tbuckley/cabot-search huggingface dataset:
A 5-Day Cytoreductive Chemotherapy Followed By Haplo-Identical HSCT (FA5-Bucy) As a Tumor-Ablative Regimen Improved the Survival of Patients with Advanced Hematological Malignancies
Authors: Ting Yang, Jinhua Ren, Qiaoxian Lin, Xiaohong Yuan, Xiaofeng Luo, Tingbo Liu, Xiaoyun Zheng, Zhizhe Chen, Jianda Hu
Journal: Blood (2016)
PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT): A Pilot Study.
Authors: Ellen McDonald, Germain Poirier, Paul Hebert, Joe Pagliarello, Graeme Rocker, Stephane Langevin, Francois LeBlanc, Geeta Mehta, Yoanna Skrobik, Robert Fowler, John Granton, Andreas Freitag, Graham Jones, Jamie Cooper, Maureen Meade, Gordon Guyatt, David Anderson, Bill Geerts, Mark Crowther, Nicole Zytaruk, Lauren Griffith, Deborah Cook
Journal: Blood (2004)
Safety and efficacy of first-line irinotecan/fluoropymidine combinations in mCRC patients &gt;65 years compared with those ≤65: The BICC-C study
Authors: J. Barrueco, J. Marshall, E. Mitchell, R. Wierzbicki, V. Ganju, M. Jeffery, J. Schultz, D. Richards, R. Soufi-Mahjoubi, C. Fuchs
Journal: Journal of Clinical Oncology (2007)

4076 Background: BICC-C was a multicenter, randomized study that assessed efficacy &amp; safety of irinotecan/fluoropyrimidines combinations in previously untreated mCRC patients. This study showed that FOLFIRI or FOLFIRI+bev were superior to their comparators (Proc ASCO 2006). We conducted a secondary analysis of efficacy &amp; safety among all patients &gt;65 years compared with those =65. Methods: Pts were randomized to: infusional FOLFIRI, modified bolus IFL (mIFL), or CapeIri; and concurrent celecoxib or placebo in a double-blind fashion. The protocol was amended in April 2004 and bevacizumab (bev) was added to the FOLFIRI and mIFL arms whereas CapeIri was discontinued. Period 1 (P1) and Period 2 (P2) designate subjects enrolled before or after the amendment. Results: Of 430 pts enrolled in P1, 150 were age &gt;65 (median 71; range, 66–87) and 280 were = 65 (median, 56; 20–65). Of 117 pts in P2, 75 were &gt;65 (median, 73; 66–84) and 42 were = 65 (median, 54; 32–65). No significant differences in efficacy or safety were observed between the two age groups. Results for P1: median progression free survival (PFS) was 6.5 and 6.7 mos; and median overall survival (OS) was 18.8 and 19.2 for &gt;65 and =65, respectively. For the FOLFIRI regimen specifically median PFS was 7.5 and 7.6 mos, and median OS was 20.1 and 24.3 mos for &gt;65 and =65, respectively. Results for P2: median PFS was 10.3 and 10.6 mos; and median OS was 19.8 and 23 mos for &gt;65 and =65, respectively. For the FOLFIRI+bev regimen specifically median PFS was 11.1 and 11.2 mos for &gt;65 and =65 respectively, and median OS has not yet been reached for either subgroup at time of analysis. Common grade = 3 AEs are listed below. Conclusions: Efficacy and safety for first line irinotecan/fluoropyrimidine regimens and for FOLFIRI &amp; FOLFIRI+bev, specifically, did not differ for older and younger mCRC patients. [Table: see text] [Table: see text]
Open-label, multicenter safety study of vemurafenib in patients with <i>BRAF<sup>V600</sup></i> mutation–positive metastatic melanoma.
