tbuckley/cabot-search huggingface dataset:
The value of personalized treatment (Rx) planning (PTP): Cost savings (sav) by the Microculture Kinetic (MiCK) chemosensitivity (CS) assay, evidence from a large American self-insured company (ASIC)
Authors: R. G. Latimer, C. A. Presant, A. E. Hallquist, M. Perree, D. Agapitos
Journal: Journal of Clinical Oncology (2009)

e17541 Background: Costs of cancer (CA) patient (PT) Rx are high. A novel CS assay MiCK was predictive of chemotherapy (CT) activity and survival in leukemia PTs (Blood. 2001;98:241b) and is in solid tumor testing. We performed a cost sav analysis for CS assay in a large ASIC population. Methods: An ASIC of 48,927 employees submitted 3.5 years claims data on all PTs with diagnoses of CA lung, breast, colon or ovary. Analysis of average Rx costs was made based upon total CT usage, Rx of selected PTs including therapeutic drug administration (admin), CT admin, supportive care (SC) drugs, CT drugs, biotherapy (BT) drugs, growth factors, home infusion costs, and cost of the MiCK assay. Average CT and BT drug costs were determined. We assumed high MiCK predictability for CT activity from solid tumor pilot studies and leukemia results. 4 models were evaluated: CT with a single active drug from MiCK for the duration actually given (ASC); CT with active drugs for the entire time (AC100); CT for 50% of the time period (AC 50) assuming a CT “holiday” for the other 50% of time; and CT with active drugs plus BT for 50% of the time (ACB 50). The costs in these 4 models were compared to actual claims payments. Results: 196 PTs had CA during the 3.5 year period. 55 had CT. Total costs for CT were $5,647,165. Costs for IV CT drugs, SC drugs and drug admin were $1,149,404. Assuming the use only of active CT selected by MiCK assay, under model ASC average sav/PT was 85.3% of CT, SC and admin costs. Under model AC100, the average sav/PT were 26.0%. Under model ACB 50, the sav were 48.6%. In model AC 50, the sav were 62.7%. When the overall costs were evaluated, model ASC sav were 17.4%, model AC 100 5.3%, model ACB 50 9.9% and model AC 50 12.8%. Conclusions: PTP using the MiCK CS assay could save a high percentage of CT costs, and a substantial percentage of overall costs of CA care in an ASIC. Sav varied from 9.9% to 62.7% depending on effectiveness and duration of Rx, and necessity for continuing BT not testable by MiCK. The true value of PTP with MiCK could be higher, since use of active CT would increase quality of life and employment, and reduce disability and side effects. [Table: see text]
Glypican-3 level assessed by the enzyme-linked immunosorbent assay is inferior to alpha-fetoprotein level for hepatocellular carcinoma diagnosis
Authors: Yejoo Jeon, Eun Sun Jang, Yun Suk Choi, Jin-Wook Kim, Sook-Hyang Jeong
Journal: Clinical and Molecular Hepatology (2016)

Glypican-3 (GPC3) protein is highly expressed in hepatocellular carcinoma (HCC) tissue. It has been suggested as a diagnostic biomarker, but its inconsistent performance means that it requires further assessment. We therefore investigated the diagnostic value of the plasma GPC3 level compared to the alpha-fetoprotein (AFP) level as a diagnostic biomarker of HCC.We enrolled 157 consecutive patients with newly diagnosed HCC and 156 patients with liver cirrhosis (LC) as the control group. GPC3 plasma levels were measured using two commercially available enzyme-linked immunosorbent assays (ELISAs, named as Assay 1 and 2), and AFP levels were measured using an enzyme-linked chemiluminescent immunoassay. The diagnostic accuracy was analyzed using the receiver operating characteristics (ROC) curve.Plasma GPC3 levels in HCC patients were very low (0-3.09 ng/mL) in Assay 1, while only 3 of the 157 patients (1.9%) showed detectable GPC3 levels in Assay 2. The median GPC3 level was not significantly elevated in the HCC group (0.80 ng/mL) compared with the LC group (0.60 ng/mL). The area under the ROC curve (AUC) for GPC3 was 0.559 in Assay 1. In contrast, the median AFP level was significantly higher in HCC (27.72 ng/mL) than in LC (4.74 ng/mL), with an AUC of 0.729.The plasma level of GPC3 is a poor diagnostic marker for HCC, being far inferior to AFP. The development of a consistent detection system for the blood level of GPC3 is warranted.
