tbuckley/cabot-search huggingface dataset:
High Microvascular Density Correlates with Poor Outcome in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with Rituximab Plus Chemotherapy (R-CT).
Authors: Teresa M Cardesa-Salzmann, Luis Colomo, Fina Climent, Eva Gonzalez-Barca, Armando López-Guillermo, Gonzalo Gutierrez, Santiago Mercadal, Randy D. Gascoyne, Joseph M. Connors, Lisa M. Rimsza, Rita M. Braziel, James R. Cook, Raymond R. Tubbs, Andreas Rosenwald, German Ott, José Luís Mate, Josep-Maria Ribera, Leonor Arenillas, Sergi Serrano, Neus Combalía, Jan Delabie, Georg Lenz, George Wright, Elaine S Jaffe, Louis M. Staudt, Wing C. Chan, Dennis Weissenburger, Elias Campo
Journal: Blood (2009)
Abstract MP15: Physical Activity is Inversely Associated with Calcified Atherosclerotic Plaque in the Coronary Arteries: The NHLBI Family Heart Study
Authors: Tasnim F Imran, Yash Patel, R C Ellison, Gerardo Heiss, Steven C Hunt, J. Jeffrey Carr, Donna K Arnett, James Pankow, J. Michael Gaziano, Luc Djoussé
Journal: Circulation (2016)

Background: Physical activity is integral to the primary prevention of cardiovascular diseases. However, studies have reported mixed findings on the association between physical activity and coronary artery calcification (CAC). Hypothesis: Our primary hypothesis is that physical activity is inversely associated with prevalent CAC. Methods: In a cross-sectional design, we studied 2,971 participants of the NHLBI Family Heart Study without a history of MI, CABG or PTCA. A standardized questionnaire was used to ascertain the number of blocks walked daily to compute block metabolic equivalent hours per week. CAC was measured by cardiac CT, and we defined prevalent CAC using an Agatston score of at least 100. Generalized estimating equations were used to calculate adjusted prevalence ratios of CAC. Results: Mean age was 55 (±12.7) years and 60.3% of participants were women. Compared to 0-4 blocks/d, prevalence ratios for CAC after adjusting for age, sex, race, BMI, hyperlipidemia, hypertension, diabetes, smoking, and alcohol abuse were 0.73, 95% CI: 0.55-0.97 for &gt;4-8 blocks/d, 0.72, 95% CI: 0.58-0.89 for &gt;8-20 blocks/d, and 0.82, 95% CI: 0.62-1.1 for &gt;20 blocks/d, p for trend 0.02. Corresponding values for total block activity were 0.84, 95% CI: 0.53-1.30 for 1-4 met-hrs/wk, 0.50, 95% CI: 0.31- 0.81 for &gt;4-7 met-hrs/wk, 0.68, 95% CI: 0.47-1.00 for &gt;7-14 met-hrs/wk, and 0.54, 95% CI: 0.33-0.88 for &gt;14-22 met-hrs/wk, p for trend 0.04 (Table 1). In a secondary analysis stratified by BMI (&lt;25 and ≥25 kg/m2), the results remained statistically significant for those with BMI ≥ 25 (p=0.01). The number of participants with BMI &lt; 25 was too small for analysis. The inverse association persisted when we repeated the main analyses using CAC cutoffs of 150 and 200, but not 50. Conclusion: The Family Heart Study data are consistent with an inverse association of mild to moderate physical activity with coronary artery calcification in adult men and women.
Fludarabine, Mitoxantrone and Rituximab (FMR) Regimen in Previously Untreated Patients with Indolent Non-Hodgkin Lymphoma: Efficacy, Safety and PET Data On 285 Patients.
Authors: Pier Luigi Zinzani, Cinzia Pellegrini, Enrico Derenzini, Alessandro Broccoli, Letizia Gandolfi, Vittorio Stefoni, Beatrice Casadei, Federica Quirini, Lisa Argnani
Journal: Blood (2012)
Allografts Selectively Photodepleted of GvHD Causing T Cells and Followed by Low-Level Immunosuppression: A Novel Method to Improve Disease Control After HLA-Matched Sibling Transplantations.
Authors: Stephan Mielke, Aarthi Shenoy, Katayoun Rezvani, Agnes S. M. Yong, Zachariah A. McIver, Vicki S. Fellowes, Bipin N. Savani, Roger Kurlander, Hanh Khuu, Carol Boss, A.John Barrett
Journal: Blood (2009)
Variation in UDP glucouronyltransferase (<i>UGT</i>) genes associated with prostate cancer mortality.
Authors: M. Kohli, D. W. Mahoney, H. S. Chai, D. W. Hillman, D. R. Rider, B. A. Costello, J. R. Cerhan
Journal: Journal of Clinical Oncology (2011)

