tbuckley/cabot-search huggingface dataset:
The prognostic value of PSA derivatives in favourable risk localised prostate cancer
Authors: N. J. van As, M. K. Ng, A. R. Norman, R. Huddart, D. Dearnaley, A. Horwich, A. Thompson, R. Woode-Amissah, V. Khoo, C. Parker
Journal: Journal of Clinical Oncology (2007)

5008 Introduction: Risk stratification in localized prostate cancer is based on PSA level, Gleason score and T stage. PSA derivatives may be of additional prognostic value. We have assessed the use of PSA derivatives in the prediction of histologic disease progression on repeat biopsy in patients on active surveillance. Methods: In a prospective cohort study of active surveillance, men with untreated, low- and intermediate-risk, clinically localized prostate cancer (T1/2a, PSA &lt; 15 ng/ml, Gleason score ≤ 3 + 4, and % positive cores ≤ 50%) had repeat octant prostate biopsies 18–24 months after diagnosis. Histologic progression was defined as primary Gleason pattern ≥ 4, or % positive cores &gt; 50 %, or an increase in Gleason score from ≤ 6 to ≥ 7. Standard clinical variables and PSA derivatives were analysed with respect to histologic progression. Multivariate analysis was performed including all standard variables both with each PSA derivative individually, and with all PSA derivatives. Results: 175 men had repeat biopsy. Median age was 67 yrs and median initial PSA, 6.5 ng/ml. Histologic disease progression was seen in 50 (29%) cases. Factors associated with histologic progression on univariate analysis were PSA velocity (p=0.0001), PSA density (p=0.0002), free-total PSA ratio (p=0.002), maximal % core involvement (p=0.009), age (p=0.003), and initial PSA level (p=0.02). On multivariate analysis, each PSA derivative was significant, independent of standard clinical variables. On combined multivariate analysis, free-total PSA ratio (p=0.0027), PSA velocity (p=0.009), age (p=0.0057) and maximal % core involvement (p=0.011) were significant determinants of histologic progression. Conclusions: Free-total PSA ratio and PSA velocity may be useful in the subclassification of favourable-risk localized disease. Larger validation studies in active surveillance patients are warranted. No significant financial relationships to disclose.
Guideline-based treatment utilization, treatment time, and cost of chemotherapy for metastatic colon cancer patients treated in U.S. community oncology practices from 2005 to 2009.
Authors: Yen Phung, Zhaohui Wang, Inga Aksamit, Sarah G. Green, Karen Todoroff, Kimberly A. Bergstrom
Journal: Journal of Clinical Oncology (2012)

e14118 Background: Adherence (Ad) to national treatment guidelines (TG) is important in improving the quality, outcomes, and cost of cancer treatment (TX) in the U.S. We examined regimens (Reg) utilized, TG-Ad, time on metastatic TX, and cost of chemotherapy prescribed by U.S. community oncology practices to treat patients (Pts) with metastatic colon cancer (MCC) in 2005 and 2009. Methods: Adult colon cancer Pts beginning first line metastatic treatment (LOT-1) in each full calendar year for 2005 and 2009 were reviewed from a large U.S. medical oncology clinical database derived from web-based drug dispensing technology. Reg utilized and 2-yr time on metastatic TX were analyzed and compared to TG recommendations. Reg costs based on Medicare reimbursement were compared. Results: The average number of LOT and number of unique drugs Pts were exposed to were similar between 2005 and 2009. About 70% of Pts received only one LOT. In LOT-1 and 2, TG regs were prescribed more often than Non-TG regs for both groups. TG-Ad was significantly higher in 2009 than in 2005 for LOT-1 (p &lt; 0.0001). Pts receiving TG-Ad Reg for LOT-1 had a significantly longer total metastatic treatment time in both 2005 and 2009. In both 2005 and 2009, FOLFOX+Bev was the most frequent LOT-1 Reg given (37% of Pts), while FOLFIRI+Bev was the most frequent LOT-2 Reg given. 