1,721,068 research outputs found
Afatinib alone or afatinib plus vinorelbine versus investigator's choice of treatment for HER2-positive breast cancer with progressive brain metastases after trastuzumab, lapatinib, or both (LUX-Breast 3): A randomised, open-label, multicentre, phase 2 trial
Full text linkBackground: Patients with advanced HER2-positive breast cancer frequently develop CNS metastases. The metastases that progress after brain radiotherapy and HER2-targeted systemic therapy are a difficult therapeutic challenge. We aimed to assess the efficacy and safety of afatinib, an irreversible blocker of the ErbB protein family, alone or combined with vinorelbine, compared with treatment of the investigator's choice in women with HER2-positive breast cancer with progressive brain metastases during or after treatment with trastuzumab, lapatinib, or both. Methods: We did this randomised, open-label, multicentre, phase 2 trial in 40 hospitals in Canada, Finland, France, Germany, Italy, Spain, South Korea, and the USA. Women older than 18 years with histologically confirmed HER2-overexpressing breast cancer and CNS recurrence or progression as determined by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) during or after treatment with trastuzumab, lapatinib, or both, were eligible. We randomly assigned patients (1:1:1) centrally to afatinib 40 mg orally once per day, afatinib 40 mg per day plus intravenous vinorelbine 25 mg/m2 once per week, or investigator's choice of treatment in cycles of 3 weeks until disease progression, patient withdrawal, or unacceptable toxicity. Treatment assignment was not masked for clinicians or patients, but the trial team was masked until database lock to reduce bias. The primary endpoint, assessed in the intention-to-treat population, was patient benefit at 12 weeks, defined by an absence of CNS or extra-CNS disease progression, no tumour-related worsening of neurological signs or symptoms, and no increase in corticosteroid dose. Safety was assessed in all patients who received at least one dose of a study drug. This completed trial is registered with ClinicalTrials.gov, number NCT01441596. Findings: Between Dec 22, 2011, and Feb 12, 2013, we screened 132 patients, of whom 121 were eligible and randomly assigned to treatment: 40 to afatinib alone, 38 to afatinib plus vinorelbine, and 43 to investigator's choice. All patients discontinued study treatment before the data collection cutoff on Oct 16, 2014. Patient benefit was achieved in 12 (30·0%; 95% CI 16·6-46·5) patients given afatinib alone (difference vs investigator's choice: -11·9% [95% CI -32·9 to 9·7], p=0·37), 13 (34·2%; 19·6-51·4) given afatinib plus vinorelbine (difference vs investigator's choice: -7·6% [-28·9 to 14·2], p=0·63), and 18 (41·9%; 27·0-57·9) given investigator's choice. The most common treatment-related grade 3 or 4 adverse events were diarrhoea (seven [18%] of 40 patients in the afatinib only group vs nine [24%] of 37 patients in the afatinib plus vinorelbine group vs two [5%] of 42 patients in the investigator's choice group) and neutropenia (none vs 14 [38%] vs four [10%]). Interpretation: Patient benefit with afatinib-containing treatments was not different from that in patients given investigator's choice of treatments; however, adverse events were frequent and afatinib-containing treatments seemed to be less well tolerated. No further development of afatinib for HER2-positive breast cancer is currently planned. Funding: Boehringer Ingelheim
Lapatinib and renal impairment: a case report
No full textThis clinical report describes durable control of disease in a postmenopausal patient receiving hemodialysis and letrozole plus lapatinib since the diagnosis of HER2-positive, estrogen receptor-positive liver metastasis from breast cancer after anastrozole plus trastuzumab failure
Progress in the treatment of Early and Advanced Breast Cancer
No full textBreast cancer represents a major health problem with more than 1,000,000 new cases and 370,000 deaths yearly worldwide. In the last decade , in spite of increasing incidence, breast cancer mortality is declining in the majority of developed countries. This is the combined result of better education, widespread screening programmes and more efficacious adjuvant treatments.
The better knowledge of breast cancer biology allows nowadays to spare the cosmetic, physical and psychological consequences of radical mastectomy to the majority of breast cancer patients. The sentinel node technique is rapidly expanding and will further reduce the extent and the consequences of surgery.
