tbuckley/cabot-search huggingface dataset:
Assessing the cost-effectiveness of adding aprepitant to the ASCO standard for prophylaxis of chemotherapy induced nausea and vomiting
Authors: S. G. Moore, J. W. Tumeh, S. Wojtanowski, C. R. Flowers
Journal: Journal of Clinical Oncology (2005)

6009 Background: Chemotherapy-induced nausea and vomiting (CINV) is cited as a great concern for cancer patients. ASCO guidelines for prophylaxis of CINV in patients receiving highly-emetogenic chemotherapy (HEC) recommend use of a 5HT3 antagonist with a corticosteroid (SOC). Aprepitant, a novel NK1 antiemetic, is approved for use with a 5HT3 antagonist and a corticosteroid to manage CINV. Although clinical studies of aprepitant have demonstrated its efficacy, the settings in which it will be cost-effective remain unclear. Methods: We developed a Markov model to compare managing CINV for a hypothetical patient cohort receiving 4 cycles of HEC with: SOC, SOC + aprepitant (A1), or SOC therapy adding aprepitant only after CINV occurs (A2). Data from published clinical trials provided probabilities and utilities for the model. Costs from a payer perspective were based on resource use for CINV management, Medicare reimbursement rates for hospital and physician services, and the average wholesale price for medications. Clinical outcomes were valued in healthy-day equivalents (HDEs) and converted to quality-adjusted life years (QALYs) for cost-effectiveness (CE) comparisons. Univariate and probabilistic sensitivity analyses addressed uncertainty in parameters. Results: The SOC strategy, provided 11.9 HDEs at a cost of $455. The A1 regimen provided 14.4 HDEs at $1,619. A2 provided 13.2 HDEs at $996. The CE ratios for the three regimens were $13,907, $41,060 and $27,619, per QALY respectively. The incremental CE ratios (compared to SOC) were $172,789/QALY for strategy A1 and $160,236/QALY for A2. In univariate analysis, A1 became CE at a cost of aprepitant of $94. In 10,000 probablistic Monte Carlo trials, A1 was not CE in 98.7% of trials using a $50,000/QALY threshold. Conclusions: Managing CINV with aprepitant is not CE when compared with the current ASCO standard of care. Probabilistic sensitivity analyses suggest that this finding holds despite wide variations in model assumptions. Adding aprepitant after CINV occurs or targeting particular high-risk populations will likely be necessary to identify a cost-effective use for this drug. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Solvay
Coronary Artery Disease
Authors: Daniel T. Richards
Journal: JAMA (1993)

<i>Coronary Artery Disease</i>, ably edited by Burton E. Sobel, MD, of Washington University School of Medicine, is a monthly journal aimed at clinicians caring for patients with coronary artery disease and cardiovascular scientists concerned with mechanisms. The journal is dedicated to the rapid review and prompt dissemination of information from multiple perspectives, ranging from basic laboratory research to clinical applications. To achieve these goals,<i>Coronary Artery Disease</i>publishes a mix of peerreviewed original reports, state-of-the-art review articles, and bibliographies of current world literature. Although published in English, the journal is intended to be international in scope, a point reflected in the excellent editorial board, which includes clinical scientists, cardiologists, and cardiac surgeons based in the United States, United Kingdom, and Europe. A typical issue of<i>Coronary Artery Disease</i>runs about 90 pages and contains no advertisements. On average there are seven original reports and five review articles or editorials in
Mid-adult development and psychopathology
Authors: S P Stein, S Holzman, T B Karasu, E S Charles
Journal: American Journal of Psychiatry (1978)

The authors studied a group of 193 psychiatric outpatients with varying diagnoses and a comparison group of 136 nonpatients across nine measures: sense of self; feelings about marriage, sex, career, and leisure time; relationship to parents, friends, and children; and sense of time passing. They found significant differences between the groups at specific ages in the areas of sense of self, feelings about career and sex, and relationship to parents, children, and friends. They discuss these results with a view toward identifying and elucidating normal and pathological factors in the adult life cycle.
The impact of chemotherapy on sarcopenia and fatigue in elderly cancer patients: A prospective pilot study
Authors: A. Luciani, A. Gilda, L. Tagliabue, L. Gilardi, S. Oldani, C. Codecà, S. Caldiera, G. Lucignani, P. Foa
Journal: Journal of Clinical Oncology (2008)