69% of Pts received Bev with LOT-1 in both 2005 and 2009; of those, 28-30% continued to receive Bev with LOT-2. Costs for the top 5 LOT-1 Regs were $17,031 to $34,400 and $5,512 to $39,835 for 2005 and 2009, respectively. Conclusions: U.S. community oncology practices significantly improved guideline Ad in the TX of MCC from 2005 to 2009. In LOT-1, TG Regs were prescribed more than non-TG Regs for both groups. TG Ad for LOT-1 significantly improved time on metastatic TX in both groups. FOLFOX+Bev and FOLFIRI+Bev were most frequently prescribed for LOT-1 and LOT-2, respectively. Costs for the five most utilized Regs vary considerably. [Table: see text]
CAPACITY FOR HEART FAILURE DIAGNOSIS AND TREATMENT IN SUB-SAHARAN AFRICA: ANALYSIS OF THE ACCESS, BOTTLENECKS, COSTS, AND EQUITY STUDY IN KENYA AND UGANDA
Authors: Selma Carlson, Herbie Duber, Jane Achan, Gloria Ilikezi, Ali Mokdad, Andy Stergachis, Alexandra Wollum, Gene Bukhman, Gregory Roth
Journal: Journal of the American College of Cardiology (2017)
IMPACT OF TIMING OF INTRA-AORTIC BALLOON COUNTERPULSATION ON MORTALITY IN CARDIOGENIC SHOCK: A SUB-ANALYSIS OF THE IABP-SHOCK II-TRIAL
Authors: Georg Fuernau, Jakob Ledwoch, Ingo Eitel, Suzanne de Waha, Steffen Desch, Karl Werdan, Gerhard Schuler, Uwe Zeymer, Holger Thiele
Journal: Journal of the American College of Cardiology (2017)
LONG TERM SAFETY AND EFFICACY OF LEFT ATRIAL APPENDAGE CLOSURE WITH LARIAT IN ATRIAL FIBRILLATION: IS IT STILL WORKING AT 5 YEARS?
Authors: Valay Parikh, Krzysztof Bartus, Madhu Reddy, Randall Lee, Dhanunjaya Lakkireddy
Journal: Journal of the American College of Cardiology (2017)
VALVULAR SURGERY WITH OR WITHOUT LEFT ATRIAL APPENDAGE EXCISION FOR ATRIAL FIBRILLATION: A CHA2DS2VASC MATCHED ANALYSIS OF THROMBOEMBOLIC OUTCOMES IN A NATIONAL DATABASE
Authors: Ayman Elbadawi, Odunayo Olorunfemi, Gbolahan O. Ogunbayo, Deola Saheed, Amole Ojo, Rowlens Melduni
Journal: Journal of the American College of Cardiology (2017)
Clinical Application of Artificial Intelligence in Patients with Chronic Myeloid Leukemia in Chronic Phase
Authors: Koji Sasaki, Hagop M. Kantarjian, Elias J. Jabbour, Susan O'Brien, Farhad Ravandi, Marina Konopleva, Gautam Borthakur, William G. Wierda, Naval Daver, Koichi Takahashi, Preetesh Jain, Jeffrey Skinner, Mary Beth Rios, Sherry Pierce, Guillermo Garcia-Manero, Jorge E. Cortes
Journal: Blood (2016)
Evaluation de la rentabilité diagnostique de la ponction transduodenale des tumeurs solides pancréatiques avec une nouvelle aiguille flexible de 19 gauges sous contrôle échoendoscopique: étude multicentrique controlée «EasyFlex»
Authors: A Laquière, C Lefort, R Gincul, B Pujol, S Leblanc, N Bertrand, P Grandval, R Laugier, O Croizet, J Boulant, S Koch, B Vedrenne, G Vanbiervliet, F Cholet, G Penranda, L Lecomte, F Prat, C Boustiere
Journal: Endoscopy (2017)

Le siège céphalique est la localisation la plus fréquente des tumeurs du pancréas. La ponction sous echoendoscopie (PE) nécessite dans ce cas un accès transduodénal techniquement difficile du fait des contraintes mécaniques dûes à la torsion de l'endoscope. Les PE avec des aiguilles rigides ou de gros diamètre sont souvent impossibles dans cette situation. L'utilisation d'une aiguille de 19G permettrait d'améliorer la qualité du prélèvement cytologique et de réduire le taux de faux négatifs. Le but principal de notre étude était donc d'évaluer la performance d'une nouvelle aiguille souple 19G, du fait d'une gaine et stylet en Nitinol, pour ponctionner des tumeurs de la tête du pancréas par voie transduodénale.
