tbuckley/cabot-search huggingface dataset:
Preliminary study of three tumor markers for hepatocellular carcinoma: AFP, AFP-L3, and Glypican-3
Authors: H. Li, K. Z. Qu, R. M. Ner, A. D. Sferruzza, R. A. Bender
Journal: Journal of Clinical Oncology (2007)

15014 Background: a-Fetoprotein (AFP) is the most widely used biochemical marker for detection of hepatocellular cancer (HCC). AFP is also elevated in acute and chronic liver disease, limiting its utility as an early indicator of HCC. Recently, AFP-L3 and glypican 3 (GPC3) have been reported for early detection of HCC. AFP-L3 is a glycoform of AFP produced by malignant liver cells. Measurement of AFP-L3 as a percentage of total AFP helps distinguish non-malignant hepatic disease from HCC. GPC3 is a heparin sulfate proteoglycan anchored to the plasma membrane. The level of GPC3 in the serum of HCC patients is higher than in the serum of healthy adults or patients with non-malignant hepatopathy. We tested the concordance of AFP, AFP, AFP-L3%, and GPC3and GPC3 to determine if their simultaneous measurement may increase the sensitivity of identifying individuals at risk for HCC. Method: De-identified clinical samples (n = 176) submitted for AFP-L3% measurement were tested. AFP and AFP-L3 levels were measured using the LiBASys automated analyzer (Wako Chemicals USA Inc, Richmond, VA). GPC3 levels were measured with a commercial ELISA kit (BioMosaics, Inc, Burlington, VT). To assess concordance we categorized results according to accepted cut-off values for AFP and AFP-L3, and a clinically established reference range for GPC3. Results: Fourteen of the 176 samples had elevated GPC3 (=180pg/mL), 6 (43%) of which had normal AFP values (&lt;20ng/mL). Forty- seven of the 176 samples had elevated AFP-L3% (L3 =10%), 6 (12.8%) of which had normal AFP levels. Conclusion: These data suggest that GPC3 and AFP-L3% may be used as supplemental markers, and the simultaneous determination of AFP, AFP-L3, and GPC3 may provide a higher sensitivity for identifying individuals with increased risk of HCC. [Table: see text] No significant financial relationships to disclose.
2-Fluorine-18-fluoro-2-deoxy-D glucose positron emission tomography in the pretreatment staging of Hodgkin's disease: Influence on patient management in a single institution
Authors: S. Partridge, A. Timothy, M.J. O'Doherty, S.F. Hain, S. Rankin, G. Mikhaeel
Journal: Annals of Oncology (2000)
O118 : Optimizing the prenylation inhibitor lonafarnib using ritonavir boosting in patients with chronic delta hepatitis
Authors: C. Yurdaydin, R. Idilman, I. Choong, C. Kalkan, O. Keskin, M.F. Karakaya, A.E. Tuzun, E. Karatayli, M. Bozdayi, D. Cory, J.S. Glenn
Journal: Journal of Hepatology (2015)
Abstract 8521: Early Extracorporeal Membrane Oxygenator-Assisted Primary Percutaneous Coronary Intervention Improved 30-Day Clinical Outcomes in Patients with STEMI Complicated with Profound Cardiogenic Shock
Authors: Jiunn-Jye Sheu, Tzu-Hsien Tsai, Sarah Chua, Hon-Kan Yip
Journal: Circulation (2011)

