tbuckley/cabot-search huggingface dataset:
Burden and Impact of Geriatric Syndromes Associated with Allogeneic Hematopoietic Cell Transplantation in Older Adults
Authors: Richard J Lin, Theresa A Elko, Patrick Hilden, Parastoo B. Dahi, Ann A. Jakubowski, Miguel-Angel Perales, Juliet Barker, H.R. Castro-Malaspina, Brian C. Shaffer, Armin Shahrokni, Roni Tamari, Esperanza B. Papadopoulos, Craig S. Sauter, Molly Maloy, Beatriz Korc-Grodzicki, Sergio Giralt
Journal: Blood (2018)
A genome-wide association study (GWAS) of docetaxel-induced neutropenia in CALGB 90401/60404 (Alliance).
Authors: Daniel Louis Hertz, Chen Jiang, Kouros Owzar, Susan Halabi, William Kevin Kelly, Flora Mulkey, Jai Narendra Patel, Michael Anthony Carducci, Michael J. Kelley, Walter Michael Stadler, Mohamed K. Mohamed, Michael J. Morris, Yusuke Nakamura, Hitoshi Zembutsu, Mark J. Ratain, Howard L. McLeod
Journal: Journal of Clinical Oncology (2014)

9612 Background: The objective of this analysis was to perform unbiased discovery of genetic variants that modulate neutropenia risk early in docetaxel treatment. Methods: Chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC) patients treated with docetaxel and prednisone ± bevacizumab on the CALGB 90401 trial who experienced grade 3+ neutropenia (ANC < 1,000 cells/mm3) within the first two treatment cycles (cases) were compared with controls who completed two cycles without grade 3+ neutropenia. All single nucleotide polymorphisms (SNPs) genotyped on the Illumina HumanHap610-Quad platform that passed quality control were included in a genome-wide association study (GWAS) in genetically-defined European subjects. SNPs selected for future replication, based on p-value and biological relevance to neutropenia, were adjusted for treatment arm, age, baseline ANC, smoking status and palliative radiation. Results: The incidence of grade 3+ neutropenia within the first two cycles was 22.6% (172/761). 590 European subjects fulfilling the case or control criteria were evaluated in a discovery GWAS of 498,022 SNPs. The top hit was an intronic SNP (rs12431732) in ACTN1, which bundles actin in the neutrophil cytoskeleton. Actin specific antibodies have been detected in auto-immune neutropenia, providing a plausible biological mechanism. Ten SNPs, many in genes involved in leukocyte homeostasis such as SERPINA3 and BAALC, were prioritized for future replication (Table). Conclusions: GWAS in a prospectively enrolled mCRPC patient cohort identified SNPs that may influence risk of docetaxel-induced neutropenia, adjusted for bevacizumab treatment. Replication in independent cohorts of docetaxel treated patients is necessary to verify the influence of these SNPs on neutropenia risk. GWAS rank rsID Gene Minor allele frequency Adjusted hazard ratio Adjusted p value 1 rs12431732 ACTN1 0.07 3.58 5.18 x10-07 2 rs533722 RNLS 0.22 2.14 4.88 x10-06 4 rs926788 SERPINA3 0.29 2.14 3.38 x10-06 8 rs12586591 ACTN1 0.20 2.24 3.02 x10-06 10 rs6468861 BAALC 0.43 0.50 1.52 x10-05 25 rs153166 ARHGAP26 0.32 1.69 8.30 x10-04 27 rs16978131 SETBP1 0.16 0.41 4.72 x10-04 30 rs2183938 DAPK1 0.21 1.94 7.81 x10-05
Rheumatoid Arthritis Causes Hematopoietic Stem Cell Reprogramming to Maintain Functionality
Authors: Taylor Mills, Giovanny Hernandez, Jennifer L Rabe, Susan Kuldanek, James Chavez, Greg Kirkpatrick, Leila Noetzli, Widian Jubair, Michelle Zanche, Jason R Myers, Brett M. Stevens, Courtney Fleenor, Biniam Adane, John M Ashton, Craig T Jordan, James Hagman, Jorge Di Paola, Michael Holers, Kristine Kuhn, Eric Pietras
Journal: Blood (2018)
Phase II dose titration study of regorafenib for patients with unresectable metastatic colorectal cancer that progressed after standard chemotherapy.
