bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized Phase II Trial of Erlotinib Versus Temozolomide or Carmustine in Recurrent Glioblastoma: EORTC Brain Tumor Group Study 26034
Authors: van den Bent Martin J. , Brandes Alba A. , Rampling Roy , Kouwenhoven Mathilde C.M. , Kros Johan M. , Carpentier Antoine F. , Clement Paul M. , Frenay Marc , Campone Mario , Baurain Jean-Francois , Armand Jean-Paul , Taphoorn Martin J.B. , Tosoni Alicia , Kletzl Heidemarie , Klughammer Barbara , Lacombe Denis , Gorlia Thierry 
Published: February 2009

Purpose Approximately 50% of glioblastomas (GBMs) are characterized by overexpression of the epidermal growth factor receptor (EGFR) and EGFR gene amplification. In approximately 25% of instances, constitutively activated EGFR mutants are present. These observations make EGFR-inhibiting drugs a logical approach for trials in recurrent GBM. Patients and Methods In a randomized, controlled, phase II trial, 110 patients with progressive GBM after prior radiotherapy were randomly assigned to either erlotinib or a control arm that received treatment with either temozolomide or carmustine (BCNU). The primary end point was 6-month progression-free survival (PFS). Tumor specimens obtained at first surgery were investigated for EGFR expression; EGFRvIII mutants; EGFR amplification; EGFR mutations in exons 18, 19, and 21; and pAkt. These results were correlated with outcome. Pharmacokinetic analysis was part of the study. Results Treatment was well tolerated in general; skin toxicity was the most frequent adverse effect of erlotinib. The 6-month PFS rate in the erlotinib arm was 11.4% (95% CI, 4.6% to 21.5%), and it was 24% in the control arm. Of all explored biomarkers, only low pAkt expression appeared to be of borderline significance to an improved outcome. None of the eight patients who had tumors with EGFRvIII mutant presence and PTEN expression had 6-month PFS. The use of enzyme-inducing anticonvulsants significantly increased erlotinib clearance, but pharmacokinetic findings were not related to outcome. Conclusion Erlotinib has insufficient single-agent activity in unselected GBM. No clear biomarker associated with improved outcome to erlotinib was identified.
Breast Cancer Subtypes and Response to Docetaxel in Node-Positive Breast Cancer: Use of an Immunohistochemical Definition in the BCIRG 001 Trial
Authors: Hugh Judith , Hanson John , Cheang Maggie Chon U. , Nielsen Torsten O. , Perou Charles M. , Dumontet Charles , Reed John , Krajewska Maryla , Treilleux Isabelle , Rupin Matthieu , Magherini Emmanuelle , Mackey John , Martin Miguel , Vogel Charles 
Published: February 2009

Purpose To investigate the prognostic and predictive significance of subtyping node-positive early breast cancer by immunohistochemistry in a clinical trial of a docetaxel-containing regimen. Methods Pathologic data from a central laboratory were available for 1,350 patients (91%) from the BCIRG 001 trial of docetaxel, doxorubicin, and cyclophosphamide (TAC) versus fluorouracil, doxorubicin, and cyclophosphamide (FAC) for operable node-positive breast cancer. Patients were classified by tumor characteristics as (1) triple negative (estrogen receptor [ER]–negative, progesterone receptor [PR]–negative, HER2/neu [HER2]–negative), (2) HER2 (HER2-positive, ER-negative, PR-negative), (3) luminal B (ER-positive and/or PR-positive and either HER2-positive and/or Ki67high), and (4) luminal A (ER-positive and/or PR-positive and not HER2-positive or Ki67high), and assessed for prognostic significance and response to adjuvant chemotherapy. Results Patients were subdivided into triple negative (14.5%), HER2 (8.5%), luminal B (61.1%), and luminal A (15.9%). Three-year disease-free survival (DFS) rates (P values with luminal B as referent) were 67% (P < .0001), 68% (P = .0008), 82% (referent luminal B), and 91% (P = .0027), respectively, with hazard ratios of 2.22, 2.12, and 0.46. Improved 3-year DFS with TAC was found in the luminal B group (P = .025) and a combined ER-positive/HER2-negative group treated with tamoxifen (P = .041), with a marginal trend in the triple negatives (P = .051) and HER2 (P = .068) subtypes. No DFS advantage was seen in the luminal A population. Conclusion A simple immunopanel can divide breast cancers into biologic subtypes with strong prognostic effects. TAC significantly complements endocrine therapy in patients with luminal B subtype and, in the absence of targeted therapy, is effective in the triple-negative population.
Follicular Lymphoma in the United States: First Report of the National LymphoCare Study
Authors: Friedberg Jonathan W. , Taylor Michael D. , Cerhan James R. , Flowers Christopher R. , Dillon Hildy , Farber Charles M. , Rogers Eric S. , Hainsworth John D. , Wong Elaine K. , Vose Julie M. , Zelenetz Andrew D. , Link Brian K. 
Published: February 2009

