Hepatitis B screening practice among older Chinese in the Greater Washington, DC, area.

Objectives: Older Chinese Americans are at greater risk of contracting hepatitis B virus (HBV) because they were born before the implementation of universal childhood vaccination policies. This study examined the prevalence of HBV screening, test results, and predictors of HBV screening among older Chinese.

Methods: Two hundred fifty-two Chinese immigrants (older than 50 years) recruited from Chinese-speaking physicians' offices in the Washington, DC, area participated in a cancer screening questionnaire.

Promoting Chinese-speaking primary care physicians' communication with immigrant patients about colorectal cancer screening: a cluster randomized trial design.

Chinese Americans underutilize colorectal cancer screening. This study evaluated a physician-based intervention guided by social cognitive theory (SCT) to inform future research involving minority physicians and patients. Twenty-five Chinese-speaking primary care physicians were randomized into intervention or usual care arms.

Ofatumumab and bendamustine in previously treated chronic lymphocytic leukemia and small lymphocytic lymphoma.

Despite initial responses > 90% with fludarabine and rituximab-based regimens, patients with chronic lymphocytic leukemia (CLL) invariably relapse and require further treatment. Ofatumumab and bendamustine have each shown efficacy in relapsed/refractory CLL with overall response rates (ORRs) of 58% and 76%, respectively. Given excellent data with bendamustine and rituximab in relapsed/refractory CLL/small lymphocytic lymphoma (SLL), this phase II study evaluated the combination of ofatumumab and bendamustine in previously treated patients.

The 6-MP versus placebo clinical trial in acute leukemia.

Background: This article gives the status of clinical cancer research in the 1950's-1960's and tells the story of the development and conduct of the 6-mercaptopurine (6-MP) versus placebo clinical trial in acute leukemia through the initiation, design, conduct and analysis stages, with emphasis on the ethical aspects of randomizing patients to 6-MP or placebo when in remission.

Purpose: The specific objective was to compare the lengths of remission for patients receiving 6-MP or placebo after achieving complete or partial remission from steroid treatment.

Methods: A randomized, double-blind, placebo controlled sequential study was conducted in which patients were paired by remission status at each of the eleven institutions participating in the study, and randomized to 6-MP or placebo within each pair of patients.

Treatment-subgroup interaction: an example from a published, phase II clinical trial.

Phase II trial designs that ignore between-patient heterogeneity and do not allow for treatment-subgroup interactions may produce very large false positive and false negative error rates if efficacy varies by subgroup. Recent discussions of this problem were illustrated with scenarios and computer simulations. In this short communication, we reanalyzed a published phase II trial to highlight the need to consider between-patient heterogeneity and the possibility of treatment-subgroup interaction when designing and analyzing phase II studies.

The properties of high-dimensional data spaces: implications for exploring gene and protein expression data.

High-throughput genomic and proteomic technologies are widely used in cancer research to build better predictive models of diagnosis, prognosis and therapy, to identify and characterize key signalling networks and to find new targets for drug development. These technologies present investigators with the task of extracting meaningful statistical and biological information from high-dimensional data spaces, wherein each sample is defined by hundreds or thousands of measurements, usually concurrently obtained. The properties of high dimensionality are often poorly understood or overlooked in data modelling and analysis.

Cyberknife radiosurgery for breast cancer spine metastases: a matched-pair analysis.

Background: There are few options for breast cancer patients with spinal metastases recurrent within a previous radiation treatment field. CyberKnife radiosurgery has been used in our institution to treat such patients. To evaluate their outcomes, as there are no comparable radiation treatment options, the outcomes were compared between 18 patients with spinal metastases from breast cancer treated with CyberKnife stereotactic radiosurgery, 17 of which had prior radiotherapy to the involved spinal region and were progressing, and 18 matched patients who received conventional external beam radiotherapy (CRT) up-front for spinal metastases.

The development of novel agents for the treatment of colorectal cancer: a critical review of current practice and some suggestions for the future.

The pathways to approval of new therapeutic agents in the United States and globally rely on the performance of well-designed clinical trials demonstrating both safety and efficacy. We recognize that the last decade has seen some great successes in improving outcomes for patients with cancer and, specifically, for patients with colorectal cancer. The development of novel agents active in colon cancer has led to improved survival and cure rates.

Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial.

