Identification of patients with early HR+ HER2- breast cancer at high risk of recurrence

Breast cancer incidence has increased in the last two decades and, simultaneously, survival has improved due to earlier detection andimproved treatment options. Despite this improvement, locoregional recurrences and distant metastases occur in up to 10 and 30% of women diagnosed with early breast cancer, respectively. Around 70% of breastcancers are hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), and associated with a persistent risk of relapse up to 20 years after diagnosis/initial treatment. We conducteda narrative review by combining PubMed searches with our clinical experience to describe patient characteristics, biomarkers, and genomic profiling tools available to clinicians for the identification of patients withHR+, HER2- early breast cancer at high risk of recurrence and to provide recommendations to classify patients into recurrence risk categories. National and international treatment guidelines are also summarised.Accurate assessment of the risk of recurrence in these patients is crucial as the predicted risk guides treatment decisions; imprecise estimations can result in over- or undertreatment, with either scenario having negative consequences for patients. Multiple prognostic tools and factors are recommended for early breast cancer, and no single test provides accurate prognosis in isolation. Since no single test can provide accurate prognosis in isolation, a combination of tools should be used. Risk thresholds are important to guide optimised and balanced therapeutic decisions in HR+, HER2- early breast cancer. However, prognostic assessment should be performed on a case-by-case basis, makingpatient-specific prognostic approaches essential to avoid over- or undertreatment

HybChive - experimental programming framework for heterogeneous architectures

High Performance Architekturen werden immer heterogener. Der Benutzer einer solchen Architektur muss verschiedene Programmiersprachen beherrschen, um alle Computing - Devices parallel nutzen zu können. Oft werden spezialisierte Programmierer beauftragt, Routinen für Teile der Architektur zu entwickeln. Die Thesis gibt zunächst einen kurzen Überblick über Technologien, die sich mit der Programmierbarkeit heterogener Architekturen beschäftigen. Anschließend werden die Anforderungen eines ganzheitlichen Workflows und einer ganzheitlichen Softwarearchitektur definiert, mit deren Hilfe die Software von einem Spezialisten für einen Endanwender entwickelt wird und die ebenfalls stetig für hinzukommende Hardware in einer heterogenen Software - Architektur ergänzt werden kann. Das im Zuge einer experimentellen Herangehensweise entwickelte Framework zielt darauf ab, Teile des Codes, die "embarassingly parallel" sind, anhand individuell gewählter Parameter zu optimieren, zum Beispiel den Datendurchsatz eines Codeteiles. Architekturen, für die das Framework entwickelt wird, bestehen aus einem Single Node mit angehängten Devices, die durch das Framework Daten in Shared Memory Segments gleichzeitig verarbeiten. Darüber hinaus werden Aspekte und Erweiterungen der Softwarearchitektur beschrieben, die ermöglichen, wichtigen Bedürfnissen der beteiligten Akteure in einer solchen Umgebung gerecht zu werden. Akteure sind hier beispielsweise der Endanwender und der Betreuer der Architektur. Mit Hilfe von Experimenten wird die Funktionalität von HybChive demonstriert und mögliche limitierende Aspekte und zukünftige Perspektiven diskutiert. Im Zuge der Arbeit wird ein Prototyp des HybChive - Frameworks entwickelt.High performance architectures become more and more heterogeneous. A user of this architecture has to know different programming languages to use all devices in parallel. Often specialised programmers are asked to develop routines for parts of the architecture. This thesis provides a brief overview at first of technologies that address the programmability of heterogeneous architectures. Afterwards, this thesis defines needs of a holistic workflow and of a holistic software architecture with the help of which software is developed by a specialist for an end user which can be steadily extended for additional hardware in a heterogeneous high performance computing architecture. As an experimental software approach, the developed framework aims at optimising embarrassingly parallel parts of the code referring to individually chosen parameters, for example the throughput of the code. Targeted architectures consist of a single node and attached devices which, by using the framework, process data stored in shared memory segments in parallel. Furthermore, software architectural aspects and extensions will be discovered and described which satisfy major needs of the participating stakeholders in such an environment, such as the user of the code as well as the maintainer of the architecture. With the help of experiments the functionality of HybChive will be demonstrated and possible limiting aspects and future directions will be discussed. The thesis will develop a prototype of the HybChive – framework

Identification of Patients with Early HR+ HER2- Breast Cancer at High Risk of Recurrence

: Breast cancer incidence has increased in the last two decades and, simultaneously, survival has improved due to earlier detection and improved treatment options. Despite this improvement, locoregional recurrences and distant metastases occur in up to 10 and 30% of women diagnosed with early breast cancer, respectively. Around 70% of breast cancers are hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), and associated with a persistent risk of relapse up to 20 years after diagnosis/initial treatment. We conducted a narrative review by combining PubMed searches with our clinical experience to describe patient characteristics, biomarkers, and genomic profiling tools available to clinicians for the identification of patients with HR+, HER2- early breast cancer at high risk of recurrence and to provide recommendations to classify patients into recurrence risk categories. National and international treatment guidelines are also summarised. Accurate assessment of the risk of recurrence in these patients is crucial as the predicted risk guides treatment decisions; imprecise estimations can result in over- or undertreatment, with either scenario having negative consequences for patients. Multiple prognostic tools and factors are recommended for early breast cancer, and no single test provides accurate prognosis in isolation. Since no single test can provide accurate prognosis in isolation, a combination of tools should be used. Risk thresholds are important to guide optimised and balanced therapeutic decisions in HR+, HER2- early breast cancer. However, prognostic assessment should be performed on a case-by-case basis, making patient-specific prognostic approaches essential to avoid over- or undertreatment

