bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of Early Death Risk in Older Patients Treated With First-Line Chemotherapy for Cancer
Authors: Soubeyran Pierre , Fonck Marianne , Blanc-Bisson Christèle , Blanc Jean-Frédéric , Ceccaldi Joël , Mertens Cécile , Imbert Yves , Cany Laurent , Vogt Luc , Dauba Jerôme , Andriamampionona Francis , Houédé Nadine , Floquet Anne , Chomy Francois , Brouste Véronique , Ravaud Alain , Bellera Carine , Rainfray Muriel 
Published: April 2012

Purpose Objective factors for making choices about the treatment of elderly patients with cancer are lacking. This investigation aimed to help physicians select appropriate treatments through the identification of factors that predict early death (< 6 months) after initiation of chemotherapy treatment. Patients and Methods Previously untreated patients greater than 70 years of age who were scheduled for first-line chemotherapy for various types of cancer were included. Baseline abbreviated comprehensive geriatric assessment (aCGA), including the Mini-Mental State Exam, Timed Get Up and Go (GUG), Activities of Daily Living (ADL), Instrumental Activities in Daily Living (IADL), Mini Nutritional Assessment (MNA), Geriatric Depression Scale (GDS15), and comorbidities index (Cumulative Index Rating Scale-Geriatric), was carried out. Prognostic factors of early death were sought from aCGA results and traditional oncology measures. Results A total of 348 patients were included across 12 centers in Southwest France (median age, 77.45 years; ratio of men to women, 1.47; advanced disease, 65%). Abnormal aCGA scores were observed for 18.1% of patients on the ADL, 73.0% of patients on the IADL, 24.1% of patients on the GUG, 19.0% of patients on the MMS, 44.0% of patients on the GDS15, and 64.9% of patients on the MNA. Advanced disease (odds ratio [OR], 3.9; 95% CI, [1.58 to 9.73]), a low MNA score (OR 2.77; 95% CI, [1.24 to 6.18]), male sex (OR, 2.40; 95% CI, [1.2 to 4.82]), and long GUG (OR, 2.55; 95% CI, [1.32 to 4.94] were associated with higher risk of early death. Conclusion In patients greater than 70 years of age with cancer, advanced disease, a low MNA score, and poor mobility predicted early death. We recommend that the MNA and GUG, performed by a trained nurse, be maintained as part of routine pretreatment workup in these patients to identify at-risk patients and to inform the decision-making process for chemotherapy.
Accelerated Radiotherapy With Carbogen and Nicotinamide for Laryngeal Cancer: Results of a Phase III Randomized Trial
Authors: Janssens Geert O. , Rademakers Saskia E. , Terhaard Chris H. , Doornaert Patricia A. , Bijl Hendrik P. , van den Ende Piet , Chin Alim , Marres Henri A. , de Bree Remco , van der Kogel Albert J. , Hoogsteen Ilse J. , Bussink Johannes , Span Paul N. , Kaanders Johannes H. 
Published: April 2012

Purpose To report the results from a randomized trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen inhalation and nicotinamide (ARCON) in laryngeal cancer. Patients and Methods Patients with cT2-4 squamous cell laryngeal cancer were randomly assigned to AR (68 Gy within 36 to 38 days) or ARCON. To limit the risk of laryngeal necrosis, ARCON patients received 64 Gy on the laryngeal cartilage. The primary end point was local control. Secondary end points were regional control, larynx preservation, toxicity, disease-free survival, and overall survival. In a translational side study, the hypoxia marker pimonidazole was used to assess the oxygenation status in tumor biopsies. Results From April 2001 to February 2008, 345 patients were accrued. After a median follow-up of 44 months, local tumor control rate at 5 years was 78% for AR versus 79% for ARCON (P = .80), with larynx preservation rates of 84% and 87%, respectively (P = .48). The 5-year regional control was significantly better with ARCON (93%) compared with AR (86%, P = .04). The improvement in regional control was specifically observed in patients with hypoxic tumors and not in patients with well-oxygenated tumors (100% v 55%, respectively; P = .01). AR and ARCON produced equal levels of toxicity. Conclusion Despite lack of benefit in local tumor control for advanced laryngeal cancers, a significant gain in regional control rate, with equal levels of toxicity, was observed in favor of ARCON. The poor regional control of patients with hypoxic tumors is specifically countered by ARCON treatment.
Cladribine, But Not Fludarabine, Added to Daunorubicin and Cytarabine During Induction Prolongs Survival of Patients With Acute Myeloid Leukemia: A Multicenter, Randomized Phase III Study
Authors: Holowiecki Jerzy , Grosicki Sebastian , Giebel Sebastian , Robak Tadeusz , Kyrcz-Krzemien Slawomira , Kuliczkowski Kazimierz , Skotnicki Aleksander B. , Hellmann Andrzej , Sulek Kazimierz , Dmoszynska Anna , Kloczko Janusz , Jedrzejczak Wieslaw W. , Zdziarska Barbara , Warzocha Krzysztof , Zawilska Krystyna , Komarnicki Mieczysław , Kielbinski Marek , Piatkowska-Jakubas Beata , Wierzbowska Agnieszka , Wach Malgorzata , Haus Olga 
Published: April 2012

