tbuckley/cabot-search huggingface dataset:
Molecular genetic testing for large genomic deletion and duplication mutations in the <i>BRCA1</i> and <i>BRCA2</i> genes for hereditary breast and ovarian cancer
Authors: R. Wenstrup, T. Judkins, K. Eliason, J. Schoenberger, S. Rajamani, C. A. Frye, L. A. Burbidge, J. T. Trost, A. M. Deffenbaugh, B. B. Roa
Journal: Journal of Clinical Oncology (2007)

10513 Background: Mutations in the BRCA1 and BRCA2 genes are comprised of a majority of mutations that are detectable by sequence analysis, and a minority of large genomic deletion and duplication mutations that are detected by methods different than sequencing. Our laboratory developed and implemented a clinical assay for large rearrangements that we refer to as BART (BRCA1/2 Rearrangement Test). We validated the performance of BART using a completely anonymous large number of breast/ovarian cancer patient samples. We also demonstrated superior performance of BART versus other dosage-sensitive methods including Multiplex Ligation-dependent Probe Amplification (MLPA). Methods: BART utilizes quantitative endpoint polymerase chain reaction (PCR) in a multiplexed fluorescent format. Eleven multiplex PCR reactions were designed to contain two amplicons targeting the promoter region, all coding exons, and flanking regions of BRCA1 and BRCA2. An automated likelihood-based analysis application normalizes target amplicon copy number between BRCA1, BRCA2 and three control genes. Deletions and duplications are identified with a statistical confidence level. Results: Based on clinical and family history criteria, 1,035 patients were identified as severe-risk during the initial months of clinical BART analysis at Myriad Genetic Laboratories. All patients were initially tested for Comprehensive BRACAnalysis which includes BRCA1 and BRCA2 full gene sequencing plus large rearrangement panel testing for 5 recurrent BRCA1 mutations. Among severe-risk patients, 302 (29.2%) were positive for a BRCA1 or BRCA2 mutation by sequencing, 9 (0.9%) were positive by large rearrangement panel testing and an additional 27(2.6%) tested positive by BART for large genomic rearrangements. The total detection rate for deleterious mutations in severe-risk individuals was therefore 32.7%. Conclusions: Our initial clinical data indicate that BART testing is appropriate for high-risk patients identified on the basis of personal and family history criteria. No significant financial relationships to disclose.
ANZ1001 SORBET: Study of estrogen receptor beta and efficacy of tamoxifen, a single arm, phase II study of the efficacy of tamoxifen in triple-negative but estrogen receptor beta-positive metastatic breast cancer.
Authors: Kelly-Anne Phillips, Belinda E. Kiely, Prudence A. Francis, Frances M. Boyle, Stephen B. Fox, Leigh Murphy, Val Gebski, Dianne Frances Lindsay, Robert L. Sutherland, Heath D. Badger, John F. Forbes
Journal: Journal of Clinical Oncology (2012)

TPS1136 Background: Targeted therapies are needed for triple negative breast cancer (BC). ERβ is expressed in at least 20% of triple negative BCs. ERβ binds estrogen and tamoxifen with a similar affinity to ERα. ERβ has 5 isoforms but only ERβ1 is fully functional. ERβ expression has been shown to be significantly associated with improved distant disease free survival and better overall survival in tamoxifen treated ERα negative patients in retrospective studies. This “proof of principle” study will determine the efficacy of tamoxifen in patients with triple negative but ERβ positive metastatic BC. Methods: This single arm phase II study, being conducted by the Australia and New Zealand Breast Cancer Trials Group, has a Simon's 2 stage optimal design. The primary end-point is objective response rate (complete and partial responses). Progression free survival and clinical benefit rate will also be assessed. Eligibility criteria include histologically or cytologically confirmed metastatic triple negative BC (ER and PR absent, HER2 ISH negative or IHC 0 or 1) and measureable disease as per RECIST 1.1. Consenting patients undergo central ERβ testing and confirmation of triple negative status on a metastatic biopsy sample. ERβ positive patients (ERβ1 nuclear staining with Allred score &gt;4) are offered trial participation. To date 12 potentially eligible patients have been screened for ERβ; 4 had Allred score &gt;4 (although 2 of these subsequently proved to be ineligible for the trial), 7 had Allred scores &lt;4 and 1 result is pending. Consenting patients receive tamoxifen 20mg per oral daily until disease progression, unacceptable toxicity or withdrawal of consent. If there are ≥2 responses in the first stage of 28 patients, an additional 38 patients will be accrued. Tamoxifen will be considered worthy of further research if there are ≥6 responses in the total 66 patients recruited. Current accrual is 1. Registered on ANZCTR (12610000506099).
Functional Analysis of the Adrenomedullin Pathway in Malignant Pleural Mesothelioma
Authors: Laurent Greillier, Asma Tounsi, Caroline Berenguer-Daizé, Nadège Dussault, Christine Delfino, Zohra Benyahia, Mylène Cayol, Kamel Mabrouk, Stéphane Garcia, Pierre-Marie Martin, Fabrice Barlesi, L’Houcine Ouafik
Journal: Journal of Thoracic Oncology (2016)
Quality of impact factors of general medical journals
Authors: M. Porta
Journal: BMJ (2003)