PurposeOptimal therapy of follicular lymphoma (FL) is not defined. We analyzed a large prospective cohort study to identify current demographics and patterns of care of FL in the United States.Patients and MethodsThe National LymphoCare Study is a multicenter, longitudinal, observational study designed to collect information on treatment regimens and outcomes for patients with newly diagnosed FL in the United States. Patients were enrolled between 2004 and 2007. There is no study-specific prescribed treatment regimen or intervention.ResultsTwo thousand seven hundred twenty-eight subjects were enrolled at 265 sites, including the 80% of patients enrolled from nonacademic sites. Using the Follicular Lymphoma International Prognostic Index (FLIPI), three distinct groups independent of histologic grade could be defined. Initial therapeutic strategy was: observation, 17.7%; rituximab monotherapy, 13.9%; clinical trial 6.1%; radiation therapy, 5.6%; chemotherapy only, 3.2%; chemotherapy plus rituximab, 51.9%. Chemotherapy plus rituximab regimens were: rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone, 55.0%; rituximab plus cyclophosphamide, vincristine, and prednisone, 23.1%; rituximab plus fludarabine based, 15.5%; other, 6.4%. The choice to initiate therapy rather than observe was associated with age, FLIPI, stage, and grade (P < .01). Significant differences in treatment (P < .01) across regions of the United States were noted. Contrary to practice guidelines, treatment of stage I FL frequently omits radiation therapy.ConclusionWidely disparate therapeutic approaches are utilized for FL. Initial therapy is deferred in a small subset of patients. There is no single standard of care for the treatment of de novo FL, although antibody use is ubiquitous when therapy is initiated. These disparate approaches to the initial care of patients with FL render a heterogeneous group of patients at relapse.
Docetaxel With Cyclophosphamide Is Associated With an Overall Survival Benefit Compared With Doxorubicin and Cyclophosphamide: 7-Year Follow-Up of US Oncology Research Trial 9735
Authors: Jones Stephen , Holmes Frankie Ann , O'Shaughnessy Joyce , Blum Joanne L. , Vukelja Svetislava J. , McIntyre Kristi J. , Pippen John E. , Bordelon James H. , Kirby Robert L. , Sandbach John , Hyman William J. , Richards Donald A. , Mennel Robert G. , Boehm Kristi A. , Meyer Wally G. , Asmar Lina , Mackey Daniel , Riedel Stefan , Muss Hyman , Savin Michael A. 
Published: February 2009

