Project description:Introduction: Peri-operative window trials, using molecular biomarkers as surrogate endpoints for treatment response, offer investigators a uniqueopportunity to obtain intact tumor samples at 2 different time-points and thus evaluate potential biomarkers over a short period of time. Here we report results of a pilot trial designed to determine if treatment-mediated changes in gene expression can be detected after a 10-day exposure to anastrozole in estrogen receptor (ER)-positive breast cancer compared to untreated controls. Methods: Paired tumor samples (biopsy and surgical) were obtained from 26 postmenopausal women with ER-positive breast cancer. Patients were assigned anastrozole (1mg/dy) for 10 days immediately prior to surgery (13 cases) or no treatment (13 controls). 502 cancer-related genes were examined by the DASL FFPE-based cDNA array (moderated t-test, p ≤ .005). Surrogate biomarkers reflecting changes in gene expression were examined by immunohistochemistry (IHC) (Wilcoxon rank-based test, p < .05). Results: Sufficient RNA was available from 19 paired samples (8 controls, 11 cases). There was no difference in age, tumor size, grade, or baseline biomarker expression between groups. Within each group, 18 genes, reflecting roles in proliferation, angiogenesis, and apoptosis showed differential expression over time from biopsy to surgery (p < 0.005). Dysregulation of estrogen-related genes was present only in the treated group. Comparison between groups identified 5 genes that were significantly dysregulated between controls and treated cases (BAG1/ING1/ERBB4/IFNGR1/TFDP1). Reduction in Ki-67 index was observed in 7 (54%) treated cases in 1 (7.7%) control patient. Conclusions: Short-term (10-day) exposure to anastrozole resulted in significant dysregulation of 18 out of 502 cancer-related genes, and Ki-67 was reduced in 54% of cases. However, the local effects of wound healing may represent a confounding factor in the interpretation of peri-operative window trials as exposed by the changes in gene expression and the increased Ki-67 index in the control group. Prospective, paired tumor samples (biopsy and surgical) were obtained from 26 postmenopausal women with ER-positive breast cancer. Patients were assigned anastrozole (1mg/dy) for 10 days immediately prior to surgery (13 cases) or no treatment (13 controls). 502 cancer-related genes were examined by the DASL FFPE-based cDNA array. Sufficient RNA for gene expression analysis was obtained from 19/26 (73%) FFPE paired (biopsy and surgery) samples (8 controls, 11 anastrozole-treated patients

Project description:Introduction: Peri-operative window trials, using molecular biomarkers as surrogate endpoints for treatment response, offer investigators a uniqueopportunity to obtain intact tumor samples at 2 different time-points and thus evaluate potential biomarkers over a short period of time. Here we report results of a pilot trial designed to determine if treatment-mediated changes in gene expression can be detected after a 10-day exposure to anastrozole in estrogen receptor (ER)-positive breast cancer compared to untreated controls. Methods: Paired tumor samples (biopsy and surgical) were obtained from 26 postmenopausal women with ER-positive breast cancer. Patients were assigned anastrozole (1mg/dy) for 10 days immediately prior to surgery (13 cases) or no treatment (13 controls). 502 cancer-related genes were examined by the DASL FFPE-based cDNA array (moderated t-test, p ≤ .005). Surrogate biomarkers reflecting changes in gene expression were examined by immunohistochemistry (IHC) (Wilcoxon rank-based test, p < .05). Results: Sufficient RNA was available from 19 paired samples (8 controls, 11 cases). There was no difference in age, tumor size, grade, or baseline biomarker expression between groups. Within each group, 18 genes, reflecting roles in proliferation, angiogenesis, and apoptosis showed differential expression over time from biopsy to surgery (p < 0.005). Dysregulation of estrogen-related genes was present only in the treated group. Comparison between groups identified 5 genes that were significantly dysregulated between controls and treated cases (BAG1/ING1/ERBB4/IFNGR1/TFDP1). Reduction in Ki-67 index was observed in 7 (54%) treated cases in 1 (7.7%) control patient. Conclusions: Short-term (10-day) exposure to anastrozole resulted in significant dysregulation of 18 out of 502 cancer-related genes, and Ki-67 was reduced in 54% of cases. However, the local effects of wound healing may represent a confounding factor in the interpretation of peri-operative window trials as exposed by the changes in gene expression and the increased Ki-67 index in the control group.

Project description:ObjectivesTo describe telephone interview completion rates among 12-month cardiac arrest survivors enrolled in the Therapeutic Hypothermia after Pediatric Cardiac Arrest In-Hospital and Out-of-Hospital trials, identify key characteristics of the completed follow-up interviews at both 3- and 12-month postcardiac arrest, and describe strategies implemented to promote follow-up.SettingCentralized telephone follow-up interviews.DesignRetrospective report of data collected for Therapeutic Hypothermia after Pediatric Cardiac Arrest trials, and summary of strategies used to maximize follow-up completion.PatientsTwelve-month survivors (n = 251) from 39 Therapeutic Hypothermia after Pediatric Cardiac Arrest PICU sites in the United States, Canada, and United Kingdom.InterventionsNot applicable.Measurements and main resultsThe 3- and 12-month telephone interviews included completion of the Vineland Adaptive Behavior Scales, Second Edition. Vineland Adaptive Behavior Scales, Second Edition data were available on 96% of 3-month survivors (242/251) and 95% of 12-month survivors (239/251) with no differences in demographics between those with and without completed Vineland Adaptive Behavior Scales, Second Edition. At 12 months, a substantial minority of interviews were completed with caregivers other than parents (10%), after calls attempts were made on 6 or more days (18%), and during evenings/weekends (17%). Strategies included emphasizing the relationship between study teams and participants, ongoing communication between study team members across sites, promoting site engagement during the study's final year, and withholding payment for work associated with the primary outcome until work had been completed.ConclusionsIt is feasible to use telephone follow-up interviews to successfully collect detailed neurobehavioral outcome about children following pediatric cardiac arrest. Future studies should consider availability of the telephone interviewer to conduct calls at times convenient for families, using a range of respondents, ongoing engagement with site teams, and site payment related to primary outcome completion.

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Therapeutic trials in adult FSGS: lessons learned and the road forward.

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Therapeutic trials in adult FSGS: lessons learned and the road forward.

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