Purpose: In an open-label trial we have previously demonstrated that paroxetine reduces hot flashes. We initiated a stratified, randomized, double-blind, cross-over, placebo-controlled trial to investigate the efficacy of paroxetine 10 mg and 20 mg compared to placebo in reducing hot flash frequency and composite score. A secondary objective was to evaluate quality of life (QOL) parameters.

A multicenter randomized clinical trial evaluating interleukin-2 activated hematopoietic stem cell transplantation and post-transplant IL-2 for high risk breast cancer patients.

Purpose: This Phase III randomized multicenter trial compared progression-free (PFS) and overall survival (OS) for autologous peripheral blood stem cell (aPBSC) transplantation with or without immunotherapy in high-risk breast cancer patients.

Methods: Eligible patients had American Joint Committee on Cancer (AJCC) 5th Edition Stage II/IIIA with > or = 4 axillary nodes, Stage IIIB, or chemotherapy-sensitive or stable Stage IV disease. Following treatment with cyclophosphamide, thiotepa and carboplatin (STAMP V), patients were randomized to aPBSC transplant with or without immunotherapy.

Activation of signal transducer and activator of transcription-5 in prostate cancer predicts early recurrence.

Purpose: We have shown previously that the signal transducer and activator of transcription-5 (Stat5) is a critical survival factor in human prostate cancer cells. In addition, we recently showed that Stat5 is activated at a high level, particularly in high-grade human prostate cancers. Here, we investigated whether activation of Stat5 in prostate cancer was linked to clinical outcome with disease recurrence as end point.

Gene selection for microarray data analysis using principal component analysis.

Principal component analysis (PCA) has been widely used in multivariate data analysis to reduce the dimensionality of the data in order to simplify subsequent analysis and allow for summarization of the data in a parsimonious manner. It has become a useful tool in microarray data analysis. For a typical microarray data set, it is often difficult to compare the overall gene expression difference between observations from different groups or conduct the classification based on a very large number of genes.

Supplementary analysis of probabilities at the termination of a group sequential phase II trial.

We consider estimation of various probabilities after termination of a group sequential phase II trial. A motivating example is that the stopping rule of a phase II oncologic trial is determined solely based on response to a drug treatment, and at the end of the trial estimating the rate of toxicity and response is desirable. The conventional maximum likelihood estimator (sample proportion) of a probability is shown to be biased, and two alternative estimators are proposed to correct for bias, a bias-reduced estimator obtained by using Whitehead's bias-adjusted approach, and an unbiased estimator from the Rao-Blackwell method of conditioning.

The nuclear receptor coactivator AIB1 mediates insulin-like growth factor I-induced phenotypic changes in human breast cancer cells.

The nuclear receptor coactivator AIB1 (amplified in breast cancer 1) is overexpressed in human breast cancers and is required for estrogen signaling. However, the role of AIB1 in breast cancer etiology is not known. Here, we show that AIB1 is rate-limiting for insulin-like growth factor I (IGF-I)-dependent phenotypic changes and gene expression in human breast cancer cells.

Progressive loss of Syk and abnormal proliferation in breast cancer cells.

The tumor suppressor gene Syk tyrosine kinase is absent or reduced in invasive breast cancer tissues and cell lines; its loss in breast tissues is linked to poor prognosis and metastasis. Also, evidence shows that in vitro Syk is involved in regulating proliferation. Here, we show by in situ hybridization on breast tissue sections that the loss of Syk expression is progressive during tumor development.

SCC-112, a novel cell cycle-regulated molecule, exhibits reduced expression in human renal carcinomas.

We report here the identification and an initial characterization of a novel cell cycle-regulated molecule, SCC-112. SCC-112 cDNA (6744 bp) encodes a longest open reading frame (ORF) comprised of 1297 amino acids, representing a approximately 150-kDa nuclear protein. SCC-112 mRNA and protein levels were relatively high during the G2/M phase of the cell cycle in MDA-MB 435 breast cancer cells.

Long-term outcomes after radical prostatectomy performed in a community-based health maintenance organization.

Background: Radical prostatectomy is used widely for the treatment of patients with localized prostate carcinoma. No long-term analysis has been reported on a series of radical prostatectomies performed in a community-based health maintenance organization.

Methods: Charts and histologic slides were reviewed from 750 patients who underwent radical prostatectomy between 1970 and 1996 at a community-based health maintenance organization.

Stat5a is tyrosine phosphorylated and nuclear localized in a high proportion of human breast cancers.