Authors: James M. G. Larkin, Michele Del Vecchio, Paolo Antonio Ascierto, Jacob Schachter, Claus Garbe, Bart Neyns, Mario Mandala, Paul Lorigan, Wilson H Miller, Alexander David Guminski, Carola Berking, Piotr Rutkowski, Paola Queirolo, Axel Hauschild, Ana Maria Arance, Michael Paul Brown, Lada Mitchell, Maria Luisa Veronese, Christian U. Blank
Journal: Journal of Clinical Oncology (2013)

9046 Background: Vemurafenib (VEM), a BRAF kinase inhibitor, has demonstrated high response rates and improved progression-free and overall survival in pts with BRAF V600 mutation–positive metastatic melanoma (mM). We present interim results from predefined subgroups from a large multicenter, open-label safety study of VEM in pts with mM (NCT01307397). Methods: Pts with BRAF V600 mutation–positive histologically confirmed mM received VEM (960 mg BID) as first-line therapy or subsequent to previous therapies. Assessments for safety and efficacy were made every 28 days. Results: As of Feb 29, 2012, 2,265 pts have received VEM. Pts had a median age of 54.0 (13-95) yrs and median time since diagnosis of mM of 6.2 (0-351.9) mos. 59% had received prior systemic therapy. Median time of exposure to VEM as of the cut-off date was 3 (0.03-11.24) mos for the overall population and majority of subgroups, and approximately 2.5 mos for pts with ECOG ≥2 and age ≥75 yrs. 1537 (68%) pts were still receiving VEM at the cut-off date. 728 (32%) pts discontinued, most frequently because of PD (538/728 pts; 74%). Adverse events (AEs) were reported for 87% of all patients, with arthralgia (32%) and rash (26%) the most frequent. The incidences of AEs in the subgroups are summarized (Table). Although efficacy analyses are limited by the short duration of follow-up, six-month OS rate was 76% (95% CI 72-79%) and median PFS was 4.1 mos (95% CI 3.9-4.5 mos). Postbaseline tumor assessments were available for 63% and 30% of pts at wk 8 and 16, respectively. At wk 8 CR: 2%, PR: 57%, SD: 30%, PD: 6%. At wk 16 CR: 3%, PR: 46%, SD: 31%, PD: 15%. Conclusions: Although the overall safety profile of VEM in this study was consistent with previous clinical data, interim analyses of subgroups suggest that very elderly pts may be at higher risk of G3 AEs. Clinical trial information: NCT01307397. [Table: see text]
IDENTIFYING THE ETIOLOGIES AND TRENDS OF 30 DAY READMISSIONS IN HEART FAILURE WITH PRESERVED EJECTION FRACTION (HFPEF) PATIENTS: A NATIONAL POPULATION-BASED COHORT STUDY
Authors: Hafeez Hassan, Shilpkumar Arora, Saman Setareh-Shenas, Nilay Patel, Robert Kornberg, Umesh Gidwani
Journal: Journal of the American College of Cardiology (2017)
Sleep problems and increased risk of mortality in the context of advanced cancer.
Authors: Kevin P Collins, David A. Geller, J. Wallis Marsh, Kevin H Kim, Allan Tsung, Thomas Kamarck, Anna Green, Lesenia Santiago, Karlie Kirk, Chanelle Labash, Weijing Sun, Daniel Buysse, Jennifer Lynne Steel
Journal: Journal of Clinical Oncology (2014)

9649 Background: Sleep problems have been linked to increased mortality in the general population. The prevalence of sleep problems in those diagnosed with cancer is even higher than the general population. The aims of the proposed study were to examine the type and prevalence sleep problems, and to determine whether sleep problems are associated with survival, in advanced cancer patients. Methods: The study was prospective in design. A total of 355 patients with advanced cancers (stage III and IV) affecting the hepatobiliary and pancreatic systems were administered a battery of questionnaires including the Pittsburgh Sleep Quality Index (PSQI) and the Center for Epidemiological Studies-Depression (CES-D) scale. Descriptive statistics, Mann Whitney U test, and Cox regression analyses were performed to test the aims. Results: The majority of patients were male (64%) and the mean age 62 years (SD=11). Fifty-nine percent of patients reported poor sleep quality (PSQI > 5); 43% reported sleeping <6 hours and 2% > 10 hours; 27% reported sleep latency greater than 30 minutes for 3 or more nights per week; 80% reported poor sleep efficiency (less than 85% time in bed spent sleeping); and 19% reported taking a sleep aid 3 or more times per week. Fifty-eight percent of patients reported clinically significant levels of depression (CES-D >16) and those with clinically significant depressive symptoms reported shorter sleep duration (median=6) than those without clinical levels of depression (median=7; p=0.02). Median survival for the entire sample was 7.6 months. After adjusting for factors known to contribute to survival (i.e., age, gender, vascular invasion, depression, and snoring), a curvilinear relationship was observed between sleep duration and mortality (Chi-square=27.8, p=<0.001). Conclusions: Consistent with findings in the general population, a curvilinear relationship between sleep duration and mortality was observed in advanced cancer patients.