Trends in the aggressiveness of end-of-life cancer care in the state of Qatar.
Authors: Azza Adel Hassan, Ayman Allam, Hassan Mohsen, Pascale Haddad
Journal: Journal of Clinical Oncology (2015)

e20513 Background: The quality of end-of-life (EOL) care is becoming recognized as a key component of excellence in cancer care. Quality indicators for EOL cancer care constitute a combination of underuse of palliative care services and overly aggressive medical care. Monitoring these quality indicators is crucial to provide continuing excellence in cancer care. Methods: This retrospective, population-based cohort study analyzed all cancer deaths in Qatar registered by the National Death Registry between January 1, 2009 and December 31, 2013. A retrospective chart review of 1,025 patients was conducted to measure markers of EOL cancer care. Aggressiveness of EOL care was then examined by a composite measure adapted from Earle et al. with scores ranging from 0 to 7, in which higher scores indicate more aggressive EOL care. Results: The proportion of patients who experienced at least one event of potentially aggressive EOL cancer care decreased during the 5-year study period from 82.3% to 71.0% (p = 0.038). The proportion of patients admitted to the ICU within 30 days of death decreased from 39.0% in 2009 to 21.1% in 2013 (p = 0.002). In addition, the proportion of patients with more than one ER visit within 30 days of death also decreased from 16.9% in 2009 to 6.0% in 2013 (p <0.01). Other measures did not exhibit any significant change. Finally, the mean composite score for the aggressiveness of EOL care was 2.10 (mean) ± 0.77 (standard deviation), decreasing significantly from 2.24 in 2009 to 1.92 in 2013 (p <0.01). This change can be attributed to significantly reduced proportions of more than one ER visits and ICU admissions within 30 days of death since 2009. Conclusions: The aggressiveness of EOL cancer care has decreased over time in Qatar, whereas the North American trends are increasing. Although trends are decreasing in Qatar, the overall rates of these measures are higher than those in North America. Continuous monitoring of quality indicators along with the integration of alternative palliative care services, such as home-care and hospice services, are required to ensure continuing excellence in cancer care in Qatar.
Age of Blood Does Not Affect Quality of Life and Hemoglobin: N– of −1 Trials in Transfusion-Dependent Patients,
Authors: Maayan Seitelbach, Ian H. Chin-Yee, Jeff Kinney, Justin Chia, Katrina Ormond, Jeff Mahon, GuangYong Zou, Larry Stitt, Cyrus C. Hsia
Journal: Blood (2011)
EVALUATION OF LEFT VENTRICULAR SYSTOLIC FUNCTION AFTER RENAL SYMPATHETIC DENERVATION BY LAYER-SPECIFIC TWO-DIMENSIONAL SPECKLE TRACKING IMAGING
Authors: Yan Jia, Wei Hu, Zhi-Yu Zhao, Hong-Ning Song, Jin-Ling Chen, Rui-Qiang Guo
Journal: Journal of the American College of Cardiology (2017)
THE PRESCRIBING OF ANTIPLATELET THERAPY ONLY IN PATIENTS WITH NONVALVULAR ATRIAL FIBRILLATION: RESULTS FROM THE GARFIELD-AF REGISTRY
Authors: Freek W.A.A. Verheugt, Wael Al Mahmeed, Giuseppe Ambrosio, Pantep Angchaisuksiri, Dan Atar, Jean-Pierre Bassand, A. John Camm, Frank Cools, John W. Eikelboom, Haiyan Gao, Gloria Kayani, Toon Wei Lim, Frank Misselwitz, Martin van Eickels, Ajay Kakkar
Journal: Journal of the American College of Cardiology (2017)
THE EFFECTIVENESS OF EXCIMER LASER ANGIOPLASTY TO TREAT CORONARY IN-STENT RESTENOSIS WITH PERI-STENT CALCIUM AS ASSESSED BY OPTICAL COHERENCE TOMOGRAPHY
Authors: Cheolmin Lee, Richard Shlofmitz, Lei Song, Theofanis Tsiamtsiouris, Thomas Pappas, Antonio Madrid, Fernando Sosa, Mitsuaki Matsumura, Dong Yin, Jeffrey Moses, Elizabeth Haag, Gary Mintz, Akiko Maehara
Journal: Journal of the American College of Cardiology (2017)
MULTIMODALITY INTRAVASCULAR IMAGING TO EVALUATE PLAQUE CHARACTERISTICS IN PATIENTS WITH DIABETES MELLITUS
Authors: Takahiro Yoshimura, Yuliya Vengrenyuk, Hiroshi Ueda, Safwan Kezbor, Choudhury Hasan, Srinivas Kesanakurthy, Javed Suleman, Nitin Barman, Joseph Sweeny, Jason Kovacic, Usman Baber, Pedro Moreno, Roxana Mehran, Jagat Narula, Samin Sharma, Annapoorna Kini
Journal: Journal of the American College of Cardiology (2017)
BRD4 degraders produce long-lasting loss of BRD4 Ppotein and robust efficacy in Burkitt’s lymphoma cells.