Several clinical and pathologic factors are used to discriminate between patients at low (<10%), average (10-40%) and high risk of relapse and international guidelines have been established to help clinicians to choose the appropriate postoperative treatments. Nodal status, tumor size, tumor grade, age, HER2 expression are universally accepted as important factors to define risk categories. Newer factors such as uPA/PAI-1, cyclin-E and other proliferative indices and gene expression profile are promising and will allow a better discrimination between patients at different risk. Their generalized use is however not yet recommended because of lack of reproducibility, necessity of fresh tumor samples, limited data and follow up. Endocrine manipulation with tamoxifen, ovarian ablation or aromatase inhibitors is the preferred option in case of endocrine-responsive tumors. Tamoxifen administered for five years has been considered for may years the standard treatment for postmenopausal patients; tamoxifen plus ovarian ablation is more effective than tamoxifen alone for premenopausal women. Recent data demonstrate that, for postmenopausal patients, the aromatase inhibitors are superior to tamoxifen with a different safety profile. At present time aromatase inhibitors represents the preferred option for postmenopausal patients.
Chemotherapy is the treatment of choice in case of steroid receptor negative tumors. Polychemotherapy is superior to single agents and anthracycline containing regimens are superior to CMF. Six courses of FEC or FAC or the sequential administration of four doses of anthracycline followed by four CMF are the recommended regimens.
New regimens including the taxanes have produced a further improvement in risk reduction and are reasonable therapeutic options. These agents are currently approved for adjuvant therapy in US and European Countries.
Chemotherapy followed by endocrine therapy represents the standard adjuvant treatment of high risk patients with endocrine responsive tumors. For Her2-neu overexpressing tumors, the addition of trastuzumab, a monoclonal antibody directed against the extra-membrane portion of the Her2 receptor, significantly reduced the risk of recurrence and death.
Primary chemotherapy is increasingly used in the treatment of locally advanced and operable breast cancer. The upfront administration of chemotherapy significantly increases the rate of breast conserving surgery and allows an in vivo chemosensitivity testing. A proportion of patients achieve a pathologic complete response and these patients have significantly better long term outcomes.
Twenty-five to forty% of breast cancer patients eventually develop distant metastases. At this stage the disease is incurable, however treatments can assure a significant prolongation of survival, symptomatic control and maintenance of quality of life. In case of hormone receptor positivity and in the absence of visceral, life threatening disease endocrine manipulation is the treatment of choice. Active treatments include tamoxifen, ovarian ablation, aromatase inhibitors, pure antiestrogens and progestins. Aromatase inhibitors are the most active agents, however the choice and the sequence of endocrine therapies is also dictated by prior adjuvant treatment. Chemotherapy has to be preferred in case of receptor negative tumors, acquired resistance to hormones and aggressive visceral disease. Combination regimens are usually associated with higher response rates and sometimes survival prolongation and this approach should be recommended in young patients with good PS and visceral disease. On the contrary single agents have a better tolerability profile and should be the treatment of choice when a careful balance between activity and tolerability is needed. In case of Her2-positive tumors the combination of trastuzumab and chemotherapy is significantly superior to chemotherapy alone both in terms of response rates and survival
Ligaments Reconstruction for Posttraumatic Ulnar Translocation of the Carpus: A Case Report
No full text
Background Posttraumatic ulnar translocation of the carpus, a result of radiocarpal ligament tear is a relatively rare condition that may lead to persistent wrist pain and loss of function.
Case Description We report a case of radiocarpal ligament tear of which we reconstruct it with a vascularized interosseous membrane with 13 years of follow-up.
Literature Review Many treatment options have been proposed for the posttraumatic ulnar translocation, ranging from open repair to partial wrist fusion. However, the long term results have been disappointing.
Clinical Relevance Though this technique of reconstruction is technically demanding, it shows promising long term clinical outcome.</jats:p
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Risposta rapida e duratura a fulvestrant in paziente con malattia metastatica e impegno viscerale
No full textCaso clinico che descrive una paziente in post-menopausa con diagnosi di recidiva linfonodale, polmonare e scheletrica di carcinoma duttale infiltrante a recettori estrogenici positivi, diagnosticata in corso di ormonoterapia adiuvante con inibitore non steroideo dell’aromatasi (in esiti
di mastectomia sinistra e chemio-ormonoterapia adiuvante) e trattata con fulvestrant 500 mg
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
- …