44 Background: We investigated the association of germline genetic variation in hormone biosynthesis and metabolism genes with prostate cancer specific mortality in a cohort of advanced prostate cancer patients. Methods: We successfully genotyped 852 single nucleotide polymorphisms (SNPs) from 97 genes in a cohort of 267 advanced prostate cancer patients at the time of progression to castration recurrence (CRPC) during on-going androgen ablation. Tagging SNPs with minor allele frequency (MAF) of &gt;5% and r 2 ≥0.8 were selected from HapMap, NIEHS and Seattle SNP databases. Medical records were queried for cause of death. The primary endpoint of time to prostate cancer specific mortality (PCSM), was pre-defined as time from development of CRPC to death from prostate cancer progression. Principle components analysis was used for gene-levels tests, and to account for multiple testing, we calculated the false discovery rate (FDR). For SNP level results, hazard ratios (HR) and 95% confidence intervals (CI) were estimated using cox regression. Results: The median age of the cohort was 72 years at CRPC. 43% had a Gleason score (GS)=8-10, 33% a GS=7, and 24% a GS&lt;7. After a median follow-up of 1.8 years (IQ range: 0.8–3.3 years), 139 patients died, of which 107 were due to prostate cancer progression. In unadjusted gene level analyses, UGT1A7 (p=0.0059; FDR=0.19), UGT1A10 (p=0.0017; FDR=0.17) and UGT1A3 (p=0.0037; FDR=0.18) were associated with PCSM. After adjusting for age and GS, SNPs strongly associated with PCSM are listed in the Table . Conclusions: Variation in UGT genes involved in hormone metabolism yield prognostic information in CRPC. Further validation is needed to develop these as prognostic biomarkers. [Table: see text] No significant financial relationships to disclose.
When the price is right: drug costing and NICE approval
Authors: Nigel Hawkes
Journal: BMJ (2016)

Price discounts are leading to a flurry of NICE approvals. Nigel Hawkes investigates

After years of standoffs and angry words, drug companies are cutting prices of cancer treatments in a bid to gain approval for use in the NHS in England.

This change of policy, unpredicted when the old Cancer Drugs Fund was wound up in July,1 has analysts puzzled. Has the industry finally recognised that its products are not worth as much as it once claimed? Or is there a subtle plan to clear the decks of unapproved drugs to make room in the revamped Cancer Drugs Fund for yet more expensive ones coming down the pipeline?

Whatever the reason, the result has been to allow the National Institute for Health and Care Excellence to approve, at the draft or final guidance stage, seven of the first nine drugs it has reviewed from the old Cancer Drugs Fund list.2 In November NICE approved three drugs for breast cancer in as many weeks and reversed …
Tumor response and outcome in localized high-risk soft tissue sarcomas (STS) treated with preoperative chemotherapy (CHT) with or without radiation therapy (RT) within a phase III trial from the Italian Sarcoma Group (ISG) and the Spanish Sarcoma Group (GEIS).
Authors: S. Stacchiotti, P. Verderio, A. Messina, C. Morosi, A. Ferraro, V. Quagliuolo, J. Martin, A. Comandone, G. Grignani, P. Picci, S. Frustaci, A. Gronchi, P. G. Casali
Journal: Journal of Clinical Oncology (2011)