Purpose The goal of this study was to evaluate whether the addition of a purine analog, cladribine or fludarabine, to the standard induction regimen affects the outcome of adult patients with acute myeloid leukemia (AML). Patients and Methods A cohort of 652 untreated AML patients with median age 47 years (range, 17 to 60 years) were randomly assigned to receive one of three induction regimens: DA (daunorubicin plus cytarabine), DAC (DA plus cladribine), or DAF (DA plus fludarabine). Postremission treatment was the same for all arms. Results Complete remission rate in the DAC arm was higher compared with the DA arm (67.5% v 56%; P = .01) as a consequence of reduced incidence of resistant disease (21% v 34%; P = .004). There was no significant difference in early outcome between the DAF and DA arms. The probability of overall survival was improved for the DAC arm (45% ± 4% at 3 years) compared with the DA arm (33% ± 4%; P = .02), and leukemia-free survival was comparable. Long-term outcome did not differ significantly for the comparison of the DAF and DA arms. A survival advantage of the DAC arm over the DA arm was observed among patients age 50 years or older (P = .005), those with initial leukocyte count above 50 × 109/L (P = .03), and those with unfavorable karyotype (P = .03). DAF revealed a significant advantage over DA in patients with adverse karyotype (P = .02). Conclusion The addition of cladribine to the standard induction regimen is associated with increased rate of complete remission and improved survival of adult patients with AML.
Phase II Study of Ganitumab, a Fully Human Anti–Type-1 Insulin-Like Growth Factor Receptor Antibody, in Patients With Metastatic Ewing Family Tumors or Desmoplastic Small Round Cell Tumors
Authors: Tap William D. , Demetri George , Barnette Phillip , Desai Jayesh , Kavan Petr , Tozer Richard , Benedetto Pasquale W. , Friberg Gregory , Deng Hongjie , McCaffery Ian , Leitch Ian , Badola Sunita , Chang Sung , Zhu Min , Tolcher Anthony 
Published: April 2012

Purpose Ganitumab is a fully human monoclonal antibody against type-1 insulin-like growth factor receptor (IGF1R). An open-label phase II study was conducted to evaluate the efficacy and safety of ganitumab monotherapy in patients with metastatic Ewing family tumors (EFT) or desmoplastic small round cell tumors (DSRCT). Patients and Methods Patients ≥16 years of age with relapsed or refractory EFT or DSRCT received 12 mg/kg of ganitumab every 2 weeks. Objective response rate (ORR) was the primary end point. Secondary end points included clinical benefit rate (CBR = complete + partial responses + stable disease [SD] ≥ 24 weeks) and safety and pharmacokinetic profiles of ganitumab. The relationship between tumor response and EWS gene translocation status and IGF-1 levels was evaluated. Results Thirty-eight patients (22 with EFT; 16 with DSRCT) received one or more doses of ganitumab. Twenty-four patients (63%) experienced ganitumab-related adverse events. Grade 3 related events included hyperglycemia (n = 2), thrombocytopenia (n = 5), neutropenia (n = 2), leukopenia (n = 1), and transient ischemic attack (n = 1). There were no grade 4 or 5 treatment-related events. Of 35 patients assessed for response, two had partial responses (ORR, 6%) and 17 (49%) had SD. Four patients had SD ≥ 24 weeks, contributing to a CBR of 17%. The pharmacokinetic profile of ganitumab was similar to that observed in the first-in-human trial. Elevation of IGF-1 levels was observed postdose. EWS-Fli1 translocations were analyzed by RNA sequencing and fluorescent in situ hybridization, and novel translocations were observed in EFT and DSCRT. No apparent relationship between tumor response and IGF-1 levels or EWS gene translocations was observed. Conclusion Ganitumab was well tolerated and demonstrated antitumor activity in patients with advanced recurrent EFT or DSRCT.
Randomized Phase II Trial of Erlotinib With and Without Entinostat in Patients With Advanced Non–Small-Cell Lung Cancer Who Progressed on Prior Chemotherapy
Authors: Witta Samir E. , Jotte Robert M. , Konduri Katrik , Neubauer Marcus A. , Spira Alexander I. , Ruxer Robert L. , Varella-Garcia Marileila , Bunn Paul A. , Hirsch Fred R. 
Published: April 2012