Purpose We previously reported that four cycles of docetaxel/cyclophosphamide (TC) produced superior disease-free survival (DFS) compared with four cycles of doxorubicin/cyclophosphamide (AC) in early breast cancer. Older women are under-represented in adjuvant chemotherapy trials. In our trial 16% of patients were ≥ 65 years. We now report 7-year results for DFS and overall survival (OS) as well as the impact of age, hormone receptor status, and HER2 status on outcome and toxicity. Patients and Methods Patients were randomly assigned to receive either four cycles of standard-dose AC (60/600 mg/m2; n = 510), or TC (75/600 mg/m2; n = 506), administered by intravenous infusion every 3 weeks. Results The median age in women younger than 65, was 50 years (range, 27 to 64) and for women ≥ 65 was 69 years (range, 65 to 77). Baseline characteristics in the two age subgroups were generally well matched, except that older women tended to have more lymph node involvement. At a median of 7 years follow-up, the difference in DFS between TC and AC was significant (81% TC v 75% AC; P = .033; hazard ratio [HR], 0.74; 95% CI 0.56 to 0.98) as was OS (87% TC v 82% AC; P = .032; HR, 0.69; 95% CI, 0.50 to 0.97). TC was superior in older patients as well as younger patients. There was no interaction of hormone-receptor status or HER-2 status and treatment. Older women experienced more febrile neutropenia with TC and more anemia with AC. Conclusion With longer follow-up, four cycles of TC was superior to standard AC (DFS and OS) and was a tolerable regimen in both older and younger patients.
Heterogeneity and Power in Clinical Biomarker Studies
Authors: Pintilie Melania , Iakovlev Vladimir , Fyles Anthony , Hedley David , Milosevic Michael , Hill Richard P. 
Published: February 2009

Purpose Many recent studies have suggested the possibility that a variety of different biomarkers may be associated with treatment outcome. However, it is also apparent that some of these biomarkers are heterogeneously distributed within a tumor. Due to this heterogeneous distribution of the biomarker, the association sought may appear weak or nonexistent. Thus, there is a wide range of conclusions in the literature on the association between a biomarker and an outcome. Results This article presents how to quantify the heterogeneity and how it influences the observed effect size and the ability to detect it (power of the study). It can be shown that the estimated effect size and the power of the study are diminished when the biomarker is measured with error. The estimated effect of the association with outcome of the average of several replicates per patient is closer to the true effect size when the number of replicates increases. Conclusion The first step in designing a study of association between a biomarker and outcome is to conduct a pilot study in which several measurements per patient are taken. Based on these data, the heterogeneity of the marker within and between individuals can be estimated and used in the process of designing an appropriate study of the association between the biomarker and outcome.
Phase II Trial of Temozolomide Plus O6-Benzylguanine in Adults With Recurrent, Temozolomide-Resistant Malignant Glioma
Authors: Quinn Jennifer A. , Jiang Sara Xiaoyin , Reardon David A. , Desjardins Annick , Vredenburgh James J. , Rich Jeremy N. , Gururangan Sridharan , Friedman Allan H. , Bigner Darell D. , Sampson John H. , McLendon Roger E. , Herndon James E. , Walker Amy , Friedman Henry S. 
Published: February 2009

Purpose This phase II trial was designed to define the role of O6-benzylguanine (O6-BG) in restoring temozolomide sensitivity in patients with recurrent or progressive, temozolomide-resistant malignant glioma and to evaluate the safety of administering O6-BG in combination with temozolomide. Patients and Methods Patients were accrued into two independent strata on the basis of histology: glioblastoma multiforme (GBM) and anaplastic glioma. Both temozolomide and O6-BG were administered on day 1 of a 28-day treatment cycle. Patients were administered a 1-hour O6-BG infusion at a dose of 120 mg/m2 followed immediately by a 48-hour infusion at a dose of 30 mg/m2/d. Temozolomide was administered orally within 60 minutes of the end of the 1-hour O6-BG infusion at a dose of 472 mg/m2. The primary end point was objective response rate. Secondary end points included progression-free survival, overall survival, and safety. Results Sixty-six of 67 patients who enrolled were treated with temozolomide and O6-BG. One of 34 patients (3%) with GBM (95% CI, 0.1% to 15%) and five of 32 assessable patients (16%) with anaplastic glioma (95% CI, 5% to 33%) were responders. The most commonly reported adverse events were grade 4 hematologic events experienced in 48% of the patients. Conclusion O6-BG when added to a 1-day dosing regimen of temozolomide was able to restore temozolomide sensitivity in patients with temozolomide-resistant anaplastic glioma, but there seemed to be no significant restoration of temozolomide sensitivity in patients with temozolomide-resistant GBM.
Breast Cancer With Synchronous Metastases: Survival Impact of Exclusive Locoregional Radiotherapy
Authors: Le Scodan Romuald , Stevens Denise , Brain Etienne , Floiras Jean Louis , Cohen-Solal Christine , De La Lande Brigitte , Tubiana-Hulin Michelle , Yacoub Sameh , Gutierrez Maya , Ali David , Gardner Miriam , Moisson Patricia , Villette Sylviane , Lerebours Florence , Munck Jean Nicolas , Labib Alain 
Published: February 2009