Objectives: This study tested the hypothesis that early extracorporeal membrane oxygenator (ECMO) offered additional benefits in improving 30-day outcomes in patients with acute ST-segment elevation myocardial infarction (STEMI) complicated with profound cardiogenic shock undergoing primary percutaneous coronary intervention (PCI). Methods: Between May 1993 and July 2002, 920 acute STEMI patients underwent primary PCI. Of these patients, 12.5% (115) with cardiogenic shock were enrolled into this study (Group 1). Between August 2002 and December 2009, 1650 acute STEMI patients underwent primary PCI. Of these patients, 13.3% (219) complicated with cardiogenic shock were enrolled (Group 2). Results: Incidence of profound shock [defined as systolic blood pressure remained ≤ 75 mmHg after intra-aortic balloon pump and inotropic agent supports] was similar in both groups (21.7% vs. 21.0%, p&gt;0.5). ECMO support, which was only available for group 2 patients, was performed at catheterization room. The results demonstrated that final thrombolysis in myocardial infarction (TIMI)-3 flow in infarct-related artery was similar between the two groups (p=0.678). However, total 30-day mortality and the mortality of profound shock patients were lower in group 2 than in group 1 (all p &lt;0.04). Additionally, the hospital-survival time was remarkably longer in group 2 than in group 1 patients (p=0.0005). Moreover, multivariate analysis demonstrated that unsuccessful reperfusion, presence of advanced congestive heart failure, profound shock, and age were independent predictors of 30-day mortality (all p&lt;0.02). Conclusion: Early ECMO-assisted primary PCI improved 30-day outcomes in STEMI patients complicated with profound cardiogenic shock (The following figure is the detailed schematic presentation of the enrollment status of the patients and their clinical outcome).
Prothrombin Time and Bleeding Events in Patients Undergoing Total Hip or Knee Replacement Surgery Receiving 10 Mg Rivaroxaban.
Authors: Sylvia Haas, Alexander GG Turpie, Michael Rud Lassen, Ajay K Kakkar, Bengt Eriksson, Kai Vogtlaender, Dagmar Kubitza, Wolfgang Mueck, Michael Gent, Frank Misselwitz, Scott D Berkowitz
Journal: Blood (2009)
Association of Immunotherapies With Outcomes in Relapsing-Remitting Multiple Sclerosis
Authors: Irene Tramacere, Cinzia Del Giovane, Graziella Filippini
Journal: JAMA (2016)

What immunotherapies for multiple sclerosis are associated with the greatest benefit and highest risk of discontinuation due to adverse events in patients with relapsing-remitting multiple sclerosis?Alemtuzumab, natalizumab, and fingolimod were associated with the greatest benefit with regard to relapse prevention. Their association with prevention of disability worsening was unclear. Fingolimod was associated with a high risk of treatment discontinuation due to adverse events.
dtect<i>Dx</i> Breast: A serum biomarker test for breast cancer detection used in conjunction with traditional mammography screening.
Authors: Meredith C. Henderson, Keri Sweeten, Sherri Borman, Christa Corn, Lindsey Gordon, David E. Reese
Journal: Journal of Clinical Oncology (2013)

18 Background: Provista Diagnostics has developed a test that analyzes serum concentrations of 5 protein biomarkers in order to detect breast cancer. The dtectDx Breast test utilizes a proprietary algorithm that has been described previously (Weber et al. 2010). In this study, it was noted that the algorithm performs best in women under age 50. The aim of this study was to evaluate the performance characteristics of dtectDx Breast in women under age 50 in a commercial setting and compare the results with data from the previous clinical study. Methods: The dtectDx Breast test measures the concentrations of IL-8, IL-12, VEGF, CEA, and HGF via ELISA. These data combined with select patient characteristics and Provista’s proprietary algorithm result in a test value that is characterized as normal or elevated. dtectDx Breast test reports issued for women under age 50 were reviewed from a 3-year time period and prescribing physicians were interviewed regarding follow-up care and outcome measures (largely imaging studies, if warranted). Results: Of the 908 patients, 8 samples were rejected based on serum quality. Of the remaining 900 patients, 121 were reported as elevated (12.7%). In 4 cases, these elevated results were confirmed cases of breast cancer. Of these, 2 patients initially showed no screening evidence of cancer, but upon further evaluation (after receipt of dtectDx Breast results) were diagnosed with breast cancer. dtectDx correctly identified DCIS 66% of the time (n=2). Conclusions: These results describe the use of dtectDx Breast in a clinical setting and confirm that the assay behaves similarly to previously published results (Weber et al 2010). While the false-positive rate is higher than predicted (12.7% vs 6.8%), the assay correctly identified 4 of 4 invasive cancers and 2 of 3 DCIS cases. Since two of the invasive cancer cases were originally not detected via standard screening procedures, the assay has demonstrated important clinical utility when used in conjunction with mammography/standard of care. Here we show that, in the commercial patient population, when combined with standard of care, dtectDx Breast improves the detection of breast cancer in women under 50.
Immunophenotyping by flow-cyotmetry in MDS and its potential role in remission assessment post treatment
Authors: D. A. Westerman, K. L. Burbury, P. Gambell, N. Came, J. F. Seymour, H. M. Prince
Journal: Journal of Clinical Oncology (2008)

