bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term follow‐up of a phase I study of high‐dose decitabine, busulfan, and cyclophosphamide plus allogeneic transplantation for the treatment of patients with leukemias
Authors: de Lima Marcos , Ravandi Farhad , Shahjahan Munir , Andersson Borje , Couriel Daniel , Donato Michele , Khouri Issa , Gajewski James , van Besien Koen , Champlin Richard , Giralt Sergio , Kantarjian Hagop 
Published: February 2003

AbstractBACKGROUNDDecitabine is a hypomethylating agent that has activity in patients with leukemia. The authors combined decitabine with busulfan and cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic stem cell transplantation.METHODSPatients with high‐risk acute myeloid leukemia (AML) (n = 12 patients); chronic myelomonocytic leukemia (CMML) (n = 1 patient); acute lymphocytic leukemia (ALL) (n = 1 patient); or late chronic phase, accelerated, or blastic phase chronic myelogenous leukemia (n = 9 patients) were eligible for the study. The treatment plan was comprised of busulfan, 12 mg/kg orally; cyclophosphamide, 100 mg/kg (n = 4 patients) or 120 mg/kg (n = 19 patients); and decitabine, intravenously at 3 dose levels: 400 mg/m2 (n = 10 patients), 600 mg/m2 (n = 8 patients), and 800 mg/m2 (n = 5 patients). Donors were human leukocyte antigen‐identical siblings in all cases, and all but one patient received peripheral blood stem cells. Graft‐versus‐host disease (GVHD) prophylaxis was tacrolimus based in all but one patient.RESULTSThe median time to neutrophil and platelet engraftment was 12.5 days and 17.5 days, respectively. Twenty‐one patients were engrafted and achieved disease remission. At a median of 3.3 years posttransplantation, 26% of patients (40% of patients with AML) were alive and disease free. The median survival for the group was 17.2 months, and the disease free survival for the group was 8.9 months. Causes of death were disease recurrence (nine patients), chronic GVHD (four patients), infections (three patients), and acute GVHD (one patient). The 100‐day mortality rate was 9%. No decitabine dose‐limiting toxicity was documented. The treatment‐related mortality rate at 3 years was 35%. Responders were treated at all three decitabine dose levels, and no dose‐response correlation was observed.CONCLUSIONSThere was a high response rate with low treatment‐related mortality, with 26% of patients alive in remission 3.3 years after transplantation. Cancer 2003;97:1242–7. © 2003 American Cancer Society.DOI 10.1002/cncr.11184
Overdiagnosis in chest radiographic screening for lung carcinoma
Authors: Yankelevitz David F. , Kostis William J. , Henschke Claudia I. , Heelan Robert T. , Libby Daniel M. , Pasmantier Mark W. , Smith James P. 
Published: February 2003

AbstractBACKGROUNDThe pattern of results in the Mayo Lung Project (MLP), which is the basis for the prevailing recommendations against radiographic screening for lung carcinoma, has led to the assertion that up to 50% of the diagnosed cases of early‐stage disease in that trial may have represented overdiagnosed, indolent cases. This finding suggests the possibility of such a high frequency of overdiagnosis in chest radiographic lung carcinoma screening in general. In the current study, the authors analyzed data from the MLP and its counterpart study at Memorial Sloan‐Kettering Cancer Center (MSK) to estimate the frequency of overdiagnosis in these studies.METHODSFor the cases diagnosed as Stage I in the MLP and the MSK studies, the doubling times of tumor volumes were calculated. The calculations were based on size measurements recorded by the original investigators from chest radiographs taken during the course of each study.RESULTSThe median doubling times were 101 days in the MLP and 144 days in the MSK, times that are somewhat shorter than those reported in published series of adenocarcinoma cases diagnosed outside screening, and only 5% had doubling times exceeding 400 days.CONCLUSIONSThe hypothesis that early‐stage lung tumors diagnosed on chest radiography during lung carcinoma screening may frequently be overdiagnosed, indolent cases needs to be rejected. Cancer 2003;97:1271–5. © 2003 American Cancer Society.DOI 10.1002/cncr.11185
A randomized, active‐control, pilot trial of front‐loaded dosing regimens of darbepoetin‐alfa for the treatment of patients with anemia during chemotherapy for malignant disease
Authors: Glaspy John A. , Jadeja Jaswant Sinh , Justice Glen , Fleishman Alex , Rossi Gregory , Colowick Alan B. 
Published: February 2003

