bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Study of Cetuximab in Combination With Chemoradiation in Patients With Stage IIIA/B Non–Small-Cell Lung Cancer: RTOG 0324
Authors: Blumenschein George R. , Paulus Rebecca , Curran Walter J. , Robert Francisco , Fossella Frank , Werner-Wasik Maria , Herbst Roy S. , Doescher Philip O. , Choy Hak , Komaki Ritsuko 
Published: May 2011

PurposeNon–small-cell lung cancer (NSCLC) commonly expresses the epidermal growth factor receptor (EGFR), which is associated with poor clinical outcome. Cetuximab is a chimerized monoclonal antibody that targets the EGFR and, in preclinical models, it demonstrates radiosensitization properties. We report a phase II trial testing the combination of cetuximab with chemoradiotherapy (CRT) in unresectable stage III NSCLC.Patients and MethodsEligibility criteria included unresectable stage III NSCLC, Zubrod performance status ≤ 1, weight loss ≤ 5%, forced expiratory volume in 1 second ≥ 1.2 L, and adequate organ function. Patients received an initial dose of cetuximab (400 mg/m2) on day 1 of week 1 and then weekly doses of cetuximab (250 mg/m2) until completion of therapy (weeks 2 through 17). During week 2, patients started CRT (63 Gy in 35 fractions) with weekly carboplatin at area under the [concentration-time] curve (AUC) 2 and six doses of paclitaxel at 45 mg/m2followed by carboplatin (AUC 6) and two cycles of paclitaxel (200 mg/m2) during weeks 12 through 17. Primary end points included safety and compliance of concurrent cetuximab and CRT.ResultsIn all, 93 patients were enrolled and 87 were evaluable. Median follow-up was 21.6 months. Response rate was 62% (n = 54), median survival was 22.7 months, and 24-month overall survival was 49.3%. Adverse events related to treatment included 20% grade 4 hematologic toxicities, 8% grade 3 esophagitis, and 7% grade 3 to 4 pneumonitis. There were five grade 5 events.ConclusionThe combination of cetuximab with CRT is feasible and shows promising activity. The median and overall survival achieved with this regimen were longer than any previously reported by the Radiation Therapy Oncology Group.
Metastatic and Locally Advanced Pancreatic Endocrine Carcinomas: Analysis of Factors Associated With Disease Progression
Authors: Panzuto Francesco , Boninsegna Letizia , Fazio Nicola , Campana Davide , Pia Brizzi Maria , Capurso Gabriele , Scarpa Aldo , De Braud Filippo , Dogliotti Luigi , Tomassetti Paola , Delle Fave Gianfranco , Falconi Massimo 
Published: May 2011

Purpose Knowledge of clinical course of pancreatic endocrine carcinomas (PECs) is poor. This study aimed to determine the time to progression of advanced PECs, and to identify predictors capable of selecting subgroups with higher risk of progression. Patients and Methods In this multicenter retrospective analysis, patients with advanced PECs were enrolled. Staging was according to European Neuroendocrine Tumors Society guidelines. Grading was based on proliferation index using Ki67 immunohistochemistry. The primary end point was progression-free survival (PFS), which was assessed using the Kaplan-Meier method. The Cox regression proportional hazard model was used to identify predictors for tumor progression. Results Two hundred two patients with PECs were enrolled, including 172 with well-differentiated and 30 with poorly differentiated endocrine carcinomas. There were 34 patients with stage III and 168 with stage IV tumors. G1 tumors were present in 19.7% of patients, whereas 60.1% of patients had G2 tumors, and the remaining 20.2% had G3 tumors. Disease progression occurred in 166 patients (82.2%), at a median interval of 10 months (interquartile range, 5 to 22) from diagnosis. Median PFS was 14 months. Different PFS were observed depending on G grade (P < .001) and tumor differentiation (P < .001) and in patients who did not receive any antitumor treatment (P = .002). The major risk factor for progression was the proliferation index Ki67 (hazard ratio, 1.02 for each increasing unit; P < .001). Overall 5-year survival was 44.1%. Conclusion The vast majority of patients with advanced PECs undergo disease progression. The major risk factor for progression is Ki67 index, which should lead physicians dealing with PECs to plan appropriate follow-up programs and therapeutic strategies.
Impact of Body Mass Index on the Efficacy of Endocrine Therapy in Premenopausal Patients With Breast Cancer: An Analysis of the Prospective ABCSG-12 Trial
Authors: Pfeiler Georg , Königsberg Robert , Fesl Christian , Mlineritsch Brigitte , Stoeger Herbert , Singer Christian F. , Pöstlberger Sabine , Steger Guenther G. , Seifert Michael , Dubsky Peter , Taucher Susanne , Samonigg Hellmut , Bjelic-Radisic Vesna , Greil Richard , Marth Christian , Gnant Michael 
Published: May 2011

