6048 results for "canc*"

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• Durvalumab and Cediranib with and without Olaparib in Recurrent Ovarian Cancer: A phase II Proof-of-Concept Study

  We report the efficacy and translational research findings of durvalumab, olaparib, and cediranib (D+O+C) and durvalumab and cediranib (D+C) therapies from the recurrent epithelial ovarian cancer (EOC) cohort within a single center, multi-arm, non-randomized, multi-cohort phase I/II trial (NCT02484404). Sixty-eight patients were enrolled (39 in D+O+C, 29 in D+C). The objective response rate (ORR) was 19.4% (95% CI, 9.5-43.5) for D+O+C and 29.6% (95% CI, 13.8-46.9) for D+C. Median progression-free survival (PFS) was 4.5 months in both arms, with each arm including four exceptional responders (PFS ≥ 12 months). Pre-treatment biopsies and paired normal peripheral blood mononuclear cells (PBMC) samples for whole exome sequencing (WES) were available for 31 patients in the D+O+C and 24 in the D+C, the remaining 13 patients were not biopsied due to safety concerns or being off treatment. WES was conducted to explore genomic profiles for potential correlations with clinical benefit (CB; partial response or stable disease [SD] with PFS ≥ 4 months) or no clinical benefit (NCB; progressive disease or SD with PFS TP53 mutations were found in most cases in both D+O+C and D+C arms. Overall, no consistent associations between baseline genomic alterations and CB were observed.

  Study phs004519

• NCTN: A Double Blind Randomization to Letrozole or Placebo for Women Previously Diagnosed with Primary Breast Cancer Completing Five Years of Adjuvant Aromatase Inhibitor either as Initial Therapy or after Tamoxifen (NCIC-MA.17R)

  Study ID: NCIC-MA.17RNCT Number: NCT00754845 Canadian Cancer Trials Group (CCTG)Submitted in collaboration with the NCTN/NCORP Data ArchiveTrial Title: NCTN: A Double Blind Randomization to Letrozole or Placebo for Women Previously Diagnosed with Primary Breast Cancer Completing Five Years of Adjuvant Aromatase Inhibitor either as Initial Therapy or after Tamoxifen (NCIC-MA.17R)Trial Description: RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known whether letrozole is more effective than a placebo in treating in women with breast cancer who have already received 5 years of aromatase inhibitor therapy.PURPOSE: This randomized phase III trial is studying letrozole to see how well it works compared with a placebo in treating women with primary breast cancer who have received 5 years of aromatase inhibitor therapy. Clinical data presented in the following publication(s):PMID 27264120 Disease type(s): Breast Neoplasm - Breast Cancer - InvasiveClinical Dataset(s) included:NCT00754845-D1 (PMID 27264120): There is one dataset for NCIC-MA.17R's primary publication 27264120. This dataset contains number of major protocol violations, time from diagnosis to randomization, baseline characteristics, hormone receptor status, sites of recurrence, survival, toxicity, stratification factors, cause of death, and QOL data.You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

  Study phs004248

• Somatic Evolution in Li-Fraumeni Syndrome

  In this study, we used ultradeep duplex sequencing (~15,000× depth) to measure somatic evolution in blood samples from a family of three individuals with Li-Fraumeni Syndrome (LFS) caused by an inherited TP53 pathogenic variant (p.R181H), and compared them to a cohort of unaffected controls using a set of genes related to Clonal Hematopoiesis of Indeterminate Potential (CHIP)/Acute Myeloid Leukemia (AML), as well as a mutagenesis panel designed to examine mutagenic processes. We found that individuals inheriting a single mutated copy of TP53 may experience less positive selection for subsequent TP53 mutations, as evidenced by a deficit of coding TP53 mutations, reduced dN/dS, and low predicted pathogenicity among the TP53 somatic mutations that do occur. However, the overall degree of mutagenesis in genomic regions without strong selection was higher in LFS patients. In addition, we investigated how LFS affects clonal evolution across multiple tissue contexts in one individual carrying p.R181H who succumbed to metastatic esophageal cancer.The data available through dbGaP includes BAM files, MAF files (mutation data), and genomic MUT files (showing per-position depth of sequencing), from ultradeep duplex sequencing of multiple tissues from a LFS patient as well blood samples from family members and controls.

