Development of a new adapted QuinteT Recruitment Intervention (QRI-Two) for rapid application to RCTs underway with enrolment shortfalls-to identify previously hidden barriers and improve recruitment.

Background: Many randomised controlled trials (RCTs) struggle to recruit, despite valiant efforts. The QRI (QuinteT Recruitment Intervention) uses innovative research methods to optimise recruitment by revealing previously hidden barriers related to the perceptions and experiences of recruiters and patients, and targeting remedial actions. It was designed to be integrated with RCTs anticipating difficulties at the outset.

Older adults with newly diagnosed high-risk/secondary AML who achieved remission with CPX-351: phase 3 post hoc analyses.

CPX-351, a dual-drug liposomal encapsulation of daunorubicin/cytarabine in a synergistic 1:5 molar ratio, is approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC). In a pivotal phase 3 study, patients aged 60 to 75 years with newly diagnosed, high-risk/secondary AML were randomized to receive CPX-351 or conventional 7+3 chemotherapy. In the primary endpoint analysis, CPX-351 demonstrated significantly prolonged median overall survival (OS) vs 7+3.

Cancer Informatics for Cancer Centers (CI4CC): Building a Community Focused on Sharing Ideas and Best Practices to Improve Cancer Care and Patient Outcomes.

Cancer Informatics for Cancer Centers (CI4CC) is a grassroots, nonprofit 501c3 organization intended to provide a focused national forum for engagement of senior cancer informatics leaders, primarily aimed at academic cancer centers anywhere in the world but with a special emphasis on the 70 National Cancer Institute-funded cancer centers. Although each of the participating cancer centers is structured differently, and leaders' titles vary, we know firsthand there are similarities in both the issues we face and the solutions we achieve. As a consortium, we have initiated a dedicated listserv, an open-initiatives program, and targeted biannual face-to-face meetings.

Application of mutagen sensitivity assay in a glioma case-control study.

Few risk factors for glioma have been identified other than ionizing radiation. The alkylating agent acrylamide is a compound found in both occupational and the general environment and identified as one of the forty known or suspected neurocarcinogens in animal models. The mutagen sensitivity assay (MSA) has been used to indirectly show reduced DNA repair capacity upon exposure to ionizing radiation in those with glioma compared to controls.

Correlation between germline mutations in MMR genes and microsatellite instability in ovarian cancer specimens.

A high proportion of ovarian cancers from women who carry germline mutations in mismatch repair (MMR) genes demonstrate microsatellite instability (MSI). The utility of pre-screening ovarian cancer specimens for MSI to identify potential patients for germline screening for MMR mutations is uncertain. 656 women with malignant ovarian cancer underwent both MSI testing and germline mutation testing for large rearrangements in three MMR genes, MLH1, MSH2 and MSH6.

Maternal stress, preterm birth, and DNA methylation at imprint regulatory sequences in humans.

In infants exposed to maternal stress in utero, phenotypic plasticity through epigenetic events may mechanistically explain increased risk of preterm birth (PTB), which confers increased risk for neurodevelopmental disorders, cardiovascular disease, and cancers in adulthood. We examined associations between prenatal maternal stress and PTB, evaluating the role of DNA methylation at imprint regulatory regions. We enrolled women from prenatal clinics in Durham, NC.

Labeled oxazaphosphorines for applications in mass spectrometry studies. 2. Synthesis of deuterium-labeled 2-dechloroethylcyclophosphamides and 2- and 3-dechloroethylifosfamides.

The prodrugs cyclophosphamide (CP) and ifosfamide (IF) each metabolize to an active alkylating agent through a cytochrome P450-mediated oxidation at the C-4 position. Competing with this activation pathway are enzymatic oxidations at the exocyclic α and α' carbons, which result in dechloroethylation of CP and IF. The incidence of oxidation at one position relative to another is believed to be at least one factor underlying the high degree of interpatient variability in both CP and IF pharmacokinetics.