9635 Background: Sarcopenia, the age related loss of lean body mass caused by physiological and pathological events, is poorly studied in elderly cancer patients.Fatigue is a symptom universally present in patients undergoing chemotherapy and can results from both oncological and not oncological comorbidities.In this prospective pilot study the effect of chemotherapy on sarcopenia and fatigue and their impact on functional status were investigated. Methods: Elderly patients(≥70 years old) with a diagnosis of advanced solid or hematological malignancies, chemotherapy naive for the advanced disease were enrolled. PS, CIRS-G index and score, polypharmacy, ADL, IADL, FSI were assessed before and after at least three months of treatment. DEXA scan was used for body composition assessment: appendicular skeletal mass (ASM), lean plus bone composition (leanBMC), total fat and t-score were calculated. Hemoglobin (Hb), albumin and pre-albumin were also measured. Descriptive statistic, t test and regression analysis were calculated. Results: 47 pts, mean age 74.4 (range 70–83, SD 2.88), 18 females (38%), 29 and males (62%) were evaluated. Main diagnosis were non-small cell lung cancer (22 pts, 47%) and colon cancer (8 pts, 17%). Mean CIRS-G score and index were 3,26 and 1,59 respectively (r 0.43); mean drugs number was 4. Mean ASM was 19,8 Kg (11,3–29) and Lean BMC 48,22 Kg (32–69). PS was 0 in 35 pts (74%) before therapy and 19 (40%) at the end of treatment (p 0.0001).The clinical/hematological parameters that changed significantly during chemotherapy were: ASM (p 0.024), Lean BMC (p 0.0001), t-score (p 0.025), Interference Score (p 0.036), ADL (p 0.032), IADL (p 0.002), Hb (p 0.0001) and albumin (p 0.011). PS was significantly influenced by ASM (p 0.031, OR 0.2) and severity of fatigue (p 0.045). IADL and ADL were significantly influenced by daily frequency of fatigue (P 0.044, OR 0.6; 0.03, OR 0.7) and ADL was related to ASM (0.036, OR 0.7). Conclusions: Our data show that chemotherapy significantly worsen muscle mass, fatigue and functional status. Fatigue and sarcopenia seem to be mediators for decline in functional status. Further studies on cause/effect relationship between these two parameters will help in identifying strategy for supportive intervention. No significant financial relationships to disclose.
Abstract 14189: Paradoxical Hemoconcentration on Admission of Acute Hypertensive Heart Failure Syndrome
Authors: Masaaki Konishi, Masaomi Gobara, Eiichi Akiyama, Kozo Okada, Yasushi Matsuzawa, Kenichirou Saka, Noriaki Iwahashi, Nobuhiko Maejima, Mitsuaki Endo, Kengo Tsukahara, Kiyoshi Hibi, Toshiaki Ebina, Kazuo Kimura, Satoshi Umemura
Journal: Circulation (2012)

Introduction As volume overload is a major profile of acute heart failure syndrome (AHFS), diuretics are a mainstay of therapeutic strategy for those patients. Though decongestion/diuretic therapy ...
Thymidilate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), and dihydrofolate reductase (DHFR) as predictive markers of capecitabine efficacy in breast cancer patients
Authors: R. Audet, C. Shen, S. Edgerton, L. Lay, K. Vang Nielsen, A. D. Thor, J. C. Chang, K. D. Miller, G. W. Sledge, B. Leyland-Jones
Journal: Journal of Clinical Oncology (2009)