10019 Background: We showed that non-dimensional criteria (i.e. contrast enhancement and tumor density) correlate with pathologic responses better than RECIST in a group of 38 high-risk STS treated with preoperative CHT +/- RT within a prospective phase III ISG-GEIS trial. We compared the prognostic relevance of RECIST versus CHOI criteria in eligible pts with measurable disease. Methods: From April 2002 to May 2007, 311 eligible pts with localized high-risk STS of extremities or trunk wall received 3 cycles of preoperative epirubicin + ifosfamide +/- RT. Responses by CT or MRI according to RECIST and CHOI were retrospectively evaluated. The prognostic impact of RECIST and CHOI on OS and RFS was evaluated by a univariate Cox regression model. On a dichotomous scale (PR and SD+PD), they were compared in terms of concordance (intechangiability) by Cohen’s k statistics. The pertinent predictive capability was also computed by means of the Harrell c statistic. Results: 242 pts were evaluable by RECIST, 157 by CHOI. Among 114 patients who received CHT alone, 64 were evaluable by both RECIST and CHOI. In these pts, responses by binary CHOI criteria correlated with OS (PD/SD vs PR: HR 4.29, 95%CI 1.84-9.98), with a trend for RFS, while the prognostic impact of responses by binary RECIST was negligible (OS: PD/SD vs PR: HR 0.97, 95%CI 0.38-2.47; RFS: PD/SD vs PR: HR 0.67, 95%CI 0.29-1.57). A reasonable agreement was found between the two diagnostic criteria, with a k statistic value of 0.25 (95%CI: 0.11-0.38). The predictive capability of Choi was greater than RECIST for both OS (0.68 vs 0.50) and RFS (0.58 vs 0.54). In all pts (242 by RECIST and 157 by Choi), we observed a better outcome for both OS and RFS in pts achieving a PR, as by RECIST (for OS: PD vs PR: HR 2.28, 95%CI 1.16-4.46; for RFS: PD vs PR: HR 2.11, 95%CI 1.12 - 3.98) and CHOI (for OS: PD vs PR: HR 5.7, 95%CI 2.81-11.64; for RFS: PD vs PR: HR 3.09, 95%CI 1.39 – 6.89). Conclusions: Response to preoperative CHT+RT were associated to a better outcome. CHOI criteria were better predictors than RECIST in pts receiving preoperative CHT alone.
Long Distance Endovascular Growth of Jugulotympanic Paraganglioma Evident in 68Ga-DOTATATE PET but Concealed on CT
Authors: Nemanja Avramovic, Matthias Weckesser, Aglaé Velasco, Markus Stenner, Benjamin Noto
Journal: Clinical Nuclear Medicine (2016)

A 60-year-old woman was referred to contrast-enhanced CT for evaluation of jugular vein thrombosis incidentally detected by ultrasound. Contrast-enhanced CT showed an enhanced tumor of the right skull base highly suspicious of jugulotympanic paraganglioma. However, the jugular veins showed a nearly symmetric contrast enhancement without clear evidence of thrombosis. Consecutive Ga-DOTATATE PET/CT depicted high tumor uptake, which comprised the entire internal jugular vein. Endovascular growth of paraganglioma might be missed on contrast-enhanced CT because of high vascularization of the lesion. Ga-DOTATATE PET is suited for accurate determination of tumor extent.
Results of a phase I/II clinical trial of BPX-101, a novel drug-activated dendritic cell (DC) vaccine for metastatic castration-resistant prostate cancer (mCRPC).
Authors: K. M. Slawin, G. Sonpavde, J. D. McMannis, Y. Bai, M. Seethammagari, J. M. C. Bull, V. Hawkins, T. Dancsak, N. Lapteva, J. M. Levitt, D. M. Spencer
Journal: Journal of Clinical Oncology (2011)