Authors: Kevin Coleman, Jing Lu, Yimin Qian, Martha Altieri, Kanak Raina, Hanqing Dong, Jing Wang, John Hines, Andrew P Crew, Craig M Crews
Journal: Journal of Clinical Oncology (2015)

8557 Background: We have created specific BRD4 degraders using PROTAC (PROteolysis TArgeting Chimera) technology. This involves creating bi-functional molecules, with one end having a ligand for BRD4 and the other end a recruiting element for the E3 ligase cereblon. These PROTACs promote the interaction of BRD4 with cereblon, resulting in its degradation via the proteasome degradation machinery. Methods: Treatment of NAMALWA, Ramos, CA-46 and Daudi Burkitt’s lymphoma cells with BRD4 PROTACs leads to rapid loss of BRD4, with near complete loss observed within 4 hours. This effect is potent and long lasting, with the most effective molecules having DC50s in the pM range, and with 1 hour treatment of cells resulting in BRD4 loss over a 3 day period. We examined the functional effects of BRD4 PROTACs in several Burkitt’s lymphoma cell lines, comparing their effects to those observed with the clinical BRD4 inhibitor OTX015. Results: We found that treatment of cells with the BRD4 inhibitor OTX015 led to a rapid and robust hyper-accumulation of BRD4 that, together with the reversible nature of binding to BRD4, may have accounted for the observed moderate suppression of MYC expression, modest inhibition of cell proliferation and lack of cellular apoptosis. In contrast, BRD4 PROTACs maintained suppression of BRD4 protein throughout the several day experiment, maintained near complete MYC suppression and caused both pronounced suppression of proliferation and robust apoptotic responses, as measured by PARP cleavage. Conclusions: These data imply that degradation of BRD4 can provide a more robust therapeutic approach to MYC-driven hematological cancers.
IGH-Mediated Translocations, Recurrent in Classic Hodgkin Lymphoma, Frequently Correlate with an Aggressive Behavior
Authors: Iwona Wlodarska, Daan Dierickx, Ursula Pluys, Kathleen Doms, Carlos Graux, Achiel Van Hoof, Peter Vandenberghe, Lucienne Michaux, Thomas Tousseyn
Journal: Blood (2016)
PREDICTION OF FUTURE CARDIOVASCULAR RISK BY ANALYSIS OF VARIOUS CT CORONARY ANGIOGRAPHY-DETERMINED QUANTITATIVE PLAQUE COMPOSITIONAL CHARACTERISTICS AMONG PATIENTS WITH DIABETES ENROLLED IN THE FACTOR-64 STUDY: THE IMPORTANCE OF THE CALCIFIED CORONARY PLAQUE
Authors: Farangis Lavasani, Heidi May, Alan C. Kwan, George Cater, Boaz D. Rosen, David Bluemke, Donald Lappe, Jeffrey Anderson, Kirk Knowlton, Joao Lima, J. Muhlestein
Journal: Journal of the American College of Cardiology (2017)
A phase II study of temsirolimus and liposomal doxorubicin for patients with recurrent and refractory bone and soft tissue sarcomas.