Predictors of complications following prostate brachytherapy
Authors: A. B. Chen, A. V. D’Amico, B. A. Neville, C. C. Earle
Journal: Journal of Clinical Oncology (2006)

6021 Background: Prior studies on complications from prostate brachytherapy have reported on single institution experiences. We assessed the prevalence and predictors of complications following brachytherapy for prostate cancer on a population basis. Methods: We analyzed the claims of Medicare-enrolled men over age 65 living in SEER surveillance areas diagnosed with locoregional prostate cancer from 1991–1999 who underwent brachytherapy as initial treatment. Two-year complications were identified using Medicare diagnosis and procedure codes from the time of brachytherapy through 2001. Results: We identified 6,879 men who had brachytherapy as initial treatment for locoregional prostate cancer, 5,682 of whom had at least two years follow-up. Of these patients, 54.63% had at least one diagnosis or procedure associated with rectal, urinary, or erectile dysfunction, and 14.33% underwent at least one invasive surgical procedure for treating bowel, urinary, or erectile morbidity within two years of brachytherapy. 10.30% of men had procedures for urinary obstruction, 0.18% had procedures for urinary incontinence, 0.77% had rectal procedures, and 4.08% had invasive procedures for erectile dysfunction. Predictors of two-year complication procedures on multivariable analysis are shown in the Table . Conclusions: A significant proportion of men have diagnoses associated with rectal, urinary, or erectile morbidity following prostate brachytherapy. Though procedures for urinary obstruction are common following brachytherapy, invasive interventions for rectal complications, urinary incontinence, and erectile dysfunction are rare. Procedures for complications following brachytherapy appear to have declined over the 1990s. [Table: see text] No significant financial relationships to disclose.
Use of RAS pathway activation or KRAS mutation status to predict cetuximab response in CRC patient-derived xenografts.
Authors: Henry Li, Dawei Chen, Sheng Guo, Jie Cai, Yiyou Chen, Jean-Pierre Wery
Journal: Journal of Clinical Oncology (2013)

3544 Background: Cetuximab was approved for treating EGFR-expressing metastatic colorectal carcinoma (mCRC) without patient stratification. Subsequent retrospective clinical studies resulted in an exclusion criterion for patients with KRAS mutations at codons 12 and 13. However, only a fraction of patients with wtKRAS benefit from the treatment. Recent analyses indicated that patients with KRAS mutation at codon 13 can also benefit. We set out to investigate whether KRAS mutations, or any other factors, are good biomarkers for CRC-cetuximab therapy patient stratification. Methods: We have established patient derived xenografts (PDX) from treatment-naive Asian CRC patients to discover biomarker predictive of cetuximab response. We conducted a clinical trial style study (“patient avatar trial”) of cetuximab using a randomly selected cohort of 26 EGFR+ PDXs. The antitumor activities were analyzed against KRAS mutation status and a published expression-signature. Results: We identified 12/26 (~46%) as cetuximab responders and 14/26 non-responders (defined by 50% tumor growth inhibition threshold). All 14 non-responders are mutated for one or more of KRAS, BRAF (V600E), EGFR, AKT and PIK3CA oncogenes. In contrast, 5/11 responders analyzed are wild-type for all these genes. Importantly, 5/11 responders have activating KRAS mutations at codons 12/13, contradictory to the currently practiced clinical exclusion criteria, but consistent with more recent clinical findings. Most interestingly, the observed cetuximab activity in this cohort of 26 PDXs has a surprisingly strong correlation to a published RAS pathway score. Conclusions: Our results indicated strong predictive power of cetuximab-CRC-PDX trial and RAS signature, and warrant prospective clinical studies for further confirmation.