Clinical Activity of Lucatumumab (HCD122) In Patients (pts) with Relapsed/Refractory Hodgkin or Non-Hodgkin Lymphoma Treated In a Phase Ia/II Clinical Trial (NCT00670592)
Authors: Arnold S. Freedman, John Kuruvilla, Sarit E. Assouline, Andreas Engert, DaeSeog Heo, Philippe Solal-Celigny, Paolo Corradini, Gregor Verhoef, Michelle A. Fanale, Jennifer Bendiske, Brett Ewald, Jyotirmoy Dey, Johan Baeck, Anas Younes
Journal: Blood (2010)
A Multicenter Phase I/Ib Study of Ipilimumab for Relapsed Hematologic Malignancies after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Matthew S. Davids, Haesook T. Kim, Caitlin L. Costello, Peter A. McSweeney, Rebecca Liguori, Alexander Lukez, David Avigan, Yi-Bin Chen, Nicole LeBoeuf, Vincent T. Ho, Corey S Cutler, John Koreth, Edwin P. Alyea, Joseph H Antin, Jerome Ritz, Philippe Armand, Edward D Ball, Asad Bashey, Robert J. Soiffer
Journal: Blood (2015)
Beta-3-adrenoceptors: a putative therapeutic target in liver cirrhosis of humans and animals
Authors: Jonel Trebicka, Martin Hennenberg, Andrea Schulze Proebsting, Frank Lammert, Wim Laleman, Lien Van Landeghem, Frederik Nevens, Joerg Heller, Tilman Sauerbruch
Journal: Hepatology (2008)
The CD40-Receptor Is Upregulated on Monocytes from Patients with Low-Risk Myelodysplastic Syndromes and Its Inhibition by a Monoclonal Anti-CD40 Antibody Can Increase Colony Formation.
Authors: Stef Meers, Ahmad Kasran, Louis Boon, Marc Boogaerts, Peter Vandenberghe, Gregor Verhoef, Catherine Verfaillie, Michel Delforge
Journal: Blood (2006)
Antitumoral effect of gemcitabine metronomic schedule in a xenograft pancreatic model
Authors: B. Laquente, C. Lacasa, M. Morell, O. Casanovas, A. Figueras, M. Galán, F. Viñals, G. Capella, J. Germá
Journal: Journal of Clinical Oncology (2006)

12031 Background: Human tumor xenografts in mice can be remarkably predictive of response in humans to cytotoxic chemotherapeutic drugs. Tumor endothelial cells are sensitive to the action of conventional cytotoxic drugs when they are regularly administrated at low doses. This concept, known as metronomic chemotherapy, has been demonstrated in preclinical studies using transplanted tumor models. We aim to investigate the potential anti-tumoral activity of Gemcitabine (G) when administered in a low-dose schedule in an ortothopic implantation model of human pancreatic carcinomas. Methods: Standard gemcitabine schedule: NP18 tumor orthotopically implanted nude mices were randomly distributed to experimental (n = 13, G100 mg/kg intraperitoneally on days 0, 3, 6 and 9 post-implantation) and control group (n = 13, saline). Animal were sacrificed after 4 weeks and we compared weigths (grams) and volume (cm3) of tumors betwen the two groups by the Mann-Whitney U test. Metronomic schedule: After a toxicological study an optimal metronomic dose of 1 mg G /kg per day was chosen. Thirty xenografted mices were randomly distributed to experimental group (n = 15, intraperitoneal G1 mg/kg) and control group (n = 15, saline) and treated for 30 days. Animal were analysed as described before. Results: Standard schedule: Tumor weight mean of treatment group was 0.01 grams ± 0.01 versus 0.54 grams ± 0.48 of the control group. Tumor volume mean in G group was 0.01 cm 3 ± 0.01 versus 0.51 cm 3 ± 0.67) in the control group.Treatment significantly inhibited NP18 tumour growth (p &lt; 0.001). No differences in mice weight were observed between both groups. Metronomic schedule: Tumor weight mean in the treatment group was 0.04 grams ± 0.08 versus 0.53 grams ± 0.46 in control group. Tumor volume mean in G group was 011 cm 3 ± 0.19 versus 0.37 cm 3. Treatment with low-dose of G significantly inhibited NP18 tumour growth (p &lt; 0.003). There were no differences in mice weight between the two groups. Conclusions: Our data show that G administered in a metronomic schedule is effective in inhibiting the growth of NP18 tumor orthotopically implanted in the nude mice. We now aim to study the angiogenic profile of tumors receiving the standard and metronomic schedule and to set up a new experiment to compare survival benefit in the animal model. No significant financial relationships to disclose.