Health-Related Quality of Life in MONARCH 2: Abemaciclib plus Fulvestrant in Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer After Endocrine Therapy

BACKGROUND: In the phase III MONARCH 2 study (NCT02107703), abemaciclib plus fulvestrant significantly improved progression-free survival (PFS) versus placebo plus fulvestrant in patients with hormone receptor-positive (HR+), HER2-negative advanced breast cancer (ABC). This study assessed patient-reported pain, global health-related quality of life (HRQoL), functioning, and symptoms. MATERIALS AND METHODS: Abemaciclib or placebo (150 p.o. mg twice daily) plus fulvestrant (500 mg, per label) were randomly assigned (2:1). The modified Brief Pain Inventory, Short Form (mBPI-sf); European Organization for Research and Treatment of Cancer (EORTC) QoL Core 30 (QLQ-C30); and Breast Cancer Questionnaire (QLQ-BR23) assessed outcomes. Data were collected at baseline, cycle 2, every two cycles 3-13, thereafter at every three cycles, and 30 days postdiscontinuation. Longitudinal mixed regression and Cox proportional hazards models assessed postbaseline change and time to sustained deterioration (TTSD) by study arm. RESULTS: On-treatment HRQoL scores were consistently maintained from baseline and similar between arms. Patients in the abemaciclib arm (n = 446) experienced a 4.9-month delay in pain deterioration (mBPI-sf), compared with the control arm (n = 223), and significantly greater TTSD on the mBPI-sf and analgesic use (hazard ratio, 0.76; 95% CI, 0.59-0.98) and QLQ-C30 pain item (hazard ratio, 0.62; 95% CI, 0.48-0.79). TTSD for functioning and most symptoms significantly favored the abemaciclib arm, including fatigue, nausea and vomiting, and cognitive and social functioning. Only diarrhea significantly favored the control arm (hazard ratio, 1.60; 95% CI, 1.20-2.10). CONCLUSION: HRQoL was maintained on abemaciclib plus fulvestrant. Alongside superior PFS and manageable safety profile, results support treatment with abemaciclib plus fulvestrant in a population of patients with endocrine-resistant HR+, HER2-negative ABC. IMPLICATIONS FOR PRACTICE: In MONARCH 2, abemaciclib plus fulvestrant demonstrated superior efficacy and a manageable safety profile for patients with in hormone receptor-positive (HR+), HER2-negative (-) advanced breast cancer (ABC). Impact on health-related quality of life (HRQoL) is important to consider, given the palliative nature of ABC treatment. In this study, abemaciclib plus fulvestrant, compared with placebo plus fulvestrant, significantly delayed sustained deterioration of pain and other patient-reported symptoms (including fatigue, nausea, vomiting), and social and cognitive functioning. Combined with demonstrated clinical benefit and tolerability, the stabilization of patient-reported symptoms and HRQoL further supports abemaciclib plus fulvestrant as a desirable treatment option in endocrine resistant, HR+, HER2- ABC.status: publishe

Second-line Treatment of Stage III/IV Non-Small-Cell Lung Cancer (NSCLC) with pemetrexed in routine clinical practice: Evaluation of performance status and health-related quality of life

<p>Abstract</p> <p>Background</p> <p>Second-line treatment of advanced non-small-cell lung cancer (NSCLC) improves overall survival. There is a lack of data regarding the impact on patients' overall health condition. This prospective, non-interventional study evaluated performance status (PS) and health-related quality of life (HR-QoL) during second-line pemetrexed treatment in routine clinical practice.</p> <p>Methods</p> <p>Stage III/IV NSCLC patients who initiated second-line pemetrexed (standard vitamin and dexamethasone supplementation) were observed for a maximum of 9 treatment cycles. The primary objective was to evaluate the proportion of patients achieving improvement of Karnofsky Index (KI) of ≥ 10% (absolute) or maintaining KI ≥ 80% after the second treatment cycle ("KI benefit response"). HR-QoL was self-rated using the EuroQoL-5D questionnaire (EQ-5D). Factors potentially associated with KI benefit response were evaluated using logistic regression models.</p> <p>Results</p> <p>Of 521 eligible patients (73.5% Stage IV, median age 66.3 yrs, 36.1% ≥ 70 yrs, 62.0% with KI ≥ 80%), 471 (90.4%) completed at least 2 treatment cycles. 58.0% (95%CI 53.6%;62.2%) achieved KI benefit response after the second cycle. Patients with baseline KI ≥ 80%, no Grade 3/4 toxicities during the first 2 cycles, or combination regimen as prior first-line therapy were more likely to achieve a KI benefit response. EQ-5D scores improved over time. Grade 3/4 toxicities were reported in 23.8% of patients (mainly fatigue/asthenia 15.9%, neutropenia 8.7%).</p> <p>Conclusions</p> <p>In this large prospective, non-interventional study of second-line pemetrexed treatment in patients with advanced NSCLC, including 36% elderly patients ( ≥ 70 years), physician-rated PS and self-rated HR-QoL were maintained or improved in the majority of patients.</p> <p>Trial registration</p> <p>Registered on ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00540241">(NCT00540241)</a> on October 4, 2007</p