Editor—Results of the analysis by Joseph add new data and a remarkable twist to existing knowledge on weaknesses in the accuracy of the data that the Institute for Scientific Information (now part of the Thomson company) uses.1 Although the institute has long struggled to avoid mistakes, the vast amount of data needed to create its products emphasises the importance of more stringent quality checks.2 These controls are impossible to perform by users of the institute's indices and databases, since most users do not have access to the original, raw data—access, for example, to data on which articles were counted to be part of the denominator of the bibliographical “impact factor”.2

The results offered by Joseph are a reminder that the impact factor is often not the scientometric indicator of choice. If you want to know the bibliographical “impact” of a journal then you should first consider looking at the total number of citations received by such a journal (not just those received over the previous two years).2,3 In passing you are likely to avoid the pitfall uncovered by Joseph: the total number of citations received is not much influenced by the “number of items” chosen to compute the bibliographical impact factor.

With increasing access via the internet to the data of the Institute of Scientific Information, more attention is being devoted to the specific number of citations received by each individual article. This will not be a magic bullet,3 but it should further contribute to avoid another intrinsic “weakness” of bibliographical impact factors, for which no one is to blame: they are just the average of a highly skewed distribution; often, 85% of citations received “by a journal” are actually received by about 15% of the articles it published.4 Much of the appeal of impact factors stems precisely from the fact that an average is so simple a measure.2,3 But as scientists we surely can go beyond that.
Neoadjuvant bevacizumab with weekly nab-paclitaxel plus carboplatin followed by doxorubicin plus cyclophosphamide (AC) for triple-negative breast cancer.
Authors: Jessica N. Snider, Robyn R. Young, Lee Steven Schwartzberg, Jeffrey Warren Allen, Yasir Ahmed Javed, Mohammad Jahanzeb, Jasgit C. Sachdev
Journal: Journal of Clinical Oncology (2012)

TPS1137 Background: Triple negative breast cancer (TNBC) predominantly clusters with “basal like” subtype on genomic profiling. Over-expression of Secreted Protein Acidic and Rich in Cysteine (SPARC) has been observed in basal like breast cancer (Charaffe-Jaufrett et al. Oncogene 2006; 2273-84). Endothelial transcytosis of nab- paclitaxel occurs via albumin- gp60 receptor-caveolin 1 interaction. SPARC entraps the albumin resulting in higher intratumoral accumulation, which may explain the increased efficacy of nab-paclitaxel (Desai et al. Translational Oncology 2009; 59-63). Exploiting this mechanism and the dysfunctional BRCA mediated DNA repair in basal tumors, we hypothesize that nab-paclitaxel + the DNA damaging drug carboplatin would produce high response rates in TNBC. Adding bevacizumab may enhance efficacy by blocking angiogenesis. In TNBC, pathologic complete remission (pCR) to neo-adjuvant therapy correlates with better disease-free survival (DFS). We hypothesize that high pCR rates can be achieved for patients with TNBC with this combination translating to an improved DFS than seen historically. Methods: Patients with palpable and operable TNBC ≥ 2 cm are eligible for this single stage phase II trial. pCR (defined as the absence of invasive tumor cells) in the breast is the primary end point, while pCR in the breast + axillary nodes and pCR + near pCR (residual tumor &lt; 5mm) in the breast are secondary end points. 57 evaluable patients are needed, assuming a pCR rate of 25% vs. 40% for the null and alternate hypotheses respectively. 34 patients have been accrued to date. Patients receive carboplatin AUC 6 day 1 and nab-paclitaxel 100mg/m 2 days 1, 8 and 15 of a 28 day cycle for 4 cycles and then dose dense AC for 4 cycles. Bevacizumab is given at 10mg/kg Q 2 weeks with chemotherapy for the first 6 cycles. Surgery and radiation are per institutional standards. Bevacizumab is continued postoperatively to complete 1 year of treatment. A core biopsy for collection of fresh tumor tissue is required prior to the start of study treatment. Blood is collected at baseline, and after 4 and 8 cycles for biomarker analysis. Gene expression profiling will be undertaken for correlation with response.
Bone health among prostate cancer survivors: Long-term follow-up from the Prostate Cancer Outcomes Study (PCOS).
Authors: Alicia Katherine Morgans, Kang-Hsien Fan, Tatsuki Koyama, Peter C. Albertsen, Michael Goodman, Ann S. Hamilton, Richard M. Hoffman, Janet L. Stanford, Antoinette M. Stroup, Christina Louise Derleth, David F. Penson
Journal: Journal of Clinical Oncology (2013)