4670 Background: We report results of a phase I/II clinical trial of BPX-101, a drug-activated autologous DC vaccine targeting PSMA. Methods: Men with progressive mCRPC following ≤1 prior chemotherapy regimen were enrolled in a 3+3 dose escalation trial evaluating BPX-101 and CD40 activating agent AP1903. BPX-101 was administered intradermally every 2 weeks for 6 doses (induction phase), and for non-progressing patients, every 8 weeks for up to 5 doses (maintenance phase). AP1903 (0.4 mg/kg) was infused 24 hours after each BPX-101 dose. Radiologic evaluation was performed every 12 weeks. Results: Planned enrollment of 12 subjects receiving 4, 12.5 or 25 x 106 cells/dose has been completed. Median Halabi-predicted survival was 13.8 months, and 9/12 subjects had Gleason scores ≥8. Toxicities were generally mild and expected (e.g. injection site reactions), with no DLTs. One high dose subject experienced a single acute grade 2 cytokine reaction during infusion of AP1903 at the second vaccination, but continued induction without further drug-related adverse events. Two subjects went off protocol prior to the end of induction due to progression, and the remaining 10/12 achieved a best response of stable disease or better. Significant PSA responses were seen in two subjects (313 ng/mL to 170 ng/mL [46% decline], and 1070 ng/mL to 169 ng/mL [85% decline]). One post-docetaxel low dose subject achieved a RECIST PR, and one chemo-naive mid dose subject with extensive visceral, nodal, and bone metastases experienced a RECIST CR with docetaxel-based chemotherapy after induction and maintains an undetectable PSA (0.025 ng/mL) 14 months after enrollment. A third, high dose subject experienced near complete elimination of multiple lung metastases with otherwise stable disease by the end of induction. Conclusions: BPX-101 can be reliably manufactured and safely administered, followed by AP1903, at doses of at least 25 x 106 cells. Contrary to the growing consensus that cancer vaccine therapy improves survival without short-term response, BPX-101-treated patients have experienced measurable disease responses, including elimination of poor-risk visceral disease.
BACH2 Directly Regulates Expression of Foxp3 in UCB CD4+ T-Cells
Authors: Mathew L. Lesniewski, Peter Haviernik, R. Patrick Weitzel, Laura Fanning, Marcie Finney, Yu-Chung Yang, Mariusz Z Ratajczak, Nicholas Greco, Paul Paul, Jaroslaw P. Maciejewski, Mary Laughlin
Journal: Blood (2008)
Brain metastases in patients treated with targeted therapy for metastatic renal cell carcinoma (mRCC).
Authors: H. Alharbi, T. K. Choueiri, C. K. Kollmannsberger, S. North, M. J. MacKenzie, J. J. Knox, B. I. Rini, D. Y. Heng
Journal: Journal of Clinical Oncology (2011)

