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., / for non-small cell lung cancer (NSCLC) and extended- 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.
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http://dx.doi.org/10.3390/cancers12051156 | DOI Listing |
Prenat Diagn
January 2025
Department of Bioethics, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Previous studies suggest that NIPT's implementation differed widely across countries but offer limited insight into what shaped these differences. To address this gap, we conducted an in-depth analysis of how NIPT was incorporated into prenatal care in the US, the Netherlands, and Japan-countries with similar economic status-to identify actionable lessons. We conducted an integrative literature review on the process of introducing and implementing NIPT, stakeholders' roles, documented considerations in the decision to introduce NIPT, implementation choices, and NIPT uptake.
View Article and Find Full Text PDFJ Immunother Precis Oncol
February 2025
Medical Affairs Division, Roche Products India Pvt Ltd, New Delhi, India.
Biologic factors limiting responsiveness to matched targeted therapies include genomic heterogeneity and complexity. Advanced tumors with unique molecular profiles can be studied by comprehensive genomic profiling (CGP) and enhance patient outcomes using principles of precision medicine. The clinical utility of CGP across all cancer types and different therapeutic interventions using overall survival (OS) and progression-free survival (PFS) data was studied in this systematic literature review.
View Article and Find Full Text PDFNeurol Genet
December 2024
From the Division of Neurology (A.H.T., S.-Y.L.), Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Programa de Pós-Graduação em Ciências Médicas da Universidade Federal do Rio Grande do Sul (P.S.-A.), Clínica Santa María, Santiago, Chile; Departamento de Farmacologia (A.F.S.S.), Universidade Federal do Rio Grande do Sul; Serviço de Neurologia (A.F.S.S.), Hospital de Clínicas de Porto Alegre, Brazil; Institute of Neurogenetics (H.M., M.L.D., C.K.), University of Lübeck, Germany; Department of Biomedical Science (A.A.-A.), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; The Michael J. Fox Foundation for Parkinson's Research (J.S., B.F.), New York; Department of Medical and Molecular Genetics (C.E.W.), Indiana University, Indianapolis; Department of Neuroscience and Brain Health (M.L.D.), Metropolitan Medical Center, Manila, Philippines; Centre for Preventive Neurology (S.D., M.T.P., A.J.N.), Wolfson Institute of Population Health, Queen Mary University of London, United Kingdom; Unidad de Trastornos del Movimiento (M.T.P.), Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain; Laboratory of Neurogenetics (M.B.M.), National Institute on Aging, National Institutes of Health, Bethesda, MD; Department of Clinical and Movement Neurosciences (M.B.M., H.R.M.), UCL Queen Square Institute of Neurology, University College London, United Kingdom; Department of Neurology (R.N.A.), Columbia University Irving Medical Center, New York; Movement Disorders Division (R.N.A.), Neurological Institute, Tel Aviv Sourasky Medical Center and Tel Aviv School of Medicine, Tel Aviv University, Israel; Molecular Medicine Laboratory and Neurology Department (K.R.K.), Concord Clinical School, Concord Repatriation General Hospital, The University of Sydney; Translational Neurogenomics Group (K.R.K.), Genomic and Inherited Disease Program, Garvan Institute of Medical Research; and St Vincent's Healthcare Campus (K.R.K.), Faculty of Medicine, UNSW Sydney, Darlinghurst, New South Wales, Australia.
Background And Objectives: In the era of precision medicine, genetic test results have become increasingly relevant in the care of patients with Parkinson disease (PD). While large research consortia are performing widespread research genetic testing to accelerate discoveries, debate continues about whether, and to what extent, the results should be returned to patients. Ethically, it is imperative to keep participants informed, especially when findings are potentially actionable.
View Article and Find Full Text PDFBMC Bioinformatics
January 2025
Technology Park of Sardinia, Bioecopest Srl, SP 55 Km 8.400, Tramariglio, Alghero, SS, Italy.
Background: The increasing availability of sequenced genomes has enabled comparative analyses of various organisms. Numerous tools and online platforms have been developed for this purpose, facilitating the identification of unique features within selected organisms. However, choosing the most appropriate tools can be unclear during the initial stages of analysis, often requiring multiple attempts to match the specific characteristics of the data.
View Article and Find Full Text PDFDespite rapid advances in genomic sequencing, most rare genetic variants remain insufficiently characterized for clinical use, limiting the potential of personalized medicine. When classifying whether a variant is pathogenic, clinical labs adhere to diagnostic guidelines that comprehensively evaluate many forms of evidence including case data, computational predictions, and functional screening. While a substantial amount of clinical evidence has been developed for these variants, the majority cannot be definitively classified as 'pathogenic' or 'benign', and thus persist as 'Variants of Uncertain Significance' (VUS).
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