tbuckley/cabot-search huggingface dataset:
Advancements in Radiation Techniques for Gastric Cancer
Authors: Matthew D. Callister, Leonard L. Gunderson
Journal: Journal of the National Comprehensive Cancer Network (2010)

All but the earliest cases of nonmetastatic gastric cancer represent a therapeutic challenge given the high propensity of these patients to develop locoregional and distant relapse. Neoadjuvant or adjuvant strategies that include chemoradiotherapy or chemotherapy have been associated with significant toxicity, but also improvement in patient survival. Technologic advances in the planning and delivery of radiotherapy (RT) have enabled significant progress in the accuracy and conformality of radiation treatment. Four-dimensional CT and image-guided RT improve the accuracy of radiation treatment. Three-dimensional RT and intensity-modulated RT allow increased conformality of radiation dose distribution, sparing of normal organs, and providing opportunity for dose escalation. Initial clinical experience with these technologies shows favorable tolerance and outcomes.
Sentinel node biopsy: The standard of care for the management of breast cancer
Authors: Z. H. Cheng, M. Mooreland, K. Sawyer, K. M. Verbanac, L. Tafra
Journal: Journal of Clinical Oncology (2005)

792 Background: Although numerous studies have demonstrated the feasibility and accuracy of the sentinel lymph node (SLN) procedure for axillary staging of breast cancer, most have limited follow-up data and relatively small numbers. Establishing SLN biopsy as the standard of care requires examining those factors affecting patient outcome, including recurrence of disease, time to disease, and overall survival. Methods: Since February 1997, 1486 patients were enrolled in an IRB-approved, multi-center study designed to systematically determine factors affecting patients undergoing sentinel lymph node procedure. Data was reviewed for patient’s age, tumor size, number of positive SLN and nonsentinel lymph nodes (NSLN), false negative rate, recurrent disease (local, axillary or distant), and time to death or recurrence. Results: The average age was 57.5 years (range 24–98), tumor size 1.83 cm (0.03–10.5 cm), total number of nodes examined 9.2 (0–40), and mean follow-up time was 39.4 months (7 days - 95 months). In this study, 818 patients underwent completion axillary nodal dissection (AND) at the time of the SLN procedure. Thirty-one patients were found to have positive NSLN with negative SLN for a false negative rate of 3.8%. Recurrent disease developed in 105 (7.1%) patients, including 1 (0.06%) axillary alone, 22 (1.5%) local in breast (LIB) alone, 67 (4.5%) distant alone, 12 (0.8%) LIB and distant, 2 (0.13%) axillary and distant, and 1 (0.06%) LIB, axillary, and distant. Fifty-two (49.5%) patients died who developed recurrent disease with a mean time of 35.3 months (10.4–84.5 months) from date of diagnosis. Of the 4 patients who developed axillary recurrence, all four patients had undergone an AND after SLN procedure. Twenty-two (4.6%) out of 481 patients who had negative SLN without AND developed LIB and/or distant recurrent disease only versus 76 (8.5%) out of 895 patients who had complete AND (ns). Conclusions: Sentinel lymph node biopsy is a safe, accurate procedure. We are able to spare patients most of the morbidity of an AND without compromising risk of recurrent disease. The SLN procedure should be the standard of care for the breast cancer patient who does not have biopsy proven axillary disease. No significant financial relationships to disclose.
WITHDRAWN: Self-assembly PEGylation retaining activity of protein drugs via supramolecular complexation with cyclodextrins
Authors: Tatsunori Hirotsu, Taishi Higashi, Irhan Ibrahim Abu Hashim, Keiichi Motoyama, Koki Wada, Hidetoshi Arima
Journal: Asian Journal of Pharmaceutical Sciences (2015)

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
Health-related quality of life (HRQOL) in non-small cell lung cancer (NSCLC): An update of a systematic review on methodological issues in randomized controlled trials (RCTs)
Authors: L. Claassens, J. van Meerbeeck, C. Coens, C. Quinten, X. S. Wang, G. Velikova, A. Bottomley
Journal: Journal of Clinical Oncology (2009)