326 Background: Patients with brain metastases from advanced RCC treated in the targeted therapy era are not well characterized. Methods: Data from patients with mRCC treated with targeted therapy were collected through the International mRCC Database Consortium from 6 centers. Results: One hundred six out of 705 (15%) patients with mRCC had brain metastases. Forty-seven patients had brain metastases at the start of first-line anti-VEGF therapy and the rest developed metastases during follow-up. Of the patients with brain metastases, 6%, 68%, and 26% were in the favorable, intermediate and poor prognosis groups, respectively, per the Heng et al JCO 2009 criteria. Ninety percent had cerebral metastases, 17% had cerebellar metastases, 40% had a Karnofsky performance status (KPS) &lt;80%, and 81% had symptoms of brain metastases. The median largest size and number of brain metastases was 1.8 cm (range 0.2–6.6) and 1 (range 1–20), respectively. Patients were treated with first-line sunitinib (n=77), sorafenib (n=23), bevacizumab (n=5), and temsirolimus (n=1). Local disease treatment included whole brain radiotherapy (81%), stereotactic radiosurgery (25%), and neurosurgery (25%). The brain metastases of 59 patients were evaluable and based on the local treatment and/or targeted therapy achieved 7 (12%) complete responses, 23 (39%) partial responses, 14 (24%) patients with stable disease, and 15 (25%) patients with progressive disease in the brain metastases. Patients with more than 4 brain metastases vs. those with no more than 4 have an overall survival time from diagnosis of brain metastasis of 3.9 vs. 15.4 months (p=0.0051). Previous nephrectomy, sarcomatoid, and non-clear cell histology are not associated with development of brain metastases. On multivariable analysis, KPS&lt;80% (p=0.0139), diagnosis to treatment with targeted therapy &lt;1 year (p=0.0012), and higher number of brain metastases (p=0.0311) were associated with worse survival from diagnosis of brain metastases. Conclusions: In patients with brain metastases from RCC, KPS at start of therapy, diagnosis to treatment time and number of brain metastases may be prognostic factors for overall survival. [Table: see text]
Determination of the Maximum Tolerated Dose of Cyclophosphamide in Conjunction with High-Dose Etoposide and Carboplatin Followed by Autologous CD34+ Hematopoietic Rescue in Pediatric Patients with Recurrent/Refractory Solid Tumors.
Authors: Michelle P. Hudspeth, Barbara Duffy, Stephen Noga, Steven Goodman, Curt I. Civin, Allen R. Chen
Journal: Blood (2006)
Primary genitourinary small cell carcinoma: Clinicopathologic and survival outcomes from SEER database.
Authors: R. Thota, S. Birdsong, S. Subbiah
Journal: Journal of Clinical Oncology (2011)

200 Background: Small cell carcinoma of genitourinary system (SCC) is a highly aggressive and rare entity. The aim of the study is to characterize the clinicopathologic characteristics and evaluate the treatment outcomes of SCC in adult patients. Methods: Retrospective analysis of 732 patents diagnosed with small cell carcinoma of bladder from 1973 to 2007 was done via SEER database. Demographics, stage, type of treatment received and cancer-specific mortality were examined. Results: 732 patients were identified with SCC of genitourinary tract of which 341 were small cell bladder cancer, 336 were small cell prostate cancer and 55 were small cell renal cancer. Of these 644 patients were males and 88 were females. Median age of diagnosis is 73 years for bladder, 72 years for prostate and 70 years for renal cancer. Majority of the patients were Caucasians (89%) followed by African Americans (6%) and other races (4.98%). Grading of the tumor revealed that 12 patients had well differentiated tumor, 18 patients had moderately differentiated tumor, 191 patients had poorly differentiated, 292 patients had undifferentiated tumor and 219 patients had unknown grade. Pathological T-stages were as follows: T1= 34 (4.6%), T2= 102 (14%), T3= 43 (9%), T4= 41 (5.6%), 38.4% unknown T stage and 67 (9%) patients had metastatic disease. In majority of the patients the treatment received was unknown (565), 90 patients received external beam radiation, and 76 patients received surgery. Cancer-specific mortality was 54% in bladder cancer, 71% in prostate cancer and 78.6% in renal cancer. Median overall survival for all stages was 15.8 months in bladder cancer, 11.3 months in prostate cancer and 8 months in renal cancer. Conclusions: Results show that SCC is a highly aggressive tumor with poor prognosis. Clinical trials involving multiple institutes are needed to accrue enough patients so that treatment paradigms for this uncommon disease can be developed. No significant financial relationships to disclose.
Evaluation of ER/PR and HER2 status by RNA sequencing in tissue core biopsies from preoperative clinical trial specimens.
Authors: S. Kamalakaran, K. Lezon-Geyda, V. Varadan, N. Banerjee, D. R. Lannin, T. Rizack, W. M. Sikov, M. M. Abu-Khalaf, A. Janevski, L. Harris
Journal: Journal of Clinical Oncology (2011)