Signal transducers and activators of transcription (STATs) are latent cytoplasmic transcription factors that are activated and translocated into the nucleus after phosphorylation at a conserved tyrosine residue. Mouse model studies have demonstrated that activated Stat5a acts as a critical survival factor for normal, preneoplastic and malignant mammary epithelial cells. Very limited information is available, however, on the expression, tyrosine phosphorylation status and nuclear localization of Stat5a in human breast cancers.

Block principal component analysis with application to gene microarray data classification.

We propose a block principal component analysis method for extracting information from a database with a large number of variables and a relatively small number of subjects, such as a microarray gene expression database. This new procedure has the advantage of computational simplicity, and theory and numerical results demonstrate it to be as efficient as the ordinary principal component analysis when used for dimension reduction, variable selection and data visualization and classification. The method is illustrated with the well-known National Cancer Institute database of 60 human cancer cell lines data (NCI60) of gene microarray expressions, in the context of classification of cancer cell lines.

On the ethical aspects of the testimony of statisticians in court.

This article considers a legal case presented by the Gore campaign to the Florida Eleventh Circuit Court in December 2000 to contest the election results giving the 25 electoral votes from the State of Florida to George W Bush--basically awarding the presidency to Bush. Consideration is given to the ethical aspects of the testimony of two statisticians, one for Gore and one for Bush, who testified about whether the certified election results rejected a number of legal votes and included a number of illegal votes sufficient to place in doubt the results of the election. It is concluded that neither statistician violated accepted ethical standards of the statistical profession, though the Bush statistician's testimony was at least borderline unethical on certain points.

Sample size and power determination for clustered repeated measurements.

It is common in epidemiological and clinical studies that each subject has repeated measurements on a single common variable, while the subjects are also 'clustered'. To compute sample size or power of a test, we have to consider two types of correlation: correlation among repeated measurements within the same subject, and correlation among subjects in the same cluster. We develop, based on generalized estimating equations, procedures for computing sample size and power with clustered repeated measurements.

Mobilization of peripheral blood stem cells with paclitaxel and rhG-CSF in high-risk breast cancer patients.

Preclinical studies have demonstrated the rapid and efficient mobilization of hematopoietic peripheral blood stem cells (PBSC) in a mouse model using the combination of paclitaxel with recombinant human granulocyte colony-stimulating factor (rhG-CSF). On the basis of these results, a clinical trial was initiated using rhG-CSF with paclitaxel for PBSC mobilization in high-risk breast cancer patients. The mobilized PBSC were evaluated for CD34(+) cell number, mononuclear cell content, and clonogenic potential.

Treatment of children and adolescents with localized parameningeal sarcoma: experience of the Intergroup Rhabdomyosarcoma Study Group protocols IRS-II through -IV, 1978-1997.

Background: We reviewed 611 patients with parameningeal sarcoma entered on Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols-II through IV (1978-1997), to delineate treatment results and evaluate prognostic factors.

Procedure: Primary sites were the middle ear/mastoid (N = 138), nasopharynx/nasal cavity (N = 235), paranasal sinuses (N = 132), parapharyngeal region (N = 29), and the pterygopalatine/infratemporal fossa (N = 77). Treatment was initial biopsy or surgery followed by multiagent chemotherapy and radiation therapy (XRT).

The role of the biostatistician in cancer research.

This article considers triumphs and challenges for biostatisticians working in oncology at the beginning of the 21st century. The impact of three major articles in biostatistics in the 20th century is considered: Cornfield's 1951 paper on estimating comparative rates from clinical data; Mantel and Haenszel's 1959 paper on obtaining summary measures of relative risk, adjusting for stratification factors in epidemiological studies; and D. R.

Phase I and pharmacokinetic study of two sequences of gemcitabine and docetaxel administered weekly to patients with advanced cancer.

Purpose: To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and effect of drug sequence on toxicities and pharmacokinetics of the combination of gemcitabine and docetaxel.

Methods: A total of 34 patients with advanced cancers were treated with gemcitabine and docetaxel on days 1 and 8 of each 21-day cycle according to the following dose escalation schedule: level 1, 800 and 30 mg/m2, respectively; level 2, 800 and 40 mg/m2; level 3, 1,000 and 40 mg/m2; and level 4, 1,250 and 40 mg/m2. At each dose level, at least three patients were assigned to one of the two sequences of drug administration: gemcitabine-->docetaxel or docetaxel-->gemcitabine.