Reply
Authors: Gitte Dam, Hendrik Vilstrup, Hugh Watson, Peter Jepsen
Journal: Hepatology (2016)

We thank Dr. Ali Khan and his colleagues for their interest in our research. They question our conclusion that proton pump inhibitors (PPIs) pose a threat to patients with cirrhosis by increasing the risks of hepatic encephalopathy and spontaneous bacterial peritonitis, arguing that the association may be due to confounding. We find it unlikely that residual confounding can account for our relative risk estimate of 1.36.1 Without confounder adjustment the hazard ratio was 1.50 (95% confidence interval 1.12-1.99), so the confounders we adjusted for were actually not strong confounders. This is also evident from the fact that the PPI users and nonusers were very similar, as shown in our article's Table 1. We disagree with Dr. Ali Khan's statement that in observational epidemiology relative risks below 2 are generally due to bias. We find that the review by Sørensen et al. offers a more balanced view of the pros and cons of observational and randomized studies.2 Despite our differences of opinion, we agree with Dr. Ali Khan and colleagues on the most important and self-evident aspect: patients with a valid indication for PPIs can use them; others should not. Such practice would probably spare patients from many hepatic encephalopathy episodes, and any risk of hepatic encephalopathy attributable to PPI use would at least be countered by beneficial effects of PPIs. When we accomplish this, we can consider how to handle the excess hepatic encephalopathy risk for those patients who need PPIs. We have no evidence base for this situation, but it is a possibility that lactulose could be preemptively coadministered together with PPIs.3 The way to obtain an evidence base seems to be a randomized PPI discontinuation trial for cirrhosis patients with a valid indication for PPIs. We believe that such a trial should be undertaken. Gitte Dam, Ph.D.1 Hendrik Vilstrup, Dm.Sci.1 Hugh Watson, Ph.D.2 Peter Jepsen, Ph.D.1,3 1Department of Hepatology and Gastroenterology Aarhus University Hospital Aarhus, Denmark 2Sanofi Aventis R&D Paris, France 3Department of Clinical Epidemiology Aarhus University Hospital Aarhus, Denmark
IL-6 promotes the differentiation of a subset of naive CD8+ T cells into IL-21–producing B helper CD8+ T cells
Authors: Rui Yang, April R. Masters, Karen A. Fortner, Devin P. Champagne, Natalia Yanguas-Casás, Daniel J. Silberger, Casey T. Weaver, Laura Haynes, Mercedes Rincon
Journal: The Journal of Experimental Medicine (2016)

IL-6 is known to contribute to the differentiation of CD4+ T cells into different subsets of effector T helper cells. Less is known about the potential of IL-6 in regulating CD8+ T cell effector function. Here, we identify IL-6 as a master regulator of IL-21 in effector CD8+ T cells. IL-6 promotes the differentiation of a subset of naive CD8+ T cells that express IL-6R into a unique population of effector CD8+ T cells characterized by the production of high levels of IL-21 and low levels of IFN-γ. Similar to CD4+ T follicular helper (Tfh) cells, IL-21–producing CD8+ T cells generated in the presence of IL-6 directly provide help to B cells to induce isotype switching. CD8+ T cell–derived IL-21 contributes to the production of protective virus-specific IgG antibodies during influenza virus infection. Thus, this study reveals the presence of a new mechanism by which IL-6 regulates antibody production during viral infection, and a novel function of effector CD8+ T cells in the protection against viruses.