106 Background: Bone complications of androgen deprivation therapy (ADT) have been described using administrative databases and smaller prospective studies with relatively short follow-up. Prospectively acquired data with long term follow-up are lacking. We assessed the relationship of patient-reported bone health and ADT exposure in a population-based prospective cohort of prostate cancer survivors followed longitudinally for 15 years from diagnosis. Methods: Using PCOS 15 year patient-reported survey data, we identified men with non-metastatic prostate cancer diagnosed from 1994-1995 and followed through 2009-2010. We evaluated subgroups receiving &gt;1 yr, ≤1 yr, and no ADT. We then queried participants regarding the development of osteoporosis, fracture, and use of osteoporosis medications. We assessed the relationship between duration of ADT and bone health outcomes using univariable logistic regression models, and evaluated the association between ADT and osteoporosis medications using multivariable logistic regression adjusted for PSA and geographic location. Results: Among 961 men who completed 15 year surveys, 157 received &gt;1 yr ADT, 120 received ≤1 yr ADT, and 684 did not receive ADT. During the study period, 12 men developed bone metastases and were excluded from the fracture analysis (7 received &gt;1 yr ADT, 2 received ≤1 yr ADT, and 3 did not receive ADT). Men receiving &gt;1 yr ADT were more likely to report osteoporosis (OR 4.29, 95% CI 2.38-7.71) or fracture (OR 1.73, 95% CI 1.04-2.89) than men not receiving ADT. When compared with men not receiving ADT, men receiving &gt;1 yr ADT were more likely to report bone mineral density testing (OR 4.59, 95% CI 3.09-6.83), and bone medication use (OR 3.22, 95% CI 2.19-4.72). Half (50.3%) of men treated for &gt;1 yr ADT reported bone medication use. Among men who reported use of bone medications, 94% reported calcium or vitamin D use and 6% reported bisphosphonate use. Conclusions: Men treated with prolonged ADT (&gt;1 yr) reported higher rates of osteoporosis and fracture at 15 year follow up. Accordingly, they reported more frequent screening and treatment for osteoporosis, with 50% of men receiving prolonged ADT reporting use of bone medications.
A single institution's experience in the use of bevacizumab in advanced non-small cell lung cancer.
Authors: A. M. Schreiber, A. Liekensohn, D. Kadaria, J. W. Allen
Journal: Journal of Clinical Oncology (2010)