9604 Background: NSCLC is a prevalent cancer site and RCTs frequently assess patient HRQOL, given the modest survival gains. This study is an update of a systematic review (JCO, 2003) on the HRQOL methodology in NSCLC RCTs. The objective was gaining insight into the evolution of HRQOL methodology over the last decades to help understand if the quality of reporting—and its benefit for clinical-decision making—has improved. Methods: A systematic literature review was undertaken through Medline. RCTs including newly diagnosed NSCLC patients with age ≥ 18, who underwent chemotherapy and/or radiotherapy; comprising patient-reported HRQOL endpoints; and published in English from 2002 to end 2008 were eligible. Two independent reviewers evaluated demographics, trial design, HRQOL measurements and statistical analysis. Results: Forty-five RCTs including 16,382 patients were selected, versus 29 trials between 1980 and 2002. Overall, the quality of HRQOL methodology reported was adequate, although no improvement over time was noticed. Comparisons to the former review led to similar results (p &gt; .05): Of the 45 RCTs, HRQOL end points were primary objectives in 20%. Significant HRQOL between-treatment differences were found in 60% of the RCTs. Adequacy of result presentation was found for a majority (71%). Few studies paid attention to clinically meaningful differences (36%). The EORTC and FACIT tools and the LCSS were most commonly applied in 56%, 18% and 13% respectively. There was sufficient detailing on domains, time points and patient compliance (&gt; 70%), but little on instrument administration methods (18%). However, HRQOL hypothesis (9%); instrument rationale (11%); verification of the cultural validity (29%); and impact of missing data (31%) were addressed to a significantly less extent than before 2002 (p &lt; .05). Conclusions: The number of RCTs incorporating HRQOL assessments in the NSCLC population has increased considerably. Despite the acceptable quality of the HRQOL methodology reporting, certain aspects remain poorly addressed. Our findings suggest the need for international standardization of HRQOL reporting, similar to the CONSORT guidelines for clinical findings. No significant financial relationships to disclose.
Past Decline Versus Current eGFR and Subsequent Mortality Risk
Authors: David M.J. Naimark, Morgan E. Grams, Kunihiro Matsushita, Corri Black, Iefke Drion, Caroline S. Fox, Lesley A. Inker, Areef Ishani, Sun Ha Jee, Akihiko Kitamura, Janice P. Lea, Joseph Nally, Carmen Alicia Peralta, Dietrich Rothenbacher, Seungho Ryu, Marcello Tonelli, Hiroshi Yatsuya, Josef Coresh, Ron T. Gansevoort, David G. Warnock, Mark Woodward, Paul E. de Jong
Journal: Journal of the American Society of Nephrology (2015)

A single determination of eGFR associates with subsequent mortality risk. Prior decline in eGFR indicates loss of kidney function, but the relationship to mortality risk is uncertain. We conducted an individual–level meta-analysis of the risk of mortality associated with antecedent eGFR slope, adjusting for established risk factors, including last eGFR, among 1.2 million subjects from 12 CKD and 22 other cohorts within the CKD Prognosis Consortium. Over a 3-year antecedent period, 12% of participants in the CKD cohorts and 11% in the other cohorts had an eGFR slope &lt;−5 ml/min per 1.73 m 2 per year, whereas 7% and 4% had a slope &gt;5 ml/min per 1.73 m 2 per year, respectively. Compared with a slope of 0 ml/min per 1.73 m 2 per year, a slope of −6 ml/min per 1.73 m 2 per year associated with adjusted hazard ratios for all-cause mortality of 1.25 (95% confidence interval [95% CI], 1.09 to 1.44) among CKD cohorts and 1.15 (95% CI, 1.01 to 1.31) among other cohorts during a follow-up of 3.2 years. A slope of +6 ml/min per 1.73 m 2 per year also associated with higher all–cause mortality risk, with adjusted hazard ratios of 1.58 (95% CI, 1.29 to 1.95) among CKD cohorts and 1.43 (95% CI, 1.11 to 1.84) among other cohorts. Results were similar for cardiovascular and noncardiovascular causes of death and stronger for longer antecedent periods (3 versus &lt;3 years). We conclude that prior decline or rise in eGFR associates with an increased risk of mortality, independent of current eGFR.
Abstract 9886: A Differential role of Cardiac and Leukocyte derived Macrophage migration Inhibitory Factor in Facilitating Inflammatory Responses and Cardiac Remodeling post Myocardial Infarction
Authors: David White, Nicole Jennings, Peter Kanellakis, Helan Kiriazis, Richard Bucala, Gúnter Fingerle-Rowson, Anthony Dart, Eric Morand, Xiao-Jun Du, Xiao-Ming Gao
Journal: Circulation (2012)