Purpose Histone deacetylase inhibitors (HDACis) have been shown to overcome resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) linked to epigenetic changes and epithelial-mesenchymal transition (EMT) state. This randomized phase II study evaluated the outcome of erlotinib with and without the isoform selective HDACi, entinostat. Patients and Methods Previously treated patients with stage IIIB/IV non–small-cell lung cancer, no prior EGFR-TKIs, and performance status ≤ 2 were randomly administered erlotinib 150 mg on days 1 through 28 plus entinostat 10 mg orally on days 1 and 15 every 28 days (EE) or erlotinib plus placebo (EP). The primary end point was 4-month progression-free survival (PFS) rate with additional end points including 6-month PFS rate, PFS, and overall survival (OS). Exploratory analyses included EMT- and EGFR-related biomarker analysis on archival tissue. Results One hundred thirty-two patients were enrolled (EE, 67; EP, 65). The 4-month PFS rate was comparable for both groups (EE, 18% v EP, 20%; P = .7). In the subset of patients with high E-cadherin levels, OS was longer in the EE group compared with the EP group (9.4 v 5.4 months; hazard ratio, 0.35; 95% CI, 0.13 to 0.92; P = .03) with a corresponding trend toward increased PFS. The adverse event (AE) profile was acceptable, with rash, fatigue, diarrhea, and nausea the most common AEs in both groups. Conclusion Erlotinib combined with entinostat did not improve the outcomes of patients in the overall study population when compared with erlotinib monotherapy. High E-cadherin expression levels at time of diagnosis indicate an increased sensitivity to HDACi/EGFR-TKI inhibition providing the basis for a biomarker-driven validation study.
Prospective, Observational Study of Pain and Analgesic Prescribing in Medical Oncology Outpatients With Breast, Colorectal, Lung, or Prostate Cancer
Authors: Fisch Michael J. , Lee Ju-Whei , Weiss Matthias , Wagner Lynne I. , Chang Victor T. , Cella David , Manola Judith B. , Minasian Lori M. , McCaskill-Stevens Worta , Mendoza Tito R. , Cleeland Charles S. 
Published: April 2012

Purpose Pain is prevalent among patients with cancer, yet pain management patterns in outpatient oncology are poorly understood. Patients and Methods A total of 3,123 ambulatory patients with invasive cancer of the breast, prostate, colon/rectum, or lung were enrolled onto this prospective study regardless of phase of care or stage of disease. At initial assessment and 4 to 5 weeks later, patients completed a 25-item measure of pain, functional interference, and other symptoms. Providers recorded analgesic prescribing. The pain management index was calculated to assess treatment adequacy. Results Of the 3,023 patients we identified to be at risk for pain, 2,026 (67%) reported having pain or requiring analgesics at initial assessment; of these 2,026 patients, 670 (33%) were receiving inadequate analgesic prescribing. We found no difference in treatment adequacy between the initial and follow-up visits. Multivariable analysis revealed that the odds of a non-Hispanic white patient having inadequate pain treatment were approximately half those of a minority patient after adjusting for other explanatory variables (odds ratio, 0.51; 95% CI, 0.37 to 0.70; P = .002). Other significant predictors of inadequate pain treatment were having a good performance status, being treated at a minority treatment site, and having nonadvanced disease without concurrent treatment. Conclusion Most outpatients with common solid tumors must confront issues related to pain and the use of analgesics. There is significant disparity in pain treatment adequacy, with the odds of undertreatment twice as high for minority patients. These findings persist over 1 month of follow-up, highlighting the complexity of these problems.
Gene Modules and Response to Neoadjuvant Chemotherapy in Breast Cancer Subtypes: A Pooled Analysis
Authors: Ignatiadis Michail , Singhal Sandeep K. , Desmedt Christine , Haibe-Kains Benjamin , Criscitiello Carmen , Andre Fabrice , Loi Sherene , Piccart Martine , Michiels Stefan , Sotiriou Christos 
Published: April 2012

