bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicenter Validation of a 1,550-Gene Expression Profile for Identification of Tumor Tissue of Origin
Authors: Monzon Federico A. , Lyons-Weiler Maureen , Buturovic Ljubomir J. , Rigl C. Ted , Henner W. David , Sciulli Christin , Dumur Catherine I. , Medeiros Fabiola , Anderson Glenda G. 
Published: March 2009

Purpose Malignancies found in unexpected locations or with poorly differentiated morphologies can pose a significant challenge for tissue of origin determination. Current histologic and imaging techniques fail to yield definitive identification of the tissue of origin in a significant number of cases. The aim of this study was to validate a predefined 1,550-gene expression profile for this purpose. Methods Four institutions processed 547 frozen specimens representing 15 tissues of origin using oligonucleotide microarrays. Half of the specimens were metastatic tumors, with the remainder being poorly differentiated and undifferentiated primary cancers chosen to resemble those that present as a clinical challenge. Results In this blinded multicenter validation study the 1,550-gene expression profile was highly informative in tissue determination. The study found overall sensitivity (positive percent agreement with reference diagnosis) of 87.8% (95% CI, 84.7% to 90.4%) and overall specificity (negative percent agreement with reference diagnosis) of 99.4% (95% CI, 98.3% to 99.9%). Performance within the subgroup of metastatic tumors (n = 258) was found to be slightly lower than that of the poorly differentiated and undifferentiated primary tumor subgroup, 84.5% and 90.7%, respectively (P = .04). Differences between individual laboratories were not statistically significant. Conclusion This study represents the first adequately sized, multicenter validation of a gene-expression profile for tissue of origin determination restricted to poorly differentiated and undifferentiated primary cancers and metastatic tumors. These results indicate that this profile should be a valuable addition or alternative to currently available diagnostic methods for the evaluation of uncertain primary cancers.
Autologous Stem-Cell Transplantation in Patients With HIV-Related Lymphoma
Authors: Balsalobre Pascual , Díez-Martín José L. , Re Alessandro , Michieli Mariagrazia , Ribera José M. , Canals Carmen , Rosselet Anne , Conde Eulogio , Varela Rosario , Cwynarski Kate , Gabriel Ian , Genet Philippe , Guillerm Gaelle , Allione Bernardino , Ferrant Augustin , Biron Pierre , Espigado Ildefonso , Serrano David , Sureda Anna 
Published: March 2009

Purpose Peripheral-blood autologous stem-cell transplantation (ASCT) in patients with HIV-related lymphoma (HIV-Ly) has been reported as a safe and useful procedure. Herein we report the European Group for Blood and Marrow Transplantation experience on patients with HIV-Ly undergoing ASCT. Patients and Methods This was a retrospective, multicentric, registry-based analysis. Results Since 1999, 68 patients from 20 institutions (median age, 41 years; range, 29 to 62 years) were included, diagnosed with non-Hodgkin's lymphoma (NHL; n = 50) or Hodgkin's lymphoma (n = 18). At the time of ASCT, 16 patients were in first complete remission (CR1); 44 patients were in CR more than 1, partial remission, or chemotherapy-sensitive relapse (chemo-S); and eight patients had chemotherapy-resistant disease. The median number of CD34+ cells infused was 4.5 × 106/kg (range, 1.6 to 21.2 × 106/kg). Median time to neutrophil and platelet engraftment were 11 days (range, 8 to 36 days) and 14 days (range, 6 to 455 days), respectively, with a cumulative incidence (CI) at 1 year of 95.6% and 87%, respectively. CI of nonrelapse mortality (NRM) was 7.5% at 12 months after ASCT, mainly because of bacterial infections. CI of relapse was 30.4% at 24 months, statistically related with not being in CR at ASCT (relative risk [RR] = 3.6), NHL histology other than diffuse large B-cell lymphoma (RR = 3.4), and use of more than two previous treatment lines (RR = 3). At a median follow-up of 32 months (range, 2 to 81 months), progression-free survival (PFS) was 56%. Patients not in CR or with refractory disease at ASCT had poorer PFS (RR = 2.4 and 4.8, respectively). Conclusion Similarly to HIV-negative patients with lymphoma, ASCT is a useful treatment for patients with HIV-Ly and is associated with low NRM, mainly when performed in early stages and chemo-S disease.
Vandetanib Versus Gefitinib in Patients With Advanced Non–Small-Cell Lung Cancer: Results From a Two-Part, Double-Blind, Randomized Phase II Study
Authors: Natale Ronald B. , Bodkin David , Govindan Ramaswamy , Sleckman Bethany G. , Rizvi Naiyer A. , Capó Adolfo , Germonpré Paul , Eberhardt Wilfried E.E. , Stockman Paul K. , Kennedy Sarah J. , Ranson Malcolm 
Published: March 2009