Inflammatory responses to myocardial infarction (MI) are essential for cardiac wound healing. However, excessive inflammation can lead to adverse cardiac remodeling and free wall ventricular rupture. We investigated whether Macrophage migration inhibitory factor (MIF); a pro-inflammatory cytokine, promotes inflammation and exacerbates cardiac injury following MI. MIF knockout (MIFKO) and Wild type (WT) mice were subjected to coronary artery occlusion to induce MI. Incidence of cardiac rupture within 1 week, was lower in MIFKO than WT mice ( 29% vs. 69%, median rupture day 5 vs. 4, p=0.002, n=29-39 ). MIFKO mice showed a lower density of CD45+ cellular infiltrates at day-3 ( 612 vs. 1213 cells/mm, n= 6-7 ), suppressed expression of IL-1β, MCP-1 and ICAM-1 ( p&lt;0.05, n= 6 ) at 24h, and lower MMP-9 and -2 activities at day-3 and day-7 by gelatin zymography ( p&lt;0.05 vs WT mice, n=5 ). Histology revealed reduced collagen deposition ( 48% vs. 59%) and increased infarct wall thickness ( 419 vs. 316 μ m ) in MIFKO hearts at day 14 post MI ( both P&lt;0.05, n=7-9 ) To differentiate the role of MIF derived from cardiomyocytes or leukocytes, we generated chimeric mice via bone marrow transplantation (BMT) i.e. WT mice received BMT from MIFKO mice (WT KO ) and MIFKO mice received BMT from WT mice (KO WT ). Compared to WT KO counterparts, KO WT mice post-MI presented a higher incidence of cardiac rupture ( 40% vs. 10%, median rupture day 10 vs. 9, p=0.003, n=38-45 ), a greater CD45+ cellular infiltration ( p&lt;0.05, n=7-8 ), reduced fractional shortening ( 16% vs. 25% ) and enlarged ventricular diameter size measured by echocardiography ( both p&lt;0.05, n=11-21 ). Moreover, histological analysis demonstrated a larger fraction of the necrotic myocardium ( 30 vs. 18%, p&lt;0.05 ), decreased collagen deposition (38 vs. 43%) and reduced infarcted wall thickness ( 245 vs. 344 μ m ) in KO WT than that in WT KO mice at day 7 and 14 post MI respectively ( all p&lt;0.05, n=7-9 ). MIF promotes inflammatory actions in the heart following MI. Global deletion of MIF protects the heart against acute cardiac remodelling and rupture via reduced inflammatory responses. Deletion of cardiac MIF delayed the onset of cardiac rupture while inflammatory cell derived MIF plays a crucial role in mediating post-MI cardiac remodelling.
Long-term results of a randomized phase II study of trabectedin by two different dose and schedule regimens in patients with advanced liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide
Authors: G. D. Demetri, S. Schuetze, J. Blay, S. Chawla, M. von Mehren, P. Casali, D. Morris, E. Bayever, V. Alfaro, A. LeCesne
Journal: Journal of Clinical Oncology (2009)

