program. Planck is a satellite of the European Space Agency (ESA) that will be launched in 2008. The scientific goal of the Planck mission is to make observations of the temperature anisotropy and polarisation of the Cosmic Microwave Background. The equivalent temperature of the observed radiation is about 3 K and the telescope baffle temperature should not exceed 60 K in order to work properly. The large Planck telescope is passively cooled by radiating to the Deep Space, so that a good knowledge of the thermo-optical properties of its coating is of utmost importance for thermal modelling. However, up to now, few measurements have been done at such low temperatures. We derived a direct measurement method for the total directional emissivity of various coatings of interest for satellites applications. The effective spectral range chosen the measurements covers 6–800 μm. We will describe the design of the measurement apparatus and present results for several coatings

Qualification and Post-Mortem Characterization of Tungsten Mock-ups Exposed to Cyclic High Heat Flux Loading

In order to evaluate the option to start the ITER operation with a full tungsten (W) divertor, high heat flux tests were performed in the electron beam facility FE200, Le Creusot, France. Thereby, in total eight small-scale and three medium-scale monoblock mock-ups produced with different manufacturing technologies and different tungsten grades were exposed to cyclic steady state heat loads. The applied power density ranges from 10 to 20 MW/m2 with a maximum of 1000 cycles at each particular loading step. Finally, on a reduced number of tiles, critical heat flux tests in the range of 30 MW/m2 were performed.Besides macroscopic and microscopic images of the loaded surface areas, detailed metallographic analyses were performed in order to characterize the occurring damages, i.e., crack formation, recrystallization, and melting. Thereby, the different joining technologies, i.e., hot radial pressing (HRP) vs. hot isostatic pressing (HIP) of tungsten to the Cu-based cooling tube, were qualified showing a higher stability and reproducibility of the HIP technology also as repair technology. Finally, the material response at the loaded top surface was found to be depending on the material grade, microstructural orientation, and recrystallization state of the material. These damages might be triggered by the application of thermal shock loads during electron beam surface scanning and not by the steady state heat load only. However, the superposition of thermal fatigue loads and thermal shocks as also expected during ELMs in ITER gives a first impression of the possible severe material degradation at the surface during operational scenarios at the divertor strike point

Everolimus plus exemestane in hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer: incidence and time course of adverse events in the phase IIIb BALLET population.

BACKGROUND: The addition of everolimus to exemestane therapy significantly improves progression-free survival in postmenopausal patients with hormone-receptor (HR)-positive HER2-negative endocrine-resistant breast cancer. However, the safety profile of this schedule still might be optimized. METHODS: Patients included in the BALLET trial were assessed. The objectives of this analysis were to provide additional information on the safety profile of this schedule depending on prior anticancer therapies and to characterize the time course of adverse events (AEs) and serious AEs (SAEs) of clinical interest throughout the study period. Non-infectious pneumonitis (NIP), stomatitis, asthenia and weight loss were selected as AEs of clinical interest. RESULTS: The safety population of this analysis comprised 2131 patients. There were similar incidences of AEs and SAEs of clinical interest regardless of previous anticancer therapies. Most stomatitis and asthenia events occurred within the first three months. Incidence of weight loss appeared to plateau except in the case of grade 3-4 events, which occurred rarely. The incidence of any grade NIP (between 2 to 6%) and grade 3-4 NIP (between 0 to 1%) was low across the study, but steady. CONCLUSIONS: Everolimus plus exemestane is a well-known therapeutic option for aromatase inhibitor pretreated advanced breast cancer patients, and its toxicity profile is similar to that described in previous studies. Close monitoring, especially within the first three months, early intervention with preventive measures and patient education to help recognize the first signs and symptoms of AEs, will help to reduce their incidence and severity.status: publishe