Authors: Toshihiro Kudo, Takeshi Kato, Yoshinori Kagawa, Daisuke Sakai, Taroh Satoh, Yuichiro Doki, Masaki Mori
Journal: Journal of Clinical Oncology (2018)

821 Background: The CORRECT study showed significant overall survival (OS) improvement in the regorafenib (REG), compared with the placebo group in metastatic colorectal cancer (mCRC) which progressed after standard chemotherapy. In Japanese subgroup analysis, the hazard ratio of OS also indicated a tendency similar to overall population. The standard starting dose of REG is 160mg/body/d, and not adjusted according to body weight and height, race of the patients, or other parameters, however, some cases require dose reduction to 120mg/d or less due to adverse events (AE). Dose modification due to AE was observed frequently in Japanese compared with non-Japanese during the study (84.6% and 51.3%). Therefore, we performed this dose titration study to investigate efficacy and safety of REG. Methods: This single arm, multicenter phase II study evaluated lower initial dose of REG (120mg/d, for 21 days, followed by 7-day break) in mCRC progressed after standard chemotherapy. Dose escalation to 160mg was allowed in 2 nd and subsequent cycle, if patients developed &lt; grade 2 AE, except for liver toxicity. Patients underwent radiographic evaluation every 8 wks. The primary endpoint was disease control rate (DCR: CR+PR+SD ≥ 6 wks). The major secondary endpoints included progression free survival (PFS), OS and safety. Results: Between September 10, 2015, and March 7, 2017, total 60 patients were enrolled into the study. Median age was 68.5 (range: 30-84), and ECOG PS 0/1 were 70%/30%. DCR was 36.7% (22/60); 7% (4/60) have had SD for 6 months or longer. Median PFS was 2.3 months (95% CI: 1.8 - 2.8). 3.3% of patients (2/60) had protocol defined REG dose escalation to 160mg; one case was from the cycle 2, and the other case was from the cycle 4. 42% (25/60) had dose reduction to 80mg due to AE, and that dose reduction was needed in 10% (6/60) at the first cycle. Grade 3-4 adverse events were observed in 55% (33/60). Conclusions: Starting dose of REG 120mg appears to have comparable efficacy to 160mg. Adverse events were generally consistent with the known safety profile of REG in this setting. Final results with additional follow-up on efficacy and safety outcome measures will be provided at the meeting. Clinical trial information: UMIN000018968.
Maximum Tolerated Dose Versus Fixed Low-Dose Hydroxyurea for Treatment of Adults with Sickle Cell Anemia - Retrospective Comparison of Two Studies
Authors: Titilola S. Akingbola, Bamidele Tayo, Chinedu A Ezekekwu, Omowunmi Sonubi, Santosh L. Saraf, Lewis L. Hsu, Jin Han, Richard S. Cooper, Victor R. Gordeuk
Journal: Blood (2018)
Off-the-Shelf Natural Killer Cells with Multi-Functional Engineering Using a Novel Anti-CD19 Chimeric Antigen Receptor Combined with Stabilized CD16 and IL15 Expression to Enhance Directed Anti-Tumor Activity
Authors: Dan S Kaufman, Ryan Bjordahl, Huang Zhu, Robert Blum, Andres Bahena, Sajid Mahmood, Greg Bonello, Tom Lee, Bruce Walcheck, Frank Cichocki, Jeffrey S. Miller, Bahram Valamehr
Journal: Blood (2018)
High neutrophil to lymphocyte ratio persistent during first-line chemotherapy to predict clinical outcome in patients with advanced urothelial cancer.