e18123 Background: Bevacizumab, a humanized monoclonal anti-VEGF antibody, has demonstrated significant clinical benefit in the first-line treatment of advanced nonsquamous non-small cell lung cancer. However, numerous exclusion factors limit the proportion of patients eligible for bevacizumab. We sought to evaluate the exact proportion of patients eligible or ineligible for bevacizumab in a consecutive series of advanced NSCLC patients in a large academic/private practice, and to characterize the reasons for exclusion or inappropriate usage of bevacizumab. Methods: A retrospective review of all new patients with stage IIIB (wet)/IV lung cancer at UTCI from January 2007 through October 2009 was conducted. Data were abstracted from the EMR. Bevacizumab eligibility criteria were those of ECOG 4599 (Sandler, 2006). University of Tennessee IRB approved. Results: 212 patients were identified of whom 199 were fit for systemic treatment (see Table). 75 patients were bevacizumab eligible, 55 of whom received bevacizumab (73.3%). Of the 20 eligible patients who did not receive bevacizumab, all received either a platinum doublet (16) or erlotinib (4). Only 13 patients (9.5%) met exclusion criteria and received bevacizumab. There was no statistically significant difference in the above groups on the basis of any demographic variables including gender, race, and age. Conclusions: In our cohort, the proportion of patients eligible for bevacizumab was low (35%). Overall, only 68/212 (32%) patients received bevacizumab. The majority of patients at our institution remain either bevacizumab ineligible or were treated with alternative regimens. Despite the survival advantage seen with bevacizumab in ECOG 4599, the majority of NSCLC patients are ineligible and future studies should target this population, either by expanding the eligibility criteria or by using novel agents. Demographics Total (N = 212) Age <65 117 ≥65 95 Sex Male 130 Female 82 Race AA 103 Ca 83 Other/NOS 26 Histology Adenocarcinoma 111 Squamous 75 Large 5 NOS 21 Stage IIIB (wet) 18 IV 194 Bevacizumab eligibility Eligible 75 Ineligible 137 Reasons for ineligibility Squamous histology 75 CNS mets 40 Uncontrolled HTN 1 Significant CV disease 7 Hemoptysis 6 Other 8 No significant financial relationships to disclose.
An update of pemetrexed (P) plus gemcitabine (G) as front-line chemotherapy for patients (pts) with malignant pleural mesothelioma (MPM): A phase II clinical trial
Authors: P. A. Janne, G. R. Simon, C. J. Langer, R. N. Taub, A. Dowlati, P. Fidias, L. P. Bloss, Z. Ye, C. Obasaju, H. L. Kindler
Journal: Journal of Clinical Oncology (2005)

7067 Background: Pemetrexed and Gemcitabine are synergistic in preclinical models. Each agent is active in MPM, but the combination has not been studied in MPM in the phase 2 setting. This study was conducted to determine efficacy in MPM pts. Methods: Gemcitabine 1250 mg/m2 was given over 30 minutes on D 1 and 8, with Pemetrexed 500mg/m2 given over 10 minutes on D 8, immediately before Gemcitabine (Cohort 1); or immediately before Gemcitabine on D 1 (Cohort 2), every 21 days for a maximum of 6 cycles. All pts received folic acid, vitamin B12 and steroid prophylaxis. Conclusions: Pemetrexed plus Gemcitabine is active in MPM and has an acceptable toxicity profile. Administering Pemetrexed on D8 is associated with a higher response rate although the median TTP is similar in both cohorts. Updated toxicity, response, and survival data will be presented. Characteristics/Results Cohort 1 (Pemetrexed D 8) Cohort 2 (Pemetrexed D 1) No. accrued, n 53 43 No. evaluable for response, n 49 30 Gender (M:F) %, (n) 88.7:11.3 (47:6) 81.4:18.6 (35:8) Median age 66.5 (range 36–88) 73 (range 47–86) Pathologic Diagnosis, % Epithelial Mixed Sarcomatoid UnclassifiedOther 67.9% 13.2% 5.7% 13.2% 58.1% 4.7% 16.3% 20.9% Performance Status, % PS 0/1 PS 2 88.7% 9.4% 86.0% 7.0% Adverse Events Gr 3 % of pts Neutropenia 43.4% 47.6% Anemia 3.8% 0% Febrile Neutropenia 7.5% 9.5% Thrombocytopenia 11.3% 2.4% Dyspnea 20.8% 7.1% Fatigue 15.1% 14.3% Nausea 5.7% 2.4% Overall Response Rate (ORR) %, (95%CI) 24.5% (13%–39%) 10.0% (2%–27%) Median Time to Progression, months (95%CI) 4.17 (3.35, 5.39) 7.56 (2.63, -) Complete response, (%) 0 0 Partial response, (%) 12 (24.5%) 3 (10.0%) Stable Disease, (%) 26 (53.1%) 20 (66.7%) Progressive Disease, (%) 11 (22.4%) 7 (23.3%) Disease control rate (ORR + SD), (%) 78% 77% Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Amgen, AstraZeneca, Aventis, Bristol-Myers Squibb, Eli Lilly, Genentech, ImClone, Novartis, Pharmacia, Sanofi Eli Lilly Eli Lilly Amgen, AstraZeneca, Aventis, Bristol-Myers Squibb, Cell Therapeutics, Eli Lilly, Genentech, ImClone, Novartis, Ortho-Biotech, Pfizer, Pharmacia, Sanofi, Schering
Abstract 14841: Energy Drink Exposures in the National Poison Data System: Epidemiology and Clinical Effects
Authors: Steven A Seifert, Kristopher L Arheart, Vivian I Franco, Alvin C Bronstein, Stacy D Fisher, Brandon J Warrick, Sara M Seifert, Steven E Lipshultz
Journal: Circulation (2014)