11033 Background: The efficacy of 5-FU and the pro-drug capecitabine (C) is mediated through the thymidylate synthase pathway and may be affected by expression of key enzymes in this pathway. The expression and/or gene copy number of TS, TP, DPD and DHFR was assessed and correlated with time-to progression (TTP) and progression-free survival (PFS). Methods: Adult female patients with pathologically confirmed breast cancer and locally advanced or metastatic disease were treated with C 1000 mg/m 2 BID days 1–14 of a 21-day cycle. Formalin-fixed, paraffin-embedded (FFPE) specimens from C-treated patients were processed for RNA extraction. Total RNA was isolated from 32 FFPE tissue samples containing at least 70% tumor cells and RNA levels for TS, TP, DPD and DHFR were quantified using real time RT-PCR and Affymetrix GeneChip microarrays. Custom made TS and TP FISH probes (Dako, Glostrup, Denmark) were used to evaluate gene copy number and gene to reference ratios in at least 60 morphologically intact non-overlapping nuclei. Markers were correlated with TTP and PFS using Cox proportional hazard models in 24 patients. Results: Higher TS gene copy number was significantly associated with a decrease in PFS (HR 1.46, 95% CI 1.08 to 1.96, p=0.014) and TTP (HR 1.49, 95% CI 1.05 to 2.13, p=0.028). However, the association between TS RNA levels (expressed as Ct values) and PFS (HR 0.82, 95% CI 0.61 to 1.11, p=0.198) or TTP (HR 0.74, 95% CI 0.49 to 1.14, p=0.172) failed to reach statistical significance. RNA levels, determined by Affymetrix, were significantly correlated with RT-PCR for TS (r= -0.5073, p=0.0004) and DHFR (r=-0.50994, p=0.003). Neither TP gene copy number nor RNA levels were significantly associated with PFS (HR 099, and HR 0.93) or TTP (HR 1.07 and HR 1.029), respectively. The association between RNA levels and PFS or TTP did not reach statistical significance for both DPD (HR 1.17 and HR 1.13) and DHFR (HR 0.68 and HR 0.63), respectively. Conclusions: These data indicate that TS gene copy number, assessed by FISH with proper standardization, might be a useful and easily accessible marker for C sensitivity in human breast cancer and warrants further investigation. [Table: see text]
Macrobiotic diets for cancer treatment and prevention.
Authors: B B Bowman, R F Kushner, S C Dawson, B Levin
Journal: Journal of Clinical Oncology (1984)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1984.2.6.702 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 6374060 Macrobiotic diets for cancer treatment and prevention. B B BowmanxB B BowmanSearch for articles by this author , R F KushnerxR F KushnerSearch for articles by this author , S C DawsonxS C DawsonSearch for articles by this author , B LevinxB LevinSearch for articles by this author https://doi.org/10.1200/JCO.1984.2.6.702 First Page PDF © 1984 by American Society of Clinical Oncology
Genome-Wide Analysis of Genetic Alterations In Acute Myeloid Leukaemia (Massively parallel, high-throughput, paired-end DNA sequencing and genotyping of an AML genome).
Authors: James X Gray, Paul J Leo, Pamela Mukhopadhyay, Evgeny A Glazov, Patrick Danoy, Marina Donskoi, Anna Brown, Ian D. Lewis, Richard J D'Andrea, Matthew A Brown, Paula Marlton, Devinder S Gill, Thomas Gonda
Journal: Blood (2010)
Abstract 14966: Small Molecule Induced Global DNA Hypomethylation Upregulates Nkx2.5 in IPS Derived Cardiac Progenitors by Targeting GPCR Signaling Pathway
Authors: Zeeshan Pasha, Muhammad Ashraf
Journal: Circulation (2012)

Background The use of induced pluripotent stem cells (IPS) is limited due to their ability to form tumors and low efficiency of differentiation into cardiac progenitors. We investigated the use of ...
Dermatological toxicities associated with MEK 1/2 inhibitor AZD6244.
Authors: P. Myskowski, Y. Balagula, K. Barth, K. Busam, M. E. Lacouture, P. B. Chapman
Journal: Journal of Clinical Oncology (2010)

e19644 Background: AZD6244 is a second generation MEK inhibitor that targets the RAF-MEK-ERK pathway and is currently in clinical trials for advanced melanoma. MEK kinase inhibitors are known to be associated with a skin rash. While cutaneous reactions to other targeted chemotherapy agents, such as epidermal growth factor receptor inhibitors (EGFRIs) have been intensely studied in recent years, the dermatological toxicities associated with MEK inhibitors have not been well characterized. Similarly, management of these adverse reactions with this class of agents may present a challenge in clinical trials. We reviewed the clinical presentation, evolution and management of dermatological toxicities associated with AZD6244. Methods: Retrospective review of medical records of 10 patients that manifested cutaneous toxicities secondary to AZD6244 was performed. Data from two phase II trials in which AZD6244 was used to treat advanced metastatic cutaneous, mucosal, or uveal melanomas was reviewed. Eight patients were treated with 100 mg of oral AZD6244 twice a day and 2 patients received 75mg orally twice a day. Parameters studied included the time to onset, clinical presentation, evolution, histology and complications of various dermatological toxicities. In addition, the clinical database was accessed to retrieve clinical photographs of these dermatological toxicities when available. Results: The following adverse effects were observed: papulopustular rash, xerosis cutis, fissures, erythema, telangiectasias, and acute paronychia. 10 patients developed papulopustular rash. Paronychia and telangiectasias were seen in 1 patient. Fissures also developed in 1 patient and xerosis was observed in two patients. In addition, secondary bacterial superinfection with Staphylococcus aureus was documented in 3 patients. Conclusions: Dermatological toxicities associated with AZD6244 in our retrospective review were similar in their clinical presentation, evolution, and potential complications such a superinfection to those seen with epidermal growth factor receptor inhibitors (EGFRIs). Treatment approaches used for EGFRIs induced cutaneous reactions may be potentially utilized to manage toxicities triggered by AZD6244. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca
A phase II study of dovitinib (TKI258), an FGFR- and VEGFR-inhibitor, in patients with advanced or metastatic renal cell cancer (mRCC).
Authors: E. Angevin, V. Grünwald, A. Ravaud, D. E. Castellano, C. C. Lin, J. E. Gschwend, A. L. Harzstark, J. Chang, Y. Wang, M. M. Shi, B. J. Escudier
Journal: Journal of Clinical Oncology (2011)