Purpose To investigate the association between chemotherapy response and gene expression modules describing important biologic processes and druggable oncogenic pathways in breast cancer (BC) subtypes. Patients and Methods We searched for publicly available gene expression studies evaluating anthracycline with or without taxane-based neoadjuvant chemotherapy and identified eight studies with 996 patients. We computed 17 gene modules and calculated odds ratios (ORs) for pathologic complete response (pCR) for one-unit increases in scaled modules with and without adjustment for clinicopathologic characteristics. Added predictive accuracy was evaluated using the area under the receiver operating characteristic curve (AUC) and integrated discrimination index (IDI). We used the false discovery rate (FDR) to adjust for multiple testing. Results High immune module scores were associated with increased pCR probability in all BC subtypes. High module scores of chromosomal instability, phosphatase and tensin homolog (PTEN) loss, and E2F3 transcription factor were associated with increased pCR probability in estrogen receptor (ER) –negative/human epidermal growth factor receptor 2 (HER2) –negative and ER-positive/HER2-negative but not in HER2-positive tumors (interactions between HER2 and each of these modules for their association with pCR: P < .05; FDR, 0.17; trend for interaction between HER2 and PTEN). High values of insulin-like growth factor 1 activation module were associated with increased pCR probability only in ER-positive/HER2-negative tumors (interaction between insulin-like growth factor 1 and ER: P = .002; FDR, 0.03). When adding the immune module to clinicopathologic characteristics, we observed substantial increases in predictive accuracy for pCR in the HER2-positive subtype (IDI, 0.093; P = .004; increase in AUC from 0.760 to 0.836). Conclusion Different processes and pathways are associated with pCR in different BC subtypes.
A High Percentage of BRAFV600E Alleles in Papillary Thyroid Carcinoma Predicts a Poorer Outcome
Authors: Guerra Anna , Fugazzola Laura , Marotta Vincenzo , Cirillo Massimo , Rossi Stefania , Cirello Valentina , Forno Irene , Moccia Tania , Budillon Alfredo , Vitale Mario 
Published: April 2012

Abstract

Context:
BRAFV600E is considered a negative prognostic marker in papillary thyroid carcinoma (PTC), but unexplained conflicting results are present in the literature. In light of the new finding that most PTC consist of a mixture of tumor cells with wild-type and mutant BRAF, we examined the associations between the percentage of BRAFV600E alleles and both the clinicopathological parameters at time of diagnosis and the disease outcome in a large series of PTCs.

Study Design:
Tumors from 168 patients with PTC were genotyped for BRAFV600E using BigDye Terminator sequencing and pyrosequencing, and the clinical parameters were analyzed. The associations between clinicopathological characteristics, including disease recurrence at follow-up (median 5.1 yr) and the percentage of mutant BRAF alleles were assessed.

Results:
The observed prevalence of BRAFV600E was higher when using pyrosequencing then when using BigDye Terminator sequencing (53.6 vs. 36.9%). In the PTC positive for BRAFV600E, the percentage of mutant alleles ranged from 5.1 to 44.7% of the total BRAF alleles, with a median of 20.6%. The presence or the percentage of BRAFV600E alleles did not correlate significantly with sex, multicentricity, lymph node metastasis, or tumor stage. The percentage of BRAFV600E alleles directly correlated with age at diagnosis and tumor volume (R2 = 0.223, P = 0.039, and R2 = 0.166, P &lt; 0.001, respectively). The percentage of BRAFV600E alleles (P = 0.014), tumor volume (P = 0.012), and lymph node metastasis (P = 0.008) predicted the disease outcome. The odds ratio of recurrence for PTC with BRAFV600E alleles of 30% or greater, compared with that for PTC with BRAFV600E alleles of less than 30%, was 5.31 (P = 0.002).

Conclusions:
A high percentage of BRAFV600E alleles defines a PTC molecular subtype and predicts a poorer disease outcome. The analysis of BRAF mutations by pyrosequencing is useful to refine the risk stratification of patients with PTC.
Words Spoken and Written: Divergent Meanings of Honor among Elites in Nineteenth-Century Rio Grande Do Sul
Authors: Monsma Karl 
Published: April 2012