10509 Background: This prospective, international randomized study evaluated two trabectedin dosing regimens [1.5 mg/m 2 24-hour i.v. infusion once every 3 weeks (q3wk 24-h) vs. 0.58 mg/m 2 3-hour i.v. infusion every week for 3 weeks of a 4-week cycle (qwk 3-h)] in adult patients (pts) with unresectable and/or metastatic liposarcoma or leiomyosarcoma following failure of at least prior anthracycline and ifosfamide chemotherapy. Methods: Pts were treated and continuously followed in this trial, and we now present final OS data with long-term follow-up (median = 41 mo). With 234 deaths, the study would have &gt;80% power to detect a minimum 45% improvement in median overall survival (OS) (2-sided 5% significance level). Results: The primary efficacy endpoint (time to progression, TTP) was superior for the q3wk 24-h arm, as previously reported [Morgan, et al. J Clin Oncol: 25(18S June 20 Suppl.) 10060 (2007)]. At cutoff, 235 deaths had occurred (13% censored). This final OS analysis confirms the previously reported trend towards improved survival with trabectedin q3wk 24-h despite crossover of 32% of pts from qwk 3-h to the q3wk 24-h dosing regimen. Pts treated with q3wk 24-h had a 16% reduction in the relative risk of death (HR=0.843; p=0.1931). Median (95%CI) OS were 13.9 mo (12.5–18.6; q3wk 24-h) and 11.8 mo (9.9–14.9; qwk 3-h) (log-rank p=0.1920). OS rates at 12 mo were 60% (q3wk 24-h) and 50% (qwk 3-h). Sensitivity analyses censoring at crossover further highlighted this favorable trend in survival with trabectedin q3wk 24-h. With longer follow-up, updated median TTP (investigator assessment, 223 progression events) was 4.2 vs. 2.5 mo [HR: 0.658; p=0.0032], favoring the q3wk 24-h arm. With 59 additional cycles (for a total of 1,532 cycles) and longer exposure, trabectedin safety profile was consistent with that previously reported. Conclusions: Final survival data reinforce the internal consistency of all efficacy-related endpoints showing improved outcomes associated with the trabectedin q3wk 24-h regimen with an acceptable safety profile in this population of patients with advanced, previously-treated leiomyosarcomas and liposarcomas. [Table: see text]
Phase I/II study of GM-CSF gene-transduced allogeneic prostate cancer cellular immunotherapy (GVAX IT) in advanced prostate cancer patients made lymphopenic by chemotherapy and infused with autologous peripheral blood mononuclear cells (MC)
Authors: B. D. Curti, I. Assman, T. Moudgil, T. Ratzow, D. Haley, E. Walker, K. Hege, N. Sacks, W. J. Urba, B. A. Fox
Journal: Journal of Clinical Oncology (2006)

14635 Background: GVAX IT has been tested in phase I/ II and is currently being tested in phase III clinical trials of patients (pts) with androgen-independent prostate carcinoma (AIPC). Immunological and PSA responses have been described in men receiving GVAX IT. Preclinical studies have shown that antitumor immune responses induced by GVAX IT could be augmented further by making animals lymphopenic and reconstituting with lymphocytes prior to vaccination. A clinical trial was designed to study the effects of lymphopenic reconstitution in pts with AIPC. Methods: All pts had MC collection by leukapheresis pre-treatment. Study groups were as follows: Arm A - GVAX IT given every two weeks for 6 months; Arm B - Cyclophosphamide (350 mg/m 2 IV on days 1–3), MC infusion on day 6, GVAX IT on day 7, then every 2 weeks for 6 months; Arm C - Cyclophosphamide (350 mg/m 2 IV on days 1–3) and fludarabine (20 mg/m 2 IV on days 1–3), MC infusion on day 6, GVAX IT on day 7, then every 2 weeks for 6 months. Results: Seven pts have been treated thus far and completed at least 2 GVAX IT treatments. Pts had ECOG performance status ≤ 1, castrate testosterone levels, ≤ 1 prior chemotherapy regimen and measurable or evaluable metastatic AIPC. Lymphopenia was induced in all pts enrolled in Arms B and C, with recovery of total granulocytes and lymphocytes within 4 weeks following treatment. Monitoring of humoral and cellular immunological responses is underway and shall be presented. Conclusions: GVAX IT and lymphopenic reconstitution is feasible in men with AIPC. Analysis of clinical and immune response is ongoing. Supported by DAMD grant PC020094 and generous support of Mr. Tom Denhart, the Chiles Foundation and the Murdock Trust. [Table: see text]
Endothelial progenitor cell clonality and response to treatment in multiple myeloma
Authors: D. M. Kahn, M. Braunstein, E. L. Smith, U. Klueppelberg, T. Ozcelik, O. Batuman
Journal: Journal of Clinical Oncology (2006)