Purpose Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) signaling. In this two-part phase II study, the efficacy and safety of vandetanib was compared with that of gefitinib, an inhibitor of EGFR signaling. Patients and Methods Patients (N = 168) with locally advanced or metastatic (stage IIIB/IV) non–small-cell lung cancer (NSCLC), after failure of first-line with or without second-line platinum-based chemotherapy, received once-daily vandetanib 300 mg (n = 83) or gefitinib 250 mg (n = 85) until disease progression or evidence of toxicity (part A). After a 4-week washout period, eligible patients had the option to switch to the alternative treatment (part B). Progression-free survival (PFS) was the primary efficacy assessment in part A, which was designed to have a higher than 75% power to detect a 33% prolongation of PFS at a one-sided significance level of .2. Results In part A, vandetanib prolonged PFS compared with gefitinib (hazard ratio = 0.69; 95% CI, 0.50 to 0.96; one-sided P = .013). Patients receiving vandetanib experienced adverse events that were manageable and generally consistent with inhibition of EGFR and VEGFR signaling, including diarrhea, rash, and hypertension. There were no unexpected safety findings with gefitinib. Overall survival, a secondary assessment, was not significantly different between patients initially randomly assigned to either vandetanib or gefitinib. Conclusion The primary efficacy objective was achieved, with vandetanib demonstrating a significant prolongation of PFS versus gefitinib. Vandetanib 300 mg/d is currently being evaluated as a monotherapy in two randomized phase III studies in advanced NSCLC.
Long-Term Outcome of Cirrhotic Patients With Early Hepatocellular Carcinoma Treated With Ultrasound-Guided Percutaneous Laser Ablation: A Retrospective Analysis
Authors: Pacella Claudio Maurizio , Francica Giampiero , Di Lascio Francesca Marta Lilja , Arienti Vincenzo , Antico Ettore , Caspani Bruno , Magnolfi Fabrizio , Megna Angelo Salomone , Pretolani Stefano , Regine Renato , Sponza Massimo , Stasi Roberto 
Published: March 2009

Purpose Percutaneous laser ablation (PLA) has been proposed as an active treatment in patients with hepatocellular carcinoma (HCC). However, large multicenter studies using this technique have not been reported. Patients and Methods We retrospectively analyzed treatment and survival parameters of 432 cirrhotic patients with nonsurgical early HCC (single nodule ≤ 4 cm or three nodules ≤ 3 cm each) who had received PLA in nine Italian centers. Results Single tumors were seen in 344 (80%) of 432 patients, and two to three nodules were seen in 88 patients (20%), for a total of 548 tumors. An initial complete response after PLA was observed in 338 patients (78%). Median overall survival time was 47 months (95% CI, 41 to 53 months). The 3- and 5-year cumulative survival rates were 61% and 34%, respectively. In multivariate analysis, independent predictors of survival were serum albumin levels more than 3.5 g/dL (P = .002; risk ratio [RR] = 0.580; 95% CI, 0.409 to 0.821), the achievement of a complete tumor ablation (P = .001; RR = 0.517; 95% CI, 0.346 to 0.771), and age less than 73 years (P < .001; RR = 0.466; 95% CI, 0.320 to 0.681). Child-Turcotte-Pugh class A patients had a 5-year cumulative survival rate of 41%; this figure increased up to 60% with a median survival time of 63 months (95% CI, 48 to 78 months) in patients with tumors ≤ 2.0 cm. Conclusion This analysis confirms that a complete tumor ablation results in improved survival in patients with nonsurgical HCC. Ideal candidates for PLA are younger patients with normal serum albumin levels and tumor size ≤ 2 cm.
Pharmacogenetic Analyses of a Phase III Trial in Metastatic Gastroesophageal Adenocarcinoma With Fluorouracil and Leucovorin Plus Either Oxaliplatin or Cisplatin: A Study of the Arbeitsgemeinschaft Internistische Onkologie
Authors: Goekkurt Eray , Al-Batran Salah-Eddin , Hartmann Jörg T. , Mogck Ulrike , Schuch Gunter , Kramer Michael , Jaeger Elke , Bokemeyer Carsten , Ehninger Gerhard , Stoehlmacher Jan 
Published: March 2009