  Study phs004484

• Prostate Cancer Upgrading Reference Set

  This study aimed to investigate clinical, demographic, and molecular features of men diagnosed with low-risk prostate cancer [ISUP Grade Group 1 (GG1)] at biopsy who underwent radical prostatectomy, and for whom an increased tumor grade (ISUP Grade Group 2 or above) was subsequently detected in the resected prostate. This phenomenon is termed upgrading. In collaboration with the Early Detection Research Network (EDRN), a blinded reference set was established to facilitate upgrading biomarker detection and validation. A prospective, multi-institutional, cohort of men with the GG1 prostate cancer and intention to undergo prostatectomy was recruited. Biospecimens (blood, urine) were collected and this biorepository comprises the official EDRN Upgrading Reference Set (URS). Recording of case-control status (case = upgrading at prostatectomy, control = no upgrading at prostatectomy) was coordinated by the Data Management and Coordinating Center (DMCC) of the EDRN, who ensured blinding of all participating researchers. A subset of the reference set (n = 192) was chosen to undergo whole genome sequencing (WGS) for the investigation of a germline genomic biomarker of upgrading. Variant calls from all sequenced URS whole genomes are available through dbGaP, with the exception of one sample for which sequencing was not successful. Among investigated clinical features, prostate-specific antigen (PSA) density and percent of cancer in pre-prostatectomy positive biopsy cores were significantly associated with upgrading. Two polygenic risk score-based biomarkers were computed in the genetic sub-cohort and tested against case-control status. Neither was predictive of upgrading.

  Study phs003670

• Improved Cardiovascular Risk Reduction to Enhance Rural Primary Care (ICARE-BioLINCC)

  Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions.Objectives: To evaluate whether a centralized, remote clinical pharmacy service could improve guideline adherence and secondary measures of cardiovascular risk in primary care offices in rural and small communitiesBackground: More than 2200 Americans die of cardiovascular disease every day. Team-based care and medication therapy management have become useful strategies to reduce gaps in the delivery of guideline-concordant therapy for cardiovascular therapy. Physician offices, especially in rural and smaller communities, lack the resources to implement team-based care with pharmacists who can provide medication therapy management. The ICARE trial developed a physician-pharmacist collaborative model to provide virtual clinical pharmacy services from a central location to 12 family medicine offices in Iowa to evaluate whether a centralized, remote clinical pharmacy service could improve outcomes.Participants: Subject inclusion involved 3 separate processes. First, subjects were required to be an English-speaking male or female over the age of 50 who had been seen in the clinic/practice at least once in the past 24 months. Second, subjects were required to have at least one of the following conditions: uncontrolled diabetes (hemoglobin A1c > 7.5%); low-density lipoprotein cholesterol (LDL-C) > 110 mg/dl for patients with a history of peripheral artery disease, coronary artery disease, stroke, transient ischemic attack, or diabetes, elevated blood pressure with systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg in persons with diabetes or chronic kidney disease, or systolic BP ≥ 150 mmHg or diastolic BP ≥ 90 mm Hg in persons with uncomplicated hypertension. Third, subjects were required to additionally have three or more of the following cardiovascular conditions or risk factors: history of myocardial infarction, coronary artery disease, stroke, transient ischemic attack, atrial fibrillation, peripheral vascular disease/claudication, current smoker, or obesity with BMI > 30.Exclusion criteria included diagnosis of primary pulmonary hypertension, a cancer diagnosis with a life expectancy of less than 2 years, residence in a nursing home or diagnosis of dementia, no telephone access or a hearing impairment that prevented telephone use, or patient had plans to move from the area or transfer care to a different clinic in the next 12 months.In total, there were 302 subjects enrolled in the ICARE trial. Of these, 259 subjects completed the 12-month visit.Design: The study included 11 private physician offices and one Federally Qualified Health Center. Offices were identified from the Iowa Research Network and screened for their ability to conduct the trial, enroll subjects, and meet quality control measures. A Study Coordinator employed in each office identified, screened, and recruited subjects. All subjects and physicians in a given office received either the intervention or usual care.Blood pressure, hemoglobin A1c, and LDL cholesterol were collected at baseline and 12 months regardless of whether the subject had a diagnosis of hypertension, diabetes, or hyperlipidemia. Baseline data were collected on case report forms by Study Coordinators and entered centrally by the research team.Three clinical pharmacy specialists located within the research offices of the principal investigator provided the intervention. Pharmacists were required to have a Doctor of Pharmacy degree and a minimum of one year of clinical residency (or equivalent practice experience). The pharmacists travelled to each intervention office to be introduced to the providers and facilitate team-building before the intervention started. These sessions explored the providers' preferred methods and frequency of communication with the pharmacists based on other telemedicine studies. Pharmacists had access to the baseline data, including BP and laboratory values, which they used to reconcile medications and update the medical records. Pharmacists monitored blood glucose values, BP readings, laboratory values, and potential adverse events from the EMR or from the patient in order to recommend medication changes to the treating medical provider. Interventions for physicians were directed at improving guideline adherence for reducing CV risk and preventive care based on the Guideline Advantage (GA) criteria.Each subject was assigned to one of the three pharmacists to maintain continuity. Subjects were assigned to the pharmacists in the order they were enrolled into the study, independent of medical office. Subjects were primarily contacted by telephone and counseled by the pharmacists about beneficial health behavior changes related to tobacco use, diet, physical activity, and alcohol consumption. Medications and dosages were reconciled. The pharmacists identified problems related to poor disease control, subject misunderstandings, poor medication adherence or failure to receive preventive health services, adverse effects, drug interactions, and cost. Pharmacists provided patient education when problems were identified and developed a plan for follow-up contacts, generally every 1-2 weeks by telephone if there were continuing problems or medication issues. The primary outcome measure was adherence to the GA criteria.Conclusions: There was no improvement in the GA score from baseline to 12 months in the control group. There was a statistically significant improvement in the intervention group in the GA score plus several criteria were significantly better for intervention subjects including appropriate statin therapy, body mass index (BMI) screening and alcohol screening. Only 13.7% of subjects with diabetes had hemoglobin A1c at goal at baseline and this increased to 30.8% and 21.0% in the intervention and control groups, respectively, at 12 months.The improvements in outcomes were modest and not statistically significant, due to higher-than-anticipated baseline guideline adherence and greater inter-office variability than anticipated.

  Study phs004679

• Epigenomics of Neurocognitive Function in Breast Cancer

  This study harnessed the data and biospecimens from the Exercise Program in Cancer and Cognition (EPICC) study (parent study) that collected data on cognitive function, demographics, other symptoms and biospecimens at two time points (T1: enrollment, T2: six months later) within the context of a six-month randomized controlled trial of a moderate intensity aerobic exercise intervention. This study collected genome wide DNA methylation data from T1 and T2 and conducted epigenome-wide association-based analyses to find genes and biological pathways explaining variability in cognitive function and explaining how exercise mitigates cognitive decline. Our initial findings identified cg10331779 near CTNND2 (p-value=9.65×10-9) associated with processing speed and cg25906741 in MLIP (p-value=2.01×10-8) associated with subjectively measured cognitive function. Additionally, differentially methylated regions were identified near SLC6A11, PRKG1/CSTF2T, and FAM3B for processing speed and near PI4KB and SGCE/PEG10 for mental flexibility.