Authors: Ugo De Giorgi, Matteo Santoni, Simon J. Crabb, Emanuela Scarpi, Lorena Rossi, Luciano Burattini, Caroline Shuet Yiu Chau, Emanuela Bianchi, Agnese Savini, Salvatore Luca Burgio, Alessandro Conti, Vincenza Conteduca, Stefano Cascinu, Dino Amadori
Journal: Journal of Clinical Oncology (2014)

4540 Background: Increased neutrophil to lymphocyte ratio (NLR), an index of systemic inflammation, is associated with poor outcome for various types of cancers. We aimed to assess the role on outcome prediction of NLR at baseline and persistent during first-line chemotherapy in patients with advanced urothelial cancer (UC). Methods: We retrospectively reviewed 292 patients with unresectable or metastatic UC treated with first-line chemotherapy between January 2003 and December 2012. The cut-off values of NLR (>3 vs ≤3) were evaluated at pre-therapy and at day 1 of the second and third cycle (follow-up NLR). After univariate analysis, a multivariate analysis was carried out by Cox regression model and included the following variables: Eastern Cooperative Oncology Group (ECOG) performance status (≥2 vs 0-1), visceral disease (present vs absent), hemoglobin (<12 g/dL vs ≥12 g/dL), pre-therapy NLR (>3 vs ≤3) and follow-up NLR (>3 vs ≤3). Results: The median follow-up was 40.2 months (range, 0.5 to 100.4). The median progression-free survival (PFS) was 5.8 months (95% confidence interval (CI) 5.0-6.6) and the median overall survival (OS) was 10.9 months (95% CI 9.6-12.4). Patients with pre-therapy and follow-up NLR > 3 had a median PFS of 3.2 months and a median OS of 5.7 months. In multivariate analysis, visceral metastases, pre-therapy hemoglobin and follow-up NLR were significant predictors of PFS (HR 1.75, p = 0.0001; HR 1.57, p = 0.0015; HR 2.77, p < 0.0001, respectively), and of OS (HR 1.60, p = 0.0023; HR 1.59, p = 0.0024; HR 2.89, p < 0.0001, respectively); whereas pre-therapy NLR remained as predictor of OS only (HR 1.53, p = 0.0101). Conclusions: An increased NLR persistent during first-line chemotherapy is an independent predictive factor for patients with advanced UC.
SIRT5 As a Therapeutic Target in Acute Myeloid Leukemia
Authors: Dongqing Yan, Anthony D. Pomicter, William L. Heaton, Clint C. Mason, Jonathan Ahmann, Anna Senina, Anca Franzini, Brayden Halverson, Hein Than, Phillip M. Clair, Jamshid S Khorashad, Thomas O'Hare, Michael W. Deininger
Journal: Blood (2018)
Outcomes, Causes of Discontinuation and Mutation Profile of Patients with Mantle Cell Lymphoma Who Progressed on Acalabrutinib
Authors: Preetesh Jain, Rashmi Kanagal-Shamanna, Shaojun Zhang, Chi Young Ok, Makhdum Ahmed, Diana Nava, Maria Badillo, Krystle Nomie, Keyur Patel, Hun Ju Lee, F. B. Hagemeister, Luis Fayad, Loretta J. Nastoupil, L. Jeffrey Medeiros, Sattva S. Neelapu, Jorge Enrique Romaguera, Nathan H. Fowler, Linghua Wang, Michael Wang
Journal: Blood (2018)
Development of an IHC-based detection method for studying indoleamine 2,3-dioxygenase 1 (IDO1) expression in human cancers.