Purpose Aromatase inhibitors are effective as endocrine treatment for patients with hormone receptor–positive breast cancer. According to the hypothesis that overweight patients have higher levels of aromatase enzyme availability, we investigated the influence of body mass index (BMI) on the efficacy of adjuvant endocrine therapy in premenopausal patients in a retrospective analysis of the Austrian Breast and Colorectal Cancer Study Group (ABCSG) 12 trial. Patients and Methods ABCSG-12 examined the efficacy of ovarian suppression using goserelin (3.6 mg subcutaneously every 28 days) in combination with anastrozole or tamoxifen with or without zoledronic acid (4 mg intravenously every 6 months) in premenopausal women with endocrine-responsive breast cancer. BMI was calculated using the prospectively collected data on patients' height and weight at study entry. BMI categories have been differentiated according to the WHO definition. Results Overweight patients treated with anastrozole had a 60% increase in the risk of disease recurrence (hazard ratio [HR], 1.60; 95% CI, 1.06 to 2.41; P = .02) and more than a doubling in the risk of death (HR, 2.14; 95% CI, 1.17 to 3.92; P = .01) compared with normal weight patients treated with anastrozole. In the overweight group, patients treated with anastrozole had a nearly 50% increase in the risk of disease recurrence (HR, 1.49; 95% CI, 0.93 to 2.38; P = .08) and a three-fold increase in the risk of death (HR, 3.03; 95% CI, 1.35 to 6.82; P = .004) compared with patients treated with tamoxifen. Conclusion BMI significantly impacts on the efficacy of anastrozole plus goserelin in premenopausal patients with breast cancer, probably through influencing aromatase availability and/or ovarian suppression by goserelin.
Risk of Recurrent Venous Thromboembolism and Mortality in Patients With Cancer Incidentally Diagnosed With Pulmonary Embolism: A Comparison With Symptomatic Patients
Authors: den Exter Paul L. , Hooijer José , Dekkers Olaf M. , Huisman Menno V. 
Published: May 2011

Purpose The routine use of modern computed tomography scanners has led to an increased detection of incidental pulmonary embolism (PE), in particular in patients with cancer. The clinical relevance of these incidental findings is unknown. Patients and Methods In this retrospective cohort study, oncology patients in whom PE was objectively proven between 2004 and 2010 and anticoagulant treatment was started, were included. Fifty-one patients with incidental PE and 144 with symptomatic PE were observed for 1 year to compare the risks of recurrent venous thromboembolism (VTE), bleeding complications, and mortality. Kaplan-Meier and Cox survival analyses were performed. Results Incidental and symptomatic patients did not differ with respect to mean age, sex, cancer type and stage, and risk factors for VTE. As a result from evolving treatment guidelines, approximately half of the patients in both groups received long-term treatment with vitamin K antagonists in stead of currently recommended low-molecular-weight heparin. The 12-month cumulative incidence of recurrent VTE was 13.3% in the incidental group versus 16.9% in the symptomatic group (P = .77). Notably, 20% VTE events recurred after premature termination of anticoagulant therapy. The risk of major bleeding complications was also comparable in the two groups (12.5% for incidental patients and 8.6% for symptomatic patients; P = .5). The respective 12-month mortality risks were 52.9% and 53.3% (P = .7). Conclusion Our findings suggest that oncology patients diagnosed with and treated for incidental PE, have similar high rates of recurrent VTE, bleeding complications, and mortality, as compared with oncology patients who develop symptomatic PE.
Clinical Features and Outcome in HIV-Associated Multicentric Castleman's Disease
Authors: Bower Mark , Newsom-Davis Tom , Naresh Kikkeri , Merchant Shairoz , Lee Belinda , Gazzard Brian , Stebbing Justin , Nelson Mark 
Published: May 2011