17546 Background: In multiple myeloma (MM), increased levels of endothelial progenitor cells (EPCs) contribute to neoangiogenesis, covary with disease activity and response to treatment. To understand the mechanisms of enhanced neoangiogenic function by EPCs in MM, we investigated whether EPCs and tumor cells share clonal identity, and related this finding to clinical progression. EPC clonality was analyzed by X-chromosome inactivation (XCI) and the presence of clonotypic immunoglobulin heavy-chain (IGH) gene rearrangement. Methods: Hair root cells and confluent EPCs from 18 female patients were studied for XCI patterns by human androgen receptor assay (HUMARA). In 6 patients, EPCs were studied for the presence of IGH gene rearrangement using family-specific PCR primers for IGH variable genes (V H ). Nine patients were treated with TDZ: thalidomide (100 mg/day), dexamethasone (10–40 mg for 4 days/3 weeks for 6 months, then reduced to 4 days/month), and zoledronate (4 mg/4 weeks). Results: Eleven of the 18 female patients displayed allelic XCI. Analysis of their EPCs for evidence of clonality revealed significant skewing (≥ 77% expression of a single allele) in 64% (n = 7). In 4 of these 7 patients, EPC XCI skewing was extreme (≥ 90% expression of a single allele) while in hair root cells XCI was random. Furthermore, sequencing of PCR products obtained with V H primers resulted in identification of the same product in EPCs and bone marrow cells in 67% (n = 4) of another 6 patients, while no IGH rearrangement was found in EPCs from healthy controls. 9 patients were subsequently treated with TDZ, 4 patients had clonal EPCs and Stage 2 MM, and 5 patients had non-clonal EPCs and Stage 3 MM. Despite having less advanced disease, patients whose EPCs were clonal had a significantly attenuated response to treatment with TDZ compared to patients whose EPCs were non-clonal (P = .05). Conclusions: Clonal identity between EPCs and neoplastic cells highlight the necessity to explore the thesis that MM cells and EPCs are derived from a progenitor cell capable of self-renewal and differentiation. The relationship between EPC clonality and impaired response to treatment underscores the pathogenic significance of EPCs in MM. No significant financial relationships to disclose.
TCT-43 Final Five-year Follow-up of the SYNTAX Trial: Optimal Revascularization Strategy in Patients with Three-vessel Disease
Authors: Friedrich Mohr, Simon Redwood, Graham Venn, Antonio Colombo, Michael Mack, A. Pieter Kappetein, Marie-Claude Morice, David Holmes, Ted Feldman, Elisabeth Ståhle, Keith Dawkins, Patrick Serruys
Journal: Journal of the American College of Cardiology (2012)
Bexarotene improves TTP in untreated, advanced NSCLC, when given in combination with carboplatin/paclitaxel
Authors: R. Bordoni, S. Khanwani, M. Saleh, M. Auerbach, F. Steinbaum, J. D. Cuevas, S. Harris, B. Howell
Journal: Journal of Clinical Oncology (2005)