Purpose To evaluate the association of germ-line polymorphisms of genes that may impact treatment outcome of platinum and fluorouracil combination chemotherapy in advanced gastric cancer (AGC). Patients and Methods Blood samples of 156 patients enrolled onto a phase III study comparing fluorouracil, leucovorin, and oxaliplatin with fluorouracil, leucovorin, and cisplatin were collected. Polymorphisms within genes of TS, MTHFR, MTR, OPRT, XPD, ERCC1, XRCC1, XPA, GSTP1, GSTT1, and GSTM1 were genotyped using polymerase chain reaction–based techniques. Results Median overall survival (OS) was 11.8 months (95% CI, 9.75 to 13.79 months) and median progression-free survival (PFS) was 5.8 months (95% CI, 4.99 to 6.61 months). The TS-3R/+6 haplotype (P = .004), the GSTT1 deletion polymorphism (P = .015), and genotypes of OPRT-Gly213Ala (P = .003) and XRCC1-Arg399Gln (P = .023) could be identified as independent predictors of OS. For PFS analyses, the TS-3R/+6 haplotye (P = .003) and MTR-A2756G (P = .01) were identified as independent positive predictors. The association between the GSTT1 deletion polymorphism and PFS showed only borderline significance (P = .053). Treatment related hematotoxicity in terms of grade 3/4 leukopenia was lowest among TS-3R/+6 haplotype carriers (P = .037). Grade 3/4 neutropenia was directly associated with the MTR-2756G/G genotype (P = .011), GSTP1-105Ile/Ile genotype (P = .02), and with the ERCC1-118T/8092C-haplotype (P = .042). In addition, significant associations between GSTP1-105Ile/Ile genotype and neurotoxicity and between the XPD-Asn312/751Gln haplotype and nephrotoxicity could be identified (P = .028 and P = .005, respectively). Conclusion These findings underline the hypothesis that germ-line polymorphisms may play an important role in individualizing chemotherapy in AGC and deserve further prospective evaluation in AGC patients.
Phase III Trial Evaluating the Addition of Paclitaxel to Doxorubicin Followed by Cyclophosphamide, Methotrexate, and Fluorouracil, As Adjuvant or Primary Systemic Therapy: European Cooperative Trial in Operable Breast Cancer
Authors: Gianni Luca , Baselga José , Eiermann Wolfgang , Porta Vincente Guillem , Semiglazov Vladimir , Lluch Aňa , Zambetti Milvia , Sabadell Dolores , Raab Günther , Cussac Antonio Llombart , Bozhok Alla , Martinez-Agulló Angel , Greco Marco , Byakhov Mikhail , Lopez Juan Josè Lopez , Mansutti Mauro , Valagussa Pinuccia , Bonadonna Gianni 
Published: March 2009

Purpose To evaluate the addition of paclitaxel to an anthracycline-based adjuvant regimen and to compare this combination with the same regimen given as primary systemic (neoadjuvant) therapy. Patients and Methods A total of 1,355 women with operable breast cancer were randomly assigned to one of three treatments: surgery followed by adjuvant doxorubicin (75 mg/m2) followed by cyclophosphamide, methotrexate, and fluorouracil (CMF; arm A); surgery followed by adjuvant paclitaxel (200 mg/m2) plus doxorubicin (60 mg/m2), followed by CMF (arm B); or paclitaxel (200 mg/m2) plus doxorubicin (60 mg/m2) followed by CMF followed by surgery (arm C). The two coprimary objectives were to assess the effects on relapse-free survival (RFS) of the addition of paclitaxel to postoperative chemotherapy (arm B v arm A) and primary chemotherapy versus adjuvant chemotherapy (arm B v arm C). Results Doxorubicin plus paclitaxel followed by CMF was well-tolerated as adjuvant or as primary chemotherapy. The addition of paclitaxel to adjuvant doxorubicin followed by CMF significantly improved RFS compared with adjuvant doxorubicin alone followed by CMF (hazard ratio [HR], 0.73; P = .03). Distant RFS was similarly improved (HR, 0.70; P = .027). There was no significant difference in RFS when the paclitaxel/doxorubicin/CMF chemotherapy was given before surgery compared with the same regimen given after surgery (HR, 1.21; P = .18). However, the rate of breast-conserving surgery was significantly higher with preoperative chemotherapy (63% v 34%; P < .001). Conclusion Incorporating paclitaxel into anthracycline-based adjuvant therapy resulted in a significant improvement in RFS and distant RFS. When given as primary systemic therapy, the paclitaxel-containing regimen allowed breast-sparing surgery in a significant percentage of patients.
Prospective Validation of a Prognostic Score to Improve Patient Selection for Oncology Phase I Trials
Authors: Arkenau Hendrik-Tobias , Barriuso Jorge , Olmos David , Ang Joo Ern , de Bono Johann , Judson Ian , Kaye Stan 
Published: March 2009