Purpose To describe clinical features, treatment outcomes and relapse rates in HIV-associated multicentric Castleman's disease (MCD) in a sizeable mature cohort. Methods From a prospective database, we identified 61 HIV-seropositive patients with histologically confirmed MCD (median follow-up, 4.2 years). Since 2003, 49 patients with newly diagnosed MCD have been treated with rituximab with (n = 14) or without (n = 35) etoposide. Results At MCD diagnosis, 55 (90%) of 61 patients met proposed clinical criteria defining an attack. Four patients (7%) had histologic evidence of coexisting lymphoma, and one developed lymphoma 2 years after treatment. The incidence of lymphoma is 28 per 1,000 patient years. With rituximab-based treatment, the overall survival was 94% (95% CI, 87% to 100%) at 2 years and was 90% (95% CI, 81% to 100%) at 5 years compared with 42% (95% CI, 14% to 70%) and 33% (95% CI, 6% to 60%) in 12 patients treated before introduction of rituximab (log-rank P < .001). Four of 49 rituximab-treated patients have died; three died as a result of MCD within 10 days of diagnosis, and one died as a result of lymphoma in remission of MCD. Eight of 46 patients who achieved clinical remission suffered symptomatic, histologically confirmed MCD relapse. The median time to relapse was 2 years, and all have been successfully re-treated and are alive in remission. The 2- and 5-year progression-free survival rates for all 49 patients treated with rituximab-based therapy were 85% (95% CI, 74% to 95%) and 61% (95% CI, 40% to 82%), respectively. Conclusion HIV-associated MCD is a remitting-relapsing disease. The outlook has improved dramatically in recent years with the introduction of rituximab-based therapy and yields high overall survival rates.
Persistence of Cytogenetic Abnormalities at Complete Remission After Induction in Patients With Acute Myeloid Leukemia: Prognostic Significance and the Potential Role of Allogeneic Stem-Cell Transplantation
Authors: Chen Yiming , Cortes Jorge , Estrov Zeev , Faderl Stefan , Qiao Wei , Abruzzo Lynne , Garcia-Manero Guillermo , Pierce Sherry , Huang Xuelin , Kebriaei Partow , Kadia Tapan , De Lima Marcos , Kantarjian Hagop , Ravandi Farhad 
Published: May 2011

Purpose To determine the prognostic impact of persistent cytogenetic abnormalities at complete remission (CR) on relapse-free survival (RFS) and overall survival (OS) in patients with acute myeloid leukemia (AML) and to examine the potential role of allogeneic stem-cell transplantation (SCT) in this setting. Patients and Methods Data from 254 adult patients with AML (excluding acute promyelocytic leukemia) who achieved CR after induction chemotherapy on various first-line protocols were examined. Results Median follow-up for surviving patients was 43 months. Patients with cytogenetic abnormalities at CR (n = 71) had significantly shorter RFS (P = .001) and OS (P < .001) compared with patients with normal cytogenetics at CR (n = 183); 3-year RFS was 15% and 45%, and 3-year OS was 15% and 56%, respectively. Among the patients with persistent cytogenetic abnormalities at CR, those who underwent SCT in first CR (CR1; n = 15) had better RFS and OS compared to those without SCT (n = 56; P = .04 and .06, respectively). In multivariate analysis, persistent cytogenetic abnormalities at CR was an independent predictor for RFS (P < .001) and OS (P = .001), but among patients with persistent cytogenetic abnormalities at CR, no significant differences in OS (P = .25) was observed between those who did or did not receive SCT with a trend favoring SCT for RFS (P = .08). Conclusion Persistent cytogenetically abnormal cells at CR predict a significantly shorter RFS and OS. SCT in CR1 may improve the clinical outcome of patients lacking cytogenetic remission after induction although this depends on patient selection.
Long-Term Use of Acetaminophen, Aspirin, and Other Nonsteroidal Anti-Inflammatory Drugs and Risk of Hematologic Malignancies: Results From the Prospective Vitamins and Lifestyle (VITAL) Study
Authors: Walter Roland B. , Milano Filippo , Brasky Theodore M. , White Emily 
Published: May 2011