AbstractBACKGROUNDAnemia in patients receiving chemotherapy can be ameliorated with recombinant human erythropoietin (rHuEPO), which is administered one to three times per week. Darbepoetin α, a new erythropoietic agent, has longer serum residence time, allowing it to be administered less frequently.METHODSPatients (n = 127) were randomized to receive study drug for 12 weeks: either rHuEPO 40,000 U with escalations to 60,000 U for nonresponders or darbepoetin α at doses of 4.5 μg/kg per week until hemoglobin concentration ≥ 12 g/dL, then 1.5 μg/kg per week (Group 1); 4.5 μg/kg per week for 4 weeks, then 2.25 μg/kg per week for 8 weeks (Group 2); or 4.5 μg/kg per week for 4 weeks, then 3.0 μg/kg every 2 weeks (Group 3). Efficacy was measured using the mean change in hemoglobin level, the proportion of patients achieving a hemoglobin response, the time to response, and the mean change in Functional Assessment of Cancer Therapy‐Fatigue Scale scores. Safety was assessed by reports of adverse events.RESULTSOverall, after 4 weeks of treatment, the mean change (95% confidence interval [95%CI]) in hemoglobin concentration was 0.53 g/dL (95%CI, 0.05–1.02 g/dL), 0.70 g/dL (95%CI, 0.11–1.29 g/dL), and 0.90 g/dL (95%CI, 0.47–1.33 g/dL) in darbepoetin α Groups 1, 2, and 3, respectively, and 0.39 g/dL (95%CI, − 0.22–1.00 g/dL) in the rHuEPO group. By the end of the study, the mean change (95%CI) in hemoglobin concentration was 1.35 g/dL (95%CI, 0.67–2.02 g/dL), 1.35 g/dL (95%CI, 0.57–2.12 g/dL), and 1.28 g/dL (95%CI, 0.84–1.73 g/dL) in darbepoetin α Groups 1, 2, and 3, respectively, and 1.03 g/dL (95%CI, 0.53–1.53 g/dL) in the rHuEPO group. The early erythropoietic response in patients who were treated with darbepoetin α was associated with an early and maintained reduction in patient‐reported fatigue. The adverse event profile was comparable with all doses of darbepoetin α and rHuEPO.CONCLUSIONSDarbepoetin α, given as a front‐loaded dose for 4 weeks and followed by lower and/or less frequent doses, appears to be efficacious and may decrease the time to response relative to treatment with rHuEPO. Cancer 2003;97:1312–20. © 2003 American Cancer Society.DOI 10.1002/cncr.11186
Chromosomal anomalies in oligodendroglial tumors are correlated with clinical features
Authors: van den Bent Martin J. , Looijenga Leendert H. J. , Langenberg K. , Dinjens Winand , Graveland Wilfried , Uytdewilligen Ludo , Sillevis Smitt Peter A. , Jenkins Robert B. , Kros Johan M. 
Published: February 2003