4551 Background: Dovitinib is a potent oral inhibitor of angiogenic factors, including the fibroblast growth factor (FGFR) and vascular endothelial growth factor receptors (VEGFR). Phase (ph) I of the study established the maximum tolerated dose of dovitinib as 500 mg/day on a 5 day on/ 2 day off dosing schedule in 28-day cycles. Methods: The primary objective was to assess the efficacy of dovitinib in clear cell mRCC patients (pts) previously treated with a VEGFR inhibitor and/or mammalian target of rapamycin (mTOR) inhibitor by assessing tumor response every 8 weeks. Results: Pt characteristics (N = 59) evaluable for safety: median age, 60 years; ECOG PS 0/1, 39%/61%; 97% received prior antineoplastic therapy; common metastatic sites of lung (37%), lymph nodes (10%), bone (14%), and liver (12%). The most common adverse events were nausea (73%; grade 3 [g3]: 9%), diarrhea (64%; g3: 9%), vomiting (56%; g3: 5%), decreased appetite (48%; g3: 7%), asthenia (36%; g3: 12%), and fatigue (36%; g3: 10%). In pts evaluable for efficacy (n = 51): the average duration of exposure was 89 days; 11 (22%) pts were ongoing, with 26 (51%) discontinuing due to progressive disease (PD). Best overall responses (ORs) per central review included: partial response (PR), 4 (8%); stable disease (SD) ≥ 4 months (mos), 19 (37%); PD, 11 (22%); unknown/not assessed, 7 (14%). Median progression-free survival (PFS) and overall survival (OS) were 6.1 and 16 mos, respectively. In pts who previously failed VEGFR and mTOR inhibitor treatment (n = 31), best ORs per central review included: PR, 3 (10%); SD ≥ 4 mos, 13 (42%); PD, 6 (19%); unknown/not assessed, 4 (13%). Median PFS and OS in these pts were 6.1 and 10.2 mos, respectively. Modest increases in VEGF (P = .193) and placental growth factor (P = .074) and a significant decrease in soluble VEGFR2 (P < .0001) were noted, suggesting VEGFR inhibition. Plasma FGF23 significantly (P < .0001) increased after 1 cycle and paired tumor biopsy demonstrated pERK inhibition, both suggesting FGFR inhibition. Conclusions: The study met the primary efficacy criteria, and 30 additional pts will be treated. Updated data will be presented. A randomized phase III (vs sorafenib) study in mRCC is planned.
Efficacy of combination of rituximab (R), obatoclax (O), and bortezomib (B) against rituximab-sensitive (RSCL) and rituximab-resistant B-cell lymphoma cell lines (RRCL).
Authors: W. Riaz, F. J. Hernandez-Ilizaliturri, C. Mavis, P. Tsai, M. S. Czuczman
Journal: Journal of Clinical Oncology (2010)