Purpose Among previous studies examining the associations of over-the-counter analgesics or nonsteroidal anti-inflammatory drugs (NSAIDs) and incident hematologic malignancies, results were inconsistent for NSAIDs but suggested an increased risk with acetaminophen (paracetamol). Herein, we used a large prospective cohort study to examine these associations. Patients and Methods In total, 64,839 men and women age 50 to 76 years were recruited from 2000 to 2002 to the Vitamins and Lifestyle (VITAL) study. Incident hematologic malignancies (n = 577) were identified through December 2008 by linkage to the Surveillance, Epidemiology and End Results cancer registry. Hazard ratios (HRs) associated with use of analgesics for total incident hematologic malignancies and cancer subcategories were estimated by Cox proportional hazards models. Models were adjusted for age, sex, race/ethnicity, education, smoking, self-rated health, arthritis, chronic musculoskeletal pain, migraines, headaches, fatigue, and family history of leukemia/lymphoma. Results After adjustment, there was an increased risk of incident hematologic malignancies associated with high use (≥ 4 days/week for ≥ 4 years) of acetaminophen (HR, 1.84; 95% CI, 1.35 to 2.50 for high use; P trend = .004). This association was seen for myeloid neoplasms (HR, 2.26; 95% CI, 1.24 to 4.12), non-Hodgkin's lymphomas (HR, 1.81; 95% CI, 1.12 to 2.93), and plasma cell disorders (HR, 2.42; 95% CI, 1.08 to 5.41), but not chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; HR, 0.84; 95% CI, 0.31 to 2.28). By comparison, there was no association with risk of incident hematologic malignancies for increasing use of aspirin, nonaspirin NSAIDs, or ibuprofen. Conclusion High use of acetaminophen was associated with an almost two-fold increased risk of incident hematologic malignancies other than CLL/SLL. Neither aspirin nor nonaspirin NSAIDs are likely useful for prevention of hematologic malignancies.
Monitoring of Minimal Residual Disease in NPM1-Mutated Acute Myeloid Leukemia: A Study From the German-Austrian Acute Myeloid Leukemia Study Group
Authors: Krönke Jan , Schlenk Richard F. , Jensen Kai-Ole , Tschürtz Florian , Corbacioglu Andrea , Gaidzik Verena I. , Paschka Peter , Onken Shiva , Eiwen Karina , Habdank Marianne , Späth Daniela , Lübbert Michael , Wattad Mohammed , Kindler Thomas , Salih Helmut R. , Held Gerhard , Nachbaur David , von Lilienfeld-Toal Marie , Germing Ulrich , Haase Detlef , Mergenthaler Hans-Günther , Krauter Jürgen , Ganser Arnold , Göhring Gudrun , Schlegelberger Brigitte , Döhner Hartmut , Döhner Konstanze 
Published: May 2011

Purpose To evaluate the prognostic value of minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) with NPM1 mutation (NPM1mut). Patients and Method RNA-based real-time quantitative polymerase chain reaction (RQ-PCR) specific for the detection of six different NPM1mut types was applied to 1,682 samples (bone marrow, n = 1,272; blood, n = 410) serially obtained from 245 intensively treated younger adult patients who were 16 to 60 years old. Results NPM1mut transcript levels as a continuous variable were significantly associated with prognosis after each treatment cycle. Achievement of RQ-PCR negativity after double induction therapy identified patients with a low cumulative incidence of relapse (CIR; 6.5% after 4 years) compared with RQ-PCR–positive patients (53.0%; P < .001); this translated into significant differences in overall survival (90% v 51%, respectively; P = .001). After completion of therapy, CIR was 15.7% in RQ-PCR–negative patients compared with 66.5% in RQ-PCR–positive patients (P < .001). Multivariable analyses after double induction and after completion of consolidation therapy revealed higher NPM1mut transcript levels as a significant factor for a higher risk of relapse and death. Serial post-treatment assessment of MRD allowed early detection of relapse in patients exceeding more than 200 NPM1mut/104 ABL copies. Conclusion We defined clinically relevant time points for NPM1mut MRD assessment that allow for the identification of patients with AML who are at high risk of relapse. Monitoring of NPM1mut transcript levels should be incorporated in future clinical trials to guide therapeutic decisions.
Classification of pituitary growth hormone producing adenomas according to SIPAP: application in clinical practice
Authors: Meyer Sofie , Valdemarsson Stig , Larsson Elna-Marie 
Published: May 2011