Authors: Alton Hiscox, Heather Gustafson, Joseph Couto, Zhiming Liao, Yifei Zhu, Xiangdong Liu, Robert Charles Newton, James Hnatyszyn
Journal: Journal of Clinical Oncology (2014)

3043 Background: Indoleamine 2,3-dioxygenase-1 (IDO1) mediates oxidative cleavage of tryptophan, an amino acid essential for cell proliferation and survival. The depletion of tryptophan and the generation of tryptophan metabolites have been shown to suppress immune functions via several cellular mechanisms, allowing tumor escape from host immune surveillance. IDO1 is induced by interferons and TLR agonists and is expressed in a variety of human cancers as well as the invading immune infiltrate and the tumor-draining lymph nodes. High IDO1 expression is significantly associated with more rapid disease progression and poor prognosis in multiple cancer types. Thus, inhibition of IDO1 activity may have therapeutic potential in cancer and furthermore, IDO1 expression could serve as a biomarker for selecting patients that are responsive to an IDO1 inhibitor-based treatment regimen. Methods: We generated and selected an anti-human IDO1 rabbit monoclonal antibody. The specificity of the antibody for IDO1 was confirmed using Western blot analyses of lysates from cells expressing human IDO1, IDO2, or TDO. Results: INCB024360, a novel IDO1-selective inhibitor, is currently being evaluated in clinical trials of cancer patients. To support the clinical development of INCB024360, we developed an immunohistochemistry (IHC)-based method for the detection of IDO1 protein in human tissues. To further evaluate the specificity and reactivity of the antibody against IDO1 in human tissues, an IHC staining protocol was established, standardized and used to stain various human normal and tumor tissues, as well as IDO1-expressing cells. We have examined IDO1 expression in several human tumors including lung, ovarian, melanoma, gastric, and pancreatic cancers. Conclusions: In summary, we have developed and standardized an IHC-based method for the specific detection of IDO1 protein in human tissues. The method will be useful to determine the prevalence of IDO1 expression in a variety of human cancers. Furthermore, incorporating this detection method into ongoing clinical trials may identify patients that are likely responsive to IDO1 inhibitor-based treatment regimens.
A first-in-human dose escalation and dose-finding phase I/II trial of IMAB027 in patients with recurrent advanced ovarian cancer (GM-IMAB-002-01).
Authors: Dirk Jaeger, Ugur Sahin, Oezlem Tureci
Journal: Journal of Clinical Oncology (2014)

TPS5623 Background: Ovarian cancer is a commonly diagnosed incurable disease with approximately 29,000 deaths annually. Surgery followed by platinum-based chemotherapy is the initial standard of care. However, the majority of patients relapse and therapy options are very limited. 25-53% of ovarian cancers express claudin 6 (CLDN6) a carcino-embryonic transmembrane protein, which is absent from normal adult tissue. IMAB027 is a chimeric antibody specifically binding to CLDN6 and not cross-reacting with other proteins. Based on preclinical data and compassionate use data, IMAB027 may provide a well tolerable treatment option with a high potential to be clinically beneficial. Methods: This first-in-human, open-label, combined dose escalation Phase I/II trial assesses the safety/tolerability and the clinical efficacy of IMAB027 in patients with ovarian cancer. The Phase I part includes two stages: stage 1 comprises an intra-patient accelerated dose escalation and stage 2 a classical 3+3 inter-patient dose escalation design to determine the MTD based on DLTs and to define the recommended dose for the subsequent Phase II part. The Phase II part is a single-arm, safety/tolerability study with a planned enrolment of about 60 patients. Our novel combinatory approach enables a smooth transition of patients from Phase I to Phase II and ensures continuous treatment of patients benefitting from IMAB027. An independent DSMB is continuously monitoring the conduct of the study. The trial was approved by responsible local regulatory authorities/ethics committees and is registered at ClinicalTrials.gov (NCT02054351). Eligible patients had to have CLDN6+ ovarian cancer which was either symptomatic or asymptomatic (patients with CA125-rise without detectable tumor lesions, who had at least one line of standard treatment). Currently, there is no treatment available for asymptomatic patients with a high risk of disease recurrence. IMAB027 may provide a non-aggressive treatment solution for such patients. In addition, we evaluate an extensive set of biomarkers with prognostic potential, and correlation analysis with clinical outcome will be performed. Clinical trial information: NCT02054351.
Early detection of lung cancer based on three-dimensional, morphometric analysis of cells from sputum.