Introduction:  Energy drinks (ED) are beverages whose stimulant properties are likely linked to their caffeine content, including pharmaceutical caffeine and, in some cases, additional caffeine from natural sources, other additives and, prior to the FDA ban, ethanol. Of particular concern are exposures in children, especially those with underlying cardiac or neurological conditions.   Methods:  This is a retrospective analysis of human exposures to single-substance ED formulations in the National Poison Data System of the American Association of Poison Control Centers from 10/1/10 - 9/30/13.   Results:  There were 10,610 cases of ED exposure, with 5,156 being single-substance exposures with identifiable contents. Over 40% involved unintentional exposures by children    Conclusions:  ED exposures reported to poison centers demonstrate a sizable proportion of pediatric cases, some with serious cardiac and neurological effects. Demographic changes over time may be related to public and professional educational efforts. Observed clinical effects are consistent with known effects of caffeine. Regulatory action has been followed by a decrease in poison center reports of ethanol-containing ED. We recommend improved labeling of caffeine content and continued efforts to decrease pediatric exposures to these products.
Efficacy of an Oral Antiangiogenic Protocol for Advanced Malignancies: A Pilot Study
Authors: W. W. Li, V. W. Li, N. Vasan, E. Kruger, M. Haber, A. S. Adler, S. Yi, C. J. Bonar
Journal: Journal of Clinical Oncology (2005)

3213 Background: Antiangiogenic therapy is a validated approach to cancer, presently relying on an infusional agent specifically targeting VEGF. Oral, multi-targeting strategies are under investigation. We developed protocol OLCAT-007, comprised of 3 oral formulary agents with antiangiogenic/anti-tumor properties: celecoxib (C), tamoxifen (T), and doxycycline (D). A pilot study was conducted in canines with advanced cancers to evaluate tolerability, survival, and quality of life. Methods: C, T, and D inhibited endothelial activity ex vivo and in vivo. Drug doses were metabolically scaled for varying dog weights (C = 25–100 mg; T = 1–5 mg; D = 50–300 mg; all BID). Pet canines with advanced cancer (n = 51; 28 breeds; 26 tumor types) received C+T+D with owner consent and veterinarian supervision at 50 sites. Study criteria included verified tumor histopathology, predicted survival at diagnosis, oral intake ability, routine blood laboratory tests, and clinical documentation of tumor response. Quality of life (QoL) was evaluated using an owner-reported index normalized to objective measures. A subgroup (n=17; 15 breeds) with a spectrum of malignancies (mammary, lung, thyroid, gastric, melanoma, basal cell, nasopharyngeal, perianal, genitourinary, lymphoma) treated for at least 8 weeks were analyzed. Data were obtained via veterinary records, pathology reports, and study forms. Results: OLCAT-007 was well tolerated and QoL was maintained or improved in all subjects. 14/17 dogs maintained or gained weight (+ 3.8% average) after 8 weeks of treatment. Tumor regression (n=4; 25–100% shrinkage), disease stabilization (n=2), and tumor progression (n=5) were observed. Tumor was not measurable in 6 subjects. Survival time increased in 15/16 of treated dogs (actual average survival = 15.6 months vs. average predicted survival = 7.0 months). Conclusions: OLCAT-007 was well tolerated and showed anti-tumor activity against advanced malignancies, resulting in increased survival, tumor response, disease stabilization, and good QoL in spontaneous canine cancers. This oral protocol may have practical application with standard cancer therapies. Based on this pilot study, human evaluation is underway. No significant financial relationships to disclose.
Use hand cleaning to prompt mindfulness in clinic
Authors: Heather M Gilmartin
Journal: BMJ (2016)

In the frenzied environment of clinical practice, we often don’t notice what we’re doing until a problem arises. Shuttling between patients and tasks may feel overwhelming.Whenwe’re hurried it’s easy to lose focus on the task at hand and to become distracted. When we’re not fully engaged in the experience of each step in our day, we may blindly react to events instead of noticing what is occurring and then responding with a focused approach. The act of cleaning hands, a simple yet important task practiced throughout the day, could serve to prompt a time of mindfulness to bring a clinician’s awareness back to the present and allow for moments of clarity, insight, and reflection during a work day. The practice of mindfulness