CpG Oligonucleotide (1018 ISS) May Overcome Rituximab (R) Resistance in Follicular Lymphoma (FL) through Enhanced ADCC, T Cell Expansion, and Alteration of Tumor Microenvironment.
Authors: Jonathan W. Friedberg, Jennifer Kelly, Jeffrey L. Kutok, Rabih Salloum, Thomas Brenn, David C. Fisher, Elizabeth Ronan, Mary McCauley, Lynn Rich, Diana Marquis, Paul G. Rothberg, Jane Liesveld, Richard I. Fisher, Robert Coffman, Tim Mosmann, Arnold S. Freedman
Journal: Blood (2005)
New Pathogenetic Insights Into Classical Hodgkin Lymphoma Revealed by Gene Expression Profiling of Microdissected Hodgkin/Reed-Sternberg Cells.
Authors: Enrico Tiacci, Verena Brune, Susan Eckerle, Wolfram Klapper, Ines Pfeil, Claudia Döring, Brunangelo Falini, Carel van Noesel, Gunhild Mechtersheimer, Andreas Bräuninger, Martin Leo Hansmann°, Ralf Küppers
Journal: Blood (2009)
A phase II trial of epothilone B analogue BMS-247550 (NSC #710428) in patients with advanced pancreas cancer: A Southwest Oncology Group Study
Authors: R. P. Whitehead, S. A. McCoy, S. E. Rivkin, H. M. Gross, M. E. Conrad, J. L. Abbruzzese
Journal: Journal of Clinical Oncology (2004)

4012 Background: Advanced metastatic pancreatic cancer has a poor prognosis and short median survival with standard therapy. BMS-247550 is a semi-synthetic analog of the natural product epothilone B and has a mode of action similar to the taxanes but has activity in model systems resistant to paclitaxel. Methods: Patients were required to have a pathologic diagnosis of pancreatic adenocarcinoma with distant metastatic disease or recurrent disease that was not resectable. Prior surgery or palliative radiation therapy was allowed but patients could not have received prior chemotherapy or chemoradiation therapy. Zubrod performance status of 0 or 1, and adequate hematologic, hepatic and renal function was required. BMS-247550 was given at a dose of 40 mg/m2 IV over 3 hours every 21 days. The study was designed with a primary endpoint of six-month survival, with a true six-month survival of 55% or greater judged important for further consideration of this regimen. Results: Sixty eligible patients were registered to the study with a median age of 60 years. Sixty percent were male. The estimated six-month survival is 59% (95% CI 46% to 71%) with a median survival of 6.9 months and a median time to treatment failure of 3.3 months. Of 54 patients with measurable disease, there were 4 confirmed partial responses, 7%, (95% CI 2%–18%), and 5 unconfirmed partial responses, 9%, for an overall response probability of 16% (95%CI 8%–29%). The most common grade 3 and 4 toxicities were neutropenia, leukopenia, nausea, vomiting, neuropathy and fatigue. There was one death, cause not determined, possibly related to treatment. Conclusions: The epothilone B analogue BMS-247550 shows activity in patients with metastatic or recurrent pancreatic cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration SuperGen SuperGen SuperGen
Bleeding Tendency and Impaired Platelet Function In a Patient Carrying a Heterozygous Mutation In Thromboxane A2 Receptor
Authors: Tsuyoshi Kamae, Kazunobu Kiyomizu, Tsuyoshi Nakazawa, Seiji Tadokoro, Shigenori Honda, Hirokazu Kashiwagi, Yuzuru Kanakura, Yoshiaki Tomiyama
Journal: Blood (2010)
The Multipartite Mitochondrial Genome of Enteromyxum leei (Myxozoa): Eight Fast-Evolving Megacircles
Authors: Dayana Yahalomi, Michal Haddas-Sasson, Nimrod D. Rubinstein, Tamar Feldstein, Arik Diamant, Dorothée Huchon
Journal: Molecular Biology and Evolution (2017)

Myxozoans are a large group of poorly characterized cnidarian parasites. To gain further insight into their evolution, we sequenced the mitochondrial (mt) genome of Enteromyxum leei and reevaluate the mt genome structure of Kudoa iwatai. Although the typical animal mt genome is a compact, 13-25 kb, circular chromosome, the mt genome of E. leei was found to be fragmented into eight circular chromosomes of ∼23 kb, making it the largest described animal mt genome. Each chromosome was found to harbor a large noncoding region (∼15 kb), nearly identical between chromosomes. The protein coding genes show an unusually high rate of sequence evolution and possess little similarity to their cnidarian homologs. Only five protein coding genes could be identified and no tRNA genes. Surprisingly, the mt genome of K. iwatai was also found to be composed of two chromosomes. These observations confirm the remarkable plasticity of myxozoan mt genomes.