Authors: Alan Nelson, Michael Meyer, Rahul Katdare, Chris Presley, David Wilbur, Thomas Neumann, Jon Hayenga, Tim Bell, Christy Lancaster
Journal: Journal of Clinical Oncology (2014)

7547 Background: Utilizing a new 3D morphometric analytical device called Cell-CT, we analyzed cells from sputum to detect lung cancer in patients with malignant nodules found using low-dose x-ray CT (LDCT). This study assesses the sensitivity and specificity of the Cell-CT analysis for lung cancer in this context. Methods: Case sensitivity was assessed by analyzing sputum from patients with biopsy-confirmed non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Spontaneously produced sputum was collected over three consecutive days and fixed. Specimens were then enriched for epithelial cells and stained with hematoxylin. These cells were imaged using VisionGate’s Cell-CT system that computes 3D cell images with isometric, sub-micron resolution. Cell images were then automatically analyzed by a computer classifier to identify abnormal cells. Of the 800 measured features, the strongest 25 were used in the classifier. The diagnosis for these cells was computer-generated and manually confirmed by a cytotechnologist. Specificity was assessed by analyzing cells in sputum from normal patients who were at high risk for lung cancer. Bronchial epithelial cells were counted to determine specimen adequacy. Results: 26 NSCLC and 4 SCLC, or 30 total cases were processed that met the criteria for adequacy. Moderate/severe dysplasia or cancer cells were found in 28 of the 30 cases. In 26 of the 28 cases, cancer cells were present. Cancer and dysplastic cells were detected by the Cell-CT for an overall case sensitivity of 93.3%. 15 of 30 cases were either stage I or stage II lung cancer, and 14 of these 15 cases (or 93.3%) were detected. 5,146 sputum cells from 17 normal patients at high risk for lung cancer were processed with zero false positive indications. The lower 95% confidence bound for specificity is 99.8%. Conclusions: With a sensitivity of 93.3% to early stage lung cancers and a lower limit to specificity of 99.8% based on a non-invasive sputum analysis, the Cell-CT platform could be deployed to help eliminate false positives from LDCT. Further studies will establish the Cell-CT performance across a broader range of clinical conditions to evaluate the potential use of the Cell-CT as a primary screener for lung cancer.
The CDK9 Inhibitor, Alvocidib, Potentiates the Non-Clinical Activity of Azacytidine or Decitabine in an MCL-1-Dependent Fashion, Supporting Clinical Exploration of a Decitabine and Alvocidib Combination
Authors: Wontak Kim, Clifford Whatcott, Adam Siddiqui-Jain, Stephen Anthony, David J. Bearss, Steven L. Warner
Journal: Blood (2018)
Abstract 14226: Physicians Speak up About Heart Health Awareness and Action: A Women’s Heart Alliance Research Report
Authors: Holly Andersen, Noel C Bairey-Merz, Adam Burns, Mary N Walsh, Phyllis Greenberger, Susan Campbell, Irene Pollin, Nancy Brown, Majorie Jenkins, Rita Redberg, Paula Johnson, British Robinson
Journal: Circulation (2015)

Introduction: Cardiovascular disease is the number one killer of women in the US. In November 2014, the Women’s Heart Alliance (WHA) launched a nationwide campaign to increase physician awareness and action toward women’s heart risk. Methods: Survey data collection from May 6-12, 2014 used the ERI (Research Now) Physician and Healthcare Professional Panel (HCP), an online invitation-only database based on AMA data and verified. The survey included 200 Primary Care Physicians (PCPs) and 100 cardiologists, currently in practice ≥3 yrs. Overall; ≥33% of PCPs and OB/GYN patients, and ≥21% of cardiologists’ patients were female. Results: Heart disease was a top concern for 39% PCPs. Among the AHA guideline-recommended heart risk assessment items for women, 16% of PCPs and 22% cardiologists implemented all eight. Only 22% of PCPs and 42% of cardiologists feel well prepared to assess heart disease risk in women. While a majority of cardiologists and PCPs are aware of the ASCVD Risk Assessment Calculator, current usage is below 50%s in both groups (Figure). A majority of PCPs (87%) and cardiologists (82%) were favorable towards a national campaign. Conclusions: Heart disease in women is not a top-tier concern for PCPs or cardiologists. Physician awareness and use of heart risk assessment is low, and a majority are supportive of a national campaign Strategies to improve healthcare provider awareness and action for heart risk assessment practice gaps are needed.