7270 Background: Bexarotene, a specific synthetic retinoid analogue, binds to the α, β, and γ subclass of RXR, providing therapeutic specificity and reduced toxicities in pts with RXR-expressing tumors. Initial phase-I/II clinical trials in NSCLC showed that bexarotene added to chemotherapy prolonged stabilization of disease (TTP) and 1, 2, and 3 yr survival. Methods: Stage IIIB with pleural effusion & Stage IV chemo-naïve patients, ECOG PS 0–2, were enrolled on study and treated with carboplatin IV AUC-6 d1 and paclitaxel IV 100mg/m2 d1, 8, and 15, every 28-d for 4 cycles. Pts were randomized using a 1:1 design to bexarotene PO 400mg/m2/d either concurrent (C) from Day 1 or sequential (S) at the completion of chemo, for up to a year. Results: From a planned total of 60 patients, 48 have been enrolled thus far; median age 62.3 (range 41–86), 43 Caucasian, 41 TNM Stage IV, 33 males, 34 ECOG PS 1. To date, 44 pts are evaluable for efficacy and toxicity based on ITT; 35 were evaluated for RR: 15 (42.8%) achieved PR (C: 7 and S: 8), 15 (42.8%) exhibited SD (C: 8 and S: 7), and 5 (14.3%) had PD (C: 2 and S: 3), during the first 112 days (C1–4 chemo). TTP analysis was done in 42 pts: 19 pts showed an overall TTP of 152 days (5.06 mo) (C=10: 148.3 days and S=9: 155.5 days); in 23 pts the TTP has not been reached after a median F/U of 79 days (range 10–203). The overall 1yr S was 58.8% with no significant difference between treatment arms (p=0.7). The treatment was well tolerated; overall, AEs were reported in 48% of pts in the S arm vs. 51% in the C arm. The incidence of Gr 3–4 AEs, regardless of the treatment arm, was < 5%. There were no treatment-associated deaths. Conclusions: so far, data suggests a comparable ORR and a potential improvement in TTP, when bexarotene is added to carboplatin/paclitaxel, compared with chemo alone. Toxicity is easily managed. Updated efficacy and toxicity data will be presented at the meeting. No significant financial relationships to disclose.
Laboratory-based surveillance for Cryptosporidium in France, 2006–2009
Authors: Karine Guyot, Francis Derouin, Patrice Agnamey, Adela Angoulvant, D. Aubert, C. Aznar, Didier Basset, Pascal Beaudeau, G. Belkadi, A. Berry, Alain Bonnin, Françoise Botterel, M.-E. Bougnoux, Patrice Bourée, Pierre Buffet, M. Cambon, Bernard Carme, Gabriela Certad, C. Chartier, B. Couprie, Frédéric Dalle, E. Dannaoui, Marie-Laure Dardé, E. Dei Cas, B. Degeilh, Nicole Desbois, Jean-Marc Dewitte, C. Duhamel, T.H. Duong, J. Dupouy-Camet, Alexandra Faussart, L. Favennec, Pierre Flori, N. Gantois, G. Gargala, Frédéric Grenouillet, Ml Grillot, D. Haouchine, Sandrine Houzé
Journal: Eurosurveillance (2010)

In 2002, the French Food Safety Agency drew attention to the lack of information on the prevalence of human cryptosporidiosis in the country. Two years later, the ANOFEL Cryptosporidium National Network (ACNN) was set up to provide public health authorities with data on the incidence and epidemiology of human cryptosporidiosis in France. Constituted on a voluntary basis, ACNN includes 38 hospital parasitology laboratories (mainly in university hospitals). Each laboratory is engaged to notify new cases of confirmed human cryptosporidiosis, store specimens (e.g. stools, duodenal aspirates or biopsies) and related clinical and epidemiological data, using datasheet forms. From January 2006 to December 2009, 407 cryptosporidiosis cases were notified in France and 364 specimens were collected. Of the notified cases, 74 were children under four years of age, accounting for 18.2%. HIV-infected and immunocompetent patients represented 38.6% (n=157) and 28% (n=114) of cases, respectively. A marked seasonal pattern was observed each year, with increased number of cases in mid to late summer and the beginning of autumn. Genotyping of 345 isolates from 310 patients identified C. parvum in 168 (54.2%) cases, C. hominis in 113 (36.4%) and other species in 29 (9.4%), including C. felis (n=15), C. meleagridis (n=4), C. canis (n=4), Cryptosporidium chipmunk genotype (n=1), Cryptosporidium rabbit genotype (n=1) and new Cryptosporidium genotypes (n=4). These data represent the first multisite report of laboratory-confirmed cases of cryptosporidiosis in France.