33 research outputs found
Phase II Trial of Lapatinib for Brain Metastases in Patients With Human Epidermal Growth Factor Receptor 2âPositive Breast Cancer
Purpose: One third of women with advanced human epidermal growth factor receptor 2 (HER-2)âpositive
breast cancer develop brain metastases; a subset progress in the CNS despite standard
approaches. Medical therapies for refractory brain metastases are neither well-studied nor
established. We evaluated the safety and efficacy of lapatinib, an oral inhibitor of epidermal growth
factor receptor (EGFR) and HER-2, in patients with HER-2âpositive brain metastases.
Patients and Methods: Patients had HER-2âpositive breast cancer, progressive brain metastases, prior trastuzumab
treatment, and at least one measurable metastatic brain lesion. Patients received lapatinib 750 mg
orally twice a day. Tumor response was assessed by magnetic resonance imaging every 8 weeks.
The primary end point was objective response (complete response [CR] plus partial response [PR])
in the CNS by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary end points
included objective response in non-CNS sites, time to progression, overall survival, and toxicity.
Results: Thirty-nine patients were enrolled. All patients had developed brain metastases while receiving
trastuzumab; 37 had progressed after prior radiation. One patient achieved a PR in the brain by
RECIST (objective response rate 2.6%, 95% conditional CI, 0.21% to 26%). Seven patients (18%)
were progression free in both CNS and non-CNS sites at 16 weeks. Exploratory analyses identified
additional patients with some degree of volumetric reduction in brain tumor burden. The most
common adverse events (AEs) were diarrhea (grade 3, 21%) and fatigue (grade 3, 15%).
Conclusion: The study did not meet the predefined criteria for antitumor activity in highly refractory patients
with HER-2âpositive brain metastases. Because of the volumetric changes observed in our
exploratory analysis, further studies are underway utilizing volumetric changes as a primary end
point
Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world
Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic.
Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality.
Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States.
Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis.
Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers âŒ99% of the euchromatic genome and is accurate to an error rate of âŒ1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
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Metastatic Breast Cancer With ESR1 Mutation: Clinical Management Considerations From the Molecular and Precision Medicine (MAP) Tumor Board at Massachusetts General Hospital
The last decade in oncology has witnessed impressive response rates with targeted therapies, largely because of collaborative efforts at understanding tumor biology and careful patient selection based on molecular fingerprinting of the tumor. Consequently, there has been a push toward routine molecular genotyping of tumors, and large precision medicine-based clinical trials have been launched to match therapy to the molecular alteration seen in a tumor. However, selecting the âright drugâ for an individual patient in clinic is a complex decision-making process, including analytical interpretation of the report, consideration of the importance of the molecular alteration in driving growth of the tumor, tumor heterogeneity, the availability of a matched targeted therapy, efficacy and toxicity considerations of the targeted therapy (compared with standard therapy), and reimbursement issues. In this article, we review the key considerations involved in clinical decision making while reviewing a molecular genotyping report. We present the case of a 67-year-old postmenopausal female with metastatic estrogen receptor-positive (ER+) breast cancer, whose tumor progressed on multiple endocrine therapies. Molecular genotyping of the metastatic lesion revealed the presence of an ESR1 mutation (encoding p.Tyr537Asn), which was absent in the primary tumor. The same ESR1 mutation was also detected in circulating tumor DNA (ctDNA) extracted from her blood. The general approach for interpretation of genotyping results, the clinical significance of the specific mutation in the particular cancer, potential strategies to target the pathway, and implications for clinical practice are reviewed in this article. Key Points ER+ breast tumors are known to undergo genomic evolution during treatment with the acquisition of new mutations that confer resistance to treatment. ESR1 mutations in the ligand-binding domain of ER can lead to a ligand-independent, constitutively active form of ER and mediate resistance to aromatase inhibitors. ESR1 mutations may be detected by genomic sequencing of tissue biopsies of the metastatic tumor or by sequencing the circulating tumor cells or tumor DNA (ctDNA). Sequencing results may lead to a therapeutic âmatchâ with an existing FDA-approved drug or match with an experimental agent that fits the clinical setting
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Nonviolent communication training and empathy in male parolees.
The purpose of this study was to determine the impact of a behavioral intervention, nonviolent communication (NVC), on the development of empathic coping and communication skills in a sample of male parolees enrolled in substance abuse treatment (SAT; N = 30). At the end of the 8-week intervention, results revealed a significant increase (p = .01) in participants' empathy levels. Findings also revealed the acceptability and utility of NVC training to men on parole. Results suggest that NVC training may (a) be a useful addition to substance abuse treatment programs for parolees, (b) be effective in addressing problematic coping and communication styles resulting from incarceration and criminal behavior, and (c) assist paroled individuals in building and sustaining positive social support networks
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Nonviolent communication training and empathy in male parolees.
The purpose of this study was to determine the impact of a behavioral intervention, nonviolent communication (NVC), on the development of empathic coping and communication skills in a sample of male parolees enrolled in substance abuse treatment (SAT; N = 30). At the end of the 8-week intervention, results revealed a significant increase (p = .01) in participants' empathy levels. Findings also revealed the acceptability and utility of NVC training to men on parole. Results suggest that NVC training may (a) be a useful addition to substance abuse treatment programs for parolees, (b) be effective in addressing problematic coping and communication styles resulting from incarceration and criminal behavior, and (c) assist paroled individuals in building and sustaining positive social support networks