Authors: Christian Frederick Meyer, Katherine Anne Thornton, Matteo Maria Trucco, Breelyn A. Wilky, Umber Shafique, Maria Carrera-Haro, Preeti Shah, Allen Ray Sing Chen, Jonathan Powell, David Mark Loeb
Journal: Journal of Clinical Oncology (2015)

10560 Background: Sarcomas are a heterogeneous group of connective tissue malignancies with limited palliative treatment options in the unresectable, metastatic setting. Standard chemotherapy treatment offers progression free survival (PFS) benefit measured in months while a significant impact from targeted therapy has not yet been realized. We conducted a phase I/II study of liposomal doxorubicin with temsirolimus in soft tissue and bone sarcomas based on preclinical data showing synergy against sarcoma stem cells. . We previously reported the phase I dose finding data. Here, we report the results of patients treated at the recommended phase II dose. Methods: 18 patients were treated at liposomal doxorubicin 30 mg/m2 monthly with temsirolimus 20 mg/m2weekly. A variety of subtypes were enrolled including 5 rhabdomyosarcomas, 3 leiomyosarcomas, and 2 mesenchymal chondrosarcomas. 11 of the 18 patients had prior doxorubicin exposure and a median of 2 prior lines of chemotherapy. Results: PFS was 315 days (range 27-799) and event free survival (EFS) was 119 days. Response rate, defined as stable disease (SD) or better for 60 days (2 cycles) was 53% (8 of 15) at the recommended phase II dosing (RP2D) and 56% (10 of 18) including the subjects treated with the higher dose of temsirolimus. Those who responded to therapy (defined as SD or better at first evaluation) tended to have prolonged responses, with median PFS for this group of 358 days (range = 75 – 799) and median EFS of 249 days. Pharmacodynamic analysis of target inhibition in 12 evaluable patients revealed concordance between inhibition of pS6K and response in 8 patients and inhibition of pAKT and response in 9 patients. The treatment was well-tolerated with only 4 patients experiencing a significant change in their ECOG performance status. Conclusions: Overall, the synergy of this combination bears further investigation of both metabolic and traditional chemotherapeutic agents in sarcomas. Clinical trial information: NCT00949325.
T-regulatory cell function analysis in locally/regionally advanced melanoma patients treated with ipilimumab.
Authors: Robert Alan VanderWeele, Lisa H. Butterfield, Hui-Min Lin, Diana E. Cunningham, Yan Lin, John M. Kirkwood, Ahmad A. Tarhini
Journal: Journal of Clinical Oncology (2013)

3041 Background: We conducted an immunogenicity and biomarker analysis in stage IIIB-C melanoma patients treated with neoadjuvant ipilimumab (ipi) and reported a significant increase in the frequency of circulating T-regulatory cells (T-reg) (CD4+CD25hi+ Foxp3+; p=0.02 CD4+CD25hi+CD39+; p=0.001) from pre-ipi (baseline) to post-ipi (6 weeks) in treated patients (Tarhini et al., ASCO 2012). Also, increases in T-reg were associated with improved PFS (p=0.034; HR=0.57). We hypothesized that ipi induces its clinical activity in part through its effect on T-reg, and despite the observed increase in circulating T-reg frequency; their suppressor function is reduced. Methods: Patients were treated with ipi (10 mg/kg IV q3weeks x 2doses) bracketing definitive surgery. PBMC were collected at baseline and at 6 weeks. T-reg were isolated from pre-ipi (baseline) and post-ipi (6 weeks) PBMC samples utilizing Miltenyi Biotec T regulatory isolation kit (CD4+CD25+CD127 dim/- ). Isolated T-reg were incubated with OKT3/IL-2/CD28-stimulated and CFSE-labeled CD4+CD25- responder T-cells from the same patient time point at 1:1, 1:2 and 1:5 ratios. Flow cytometery was used to evaluate the number of cell divisions of CFSE labeled responder cells and, therefore, the degree of T-reg proliferation suppression. Results: Thirty-five patients were enrolled in the study; of those, 18 patients had adequate PBMC samples with sufficient T-reg isolated for T-reg functional analysis. Preliminary analysis of the first 13 patients shows a trend toward decreased suppressive function of T-reg after treatment with ipi. Expressed as “percent of maximum inhibition”, pre- vs. post-ipi T-reg showed 61% vs. 47% suppressive activity (p=0.15) at the 1:1 ratio. Conclusions: There was a trend toward decreased suppressive function of T-reg after treatment with ipi, supporting the function modulation hypothesis. T-reg functional analysis for the remaining 5 patients is ongoing and we will perform comparative studies of changes in T-reg function with changes in T-reg frequency and clinical outcomes in the entire cohort.