Phase 3, Placebo-Controlled, ASPIRE Study (TRC114968) of Eltrombopag (EPAG) Treatment of Thrombocytopenia (TCP) in Advanced Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML): Assessment of Clinical Benefit, Safety, and Tolerability
Authors: Moshe Mittelman, Uwe Platzbecker, Boris V Afanasyev, Sebastian Grosicki, Raymond SM Wong, Achilles Anagnostopoulos, Benjamin Brenner, Claudio Denzlinger, Giuseppe Rossi, Arnon Nagler, Ana Isabel Rosell Mas, Frank Mannino, Nicole L. Stone, Geoffrey Chan, Yasser Mostafa Kamel, Dominik L.D. Selleslag
Journal: Blood (2015)
HER2 status of breast carcinoma developed as a secondary malignancy after Hodgkin lymphoma treatment.
Authors: Z. M. Tomasevic, D. Kolarevic, Z. Tomasevic, Z. Milovanovic
Journal: Journal of Clinical Oncology (2010)

e21112 Background: HER2 overexpression is present in ∼20% of all breast carcinoma (BC) but it is not quite known whether this percentage is maintained in potentially radiotherapy induced BC. Radiotherapy is frequently part of curative treatment for Hodgkin lymphoma (HL) and BC is most frequent secondary malignancy in those patients.The aim of this analysis is to explore HER2 status in BC developed as a secondary malignancy after HL treatment. Methods: From January 2000 to December 2008, 10 female patients with unilateral BC stage I-III, and previous history of HL were identified. HL was diagnosed from 1981-2004. All patients have been treated with chemotherapy, and 7/10 also with radiotherapy to the chest wall. All patients underwent radical mastectomy, postoperative chemotherapy, and hormonal therapy in 7/10. Median follow up after BC is 3 years (range 1-8). Pathological specimens for IHC (HerceptTest Dako) were identified for 9/10. All HER2 2+ results were tested with CISH. Results: Results are presented in the Table. Conclusions: Seven patients developed BC after previous radiotherapy to the chest wall and three without previous radiotherapy. In this small subgroup of BC patients previously treated for HL, HER2 3 + have not been registered. No (%) Median age at HL diagnosis (years) Median interval to BC diagnosis (months) Previous radiotherapy to the chest Median age et BC diagnosis (years) HER-2 negative(0, 1+, 2+) HER-2 positive (3+, CISH+) NA 10 (67%) 26.8 (13-53) 185.2 (72-348) 7/10 43.5 (26-69) 9/9 0/9 1/10 No significant financial relationships to disclose.
POSTPONING THE ADMINISTRATION OF PATENTERAL NUTRITION REDUCES THE NEED FOR ANTIFUNGAL THERAPY: A POST-HOC ANALYSIS OF THE EPANIC CLINICAL TRIAL
Authors: Tom Fivez, Michael P Casaer, S Vanderheyden, Pieter Wouters, Frauke Beyls, Thomas De Rijdt, Greet Van den Berghe, Dieter Mesotten
Journal: Intensive Care Medicine (2013)
Salvage endoscopic ultrasound–radiologic rendezvous to re-establish biliary flow following duodenectomy with ablation of papilla
Authors: Gianfranco Donatelli, Serge Derhy, David Fuks, Hugues Levard, Bruno Meduri, Brice Gayet
Journal: Endoscopy (2016)

A 54-year-old woman underwent curative duodenectomy with duodenojejunal anastomosis for adenocarcinoma. The day after the procedure she developed jaundice. The computed tomography (CT) scan showed a staple line on the lower part of the common bile duct (CBD) with biliary tree dilatation ([Fig. 1]) and a normal pancreatic duct. Under endoscopic ultrasound (EUS) control a transbulbar cholangiography was performed on the lower part of the CDB, confirming biliary dilatation without any leakage of contrast medium into the duodenum ([Video 1]). A fistulotomy (6 Fr) was then performed ([Video 2]). Although different guidewires and catheters were used, selective cannulation of the cystic stump was achieved without reaching the intrahepatic ducts because of the anatomically low cystic duct insertion ([Fig. 2]). A transhepatic cholangiography was performed. Passage of the guidewire into the duodenum was easily done through the bilioduodenal access previously created by EUS fistulotomy ([Fig. 3]). A fully covered self-expanding metal stent (FCSEMS) and a plastic stent were delivered to maintain biliary flow ([Fig. 4]). Follow-up was uneventful with normalization of liver function test results, and endoscopic retrograde cholangiopancreatography (ERCP) was scheduled for stent replacement.
