Genomic profiling of esophagogastric (EG) tumors in clinical practice.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 57-57 ◽  
Author(s):  
Jamie Cathleen Riches ◽  
Nikolaus Schultz ◽  
Geoffrey Yuyat Ku ◽  
Tooba Imtiaz ◽  
David Paul Kelsen ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Cancer Genomics ◽  
Routine Clinical Practice ◽  
The Cancer Genome Atlas ◽  
Therapeutic Interventions ◽  
Genomic Alteration ◽  
Molecular Testing ◽  
Genomic Profiling ◽  
Cell Cycle Regulators ◽  
Web Resource

57 Background: Esophagogastric (EG) cancer is a phenotypically heterogeneous disease. The Cancer Genome Atlas (TCGA) identified four distinct subsets: 1) Epstein Barr Virus (EBV) tumors with PIK3CA mutations, PD-L1/2 amplification (amp), 2) Tumors with Microsatellite instability (MSI-H), 3) chromosomally unstable (CIN) tumors with frequent amplifications, 4) chromosomally stable/diffuse type tumors with RHOA mutations. We explore the utility/feasibility of genomic profiling of EG tumors in routine clinical practice. Methods: Patients (pts) with metastatic EG adenocarcinoma undergoing treatment at MSKCC were consented for molecular testing under institutional protocol. Archival formalin fixed paraffin embedded (FFPE) samples were analyzed using an on-site 341 cancer-associated gene bait capture, next generation sequencing (NGS) assay. Results: Of 70 analyzed EG tumors, 66 (94%) harbored at least one genomic alteration, the most frequent being TP53 mutations (77%), HER2 amp (30%) and EGFR amp (10%). Alterations in PI3K/AKT/mTOR (9%) and G1-S1 cell cycle regulators (CDK12 (11%), CDKN2A (10%)) were also observed. A comparison with the TCGA results revealed an over-representation of the CIN subtype (65% vs 50% in TCGA). We found very few EBV or MSI tumors (3% each), with the remaining 29% being chromosomally stable. Data is reported in the clinical medical record and maintained in the MSKCC-internal cBioPortal for Cancer Genomics ( http://cbioportal.org ) (Gao, et al.). The portal is a web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data and when available, to link these data to therapeutic interventions and clinical outcomes. Conclusions: CIN tumors with frequent amplifications represent majority of metastatic EG cancer at our institution. Optimal development of target-specific therapy for EG tumors will require genomic characterization. Comprehensive molecular profiling is feasible in routine clinical practice and has created a roadmap for pt stratification and genome-guided trial development.

scholarly journals Comprehensive genomic profiling in routine clinical practice leads to a low rate of benefit from genotype-directed therapy

BMC Cancer ◽  
2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Talal Hilal ◽  
Mary Nakazawa ◽  
Jacob Hodskins ◽  
John L. Villano ◽  
Aju Mathew ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Routine Clinical Practice ◽  
Genomic Profiling ◽  
Comprehensive Genomic Profiling ◽  
Low Rate

CGE19-064: Patient Access to Comprehensive Genomic Profiling for Hematologic Malignancies: Analysis of the Payer Coverage Landscape and Results of Testing in 3,600 Patients

2019 ◽  
Vol 17 (3.5) ◽  
pp. CGE19-064
Author(s):  
Kristi Maxwell ◽  
Eric A. Severson ◽  
Meagan Montesion ◽  
Ingrid Marino ◽  
Rachel Anhorn ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Clinical Utility ◽  
Triple Negative ◽  
Standard Of Care ◽  
Hematologic Malignancies ◽  
Molecular Testing ◽  
Genomic Profiling ◽  
Patient Access ◽  
Nccn Guidelines ◽  
Comprehensive Genomic Profiling

Comprehensive genomic profiling (CGP) for patients with advanced solid tumors is on the trajectory of becoming standard of care through incorporation into clinical practice, professional society guidelines, availability of an FDA-approved assay, and a national coverage determination from Medicare. For hematologic malignancies, the clinical utility of CGP can be diagnostic, prognostic, or predictive depending on the type of malignancy. Molecular testing has been standard of care for many years for hematologic malignancies, and payer coverage of the CGP approach must now be considered to keep pace with advances in the field of hematology-oncology. Based on American Medical Association CPT coding definitions, molecular testing for hematologic malignancies is categorized as testing for individual genes and gene panels of 5–50 genes or >50 genes. Our review of payer coverage policies from the Policy Reporter database in October 2018 demonstrated that payer coverage for >50 genes in hematologic malignancies is limited. As an example of coverage limitations, a recently updated Medicare Local Coverage Determination limits coverage to 50 genes or less. Coverage decisions such as these are being made during a time of increasing demand for an expanded approach. Data from the Foundation Medicine, Inc. database shows that as of April 2018, over 3,600 patients with AML, MDS, and MPN have undergone clinical testing with FoundationOne Heme, a CGP assay for hematologic malignancies. In an analysis of over 1,300 AML cases tested with FoundationOne Heme, 62% had an alteration that is included in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), and 91% had a clinically relevant alteration identified that could inform diagnosis, prognosis, or treatment selection. In an analysis of over 1,300 MDS cases tested, 70% had at least one clinically relevant alteration identified. In an analysis of over 200 MPN cases tested, 48% were triple negative for CALR, JAK2, and MPL, and of those triple negative cases, 55% had another clinically relevant alteration. These data demonstrate that FoundationOne Heme is a clinically important assay for patients with hematologic malignancies including AML, MDS, and MPN, and stakeholders within the system must now come together to further refine the clinical utility, improve payer coverage, and ensure patient access to this impactful testing as the field advances.