Purpose With the aim of improving patient selection for phase I trials, we previously performed a retrospective analysis of 212 phase I oncology patients where we were able to develop a prognostic score predicting overall survival (OS). This prospective study was performed to test the validity of the prognostic score. Patients and Methods On the basis of our retrospective multivariate analysis, three factors were associated with poor survival (albumin < 35 g/L, lactate dehydrogenase [LDH] > upper limit of normal [ULN], and > two sites of metastases). We integrated these into a prognostic score ranging from 0 to 3 and analyzed this score in a prospectively selected cohort of 78 patients enrolled onto phase I trials. Results All patients had progressive disease before study entry. The median age was 56 years (range, 18 to 79 years). After a median follow-up time of 27.3 weeks, patients with a prognostic score of 0 to 1 (n = 43) had superior OS (33.0 weeks; 95% CI, 24 to 42 weeks) compared with patients with a score of 2 to 3 (n = 35; 15.7 weeks; 95% CI, 11 to 21 weeks). Our multivariate analysis confirmed that our prognostic score was an independent marker for OS, with a hazard ratio of 1.4 (95% CI, 1.02 to 1.9; P = .036). Conclusion This is the first prospective analysis confirming that a prognostic score based on objective markers, including albumin less than 35 g/L, LDH more than ULN, and more than two sites of metastasis, is a helpful tool in the process of patient selection for phase I trial entry.
Edema Control by Cediranib, a Vascular Endothelial Growth Factor Receptor–Targeted Kinase Inhibitor, Prolongs Survival Despite Persistent Brain Tumor Growth in Mice
Authors: Kamoun Walid S. , Ley Carsten D. , Farrar Christian T. , Duyverman Annique M. , Lahdenranta Johanna , Lacorre Delphine A. , Batchelor Tracy T. , di Tomaso Emmanuelle , Duda Dan G. , Munn Lance L. , Fukumura Dai , Sorensen A. Gregory , Jain Rakesh K. 
Published: March 2009

Purpose Recent clinical trials of antivascular endothelial growth factor (VEGF) agents for glioblastoma showed promising progression-free and overall survival rates. However, available clinical imaging does not separate antitumor effects from antipermeability effects of these agents. Thus although anti-VEGF agents may decrease tumor contrast-enhancement, vascularity, and edema, the mechanisms leading to improved survival in patients remain incompletely understood. Our goal was to determine whether alleviation of edema by anti-VEGF agents alone could increase survival in mice. Methods We treated mice bearing three different orthotopic models of glioblastoma with a VEGF-targeted kinase inhibitor, cediranib. Using intravital microscopy, molecular techniques, and magnetic resonance imaging (MRI), we measured survival, tumor growth, edema, vascular morphology and function, cancer cell apoptosis and proliferation, and circulating angiogenic biomarkers. Results We show by intravital microscopy that cediranib significantly decreased tumor vessel permeability and diameter. Moreover, cediranib treatment induced normalization of perivascular cell coverage and thinning of the basement membrane, as mirrored by an increase in plasma collagen IV. These rapid changes in tumor vascular morphology and function led to edema alleviation—as measured by MRI and by dry/wet weight measurement of water content—but did not affect tumor growth. By immunohistochemistry, we found a transient decrease in macrophage infiltration and significant but minor changes in tumor cell proliferation and apoptosis. Systemically, cediranib increased plasma VEGF and placenta growth factor levels, and the number of circulating CXCR4+CD45+ cells. However, by controlling edema, cediranib significantly increased survival of mice in the face of persistent tumor growth. Conclusion Anti-VEGF agents may be able to improve survival of patients with glioblastoma, even without inhibiting tumor growth.
A Column Generation Algorithm for Choice-Based Network Revenue Management
Authors: Bront Juan José Miranda , Méndez-Díaz Isabel , Vulcano Gustavo 
Published: March 2009