Checkpoint Blockade Therapy May Sensitize Hodgkin Lymphoma to Subsequent Therapy
Authors: Nicole A Carreau, Orrin Pail, Philippe Armand, Reid W Merryman, Ranjana H Advani, Michael A Spinner, Alex F. Herrera, Robert W. Chen, Sarah Tomassetti, Radhakrishnan Ramchandren, Muhammad Hamid, Sarit Assouline, Raoul Santiago, Nina D. Wagner-Johnston, Suman Paul, Jakub Svoboda, Steven M. Bair, Stefan Klaus Barta, Yang Liu, Sunita Nathan, Madelyn Burkart, Reem Karmali, Pallawi Torka, Kevin A. David, Catherine Wei, Frederick Lansigan, Lukas Emery, Daniel Persky, Sonali M. Smith, Julio C. Chavez, Yuhe Xia, Andrea B Troxel, Catherine Diefenbach
Journal: Blood (2018)
Moderate Aortic Stenosis and Heart Failure With Reduced Ejection Fraction
Authors: Philippe Pibarot, David Messika-Zeitoun, Ori Ben-Yehuda, Rebecca T. Hahn, Ian G. Burwash, Nicolas M. Van Mieghem, Ernest Spitzer, Martin B. Leon, Jeroen Bax, Catherine M. Otto
Journal: JACC. Cardiovascular imaging (2019)
Use of a new prognostic score as a tool to optimize medical treatment in malignant bowel obstruction.
Authors: Yolanda Vidal, Maria Vieito, Nieves Martinez Lago, Sonia Candamio, Francisca Vazquez, Rafael Lopez, Francisco J. Barón
Journal: Journal of Clinical Oncology (2014)

e20662 Background: The optimal medical treatment for bowel obstruction has not been established by large prospective randomized trial but from small studies in heterogeneous populations. Methods: We generated a 4 item prognostic index analysing 114 consecutive cancer patients treated at our institution from 2008-2010 for a first episode of bowel obstruction. We analysed the influence of treatment for four principal outcomes in the high nd low risk population, as established by the score. Results: Four clinical variables were statistically associated with survival (p< 0,005 multivariate Cox regression): presence of ascites, delirium and low conscience level, a non gynaecological-non intestinal primary, and known metastatic disease at admission. Three variables were correlated with resolution of symptoms (p< 0,05 Chi Square): a PS score of less than 3, absence of progressive disease, and a non gynaecological-non intestinal primary.Using this variables we generated a 4 item score with an AUC of 0.751. Using a threshold of 2 risk factors permitted us to categorize 51,7% and 45,6% of the patients respectively as low risk patients. The four item score allowed us to predict the resolution of symptoms with sensitivity of 74,5 and a specificity of 73%, and the possibility of discharge with a sensitivity of 76% and a specificity of 68%. The median overall survival in patients with a low risk score was 14 weeks versus 2 weeks for high risk(p< 0,01 log rank test) and the median length of hospitalization was 15 vs 52 days (p< 005 log rank test). Conclusions: Not all the patients with bowel obstruction treated medically have the same prognosis. A score of 4 items based in clinical variables could be useful to stratify patients in clinical trials.
Identification of High Risk Group for Leukemic Transformation in Higher Risk MDS Patients Using Targeted RNA-Sequencing: Hematopoietic Stem Cell Signature As a High Risk Profile for Leukemic Transformation
Authors: Joon Ho Moon, Taehyung Kim, Jae-Sook Ahn, Seo-Yeon Ahn, Sung-Hoon Jung, Deok-Hwan Yang, Je-Jung Lee, Seunghyun Choi, Yoojin Lee, Sang Kyun Sohn, Hyeoung-Joon Kim, Zhaolei Zhang, Dennis Dong Hwan Kim
Journal: Blood (2018)