scholarly journals Assessment of Luminal and Basal Phenotypes in Bladder Cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Charles C. Guo ◽  
Jolanta Bondaruk ◽  
Hui Yao ◽  
Ziqiao Wang ◽  
Li Zhang ◽  
...  
Keyword(s):  
Primary Care ◽  
Bladder Cancer ◽  
Clinical Practice ◽  
Molecular Subtypes ◽  
Routine Clinical Practice ◽  
Cancer Center ◽  
Genomic Profiling ◽  
Protein Expressions ◽  
Cancer Tumor ◽  
Md Anderson

Abstract Genomic profiling studies have demonstrated that bladder cancer can be divided into two molecular subtypes referred to as luminal and basal with distinct clinical behaviors and sensitivities to frontline chemotherapy. We analyzed the mRNA expressions of signature luminal and basal genes in bladder cancer tumor samples from publicly available and MD Anderson Cancer Center cohorts. We developed a quantitative classifier referred to as basal to luminal transition (BLT) score which identified the molecular subtypes of bladder cancer with 80–94% sensitivity and 83–93% specificity. In order to facilitate molecular subtyping of bladder cancer in primary care centers, we analyzed the protein expressions of signature luminal (GATA3) and basal (KRT5/6) markers by immunohistochemistry, which identified molecular subtypes in over 80% of the cases. In conclusion, we provide a tool for assessment of molecular subtypes of bladder cancer in routine clinical practice.

scholarly journals Impact and Diagnostic Gaps of Comprehensive Genomic Profiling in Real-World Clinical Practice

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1156
Author(s):  
Aditi P. Singh ◽  
Elaine Shum ◽  
Lakshmi Rajdev ◽  
Haiying Cheng ◽  
Sanjay Goel ◽  
...  
Keyword(s):  
Academic Community ◽  
Clinical Impact ◽  
Cancer Center ◽  
Genomic Alteration ◽  
Molecular Testing ◽  
Genomic Profiling ◽  
National Guidelines ◽  
Genomic Alterations ◽  
Cancer Management ◽  
Comprehensive Genomic Profiling

Purpose: next-generation sequencing based comprehensive genomic profiling (CGP) is becoming common practice. Although numerous studies have shown its feasibility to identify actionable genomic alterations in most patients, its clinical impact as part of routine management across all cancers in the community remains unknown. Methods: we conducted a retrospective study of all patients that underwent CGP as part of routine cancer management from January 2013 to June 2017 at an academic community-based NCI-designated cancer center. CGP was done in addition to established first tier reflex molecular testing as per national guidelines (e.g., EGFR/ALK for non-small cell lung cancer (NSCLC) and extended-RAS for colorectal cancer). Results: 349 tests were sent for CGP from 333 patients and 95% had at least one actionable genomic alteration reported. According to the reported results, 23.2% had a Food and Drug Administration (FDA) approved therapy available, 61.3% had an off-label therapy available and 77.9% were potentially eligible for a clinical trial. Treatment recommendations were also reviewed within the OncoKB database and 47% of them were not clinically validated therapies. The CGP results led to treatment change in only 35 patients (10%), most commonly in NSCLC. Nineteen of these patients (54% of those treated and 5% of total) had documented clinical benefit with targeted therapy. Conclusion: we demonstrate that routine use of CGP in the community across all cancer types detects potentially actionable genomic alterations in a majority of patients, however has modest clinical impact enriched in the NSCLC subset.

scholarly journals Unlocking Access to Broad Molecular Profiling: Benefits, Barriers, and Policy Solutions

2021 ◽  
pp. 1-10
Author(s):  
David M. Thomas ◽  
Joanne M. Hackett ◽  
Stjepko Plestina
Keyword(s):  
Clinical Practice ◽  
Individual Variability ◽  
Routine Clinical Practice ◽  
Healthcare Personnel ◽  
Genomic Profiling ◽  
Published Evidence ◽  
Regulatory Standards ◽  
Comprehensive Genomic Profiling ◽  
Potential Benefits ◽  
Policy Proposals