18008 Background: Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms with abnormal maturation and differentiation of one or more cell lineages. Diagnosis is complex and attained by evaluation of peripheral blood, bone marrow biopsy and cytogenetics/FISH. Immunophenotyping (IP) has recently been recommended as a co-criterion for diagnosis in a recent consensus publication by Valent et al. Its role in remission assessment is yet to be defined. Our aim was to evaluate the role of IP in a prospective MDS cohort treated with lenalidomide and stem cell factor and correlate morphological response with a modified MDS flow-cytometric scoring system by Wells et al. This scoring system encompasses aberrancy of myelomonocytic populations ranging from 0 in normals to 8 if multiple myelomonocytic aberrancy is determined. Methods: Four colour flow-cytometric analysis was performed to assess blast, granulocytic and monocytic populations. Antibody combinations were compared against isotype controls. Patterns of antibody expression were assessed on marrow samples from 5 normal volunteer donors and 16 haematology patients with a normal peripheral blood and bone marrow evaluation. Sequential assessment was performed using Cheson 2006 morphologic response criteria and modified MDS flow-cytometric scoring system. Results: Normal volunteers included 3 males, median age 27 (range 25–43). The haematology cohort included 16 lymphoma patients, median age 46 (range 19–79). 8 MDS patients were evaluable, median age 57 (range 43–89), including 6 males. MDS WHO subtypes included 3 cases 5q- syndrome, 2 RCMD ± (RS), 2 MDS-U, 1 RAEB type I. 5q- syndrome patients had isolated karyotypic anomalies, 5 patients had a normal karyotype. MDS flow scores pretreatment ranged from 3–5. Of the 6 patients who responded (4 CR, 2 PR) 4 demonstrated substantial improvement in their MDS flow scores with one attaining a normal score. 1 patient did not have sequential immunophenotyping after early withdrawal from the trial. Conclusions: This early cohort demonstrates potential utility of the MDS scoring system not only as a diagnostic tool but in post treatment response assessment. Larger numbers of patients are required in a prospective setting for confirmation of these findings. No significant financial relationships to disclose.
Abstract 16377: Normal Cardiac Adaptation During Pregnancy - Assessment by Velocity Vector Imaging and Three-Dimensional Echocardiography in Healthy Pregnant Women
Authors: Tasneem Z Naqvi, Ming Sum Lee, Michael Aldridge, Reza Rafie, Alyssa Bamba, Meena Narayanan
Journal: Circulation (2013)

Background: The heart undergoes morphological and physiological changes during pregnancy. Three-dimensional (3D) echocardiography (echo) allows chamber volume assessment independent of geometric as...
Survey of long-term follow-up programs in the United States for adult survivors of childhood brain tumors
Authors: D. C. Bowers, S. Adhikari, Y. M. El-Khashab, L. Gargan, K. C. Oeffinger
Journal: Journal of Clinical Oncology (2008)

10047 Background: Despite recognition that childhood brain tumor survivors often suffer multiple late effects following therapy, little is known regarding the long-term follow-up (LTFU) programs for these patients. Methods: A 16 question survey was mailed to member institutions (n = 197) of the Children’s Oncology Group (COG) in the US. The survey asked about the size of the childhood brain tumor program, activities of the LTFU program, and barriers to follow-up. Results: 143 (72.6%) institutions returned surveys. Variation existed in the size of brain tumor centers, including <4 brain tumor patients/year (15.7%); 5 - 14 patients/year (41.0%); 15 - 29 patients/year (20.1%); and 30+ patients/year (23.1%). Care for brain tumor patients who were < 18 years old at diagnosis but are now > 21 years old was provided at a designated LTFU clinic for young adults (24.8%), neuro-oncology clinic (21.7%), pediatric oncology clinic (19.4%), adult neuro-oncology program (10.9%), or by other means (23.3%). 90.4% of programs reported integrating COG LTFU Guidelines into the care of their brain tumor survivors. Among medulloblastoma survivors, great variability existed among institutions’ reported use of growth hormone. Larger programs reported higher frequencies of growth hormone use among medulloblastoma survivors than smaller programs (p = < 0.001). Variability existed with regard to interval until discontinuation of surveillance MRIs among medulloblastoma survivors: < 5 years = 20.6%; 6 - 10 years = 37.4%; 11 - 20 years = 17.6%; and never = 24.4%. Among perceived barriers to care, respondents cited lack of insurance (35.3%), lack of funding or dedicated time for providers (24.4%), patients’ uncertainty or unwillingness to follow-up (22.7%), or patients being lost to follow-up (17.6%). Conclusions: Considerable variability exists among LTFU programs for adult survivors of childhood brain tumors. We recommend integration of the COG LTFU Guidelines and efforts to eliminate barriers to follow-up. No significant financial relationships to disclose.
Where is the care in healthcare? How health systems are feeding their own negative spiral of cost and disability
Authors: Jørgen Jevne
Journal: British Journal of Sports Medicine (2015)