Purpose Several studies suggest that surgical excision of the primary tumor improves survival among patients with stage IV breast cancer at diagnosis. Exclusive locoregional radiotherapy (LRR) is an alternative form of locoregional treatment (LRT) in this setting. We retrospectively studied the impact of LRT on the survival of breast cancer patients with synchronous metastases. Patients and Methods Among 18,753 breast cancer patients treated in our institution between 1980 and 2004, 598 patients (3.2%) had synchronous metastasis at diagnosis. Demographic data, tumor characteristics, metastatic sites, and treatments were prospectively recorded. The impact of LRT on overall survival (OS) was evaluated by multivariate analysis including known prognostic factors. Results Among 581 eligible patients, 320 received LRT (group A), and 261 received no LRT (group B). LRT consisted of exclusive LRR in 249 patients (78%), surgery of the primary tumor with adjuvant LRR in 41 patients (13%), and surgery alone in 30 patients (9%). With a median follow-up time of 39 months, the 3-year OS rates were 43.4% and 26.7% in group A and group B (P =.00002), respectively. The association between LRT and improved survival was particularly marked in women with visceral metastases. LRT was an independent prognostic factor in multivariate analysis (hazard ratio [HR] = 0.70; 95% CI, 0.58 to 0.85; P = .0002). The adjusted HR for late death (≥ 1 year) was 0.76 (95% CI, 0.61 to 0.96; P = .02). Conclusion In our experience, LRT, consisting mainly of exclusive LRR, was associated with improved survival in breast cancer patients with synchronous metastases. Exclusive LRR may thus represent an active alternative to surgery.
Treatment of Nonmetastatic Cranial Parameningeal Rhabdomyosarcoma in Children Younger Than 3 Years Old: Results From International Society of Pediatric Oncology Studies MMT 89 and 95
Authors: Defachelles Anne-Sophie , Rey Annie , Oberlin Odile , Spooner David , Stevens Michael C.G. 
Published: February 2009

PurposeTo explore a strategy by which radiotherapy (RT) could be avoided in the treatment of young children with parameningeal rhabdomyosarcoma (PM RMS).Patients and MethodsFifty-nine children (median age, 2 years 3 months) with nonmetastatic cranial PM RMS were treated in the International Society of Pediatric Oncology MMT 89 and 95 trials between 1989 and 2003.ResultsFive-year EFS and OS rates were 46% and 54%, respectively, for the whole group. No standard clinical or pathologic variables had prognostic impact. Fifty (85%) of 59 patients achieved complete local control either with (n = 28) or without (n = 22) RT administered as part of their primary treatment. Nine patients (15%) did not achieve local control (four of whom had had RT), and all died. Patients who received RT had a significantly superior 5-year EFS rate compared with patients who did not receive RT (59% v 28%, respectively). Twenty-three patients (48%) experienced relapse at a median interval of 15 months. Ultimately, only seven patients (12%) were cured without RT, although this represented 32% of those who achieved local control with initial chemotherapy.ConclusionDespite concerns about the late effects of its use in young children, cure of PM RMS remains unlikely without systematic use of RT. The accurate prediction of the small subset of patients who achieve local control without RT and who do not experience relapse would provide an opportunity for a minority of patients to avoid RT.
Development of a method to compute the kingpin axis using screw axis theory based on suspension-parameter-measuring device data
Authors: Heo J-H , Lee U-K , Lee S-H 
Published: February 2009