<b><i>Objectives:</i></b> “Personalized healthcare” is generating new approaches to disease management by considering inter-individual variability in genes, environment, and lifestyle. Technologies such as comprehensive genomic profiling (CGP) are drivers of this shift. Here, we address the significant hurdles to the equitable implementation of CGP into routine clinical practice. <b><i>Methods:</i></b> This article draws on published evidence on the value of genomic profiling, as well as interviews with nine academic and clinical experts from six different countries to validate findings and test policy proposals for reforms. <b><i>Results:</i></b> The potential benefits of CGP extend beyond direct patient outcomes, to healthcare systems with societal and economic impacts. Among key barriers impeding integration into routine clinical practice are the lack of infrastructure to ensure reliable clinical testing and the limited understanding of genomics among healthcare personnel. In addition, the absence of health economic evidence supporting broader use of CGP is creating concerns for payers regarding the systemic benefits and affordability of this technology. <b><i>Conclusion:</i></b> Policy proposals that aim to improve equitable patient access to CGP will need to consider new funding models, health technology assessment processes that capture both patient and systemic benefits, and appropriate regulatory standards to determine the quality of genomic profiling tests.

scholarly journals ExSurv: A Web Resource for Prognostic Analyses of Exons across Human Cancers Using Clinical Transcriptomes

2016 ◽  
Vol 15s2 ◽  
pp. CIN.S39367 ◽  
Author(s):  
Seyedsasan Hashemikhabir ◽  
Gungor Budak ◽  
Sarath Chandra Janga
Keyword(s):  
Biomarker Discovery ◽  
Cancer Genomics ◽  
Expression Profiles ◽  
Treatment Options ◽  
The Cancer Genome Atlas ◽  
Cancer Type ◽  
Biomedical Sciences ◽  
Regulatory Pathways ◽  
Web Resource ◽  
Cancer Types

Survival analysis in biomedical sciences is generally performed by correlating the levels of cellular components with patients’ clinical features as a common practice in prognostic biomarker discovery. While the common and primary focus of such analysis in cancer genomics so far has been to identify the potential prognostic genes, alternative splicing – a posttranscriptional regulatory mechanism that affects the functional form of a protein due to inclusion or exclusion of individual exons giving rise to alternative protein products, has increasingly gained attention due to the prevalence of splicing aberrations in cancer transcriptomes. Hence, uncovering the potential prognostic exons can not only help in rationally designing exon-specific therapeutics but also increase specificity toward more personalized treatment options. To address this gap and to provide a platform for rational identification of prognostic exons from cancer transcriptomes, we developed ExSurv ( https://exsurv.soic.iupui.edu ), a web-based platform for predicting the survival contribution of all annotated exons in the human genome using RNA sequencing-based expression profiles for cancer samples from four cancer types available from The Cancer Genome Atlas. ExSurv enables users to search for a gene of interest and shows survival probabilities for all the exons associated with a gene and found to be significant at the chosen threshold. ExSurv also includes raw expression values across the cancer cohort as well as the survival plots for prognostic exons. Our analysis of the resulting prognostic exons across four cancer types revealed that most of the survival-associated exons are unique to a cancer type with few processes such as cell adhesion, carboxylic, fatty acid metabolism, and regulation of T-cell signaling common across cancer types, possibly suggesting significant differences in the posttranscriptional regulatory pathways contributing to prognosis.

Diagnosis and Management of Cardiomyopathies – A Focus on Genetics, Cardiac Magnetic Resonance and Clinical Features

2011 ◽  
Vol 7 (3) ◽  
pp. 225
Author(s):  
Gianfranco Sinagra ◽  
Michele Moretti ◽  
Giancarlo Vitrella ◽  
Marco Merlo ◽  
Rossana Bussani ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Cardiac Magnetic Resonance ◽  
Magnetic Resonance ◽  
Imaging Techniques ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Routine Clinical Practice ◽  
Clinical Approach ◽  
Diagnosis And Management ◽  
Made In

In recent years, outstanding progress has been made in the diagnosis and treatment of cardiomyopathies. Genetics is emerging as a primary point in the diagnosis and management of these diseases. However, molecular genetic analyses are not yet included in routine clinical practice, mainly because of their elevated costs and execution time. A patient-based and patient-oriented clinical approach, coupled with new imaging techniques such as cardiac magnetic resonance, can be of great help in selecting patients for molecular genetic analysis and is crucial for a better characterisation of these diseases. This article will specifically address clinical, magnetic resonance and genetic aspects of the diagnosis and management of cardiomyopathies.

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