Review of electronic patient-reported outcomes systems used in cancer clinical care.

Purpose: The use of electronic patient-reported outcomes (PRO) systems is increasing in cancer clinical care settings. This review comprehensively identifies existing PRO systems and explores how systems differ in the administration of PRO assessments, the integration of information into the clinic workflow and electronic health record (EHR) systems, and the reporting of PRO information.

Methods: Electronic PRO (e-PRO) systems were identified through a semistructured review of published studies, gray literature, and expert identification.

A randomized phase II study of immunization with dendritic cells modified with poxvectors encoding CEA and MUC1 compared with the same poxvectors plus GM-CSF for resected metastatic colorectal cancer.

Objective: To determine whether 1 of 2 vaccines based on dendritic cells (DCs) and poxvectors encoding CEA (carcinoembryonic antigen) and MUC1 (PANVAC) would lengthen survival in patients with resected metastases of colorectal cancer (CRC).

Background: Recurrences after complete resections of metastatic CRC remain frequent. Immune responses to CRC are associated with fewer recurrences, suggesting a role for cancer vaccines as adjuvant therapy.

Kernel canonical correlation analysis for assessing gene-gene interactions and application to ovarian cancer.

Although single-locus approaches have been widely applied to identify disease-associated single-nucleotide polymorphisms (SNPs), complex diseases are thought to be the product of multiple interactions between loci. This has led to the recent development of statistical methods for detecting statistical interactions between two loci. Canonical correlation analysis (CCA) has previously been proposed to detect gene-gene coassociation.

The effect of metastatic site and decade of diagnosis on the individual burden of metastatic melanoma: contemporary estimates of average years of life lost.

Objectives: Metastatic melanoma (MM) is a leading cause of years of life lost due to malignancy. This study aimed to identify the average years of life lost (AYLL) in MM patients.

Methods: MM patients were identified from a prospectively maintained database, and a linear model predicting AYLL was developed.

Need for global partnership in cancer care: perceptions of cancer care researchers attending the 2010 australia and Asia pacific clinical oncology research development workshop.

Purpose: To understand the diversity of issues and the breadth of growing clinical care, professional education, and clinical research needs of developing countries, not typically represented in Western or European surveys of cancer care and research.

Methods: A cross-sectional survey was conducted of the attendees at the 2010 Australia and Asia Pacific Clinical Oncology Research Development workshop (Queensland, Australia) about the most important health care questions facing the participant's home countries, especially concerning cancer.

Results: Early-career oncologists and advanced oncology trainees from a region of the world containing significant low- and middle-income countries reported that cancer is an emerging health priority as a result of aging of the population, the impact of diet and lifestyle, and environmental pollution.

Core elements of the patient protection and affordable care act and their relevance to the delivery of high-quality cancer care.

The Affordable Care Act (ACA) contains many provisions that affect cancer care. The provisions of health care reform aim to improve access to quality cancer care, particularly among the most vulnerable Americans. However, health care reform also offers many challenges and opportunities that affect every stakeholder in oncology.

Increasing vaccine potency through exosome antigen targeting.

While many tumor associated antigens (TAAs) have been identified in human cancers, efforts to develop efficient TAA "cancer vaccines" using classical vaccine approaches have been largely ineffective. Recently, a process to specifically target proteins to exosomes has been established which takes advantage of the ability of the factor V like C1C2 domain of lactadherin to specifically address proteins to exosomes. Using this approach, we hypothesized that TAAs could be targeted to exosomes to potentially increase their immunogenicity, as exosomes have been demonstrated to traffic to antigen presenting cells (APC).

Depleting regulatory T cells with arginine-rich, cell-penetrating, peptide-conjugated morpholino oligomer targeting FOXP3 inhibits regulatory T-cell function.