Kingpin geometry is one of the most important design features in vehicle development, as it determines the steering feeling of drivers, the handling performance, and the steering stability of a vehicle. The idea of a geometric kingpin axis has been used to design a relatively simple suspension mechanism such as a double-wishbone type, and various techniques have been developed to design the kingpin axis of multi-link suspensions. However, a kingpin axis for a real vehicle has been unknown so far because there has been no method to measure or compute it. This paper presents the development of a method to compute the kingpin axis of a vehicle using screw theory and suspension-parameter-measuring device (SPMD) data. SPMD data, such as the wheel centre displacement, toe, camber, and side view angles, are used to derive the finite displacement matrix of the wheel. The finite screw axis is computed on the basis of the displacement matrix, and its compatibility with the kingpin axis is verified by an in-house kinematic analysis program and ADAMS/Car. The result of the finite screw axis method (FSAM) is also verified indirectly by comparing suspension parameters such as the caster trail with the SPMD test result. Both verification results show that the FSAM can successfully compute the kingpin axis of a real vehicle.
Is laparoscospic orchidectomy the treatment of choice in adults with impalpable testis in rural hospitals in the developing world?
Authors: Mir Iqbal Saleem , Mohsin Mir , Kirmani Omar , Cheachek Bashir A , Alam Intikhab , Wani Mumtazuddin 
Published: February 2009

This study was undertaken in order to evaluate the feasibility and safety of performing laparoscopic orchidectomy (LO) in men for unilateral impalpable testis in non-teaching rural hospitals in a developing country. We also investigated the possibility of reducing the cost and length of stay in hospital for patients undergoing LO. This is a prospective analysis of patients with impalpable testis undergoing LO in three non-teaching rural hospitals in the Kashmir Valley from January 2001 to March 2007. The cohort represented men requiring LO aged 15 to 62 (mean 36.2) years. The main outcome parameters assessed included mortality, conversion to an open procedure, complications, reduction in the costs and the length of the hospital stay. Forty-eight men with unilateral undescended testis on physical examination were studied. During laparoscopy the testis was identified near the deep ring in 30 patients, intra-abdominally in 16, and two had blind-ending vas and spermatic vessels near the deep ring. In 46 patients orchidectomy was performed. There were no deaths and none of the patients required conversion to an open procedure. Using reusable instruments, 00° polyglactin sutures and self-made extraction bags, about US$ 300/patient was saved. There was no case of malignancy of the testis on histopathology examination. LO is one of the most satisfactory methods for the management of men with impalpable testis, having both a diagnostic and a therapeutic role especially for patients in the underdeveloped countries. These simple methods can reduce the cost and the length of the hospital stay.
Precision performance at low levels and 99th percentile concentration of the Access® AccuTnI® assay on two different platforms
Authors: Zaninotto Martina , Mion Monica Maria , Novello Enrica , Moretti Marco , Delprete Ernesto , Rocchi Marco Bruno , Sisti Davide , Plebani Mario 
Published: February 2009

Abstract: Cardiac troponins currently represent the preferred biomarkers for the detection of myocardial necrosis. The objective of the present study was to compare the performance of the Access: The Access: cTnI concentrations are given in μg/L. 10% CV values (95% confidence interval, CI) were 0.0577 (0.0467–0.0750) (UniCel: Our data confirm the reliability of the evaluated cTnI assay and demonstrate the comparability of the cTnI values between the platforms studied.Clin Chem Lab Med 2009;47:367–71.
A study of anthraquinone-fortified green liquor pretreatment of loblolly pine chips
Authors: Ban Weiping , Liu Qiujuan , Guo Jiqiang , Mao Haibo , Lucia Lucian A. 
Published: February 2009

Abstract
Green liquor (GL) pretreatment for kraft pulping technologies was modified by applying anthraquinone (AQ) during the pretreatment stage. Analysis of the pulp lignin contents and final pulp yields demonstrated that the addition of AQ improved delignification selectivity. A proposed mechanism for the behavior of AQ during the GL pretreatment is that it amplifies delignification rather than preserves hemicelluloses. An analysis of the pulp carboxylic acid groups indicated that AQ did not affect the total carboxylic acid content in the pulp, but provided a lower hexenuronic acid content at a specific level of lignin content. In general, green liquor pretreatment reduces the energy requirement for pulping and improves chemical reactivity during delignification. As a result, net pulping efficiency for a kraft pulping operation can be improved.