Background In 1997, the SIPAP classification was introduced, a guide designed for MRI, to characterize pituitary adenomas with emphasis on extrasellar extensions and impact on adjacent structures. To our knowledge no previous evaluation of the inter-observer agreement of the SIPAP classification has been performed. Purpose To evaluate the inter-observer agreement of the SIPAP classification. Material and Methods Sixty patients operated on for growth hormone producing pituitary adenomas at Lund University Hospital 1991–2007 had an assessable preoperative MRI scan. Forty-five of them also had an assessable postoperative MRI scan. The mean time between surgery and postoperative MRI scans was 11 months. Two observers evaluated all the MRI scans independently. The outcome of the evaluation is presented as the percentage of concordance in each of the evaluated directions and the degree of discrepancy for each of the directions evaluated. Results In 284 (79%) of 360 preoperative gradings both observers agreed completely. In 17 of the 60 preoperative MRI scans, both observers made identical assessments according to the SIPAP classification in all the six different directions of tumor extension. In 76 gradings the results differed between the observers. The difference was 1 grade (or less) in 69 cases. In 230 (85%) of 270 postoperative gradings the results were identical for both observers. In 18 of the 45 postoperative MRI scans, both observers made the same assessments according to the SIPAP classification in all the six different directions of tumor extension. In 40 gradings the results differed between the observers. The difference was 1 grade (or less) in all 40 cases. Conclusion We found a relatively high inter-observer agreement both pre- and postoperatively, supporting the usefulness and easy applicability of the SIPAP system for grading of pituitary adenomas pre- as well as postoperatively.
Human chorionic gonadotropin and a 15 amino acid hCG fragment of the hormone induce downregulation of the cytokine IL-8 receptor in normal breast epithelial cells
Authors: Noronha Samuel M.R. , Correa-Noronha Silvana A.A. , Russo Irma H. , de Cicco Ricardo López , Santucci-Pereira Julia , Russo José 
Published: May 2011

AbstractCytokine receptors are associated with tumor cell growth by increasing proliferation, metastasis and regulating self-renewal of cancer stem cells (SCs). There is a strong association between cytokine IL-8 receptor (CXCR1) over-expression and cells displaying SC characteristics. Human chorionic gonadotropin (hCG) causes differentiation, inhibition of cell proliferation and increased apoptosis of the breast epithelium. hCG receptor (LHCGR) expression in breast tumors and in breast cancer cell lines is undetectable or low. In this study, our objective was to assess and compare the effects of hCG and a 15 amino acid hCG fragment of the hormone on mRNA expression of CXCR1 and LHCGR on normal breast epithelial cells (MCF-10F) by real time RT-PCR after treatment with hCG or a hCG fragment for 15 days. Cell proliferation was also measured. hCG and the hCG fragment decreased cell proliferation in both groups. The compounds upregulated LHCGR expression and downregulated CXCR1 expression. It is possible to postulate that an increase of LHCGR mRNA seems to respond to the decrease of CXCR1 expression. These genes probably act synergistically to reduce the amount of cancer SCs in the mammary gland. Thereby, the use of hCG or the hCG fragment as a therapeutic or preventive tool should be considered.
Increasing bat abundance in a major winter roost in central Poland over 30 years
Authors: Lesiński Grzegorz , Ignaczak Maurycy , Kowalski Marek 
Published: May 2011

Abstract
A bat census in the years 1981–2010 (repeated twice during each hibernation period in January and March) showed upward trends in many populations of bats hibernating in the Szachownica Cave (central Poland). Total numbers of the bat assemblage, which consisted of 11 species, increased within the study period from 178 to 1477 individuals in the first decade to 835–2902 in the past decade of the study, with the highest rates of increase noted in Barbastella barbastellus, Plecotus auritus and Myotis nattereri. Myotis myotis and Myotis daubentonii showed only slight upward trends. In the years 2009–2010, Myotis bechsteinii occurred in markedly higher numbers (up to 24 individuals) as compared to previous years.
Inter-individual variations in male and female mating bonds within a population of Eld’s deer in Hainan Island, China
Authors: Zeng Zhi-Gao , Song Yan-Ling , Zhang Qiong 
Published: May 2011

Abstract
The mating system of a semi-captive population of Hainan Eld’s deer Cervus eldi hainanus was investigated in the Datian National Nature Reserve, China. In total, 18 females and 11 males out of 61 semi-captive deer were involved in mating, and 43 copulations were observed. The mating system of this population was polygynous, with an inter-individual variation in the type of mating bonds among males (i.e., polygyny, promiscuity) and among females (i.e., serial monogamy, polyandry, promiscuity). During the rut, 13 out of these 18 females (72.2%) copulated with only one male, four of the 11 males (36.4%) mated with more than one female but obtained 81.4% mating opportunities (35 of 43 copulations). Dominant males served significantly more females in estrus than subordinate males. Dominant males can monopolize copulations despite the long duration (over 3 months) of the breeding season, and asynchronous estrus of females makes this possible without increasing energetic costs for dominant males. Mating dominance of a dominant male continued for at least 87 days during the rut, thus the male copulated with a total of 11 females. Our results suggest that the inter-individual variations in male and female mating bonds largely depends on mating strategies of dominant males, operational sex ratio as well as multiple estrous periods in females.