46 Background: Next-generation sequencing for measuring RNA (RNASeq) offer increased sensitivity, dynamic range and provide unbiased detection of all transcripts. To evaluate the clinical utility of such methods, we sequenced entire transcriptomes from fresh-frozen biopsies in a cohort of 120 patients enrolled on a preoperative therapy trial receiving carboplatin, nab paclitaxel and either bevacizumab (HER2-) or trastuzumab (HER2+). Methods: Total RNA was extracted and amplified from frozen breast core biopsies and libraries constructed using TruSeq (Illumina). Sequencing was performed on the Illumina GAII platform. 75bp reads were mapped using Tophat and transcript abundance in FPKM units (Fragments per kilo-base of mRNA per million reads) calculated using Cufflinks. CLIA approved assays were performed for ER, PR, HER2 (IHC+/- FISH) on patient tumors. Four tumors from each subtype (ER +ve/HER2 -ve; HER2 +ve; ER/HER2 -ve) were analyzed for correlation with clinical status. PAM50 classification will be provided for verification of molecular subtypes. Results: RNA-Seq library construction/sequencing were successful in 12/12 samples with 50-90% reads mapped. ER +ve tumors ranged in FPKM values from 1.76-22.67 and ER -ve tumors ranged from 0.00-0.79. i.e. ER RNASeq measurements can separate clinical ER status. HER2 +ve tumors ranged in FPKM values from 2.62-21.71 and HER2 -ve tumors from 0.21-1.79. Of note, 7/8 HER2 -ve tumors ranged from 0.21-0.87 with one ‘outlier’ at 1.79±0.3. This outlier was HER2 IHC 2+, FISH ratio 1.1 with 45% of tumor cells with polysomy chromosome 17. Correspondence of ER/PR and HER2 status with molecular subtyping by PAM50 analysis will be presented. Conclusions: RNASeq has potential to provide in depth analysis of the breast cancer transcriptome and a single analysis test for standard markers. In addition, RNASeq may uncover unexpected expression patterns in conventionally-defined HER2 -ve tumors. If reproducible in larger datasets, this technology may provide both standard and novel information previously unavailable to oncologists and their patients.
Splenectomized Patients Have Reduced CD27+ Memory B Cells but Protective Antibody Responses to Pneumococcal Vaccination.
Authors: Heather A. Wasserstrom, Charlotte Cunningham-Rundles, Lony C.L. Lim, Nadia T. Guerrero, Megan H. Wissert, Lin Radigan, James B. Bussel
Journal: Blood (2004)
Analysis of DNA Methylation and Transcription During Granulopoiesis Reveals Timed Methylation Changes in Low CpG Areas That Correlate with Changed Transcriptional Activity.
Authors: Rönnerblad Michelle, Olofsson Tor, Iyadh Douagi, Sören Lehmann, Karl Ekwall, Erik Arner, Andreas Lennartsson
Journal: Blood (2012)
Quantitation of Leukemic Stem Cell Populations Predicts Clinical Outcome in Acute Myeloid Leukaemia
Authors: Charles F. Craddock, Nicolas Goardon, Lynn Quek, Sylvie Freeman, Shamyla Siddique, Manoj Raghavan, Anna Schuh, David Grimwade, Robert K Hills, Cassandra Brookes, Michael Griffiths, James D. Cavenagh, Ravindra Majeti, Irving L. Weissman, Alan K Burnett, Paresh Vyas
Journal: Blood (2011)
Blinatumomab Monotherapy Shows Efficacy in Patients with Relapsed Diffuse Large B Cell Lymphoma
Authors: Andreas Viardot, Mariele Goebeler, Richard Noppeney, Stefan W. Krause, Stefan Kallert, Barbara Ferstl, Andreas Mackensen, Kathrin Rupertus, Martin Soekler, Lothar Kanz, Stefan Knop, Max S. Topp, Jurgen Scheele, Dirk Nagorsen, Gerhard Zugmaier, Evelyn Degenhard, Margit Schmidt, Peter Kufer, Martin Libicher, Hermann Einsele, Ralf Bargou
Journal: Blood (2011)