AbstractBACKGROUNDPatients who have oligodendrogliomas (OD) that demonstrate loss of both 1p and 19q appear to have a better prognosis after they receive chemotherapy and radiotherapy compared with patients who have OD without these characteristics. It is unclear whether this improvement in outcome is due only to a better response to treatment. The authors investigated the correlation between genetic and clinical characteristics of OD in 33 patients who received chemotherapy with procarbazine, lomustine, and vincristine for recurrent disease after receiving radiotherapy.METHODSThe initial presentation, prior treatments, overall survival, and response to chemotherapy were assessed. The 1p and 19q status in OD lesions was determined with fluorescence in situ hybridization on paraffin embedded, archival material using locus specific probes. P53 mutations were assessed by polymerase chain reaction–single‐strand conformation polymorphism analysis and immunohistochemistry for P53; the proliferation index was assessed with the MIB‐1 antibody.RESULTSPatients who had OD lesions with a combined loss of 1p and 19q typically presented with low‐grade tumors that manifested with seizures of long‐standing duration. In contrast, patients who had OD lesions without a combined loss of 1p and 19q usually presented with focal deficits that required immediate treatment. Both the response rate to chemotherapy and the time to disease progression after chemotherapy were significantly better in patients who had a combined loss of 1p and 19. Tumors with classic OD morphology more often had a combined loss of 1p and 19q, although the genotype was better at identifying patients with chemoresponsive tumors. P53 mutations were observed in three tumors, none of which had a combined loss of 1p and 19q.CONCLUSIONSOD lesions with combined a loss of 1p and 19q have a more indolent nature compared with OD lesions that do not have these losses. Virtually all patients with these tumors present with low‐grade tumors accompanied by seizures and remain stable for prolonged periods. Future trials must keep these tumor types apart. Cancer 2003;97:1276–84. © 2003 American Cancer Society.DOI 10.1002/cncr.11187
Ki‐67 expression in breast carcinoma
Authors: Trihia Helen , Murray Susan , Price Karen , Gelber Richard D. , Golouh Rastko , Goldhirsch Aron , Coates Alan S. , Collins John , Castiglione‐Gertsch Monica , Gusterson Barry A. 
Published: February 2003

AbstractBACKGROUNDThe number of mitoses and, thus, the proliferative capacity of a tumor is one of the most crucial variables for tumor grading. The Ki‐67 nuclear antigen may be considered as an alternative to mitotic counts in grading schemes and as a single parameter that can be used in fine‐needle aspirates and small biopsies.METHODSImmunohistochemistry using the anti‐Ki‐67 antibody MIB‐1 was performed on 434 breast carcinoma specimens from the International Breast Cancer Study Group (formerly Ludwig) Trial V. Three groups based on Ki‐67 percent were used to replace the mitotic counts component in the Nottingham grade (NHG) to produce the Nottingham/Ki‐67 grade (NKG) and to assess Ki‐67 as a single parameter.RESULTSIn both the lymph node positive subgroup and the lymph node negative subgroup, the NKG and Ki‐67 group was correlated significantly with Bloom–Richardson grade (BRG), NHG, and Nottingham type. Tumor size in the lymph node negative cohort and estrogen receptor status, progesterone receptor status, and c‐erbB‐2 expression in the lymph node positive cohort also were correlated significantly with NKG. Ki‐67 percentage was correlated significantly with c‐erbB‐2 expression in the lymph node positive cohort only. NKG was similar to BRG and NHG when it was evaluated for prognostic significance. Patients with higher categoric Ki‐67 percentages had worse overall and disease free survival in all groups except for the untreated, lymph node negative group.CONCLUSIONSKi‐67 detection represents a valuable tool and is a good objective substitute for mitotic counts when used in a grading system. When it is used alone, Ki‐67 detection provides valuable information, although it is necessary to combine this with other parameters in the study of core biopsies and fine‐needle aspirates. Cancer 2003;97:1321–31. © 2003 American Cancer Society.DOI 10.1002/cncr.11188
Childhood cancer patients' access to cooperative group cancer programs
Authors: Liu Lihua , Krailo Mark , Reaman Gregory H. , Bernstein Leslie 
Published: February 2003