Musculoskeletal (MSK) pain is a global problem: low back pain, neck pain and osteoarthritis are leading causes for disability worldwide. Exercise therapy has historically been a dark horse in MSK treatment, with pain-medication, injection and surgery representing the elixir of medical management. However, given the questionable evidence for these procedures that are not without risk, one could argue that exercise prescribed within a biopsychosocial framework may be considered a panacea for many diseases including MSK pain.1 ,2 Unfortunately, a major problem with exercise therapy is compliance with long-term strategies demanding time and effort,3 thus potentially paving the way for more invasive alternatives. The reimbursements seen in many modern health systems are largely based on history and tradition, and this dysfunctional funding might actually play an important role in the negative spiral surrounding MSK management. Surprisingly, this is frequently a overlooked factor in the current literature.

The global burden of MSK disease is a …
Long median survival with capecitabine (X) single-agent therapy for patients (pts) with anthracycline- and taxane-pretreated metastatic breast cancer (MBC)
Authors: R. Largillier, P. Fumoleau, C. Clippe, V. Dieras, H. Orfeuvre, T. Lesimple, S. Culine, B. Audhuy, D. Serin, L. Bobadilla
Journal: Journal of Clinical Oncology (2006)

10710 Background: X (Xeloda) is an oral fluoropyrmidine with consistently high activity in MBC, a good safety profile with little myelosuppression and no alopecia, and the convenience of oral administration. The addition of X to docetaxel in anthracycline-pretreated pts also increases survival. This non-randomized phase II study was conducted to evaluate the efficacy, safety and impact on quality of life (QoL) of X in pts with MBC pretreated with anthracyclines and taxanes. Main findings from this trial have been published previously [Fumoleau et al. Eur J Cancer 2004;40:536–42]. Here we present mature data after a follow-up of 48 months. Methods: Pts with anthracycline- and taxane-pretreated MBC received X 1250 mg/m 2 twice daily on days 1–14 every 3 weeks for a median of 6 cycles (range 1–15). Results: Baseline characteristics of the 126 pts enrolled were typical of a pretreated MBC population. X achieved complete/partial response or stable disease in 63% of patients (overall response rate, 28%). Median time to progression was 4.9 months (95% CI: 4.0–6.4).Median duration of response was 5.9 months (95% CI: 4.5–12.7). The only grade 3/4 events occurring in ≥ 10% of patients were diarrhea (10%) and HFS (21%). The most common grade 3/4 laboratory abnormality was granulocytopenia (14%). After a follow-up of 48 months, 8 patients are still alive. Updated median overall survival is 15.9 months (95% CI: 13.5–21.3). 1-, 2- and 3-year survival rates are 63%, 37% and 17%, respectively. QoL assessment showed that X treatment was associated with an increase in mean Global Health Score up to cycle 6, with the increase maintained at subsequent evaluations. Conclusions: X is highly active in patients with anthracycline- and taxane-pretreated MBC, leading to a long median survival of 15.9 months. X is also well tolerated and improves QoL. [Table: see text]
Thrombosis complicating advanced non-small cell lung cancer (NSCLC) treatment
Authors: K. B. Alguire, J. Rigas, K. Dragnev, L. Zacharski, B. Virginia, W. Disalvo, I. Williams, M. Carey
Journal: Journal of Clinical Oncology (2004)