Abstract
The article concerns differences in the nature and signs of honor among nineteenth-century Brazilian elites. Based primarily on the court records of a dispute between a frontier rancher and a wealthy urban merchant in Rio Grande do Sul, as well as the correspondence of the merchant with a wide variety of commercial and political contacts, it argues that honor symbolized the value and reliability of exchange partners among all elite groups, but differences in the nature of exchanges led to different means of gauging honor. Landowners involved mainly in local face-to-face exchanges evaluated male honor primarily by the observance of spoken agreements and promises, whereas merchants involved in long-distance trade emphasized careful accounting and the fulfillment of written obligations. In a vast country with severely limited educational opportunities for the great majority of the population, fluency in written communication and accounting skills became important means to accumulate wealth and power, allowing individuals with these skills to occupy central positions in long-distance trade and patronage networks. Differences in the nature of honor also fueled disdain and hatred in the civil wars of nineteenth-century Rio Grande do Sul, which tended to pit frontier ranchers against urban commercial and political elites.
The conceptual bases of metaphors of dirt and cleanliness in moral and non-moral reasoning
Authors: Lizardo, Omar 
Published: April 2012

AbstractIn this paper I propose a new understanding of the often-noted phenomenon that much of our conceptualization and reasoning about moral propriety is framed by a set of metaphors that originate from a conceptual structure generated from our experiences with dirt and cleanliness. I argue that reliance on the dirty-clean dichotomy to conceptualize moral propriety or impropriety emerges from metaphorical extensions into various realms of experience (e.g., sports, governance, introspection) grounded in an idealized cognitive model in which dirt is conceptualized as matter out of place and clean is conceptualized as ordered arrangement. The analysis provides a unified framework with which to understand the use of dirty and clean as metaphors to categorize objects, events and actions in the moral domain. Finally, I suggest that the dirty-clean distinction is useful for understanding broader cultural issues (such as moral panics regarding media, immigration and disease), and I show that the conceptualization of certain non-moral properties can be understood using the same framework (e.g., the quality of being exceptional) of objects and actions.
Cutting and breaking in Äiwoo: Event integration and the complexity of lexical expressions
Authors: Næss, Åshild 
Published: April 2012

AbstractThis paper examines the lexical encoding of events of “cutting and breaking” in the Oceanic language Äiwoo. It shows that this language differs from previously described languages in this domain in several ways: in having complex “cut and break” forms consisting of two bound elements referring to distinct aspects of the cut and break event; in integrating these forms into a cline of lexicalisation vs. serialisation, arguably reflecting a conceptual-semantic continuum of event integration; and in violating previously suggested generalisations concerning the behaviour of verbs of cutting and breaking in inchoative alternations. It shows that lexicalisation may clearly be a matter of degree, and that the degree to which an event is construed as being constituted by independent subevents vs. subevents which cannot occur independently may be directly reflected in the type of formal expression a language provides to describe it. Furthermore, it suggests that the distinction between “cut” and “break” expressions, assumed in some of the literature to be a fairly straightforward bipartition, may in fact be more of a cline. The paper thus demonstrates the complexity of the cognitive domain of cutting and breaking events and the range of strategies that may be employed by a language in describing them.
Expression of thyroid-stimulating hormone receptor, octamer-binding transcription factor 4, and intracisternal A particle-promoted polypeptide in human breast cancer tissues
Authors: Govindaraj Vijayakumar , Yaduvanshi Nirmala Singh , Krishnamachar Harish , Rao A. Jagannadha 
Published: April 2012

Abstract

Background: Thyroid-stimulating hormone receptor (TSHR) is one of the members of glycoprotein hormone receptor family; activation of TSHR by thyroid-stimulating hormone (TSH) regulates thyroid function, proliferation, and differentiation. The other family members of glycoprotein hormone receptors, such as leutinizing hormone receptor (LHR), human chorionic gonadotropin (hCG), and follicle-stimulating hormone (FSH) are known to be expressed in nonendocrine tissues including human breast cancer and regulate proliferation and differentiation. The involvement of thyroid hormones in the growth and differentiation of normal breast tissue is well documented. However, the presence of TSHR in breast cancer has not been demonstrated. The aim of the present study was to establish the expression pattern of TSHR along with transcription factors, such as octamer 4 (OCT4) and intracisternal A particle-promoted polypeptide (IPP) in human breast tumor.

Materials and methods: For this study, patients with stages I–III breast cancers and adjacent noncancerous tissues were prospectively accrued and analyzed. We employed semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis to determine the expression levels of TSHR in normal and human breast cancer tissues.

Results: The results indicated that a significant increase in TSHR expression was observed in tumor tissues compared to normal breast tissues. RT-PCR analysis of OCT4 and IPP also revealed a significant increase in breast tumor tissues over the controls.

Conclusions: To our knowledge, this is the first report demonstrating expression of TSHR and IPP in normal breast and breast tumors. The expression of TSHR, IPP, and OCT4 increased in the human breast tumor samples over the noncancer tissues. However, further studies are needed to establish an unequivocal role for TSHR in breast tumor progression.