P3-266: Tumor positive frozen section analysis of the bronchial resection margin and subsequent surgery has no effect on survival
Authors: Erik Thunnissen, Harry Groen, Wim Timens, Bernard Hol, Robrtjan v. Suylen, Matthijs v. Oosterhout, Ad Verhagen, Carolien Wijnen-Dubbers
Journal: Journal of Thoracic Oncology (2007)
Perceptions and beliefs related to cancer care among African-American and Caucasian patients
Authors: R. K. Matsuyama, L. J. Lyckholm, C. Grange, S. Utsey, T. J. Smith
Journal: Journal of Clinical Oncology (2006)

8518 Background: Without a clear understanding of belief systems and cultures it is not possible to provide optimal care to ethnic minority individuals. This study examined perceptions and beliefs of African-Americans and Caucasians related to cancer care. Methods: Eleven focus groups were conducted with 39 African-American and Caucasian cancer patients recruited from a university-affiliated cancer clinic, using established qualitative methodology. Data analysis included whole group analysis with a team of 4 researchers. Atlas Ti software was used to validate the coding and establish Intra-rater and inter-rater reliability. Results: There were consistent themes across both ethnicities that related to reactions to diagnosis, wanting certain types of information, wanting to stay positive, coping, and social connectivity. Cultural differences were also apparent (Table). Differences based on ethnicity Conclusions: African-American participants described increased religiosity and faith after diagnosis and were more likely than Caucasian participants to seek information about cancer issues from friends, family, and community. There also were differences in perceptions of how health care providers demonstrate care for patients. Findings have implications for training professionals regarding ways patients seek information, the role of spirituality and religion in care and behaviors that patients perceive as indicative of caring. [Table: see text] No significant financial relationships to disclose.
P0225 : Combination of CD40L co-stimulation with alpha-fetoprotein pulsed dendritic cells induced an early and strong TH1-shift in the tumor environment and synergistic antitumoral effects in subcutaneous and orthotopic murine hepatocellular carcinoma model
Authors: A. Vogt, C. Schneider, T.H. Ayub, G. Decker, J. Prieto, S. Conchon, I.G. Schmidt-Wolf, C.P. Strassburg, M.A. Gonzalez-Carmona
Journal: Journal of Hepatology (2015)
European multicenter evaluation of survival for patients with hepatocellular carcinoma (HCC) treated by radioembolization with <sup>90</sup>y-labeled resin microspheres.
Authors: B. Sangro, L. Carpanese, R. Cianni, R. Golfieri, D. Gasparini, S. Ezzidin, R. Hoffman, F. Fiore
Journal: Journal of Clinical Oncology (2010)

4027 Background: The prognosis in HCC was evaluated in a large series of patients receiving radioembolization (RE). Methods: 250patients with unresectable HCC were recruited consecutively from 8 European centers and received RE using 90Y-labeled resin microspheres (SIR-Spheres). Prognostic factors significant on univariate analysis were combined in multivariate models to identify the predictors of survival. Results: Patients (mean age 65.2 years) received a median activity of 1.7 GBq. Most patients were Child-Pugh class A (81%), with multinodular disease (74%) and 16% had portal vein occlusion. Common early adverse events (primarily grade 1/2) were early (days 1-7) abdominal pain (24%) and fatigue (30%). Hyperbilirubinemia was an intermediate (8 days to 3 mo) or late (3-6 mo) event in 33% and 28% of patients, a minority experiencing grade 3 events (3.6% and 5.7%), respectively. Median survival was 14.1 mo (95% CI 12.7-17.9). Survival varied significantly by CLIP: CLIP 0: 24.4 mo (19.6-not reached), CLIP 1: 19.4 mo (12.8-23.2), CLIP 2: 10.9 mo (8.7-15.3), CLIP 3/4: 7.6 mo (6.5-11.7) (p < 0.001); BCLC: A: 22.1 mo (15.5-46.8), B: 19.4 mo (13.6-23.7), C: 10.0 mo (7.7-11.7), D: 2.4 mo (0.4-4.4) (p < 