AbstractBACKGROUNDThe Children's Oncology Group (COG), a merger of the Children's Cancer Group (CCG) and the Pediatric Oncology Group (POG), conducts clinical trials for the treatment of childhood cancer. To assess the feasibility of developing a nationwide childhood cancer registry, the authors attempted to determine whether COG could serve as a resource for identifying all children with cancer.METHODSA consolidated file of children age < 20 years who were diagnosed with cancer between 1992–1997 and registered with either CCG or POG was linked with records from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program. Age‐specific registration rates and age‐adjusted registration rates (AARR) were calculated overall and by year of diagnosis, gender, race/ethnicity, stage of disease at diagnosis, and type of cancer.RESULTSOf 10,108 children age < 20 years with cancer who were identified by the 11 SEER registries between 1992–1997, 5796 were registered with CCG or POG. The AARR was 71% for children age < 15 years, 24% for adolescents ages 15–19 years, and 57% for children age < 20 years. Registration rates were stable over the years studied, varied by geographic region, and were found to be higher among children with more advanced disease. Registration rates were highest for children with leukemia, hepatic tumors, and renal tumors, and were lowest for carcinoma and retinoblastoma.CONCLUSIONSThe results of the current study demonstrate that not all children with cancer are registered by the cooperative groups; however, a national registry program can be achieved by supplementing cases identified through COG with data collected by statewide population‐based cancer registries. Such a partnership would be mutually beneficial, allowing COG to achieve 100% registration of children with cancer and, for the statewide cancer registries, improving the timeliness of case‐finding and follow‐up information for cancer outcomes. Cancer 2003;97:1339–45. © 2003 American Cancer Society.DOI 10.1002/cncr.11192
Caveolin‐1 expression is a predictor of recurrence‐free survival in pT2N0 prostate carcinoma diagnosed in Japanese patients
Authors: Satoh Takefumi , Yang Guang , Egawa Shin , Addai Josephine , Frolov Anna , Kuwao Sadahito , Timme Terry L. , Baba Shiro , Thompson Timothy C. 
Published: February 2003

AbstractBACKGROUNDThe authors previously identified elevated caveolin‐1 expression in human prostate carcinoma and determined that caveolin‐1 levels as detected by immunohistochemistry of radical prostatectomy specimens offered novel prognostic information. A higher incidence of caveolin‐1 expression also was reported in African‐American men compared with white men in the U.S. To explore these ethnic/racial differences in caveolin‐1 expression further, the authors evaluated caveolin‐1 expression as a predictive marker in Japanese men with prostate carcinoma.METHODSImmunohistochemical staining with a caveolin‐1 specific antibody was performed on routinely processed paraffin sections from 152 consecutively collected radical prostatectomy specimens. The mean patient age was 64.3 years (range, 49–74 years; median, 64.5 years) and the mean follow‐up period was 49.5 months (range, 1.3–103.3 months; median, 48.2 months). Caveolin‐1 immunoreactivity was evaluated in association with patient's age; preoperative prostate specific antigen level; clinical stage; and pathologic features including Gleason score, extraprostatic extension, status of surgical margins, seminal vesicle involvement, lymph node involvement, and time to disease progression after surgery.RESULTSPositive caveolin‐1 immunostaining was detected in 46 of the 152 tumors (30.3%) and was found to be associated significantly with a positive surgical margin (P= 0.022). A higher incidence of caveolin‐1 expression tended to be found in patients with poorly differentiated tumors (Gleason score > 7, 6–7, and < 6, 35.0% vs. 34.9% vs. 20.4%, respectively) or in patients with extraprostatic extension versus those without extraprostatic extension (35.4% vs. 24.7%) or patients with lymph node involvement compared with those without lymph node involvement (50% vs. 29.5%), although these differences did not reach statistical significance (P= 0.100,P= 0.150, andP= 0.178, respectively, by the Spearman correlation test). Kaplan–Meier analysis revealed that increased caveolin‐1 expression was associated with an increased risk of disease progression at 5 years (P= 0.0122 by the log‐rank test). In patients with organ‐confined (pT2N0) disease, univariate Cox proportional hazards regression analysis revealed that positive caveolin‐1 expression was the only significant predictor of disease recurrence after radical prostatectomy (P= 0.011; hazards ratio = 4.75; and 95% confidence interval, 1.43–15.76).CONCLUSIONSThe results of the current study confirm that positive caveolin‐1 expression is associated with clinical markers of disease progression and is predictive of poor clinical outcome after surgery in Japanese patients with pT2N0 prostate carcinoma. Cancer 2003;97:1225–33. © 2003 American Cancer Society.DOI 10.1002/cncr.11198
Capecitabine in combination with docetaxel and epirubicin in patients with previously untreated, advanced breast carcinoma
Authors: Venturini Marco , Durando Antonio , Garrone Ornella , Colozza Maria Antonietta , Contu Antonio , Stevani Ilaria , Genta Franco , Bighin Claudia , Lambiase Antonio , Del Mastro Lucia 
Published: February 2003