CD4+CD25+regulatory T cells (T(reg)) impair anti-tumor and anti-viral immunity. As there are higher T(reg) levels in cancer patients compared with healthy individuals, there is considerable interest in eliminating them or altering their function as part of cancer or viral immunotherapy strategies. The scurfin transcriptional regulator encoded by the member of the forkhead winged helix protein family (FOXP3) is critical for maintaining the functions of T(reg).

Breast medical oncologists' use of standard prognostic factors to predict a 21-gene recurrence score.

Background: Half of all breast cancers are early stage, lymph node negative, and hormone receptor positive. A 21-gene (Oncotype DX®; Genomic Health, Inc., Redwood City, CA) recurrence score (RS) is prognostic for recurrence and predictive of chemotherapy benefit.

Systematic review of efficacy of dose-dense versus non-dose-dense chemotherapy in breast cancer, non-Hodgkin lymphoma, and non-small cell lung cancer.

Randomized controlled trials (RCTs) have suggested a potential advantage of dose-dense chemotherapy in improving disease-free and overall survival in patients with certain malignancies. This systematic review summarizes the literature on the efficacy of dose-dense chemotherapy across various cancers (breast cancer, non-Hodgkin lymphoma [NHL], and non-small cell lung cancer) and chemotherapy regimens. Among the 17 trials identified, few reported statistically significant differences between dose-dense and standard chemotherapy, and most were small with limited statistical power.

HER2 overexpression elicits a proinflammatory IL-6 autocrine signaling loop that is critical for tumorigenesis.

HER2 overexpression occurs in approximately 25% of breast cancers, where it correlates with poor prognosis. Likewise, systemic inflammation in breast cancer correlates with poor prognosis, although the process is not understood. In this study, we explored the relationship between HER2 and inflammation, comparing the effects of overexpressing wild-type or mutated inactive forms of HER2 in primary human breast cells.

Venous thromboembolism in the patient with cancer: focus on burden of disease and benefits of thromboprophylaxis.

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in patients with cancer. The risk of VTE varies over the natural history of cancer, with the highest risk occurring during hospitalization and after disease recurrence. Patient and disease characteristics are associated with further increased risk of VTE in this setting.

Guest editors' introduction to the special section on information technology and evidence implementation.

Healthcare is experiencing a transformation-perhaps as significant as the publication of the first randomized controlled trial-in the ways in which basic discovery is translated into effective practice. The change is being precipitated by efforts to undergird the healthcare industry with the same transformational capacities from information technology as is afforded to other sectors in the economy. Although the transformation has been slow in materializing, change is expected to accelerate under the stimulating influence of the Health Information Technology for Economic and Clinical Health Act of 2009 and the Patient Protection and Affordable Care Act of 2010.

Applying motivational interviewing techniques to palliative care communication.

Palliative care relies heavily on communication. Although some guidelines do address difficult communication, less is known about how to handle conversations with patients who express ambivalence or resistance to such care. Clinicians also struggle with how to support patient autonomy when they disagree with patient choices.

Antiangiogenic therapies in epithelial ovarian cancer.

Background: Angiogenesis is a critical component of tumor development and proliferation, and increased angiogenesis has been associated with a worse clinical outcome in a number of solid tumors, including ovarian cancer. Therefore, agents that target the angiogenic process are of considerable interest in the treatment of ovarian cancer.

Methods: Studies evaluating the efficacy of antiangiogenic agents in ovarian cancer are reported.

Dasatinib (BMS-35482) has synergistic activity with paclitaxel and carboplatin in ovarian cancer cells.

Purpose: To explore the activity of dasatinib alone and in combination with paclitaxel and carboplatin in ovarian cancer cells and to determine if dasatinib activity can be predicted based on evaluation of the SRC pathway.

Experimental Design: Microarray analysis was performed for IGROV1, OVCAR3, A2780 and SKOV3 ovarian cancer cells and the status of the genomic SRC signature pathway was determined. Cells were treated with carboplatin, paclitaxel and dasatinib individually and in combination.