Nuclear localization of NF-kappaB p65 in primary prostate tumors is predictive of pelvic lymph node metastases
Authors: L. Lessard, P. Bellon-Gagnon, M. Alam-Fahmy, P. Karakiewicz, A. Mes-Masson, F. Saad
Journal: Journal of Clinical Oncology (2006)

10077 Background: Pelvic lymph node metastases are associated with a greater risk of prostate cancer recurrence and peripheral metastasis. Unfortunately, markers predictive of lymph node metastasis and/or recurrence after radical prostatectomy are limited and new molecular markers are needed to identify patients at higher risk of progression. NF-kB (p65) is a candidate molecular marker already associated with poor clinical outcomes such as biochemical recurrence and bone metastasis. We have also reported elevated nuclear p65 expression in prostate cancer lymph node metastasis. Pertinent to this issue, we tested whether the nuclear localization of p65 in radical prostatectomy specimens could predict the presence of lymph node metastases. Methods: Following informed consent, 51 patients who underwent radical prostatectomy were included in the study: 20 patients had lymph node metastasis at surgery and 31 patients had no evidence of lymph node metastasis and were used as the control group. All cases in the control group had no biochemical relapse 5 years following radical prostatectomy. NF-kB expression in prostate tumor sections was assessed by immunohistochemistry using a monoclonal NF-kB p65 antibody. The relation between nuclear p65 expression in primary tumors and lymph node metastasis was tested in univariate and multivariate Cox regression models. Results: Primary tumors of metastatic patients had an average of 21.25% of tumor cells with nuclear p65 expression as opposed to 9.42% of tumor cells of control patients (p=0.001). Univariate Cox regression demonstrated a 7.5% increased risk of having lymph node metastases for each percent increase in p65 nuclear staining (p=0.003). In the multivariate model, after controlling for pre-operative PSA (p=0.175), Gleason patterns (p=0.382), pathological stage (p=0.436), extracapsular extension (p=0.243) and seminal vesicle invasion (p=0.016), nuclear p65 was associated with an 8.8% increased risk for lymph node metastases (p=0.024). Conclusion: In univariate and multivariate analyses, p65 nuclear expression was strongly predictive of lymph node invasion. We propose that nuclear NF-kB (p65) may serve as a useful independent molecular marker for stratifying patients at risk for lymph node metastases. No significant financial relationships to disclose.
Epidural Spinal Cord Compression from Metastatic Tumor: An Analysis of Eighty-Three Patients Treated with Radiation Therapy and Steroids
Authors: H. S. Greenberg
Journal: Neuro-Oncology (1980)

At Memorial Sloan-Kettering Cancer Center epidural cord compression is the second most frequent neurologic metastatic complication of cancer, only cerebral metastases occurring more frequently.
HEART FAILURE CARE TRANSITIONS: QUEUING THEORY-BASED COST-EFFECTIVENESS ANALYSIS OF OUTPATIENT CLINIC CAPACITY SIZING
Authors: Raja Kannan Mutharasan, Preeti Kansal, Hannah Alphs Jackson, Allen Anderson, Michael Abecassis, Charles Davidson, Gary Noskin, Itai Gurvich, Jan Van Mieghem, Clyde Yancy
Journal: Journal of the American College of Cardiology (2017)
PLASMA EICOSAPENTAENOIC ACID AND THE EICOSAPENTAENOIC ACID TO ARACHIDONIC ACID RATIO IN 8,010 PATIENTS WITH SEVERELY ELEVATED LDL-C (&gt;190 MG/DL): CAUSE FOR ALARM?
Authors: Mike Mehan, John Nelson, Rosalynn Gill, Ernst Schaefer
Journal: Journal of the American College of Cardiology (2017)