AbstractBACKGROUNDThe objective of this study was to evaluate the activity and safety of oral capecitabine in combination with docetaxel and epirubicin (TEX) as first‐line treatment for patients with locally advanced/metastatic breast carcinoma.METHODSThis open‐label, Phase II study was conducted at six Italian centers. Treatment consisted of epirubicin, 75 mg/m2 (intravenous bolus), and docetaxel, 75 mg/m2 (1‐hour infusion), both administered on Day 1, plus oral capecitabine, 1000 mg/m2 twice daily, on Days 1–14 of each 3‐week treatment cycle.RESULTSA total of 67 patients received 392 cycles of treatment, with a median of 6 cycles in patients with Stage III disease (n = 34 patients) and a median of 8 cycles in patients with Stage IV disease (n = 33 patients). The objective response rate was 82%, including complete responses in 21% of patients. A greater proportion of patients with Stage III disease achieved tumor responses compared with patients who had Stage IV disease (97% vs. 67%, respectively). Among 34 patients with Stage III disease, pathologic complete responses were confirmed in 10 patients (29%). TEX chemotherapy demonstrated an acceptable safety profile. There was a low incidence of Grade 3 adverse events, and Grade 4 adverse events were particularly rare (4%). The most common Grade 3–4 adverse event was febrile neutropenia, which occurred in 16% of patients.CONCLUSIONSTEX combination therapy has important antitumor activity and an acceptable safety profile in this setting. A large, randomized, Phase III trial is ongoing to compare TEX chemotherapy with an epirubicin plus docetaxel regimen in patients with untreated, advanced breast carcinoma. Cancer 2003;97:1174–80. © 2003 American Cancer Society.DOI 10.1002/cncr.11203
Increased telomerase activity is associated with shorter survival in patients with chronic phase chronic myeloid leukemia
Authors: Verstovsek Srdan , Kantarjian Hagop , Manshouri Taghi , Cortes Jorge , Faderl Stefan , Giles Francis J. , Keating Michael , Albitar Maher 
Published: February 2003

AbstractBACKGROUNDSignificantly elevated telomerase activity (TA) has been found in samples from patients with many malignant hematologic diseases. However, the impact of elevated TA on the course of patients with chronic phase chronic myeloid leukemia (CP‐CML) is unknown.METHODSUsing a modified polymerase chain reaction‐based telomeric repeat amplification protocol assay, the authors measured TA in bone marrow samples from 93 patients with CP‐CML and correlated it with patient characteristics and survival. TA also was measured in bone marrow samples from 29 patients with accelerated/blastic phase CML.RESULTSPatients with accelerated/blastic phase CML were found to have somewhat higher levels of TA compared with patients with CP‐CML (P = 0.07). Among patients with CP‐CML, those with high TA progressed to advanced stages of disease sooner (P = 0.05) and had a significantly shorter survival (P = 0.04) than patients with low TA. No correlation was found between TA and patient age, hemoglobin, platelet and leukocyte counts, percentage of peripheral or bone marrow blasts or basophils, or bone marrow cellularity. On multivariate analysis, high TA retained its significance as a factor associated with shorter patient survival (P = 0.02).CONCLUSIONSThe current study data suggest that TA plays a role in the propagation of CP‐CML and that the potential of telomerase inhibitors in patients with CML should be explored, even in those with early phase disease. Cancer 2003;97:1248–52. © 2003 American Cancer Society.DOI 10.1002/cncr.11217
Attractors of reaction‐diffusion systems in unbounded domains and their spatial complexity
Authors: Zelik Sergey V. 
Published: February 2003