0.001); Child-Pugh: A: 15.9 mo (13.1-20.8), B: 10.3 mo (7.4-12.6), C: 2.4 mo (0.4-4.4) (p < 0.001); tumor burden: ≤ 5 nodules: 19.1 mo (14.5-23.2), > 5 nodules: 8.7 mo (7.2-11.4) (p < 0.001); and extrahepatic disease: present: 7.5 mo (4.3-13.1), absent: 14.9 mo (12.5-19.1) (p = 0.001). On univariate analysis, these factors as well as ECOG performance, bilobar disease and raised (> median) total bilirubin, ALT or AFP were significant predictors of survival. On multivariate analysis, the most consistent predictors of survival were: extrahepatic disease: HR 3.8 (2.0-7.4) (p < 0.001); raised total bilirubin: HR 1.54 (1.1-2.2) (p = 0.025); number of nodules: HR 1.48 (1.1–1.9) (p = 0.004); and CLIP: HR 1.33 (1.1-1.6) (p = 0.006). Conclusions: Y90 RE was relatively well tolerated. CLIP staging (which incorporates Child-Pugh, extent of hepatic disease, AFP and PVO) and extent of disease at treatment (intra/extrahepatic) are key predictors of survival. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sirtex Medical
The Prognosis of Children Acute Lymphoblastic Leukemia (ALL) with Minimal Residual Disease (MRD) ≥10-2 After Induction (TP1) Depends on the Prephase Response and on the Level of the MRD After Consolidation (TP2): Results of the 58951EORTC Trial
Authors: Yves Bertrand, Stefan Suciu, Nathalie Grardel, Marleen Bakkus, Francoise Mazingue, Karima Yacouben, Anne Uyttebroeck, Patrick Lutz, Dominique Plantaz, Sandrine Girard, Nicole Dastugue, Yves Benoit, Hélène Cavé
Journal: Blood (2011)
Sensitive detection of gamma-H2AX induction as a pharmacodynamic marker for profiling patients with cancer treated with topotecan.
Authors: D. W. Davis, D. Mittelman, G. Copper, Y. Zhang, S. Sukumaran, W. Yutzy, J. J. Ji
Journal: Journal of Clinical Oncology (2010)

3093 Background: Chemotherapies for cancer patients are often designed to inhibit growth or induce apoptosis in malignant cells. Several genotoxic agents have proved effective in inducing significant DNA damage, such that apoptosis is triggered in the cell. Topotecan is a chemical inhibitor of DNA topisomerases. The inhibition of topisomerases blocks the ligation of the phosphate backbone of DNA and leads to the generation of strand breaks. In this study we evaluated gamma-H2AX as marker for drug efficacy, using antibodies that recognize the phosphorylated S139 epitope. Results: We present an automated blood-based assay for detecting phosphorylated gamma-H2AX before and after drug treatment. We first screened subpopulations of the blood for cell types that exhibit the great response in gamma-H2AX induction after drug treatment. Using this sub-phenotype, we then developed two approaches for isolating these cell types: immunomagentic enrichment of the top responding cell types, and immunophenotyping of the top responding cell subtypes. We measured gamma-H2AX, using laser scanning cytometry and found that the induction magnitude of the biomarker (1) correlates to treatment with the topotecan in set of ex vivo patient samples and in clinical trial patients; and (2) and is at least as sensitive as manually measurements of gamma-H2AX foci using conventional methods in comparison of 10 patient samples. We have begun a clinical validation study to determine whether this induction correlates to clinical outcome and additionally are investigating whether early response to topotecan, in the form of biomarker induction, is predictive of outcome. Preliminary results in 10 patient samples show that the early gamma-H2AX response to DNA damage is highly variable from patient to patient, ranging from no measurable induction, to an induction of 65%. Conclusions: We have developed an automated system for measuring gamma-H2AX induction in cancer patients treated with topotecan. Studies correlating the marker to outcome are ongoing. If this assay is predictive, it would be invaluable for rapidly stratifying patients in clinical trials that involve therapies that induce DNA damage. No significant financial relationships to disclose.