Microfabrication of Individual 200μm Diameter Transdermal Microconduits Using High Voltage Pulsing in Salicylic Acid and Benzoic Acid

We describe an extension of semiconductor fabrication methods that creates individual ≈ 200;μm diameter aqueous pathways through human stratum corneum at predetermined sites. Our hypothesis is that spatially localized electroporation of the multilamellar lipid bilayer membranes provides rapid delivery of salicylic acid to the keratin within corneocytes, leading to localized keratin disruption and then to a microconduit. A microconduit penetrating the isolated stratum corneum supports a volumetric flow of order 0.01;ml per s with a pressure difference of only 0.01;atm (about 102;Pa). This study provides a method for rapidly microengineering a pathway in the skin to interface future devices for transdermal drug delivery and sampling of biologically relevant fluids

Comparative Genomic Hybridization Analysis of Astrocytomas: Prognostic and Diagnostic Implications.

Astrocytoma is comprised of a group of common intracranial neoplasms that are classified into four grades based on the World Health Organization histological criteria and patient survival. To date, histological grade, patient age, and clinical performance, as reflected in the Karnofsky score, are the most reliable prognostic predictors. Recently, there has been a significant effort to identify additional prognostic markers using objective molecular genetic techniques. We believe that the identification of such markers will characterize new chromosomal loci important in astrocytoma progression and aid clinical diagnosis and prognosis. To this end, our laboratory used comparative genomic hybridization to identify DNA sequence copy number changes in 102 astrocytomas. Novel losses of 19p loci were detected in low-grade pilocytic astrocytomas and losses of loci on 9p, 10, and 22 along with gains on 7, 19, and 20 were detected in a significant proportion of high-grade astrocytomas. The Cox proportional hazards statistical modeling showed that the presence of +7q and -10q comparative genomic hybridization alterations significantly increased a patient\u27s risk of dying, independent of histological grade. This investigation demonstrates the efficacy of comparative genomic hybridization for identifying tumor suppressor and oncogene loci in different astrocytic grades. The cumulative effect of these loci is an important consideration in their diagnostic and prognostic implications

Measuring Disease-Free Survival and Cancer Relapse Using Medicare Claims From CALGB Breast Cancer Trial Participants (Companion to 9344)

To determine the accuracy with which Medicare claims data measure disease-free survival in elderly Medicare beneficiaries with cancer, we performed a criterion validation study. We merged gold-standard clinical trial data of 45 elderly patients with node-positive breast cancer who were treated on the Cancer and Leukemia Group B (CAL-GB) adjuvant breast trial 9344 with Centers for Medicare and Medicaid Services (CMS) data files and compared the results of a CMS-based algorithm with the CALGB disease-free survival information to determine sensitivity and specificity. For 5-year disease-free survival, the sensitivity of the CMS-based algorithm was 100% (95% confidence interval [CI] = 81% to 100%), the specificity was 97% (95% CI = 83% to 100%), and the area under the receiver operator curve was 97% (95% CI = 90% to 100%). For 2-year disease-free survival, the test characteristics were less favorable: sensitivity was 83% (95% CI = 36% to 100%), specificity was 95% (95% CI = 83% to 100%), and area under the receiver operator curve was 84% (95% CI = 66% to 100%)

Peak oxygen consumption and long-term all-cause mortality in nonsmall cell lung cancer

Identifying strong markers of prognosis is critical to optimize treatment and survival outcomes in patients with non-small cell lung cancer (NSCLC). We investigated the prognostic significance of preoperative cardiorespiratory fitness (VO2peak) among operable candidates with NSCLC

Phase II Trial of Paclitaxel and Cisplatin in Patients with Extensive Stage Small Cell Lung Cancer: Cancer and Leukemia Group B Trial 9430

Cancer and Leukemia Group B (CALGB) trial 9430 was a randomized phase II trial which investigated the safety and activity of four novel doublets in untreated extensive stage small cell lung cancer (ES-SCLC). The results of the paclitaxel and cisplatin arm have not been reported

Phase II Trial of Weekly Dose-Dense Paclitaxel in Extensive-Stage Small Cell Lung Cancer: Cancer and Leukemia Group B Study 39901

INTRODUCTION: Paclitaxel is an active agent in extensive-stage (ES) small cell lung cancer (SCLC). Nevertheless, the optimal schedule is uncertain. A dose-dense schedule was previously evaluated in a Cancer and Leukemia Group B study of patients with non-SCLC, resulting in a 42% response rate and median survival of 12.3 months. Because of these promising results, this dose and schedule of paclitaxel was evaluated in patients with ES-SCLC. METHODS: Patients were eligible for this phase II trial (Cancer and Leukemia Group B 39901) if they had documented ES-SCLC, no prior chemotherapy, and performance status of 0 to 2. Paclitaxel was administered as an intravenous infusion at 150 mg/m2 over 3 hours weekly for 6 consecutive weeks every 8 weeks. RESULTS: Thirty-six patients with median age of 65 were enrolled. Of them 25 were men and 33 with a performance status 0 to 1. A median of two 8-week cycles were delivered. The percent of patients with grade 3/4 toxicity included neutropenia 22%, anemia 9%, febrile neutropenia 6%, fatigue 20%, sensory neuropathy 26%, motor neuropathy 11%, and dyspnea 17%. There were two treatment-related deaths, both from pneumonitis. The overall response rate was 33% (3% complete response and 30% partial response). Median progression-free and overall survivals were 3.7 and 9.2 months, respectively. One-year progression-free and overall survivals were 17% and 36%, respectively. CONCLUSIONS: For patients with ES-SCLC, dose-dense weekly paclitaxel was associated with fairly mild hematologic toxicity. Nevertheless, nonhematologic toxicities, including neuropathy, fatigue, and dyspnea required frequent dose delays and reductions. The overall response rate is disappointing and much lower than that seen with standard platinum-based combinations. Paclitaxel in this dose and schedule should not be used as front-line therapy for patients with ES-SCLC

Brief Report: Correlates of Quality of Life-related Outcomes in Breast Cancer Patients Participating in the Pathfinders Pilot Study

In a pilot study, participation in the Pathfinders program was associated with reductions in distress and despair and improvements in quality of life (QOL) among advanced breast cancer patients. This paper explores the relationship between psychosocial resources invoked through the Pathfinders intervention and outcomes

Phase 2 pilot study of Pathfinders: a psychosocial intervention for cancer patients

Pathfinders is a multi-faceted psychosocial care program for cancer patients; it was developed in community oncology and adapted to the academic oncology setting. This prospective, single-arm, phase 2 pilot study examined the acceptability and feasibility of Pathfinders for women with metastatic breast cancer