8082 Background: Lung cancer is the leading cause of cancer death and thromboembolism (TE) is a significant cause of morbidity and mortality in this disease. The exact incidence of TE in lung cancer is unknown (Am J Hematol 72: 43–52, 2003). This study reports the incidence of TE in patients (pts) with advanced NSCLC participating in a randomized clinical trial comparing chemotherapy regimens with and without platinum. Methods: Eligibility: pathological stage IIIB/IV NSCLC, PS 0–2, and no prior chemotherapy. Randomized pts received either a platinum based (PB, carboplatin and docetaxel) or a non-platinum based (NPB, gemcitabine and docetaxel) therapy. The incidence of serious adverse events (SAEs) was collected for all pts and analyzed by treatment group. SAE criteria 1) death; 2) inpatient hospitalization, 3) prolongation of existing hospitalization; 4) significant disability/incapacity; 5) a congenital anomaly/birth defect; or 6) a life-threatening event. Results: To date, 732 pts have been enrolled: The study groups are balanced for gender, age, PS, stage, and histology. A total of 319 SAEs by pt have been reported; 135 pts on PB and 184 pts on NPB. 25% of the SAEs were treatment related and 91% were hospitalizations. The most common SAEs were pneumonia (69 pts - 9%), progressive disease (47 pts - 6%), and dehydration (27 pts - 3.7%). TE was the primary SAE in 42 pts (6%), 26 pts on the NPB arm and 16 pts on the PB arm. The Fischer's exact test for difference between treatment arms was p = 0.09. Of the TEs, 52% were pulmonary emboli, 36% deep venous thrombosis, and 12% both. Conclusions: To our knowledge, this is the first large prospective trial to evaluate the incidence of clinically significant thrombosis in advanced NSCLC. There is no statistical difference between the arms in terms of TE, although TE was more common in patients treated with NPB therapy. TEs are serious adverse events of which may potentially be prevented by prophylactic heparin. Unfractionated and low molecular weight heparin have demonstrated favorable effects on the course of NSCLC and these effects are currently under investigation in our institution. Funded in part by CA23108. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis Abbott; Amgen; Aventis; Bristol-Myers Squibb; Genentech; GlaxoSmithKline; Ortho Biotech; Ligand; Merck; Pfizer; OSI; Roche
A gene expression signature associated with sensitivity to the multikinase inhibitor dasatinib: Implications for development of a noninvasive biomarker for personalized therapy based on circulating tumor cell analysis.
Authors: N. Mitsiades, Y. Antipin, B. Reva, N. Schultz, D. C. Danila, C. C. Sung, A. Anand, C. Sander, H. I. Scher
Journal: Journal of Clinical Oncology (2010)

4544 Background: Src and other Src-family kinases (SFKs) promote prostate cancer (PC) cell growth, survival, invasion, migration and the transition from castration-sensitive to castration-resistant PC (CRPC). Dasatinib, an oral inhibitor of SFKs and other kinases, is active in preclinical CRPC models and in a subset (∼20%) of CRPC patients. These results support the use of dasatinib as a targeted therapy for CRPC, but highlight an unmet need to qualify predictive biomarkers of sensitivity to the drug to guide treatment selection. Methods: Anovel statistical approach for determining characteristically expressed genes (biomarkers) and optimal clustering of discretized expression profiles was applied to a published gene expression dataset of PC cell lines with variable sensitivity to dasatinib (GSE9633) and to a panel of 150 banked primary and metastatic PC specimens. Results: We identified 68 unique transcripts, each predicting in vitro sensitivity or resistance to dasatinib with 100% accuracy. Many of the transcripts identified regulate transcription, TGFβ, Myc, Akt/PTEN and hormone-independent signalling, and have established roles in CRPC pathophysiology, supporting the biological relevance of the signature. Moreover, 56/131 (43%) primary and 5/19 (26%) metastatic tumor specimens were predicted to be sensitive to dasatinib. Applying this PC-derived signature to a panel of breast cancer cell lines predicted in vitro sensitivity to the drug with 78% accuracy, suggesting the presence of common biological pathways. Conclusions: The predicted frequency of sensitivity to dasatinib in metastatic PC specimens was comparable to the PSA decline rate in phase II trials enrolling unselected CRPC patients. We are currently quantifying the expression of these transcripts by multiplex qRT-PCR in circulating tumor cells harvested from CRPC patients that will be enrolled in a clinical trial to generate evidence to qualify the signature as a noninvasive predictive biomarker of sensitivity to dasatinib in patients with CRPC. No significant financial relationships to disclose.