FIRST REPORT OF CLINICAL OUTCOMES WITH THE NEXT-GENERATION LOTUS EDGE VALVE SYSTEM: RESULTS FROM THE LOTUS EDGE FEASIBILITY TRIAL
Authors: Darren Walters, Robert Gooley, O. Christopher Raffel, Liam M. McCormick, Anne Cornaille, Dominic J. Allocco, Ian Meredith
Journal: Journal of the American College of Cardiology (2017)
Imatinib’s Potential Effects on Fertility, Immunity and Pulmonary Function: A Prospective Study in Patients with Previously Untreated CML.
Authors: John Francis Seymour, Andrew Grigg, John Reynolds, Jane Matthews, Anthony P. Schwarer, Richard Herrmann, Kerry McDonald Taylor, Mark S. Hertzberg, Anthony Mills, Nancy Guzzo-Pernell, Michael Copeman, Kevin Lynch, Timothy Hughes
Journal: Blood (2004)
Prevalence of mutations in a panel of breast cancer susceptibility genes in patients with early onset breast cancer.
Authors: Kara Noelle Maxwell, Bradley Wubbenhorst, Bradley Garman, Kurt P D'Andrea, Katherine Rathbun, Jessica Long, Jacquelyn Powers, Jill Stopfer, Angela R. Bradbury, Angela DeMichele, Susan M. Domchek, Katherine L. Nathanson
Journal: Journal of Clinical Oncology (2014)

1510 Background: Approximately 5-10% of breast cancers are attributable to inherited single gene mutations. Clinical testing for germline variation in multiple cancer susceptibility genes is available using massively parallel sequencing. However, data is needed on the spectrum of mutations and variants of uncertain significance (VUSs) in defined patient populations. Methods: We performed massively parallel sequencing using targeted capture of 19 cancer susceptibility genes in 277 BRCA1/2 negative patients with early onset breast cancer (EOBC). Results: Excluding synonymous variants, 60% of patients were identified to have at least one rare variant. Twenty-eight patients (10%) were found to have a pathogenic mutation (Class 5 variant) or likely deleterious VUS (Class 4). Seven of these patients (2.5% overall) were found to have Class 4/5 variants in genes for which clinical guidelines exist for management, namely TP53 (4), CDKN2A (1) and MSH2 (2). Twenty-one patients (7.6%) had Class 4/5 variants in a moderate penetrance cancer susceptibility gene for which clinical guidelines are lacking. Four patients (1.4%) were heterozygous carriers of a pathogenic MUTYH mutation. In addition, 49 patients (18%) were found to carry a Class 3 VUS in a high penetrance or moderate penetrance gene. Conclusions: These data show that massively parallel sequencing identifies reportable (Class 3, 4 or 5) variants in known cancer susceptibility genes in 30% of patients with early onset breast cancer. However, only rare patients (2.5%) have definitively actionable mutations given current clinical management guidelines. Large-scale cooperative group studies are therefore needed to determine the clinical utility of multiplex panel testing in patients with early onset breast cancer.
Analysis of <i>KRAS and NRAS</i> mutations in 126 patients with KRAS exon 2 wild type for metastatic colorectal cancer (mCRC) in a single institution.