8094 Background: The interactions between the members of the Bcl-2 like proteins play an important role in the development, progression and prognosis in various subtypes of B-cell lymphomas. R is an anti-CD20 chimeric monoclonal antibody, O (obatoclax) is a novel pan bcl-2 inhibitor, and B is a proteasome inhibitor with multiple mechanisms of action. These agents can alter the balance/interaction of Bcl-2 family members to induce cell death. Methods: In an effort to expand the targeted therapeutic options for B-cell lymphoma patients, we evaluated the biological activity of combining R, B and O against RSCL (Raji, RL, SU-DHL6, OCI-LY3 and OCI-LY19) and RRCL (Raji-4RH and RL-4RH). We developed RRCL by exposing R-naive cells to escalating doses of R ± human serum (HS). Lymphoma cells were incubated with either RPMI or O (2.5 μ M) with or without B (10nM) for 42 hours. Subsequently, cells were exposed to either R or Isotype control (1μ g/ml) + HS (12.5%). Following an additional 6 hours period of incubation, changes in mitochondrial potential and cell viability were measured by alamar blue reduction. Lymphoma cells were exposed for 48 hrs to R, O, B or various combinations (BO, RB, RBO, etc), and changes in Bcl-2 family members were determined by Western blotting. Results: Significant anti-tumor activity was observed with each agent alone in RSCL and to a lesser degree in RRCL. O was equally effective in both RSCL and RRCL. Enhanced anti-tumor activity was observed by combining R+O or O+B. Furthermore, the triple combination of R+B+O resulted in maximum cell kill (80%) in both RSCL and RRCL. In vitro exposure of lymphoma cells to B or O altered the levels of pro-apoptotic (Bak, PUMA, Noxa) and anti-apoptotic (Mcl-1, Bcl-XL) proteins. Conclusions: Our data suggest that deregulation of apoptosis by combining B, R and O is a potent strategy in both RSCL and RRCL. Ongoing in vivo studies will further define the therapeutic role of combining these three targeted agents in B-cell lymphoma. No significant financial relationships to disclose.
Abstract 3847: MSI status frequency, MSI-target genes mutation profile and ancestry proportions in Brazilian colorectal carcinoma patients
Authors: Gustavo N. Berardinelli, Cristovam Scapulatempo-Neto, Ronilson Duraes, Denise Peixoto-Guimaraes, Armando Melani, Rui Pereira, Rui Reis
Journal: Cancer Research (2015)

Abstract Introduction: Colorectal cancer (CRC) is the fourth in incidence and in mortality worldwide for both sexes. There are three pathways in the pathogenesis of CRC: chromosome instability (CIN), microsatellite instability (MSI) and CpG island methylator phenotype (CIMP). These pathways are closely related and some tumors may harbor alterations in multiple pathways. The MSI is the less common and is more frequently related with HNPCC Syndrome. In Brazil, CRC incidence is increasing and the frequency of MSI and its biological and clinical impact are largely unexplored. Furthermore, the literature has reported the influence of ancestry factors on the incidence and prognosis in this tumor type. Goals: to assess the frequency of MSI status in Brazil CRC tumors; to analyze the mutation profile of MSI target genes in MSI-positive tumors and to determine the patients ancestry by molecular markers. Materials and Methods: 1013 CRC patients were enrolled in the study. The MSI evaluation was performed using a multiplex PCR comprising 5 markers (NR27, NR21, NR24, BAT25, and BAT26). The MSI-H tumors were also assessed for mutations in a panel of 25 MSI-target genes, and their genetic ancestry will be evaluated using a panel of 46 AIMs (Ancestry-Informative Markers). Results: MSS status was observed in 86.0%, MSI-L in 4.0% and MSI-H in 10.0% of cases. The analysis of 25 MSI-target genes in 101 MSI-H cases showed distinct mutations frequencies, with the highest mutated genes been ATM (83.0%), EGFR (80.0%) and MRE11 (78.0%) and the lowest mutated genes been BLM (3.0%), WISP3 (2.0%) and TRBP2 (1.0%). No alterations were observed in BRCA1, BRCA2, XRCC2, PTEN and XPO5. We showed that the average ancestry proportions for MSS+MSI-L group were 74.1% of European, 12.3% of African, 6.6% of Native Americans, and 7.0% of East Asian, while for MSI-H group were 73.7% of European, 14.3% of African, 6.8% of Native Americans, and 5.2% of East Asian. So, no statistical difference was observed between distinct MSI status groups. Conclusion: The MSI frequencies identified in Brazilian CRC patients are in agreement with the international literature. We identify altered MSI-target genes in MSI-H tumors samples with potential clinical impact. For while, the ancestry proportions not showed an important factor for MSI status in Brazilian CRC patients. Citation Format: Gustavo N. Berardinelli, Cristovam Scapulatempo-Neto, Ronilson Duraes, Denise Peixoto-Guimaraes, Armando Melani, Rui Pereira, Rui Reis. MSI status frequency, MSI-target genes mutation profile and ancestry proportions in Brazilian colorectal carcinoma patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3847. doi:10.1158/1538-7445.AM2015-3847