  Study phs003959

• Human GPR15 Deficiency Reveals CD8+ T Regulatory Cell-Macrophage Crosstalk in Intestinal Inflammation

  Inflammatory bowel disease (IBD) causes lifelong suffering from gastrointestinal inflammation and dysfunction with severe complications including colon cancer. The disease is increasing in global prevalence, and current therapies are insufficient, highlighting an urgent need to understand its pathogenic mechanism. We reported multiple patients with GPR15 deficiency which result in severe early-onset IBD. GPR15, a G protein-coupled receptor (GPCR), expressed in immune cells and previously described as an entry co-factor for human and simian immunodeficiency viruses, is a crucial marker and homing receptor for a unique subset of intramucosal GPR15-guided regulatory CD8+ T lymphocytes (CD8+ TIGR). These cells potently kill macrophages that become aggressively activated in response to intestinal damage or disease. Thus, our identification of CD8+ TIGR cells yields new insights into organ-specific immune regulation and potential treatment strategies for IBD.

  Study phs003950

• Combined PDCD1, BRAF and MAP2K7 Inhibition in BRAFV600E Colorectal Cancer: A Phase 2 Trial

  In this study, we evaluated the clinical efficacy of combined PDCD1, BRAF, and MAP2K7 inhibition in metastatic BRAFV600E Colorectal Cancer (CRC) patients (NCT03668431). We performed bulk whole exome sequencing (WXS) and bulk RNA sequencing (RNA-Seq) in 35 pre-treatment tumor biopsies and matching germline for tumor mutational burden (TMB), BM1/BM2 transcriptional subtypes, and consensus molecular subtypes (CMS) analysis, which were previously reported to affect prognosis and response to therapy (PMIDs: 32047001, 27354468, and 26457756). Analysis of bulk data showed that TMB, BM1/BM2 subtypes, and CMS did not correlate with clinical response in this study. Analysis of single cell RNA sequencing (scRNA-Seq) data of tumor epithelial cells from 23 paired day 0 and day 15 tumor biopsies revealed greater induction of tumor cell-intrinsic immune programs and more complete MAPK inhibition in patients with better clinical outcome.

  Study phs003178

• Childhood Cancer Data Initiative (CCDI): Single-Cell Atlas of NF1 Nerve Sheath Tumors

  The worst outcome of NF1 is the development of the aggressive and highly metastatic malignant peripheral nerve sheath tumors (MPNST), which transform from benign plexiform neurofibroma (PN) and lack effective treatment. In this study, we performed single-cell RNA sequencing of 63 clinically annotated NF1-associated peripheral nerve sheath tumors, including 24 PN, 34 premalignant atypical neurofibromas, and 5 MPNSTs. These results improve the ability of identifying high-risk neurofibromas and provide a unique opportunity for early detection of MPNST.

  Study phs003519

• Single Cell RNA-Sequencing of BCG Naive and Recurrent Non-Muscle Invasive Bladder Cancer Reveals a CD6/ALCAM-Mediated Immune-Suppressive Pathway

  Non-muscle invasive bladder cancer (NMIBC) represents 70–80% patients with newly diagnosed bladder cancer, and Bacillus Calmette-Guerin (BCG) remains a cornerstone treatment for intermediate- and high-risk NMIBC to prevent disease recurrence and progression. However, a significant number of patients experience recurrence after their first course of BCG, posing significant challenges in the management of the disease. We conducted single cell RNA sequencing (scRNA-Seq) on freshly collected NMIBC samples, distinguishing between those naive to BCG treatment and those that recurred post-BCG treatment. We observed a clear activation of inflammatory pathways across cell types during recurrence, but these were not associated with canonical immune checkpoint or T cell exhaustion phenotypes. Analysis of cell-to-cell communication revealed enhanced interactions between T cells and urothelial cells in BCG-recurrence, predominantly modulated by CD6 and activated leukocyte cell adhesion molecule (ALCAM). Furthermore, we found CD6hi T cells to be immunosuppressed and enriched in recurrent samples, suggesting a potential role for CD6 as an immune evasion signal in NMIBC.

  Study phs003742