During the past few years, there has been a trend to enrich traditional revenue management models built upon the independent demand paradigm by accounting for customer choice behavior. This extension involves both modeling and computational challenges. One way to describe choice behavior is to assume that each customer belongs to a segment, which is characterized by a consideration set, i.e., a subset of the products provided by the firm that a customer views as options. Customers choose a particular product according to a multinomial-logit criterion, a model widely used in the marketing literature. In this paper, we consider the choice-based, deterministic, linear programming model (CDLP) of Gallego et al. (2004) [Gallego, G., G. Iyengar, R. Phillips, A. Dubey. 2004. Managing flexible products on a network. Technical Report CORC TR-2004-01, Department of Industrial Engineering and Operations Research, Columbia University, New York], and the follow-up dynamic programming decomposition heuristic of van Ryzin and Liu (2008) [van Ryzin, G. J., Q. Liu. 2008. On the choice-based linear programming model for network revenue management. Manufacturing Service Oper. Management 10(2) 288–310]. We focus on the more general version of these models, where customers belong to overlapping segments. To solve the CDLP for real-size networks, we need to develop a column generation algorithm. We prove that the associated column generation subproblem is indeed NP-hard and propose a simple, greedy heuristic to overcome the complexity of an exact algorithm. Our computational results show that the heuristic is quite effective and that the overall approach leads to high-quality, practical solutions.
Total ankle replacement in patients with significant pre-operative deformity of the hindfoot
Authors: Hobson S. A. , Karantana A. , Dhar S. 
Published: March 2009

We carried out 123 consecutive total ankle replacements in 111 patients with a mean follow-up of four years (2 to 8). Patients with a hindfoot deformity of up to 10° (group A, 91 ankles) were compared with those with a deformity of 11° to 30° (group B, 32 ankles). There were 18 failures (14.6%), with no significant difference in survival between groups A and B. The clinical outcome as measured by the post-operative American Orthopaedic Foot and Ankle Surgeons score was significantly better in group B (p = 0.036). There was no difference between the groups regarding the post-operative range of movement and complications. Correction of the hindfoot deformity was achieved to within 5° of neutral in 27 ankles (84%) of group B patients. However, gross instability was the most common mode of failure in group B. This was not adequately corrected by reconstruction of the lateral ligament. Total ankle replacement can safely be performed in patients with a hindfoot deformity of up to 30°. The importance of adequate correction of alignment and instability is highlighted.
Revision following cemented and uncemented primary total hip replacement
Authors: Hooper G. J. , Rothwell A. G. , Stringer M. , Frampton C. 
Published: March 2009

We have reviewed the rate of revision of fully cemented, hybrid and uncemented primary total hip replacements (THRs) registered in the New Zealand Joint Registry between 1999 and December 2006 to determine whether there was any statistically significant difference in the early survival and reason for revision in these different types of fixation. The percentage rate of revision was calculated per 100 component years and compared with the reason for revision, the type of fixation and the age of the patients. Of the 42 665 primary THRs registered, 920 (2.16%) underwent revision requiring change of at least one component. Fully-cemented THRs had a lower rate of revision when considering all causes for failure (p < 0.001), but below the age of 65 years uncemented THRs had a lower rate (p < 0.01). The rate of revision of the acetabular component for aseptic loosening was less in the uncemented and hybrid groups compared with that in the fully cemented group (p < 0.001), and the rate of revision of cemented and uncemented femoral components was similar, except in patients over 75 years of age in whom revision of cemented femoral components was significantly less frequent (p < 0.02). Revision for infection was more common in patients aged below 65 years and in cemented and hybrid THRs compared with cementless THRs (p < 0.001). Dislocation was the most common cause of revision for all types of fixation and was more frequent in both uncemented acetabular groups (p < 0.001). The experience of the surgeon did not affect the findings. Although cemented THR had the lowest rate of revision for all causes in the short term (90 days), uncemented THR had the lowest rate of aseptic loosening in patients under 65 years of age and had rates comparable with international rates of aseptic loosening in those over 65 years.
The influence of the mechanical environment on remodelling of the patellar tendon
Authors: Rumian A. P. , Draper E. R. C. , Wallace A. L. , Goodship A. E. 
Published: March 2009

An understanding of the remodelling of tendon is crucial for the development of scientific methods of treatment and rehabilitation. This study tested the hypothesis that tendon adapts structurally in response to changes in functional loading. A novel model allowed manipulation of the mechanical environment of the patellar tendon in the presence of normal joint movement via the application of an adjustable external fixator mechanism between the patella and the tibia in sheep, while avoiding exposure of the patellar tendon itself. Stress shielding caused a significant reduction in the structural and material properties of stiffness (79%), ultimate load (69%), energy absorbed (61%), elastic modulus (76%) and ultimate stress (72%) of the tendon compared with controls. Compared with the material properties the structural properties exhibited better recovery after re-stressing with stiffness 97%, ultimate load 92%, energy absorbed 96%, elastic modulus 79% and ultimate stress 80%. The cross-sectional area of the re-stressed tendons was significantly greater than that of stress-shielded tendons. The remodelling phenomena exhibited in this study are consistent with a putative feedback mechanism under strain control. This study provides a basis from which to explore the interactions of tendon remodelling and mechanical environment.