AbstractThe nonlinear reaction‐diffusion system in an unbounded domain is studied. It is proven that, under some natural assumptions on the nonlinear term and on the diffusion matrix, this system possesses a global attractor 𝒜 in the corresponding phase space. Since the dimension of the attractor happens to be infinite, we study its Kolmogorov's ϵ‐entropy. Upper and lower bounds of this entropy are obtained.Moreover, we give a more detailed study of the attractor for the spatially homogeneous RDE in ℝn. In this case, a group of spatial shifts acts on the attractor. In order to study the spatial complexity of the attractor, we interpret this group as a dynamical system (with multidimensional “time” if n > 1) acting on a phase space 𝒜. It is proven that the dynamical system thus obtained is chaotic and has infinite topological entropy.In order to clarify the nature of this chaos, we suggest a new model dynamical system that generalizes the symbolic dynamics to the case of the infinite entropy and construct the homeomorphic (and even Lipschitz‐continuous) embedding of this system into the spatial shifts on the attractor.Finally, we consider also the temporal evolution of the spatially chaotic structures in the attractor and prove that the spatial chaos is preserved under this evolution. © 2003 Wiley Periodicals, Inc.
Vortex disaggregation for flow cytometry allows direct histologic correlation: A novel approach for small biopsies and inaspirable bone marrows
Authors: Vos Jeffrey A. , Simurdak Jerry H. , Davis Brad J. , Myers Jerome B. , Brissette Mark D. 
Published: February 2003

AbstractBackgroundMany approaches to obtaining single cells from tissue for flow cytometric immunophenotyping are used; however, these methods result in tissue that is too disrupted for subsequent histologic examination. We introduce a new technique for cell dissociation of hematopoietic malignancies that preserves tissue for histology. This is especially important with small specimens for which this type of correlation is critical.MethodsFresh tissue from lymph node, gastrointestinal (GI) tract, skin, and other soft tissue biopsies, in addition to cores of inaspirable bone marrows, were briefly vortexed until the RPMI cell culture medium became cloudy. Larger specimens such as lymph nodes were sectioned before disaggregating, whereas smaller ones were vortexed in toto. Resultant flow cytometric analyses were compared with the histology and, in some cases, the immunohistochemistry (IHC) to determine whether the data were concordant. Cell suspensions of 104 specimens–composed of 48 lymph nodes, 19 bone marrow cores (BMCs), 11 GI biopsies, 11 skin/soft tissue biopsies, and 15 miscellaneous specimens–were prepared via vortex disaggregation.ResultsFlow cytometric analysis of 96 specimens (92.3%) showed adequacy of material and diagnostic correlation with the histology and IHC. Of the eight cases (7.7%) that were discordant, seven were attributable to significant specimen fibrosis or necrosis. With respect to tissue type, this method produced diagnostic cell suspensions for most lymph nodes (95.8%), GI biopsies (90.9%), and BMCs (89.5%); however, it was less useful for skin/soft tissue samples (81.8%).ConclusionsDisaggregation of tissue for flow cytometric analysis by vortexing appears to provide adequate and representative cellular material. This technique is ideal for inaspirable bone marrows and small biopsies where tissue preservation for histology is paramount. Cytometry Part B (Clin. Cytometry) 52B:20–31, 2003. Published 2003 Wiley‐Liss, Inc.