Authors: Braulio Martin Calero, Marta Llanos, Beatriz Alonso Alvarez, Raquel Hernández San Gil, Eduardo Salido, Juana Maria Oramas Rodriguez, Josefina Cruz, Luz Milva Rodriguez Rodriguez, Rosa Garcia Marrero, Isaac Ceballos Lenza, Jose Enrique Lorenzo Barreto, Alejandra Rodriguez Capote, Airam Padilla Alvarez, Maria Nieves Gomez Camacho, Sonal Varma, J. Norberto Batista
Journal: Journal of Clinical Oncology (2015)

e14589 Background: To know the prevalence of mutations in the RAS family in our hospital, and to determine the effect of new mutations in KRAS and NRAS in overall survival and progression-free survival. Methods: This is a retrospective observational trial. We selected a group of 126 patients with metastatic colon cancer KRAS exon 2 wild type, who received first-line treatment in our center between 01/2007 and 12/2013. Determination was performed KRAS (exon 3 and 4) and NRAS mutation (exon 2, 3 and 4) by pyrosequencing. Results: We have made the determination of 90 patients (see table below). Of the patients studied, 79% of patients remained RAS wild type. 16% had new mutations: 54% NRAS codon 61, 38% NRAS codon 12 and 8% NRAS codon 13. Regarding the clinical impact, the new RAS wild type group (n = 73) has an overall survival of 30 months (95% CI 20 to 39.7) and a progression-free survival of 8 months (95% CI 7, 5 to 10.1). Mutated RAS group (n = 13) has an overall survival of 29 months (95% CI: 5-52) and a progression-free survival of 8 months (95% CI: 5.6 to 12.3). Conclusions: The frequency of mutations in KRAS/NRAS in our center was similar to clinical trials. In our institution, overall survival and progression-free survival in RAS wild type were similar to the previously reported. RAS mutated patients were not enough to extrapolate conclusions. Mutation Total patients (n = 90) Wild type samples 73 NRAS codon 12 mutant 5 NRAS codon 13 mutant 1 NRAS codon 61 mutant 7 Failed 4
HER2 status in primary tumors and metastatic regional lymph nodes in patients with esophageal adenocarcinoma (EAC).
Authors: Harry H. Yoon, Qian Shi, William R. Sukov, Christopher A. Sattler, Rakhee Vaidya, Anne E. Wiktor, Robert B. Diasio, Tsung-Teh Wu, Robert B. Jenkins, Frank A. Sinicrope
Journal: Journal of Clinical Oncology (2013)

4071 Background: Selection of patients for HER2-targeted therapy is based on HER2 analysis in primary EACs. Since EACs metastasize via regional lymph nodes, concordance of HER2 gene amplification results between primary tumors and their metastatic lymph nodes (MLN) is a clinically important issue. Methods: Resected EACs (N = 103) having at least three distinct regional MLNs (total 508 MLNs; median 4 [range 3-11]) were sectioned using routine procedures and tested for HER2 amplification by fluorescence in situ hybridization (FISH). Primary tumors were also evaluated for HER2 protein expression by immunohistochemistry (IHC) and by FISH. Amplification was defined as HER2/CEP17 ≥ 2. IHC was scored as 0, 1+, 2+, or 3+. Primaries whose HER2 status was positive by both FISH and IHC (ie, amplified and IHC3+), or negative by both (ie, nonamplified and IHC0-1+), were selected. HER2 status was compared between primaries and their MLNs (kappa). Results: Concordant HER2 results between primaries and their MLNs were found in 92% (95/103) of EACs (Table; κ = .76 [95% CI .60 - .92]). However, among patients with HER2-positive primaries, 19% (4/21) had HER2-nonamplified MLNs; among these cases, either all MLNs were HER2-nonamplified (n = 2), or both HER2-nonamplified and –amplified MLNs were present (n = 2). Among HER2-negative primary EACs, 5% (4/82) of cases had MLNs that were all HER2-amplified (n = 3) or both HER2-nonamplified and -amplified (n = 1). Conclusions: A patient subset whose primary EACs were HER2-positive (by both FISH and IHC) were unexpectedly found to lack HER2 amplification in corresponding MLNs. Conversely, a subgroup with HER2-negative primaries had HER2-amplified MLNs, and would have been deemed ineligible for HER2-targeted therapy. These preliminary data suggest that evaluating MLNs in resected EACs has the potential to better identify patients who benefit from HER2-targeted therapy. [Table: see text]