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EPCT-21. NEXT-GENERATION SEQUENCING OF CEREBROSPINAL FLUID FOR CLINICAL MOLECULAR DIAGNOSTICS IN ADOLESCENT AND YOUNG ADULT (AYA) BRAIN TUMOR PATIENTS

PURPOSE: Pediatric central nervous system tumors remain a leading cause of cancer-related death in children and adolescents. Safe sampling of tumor tissue for diagnostic purposes may be challenging. Subclinical detection of disease prior to clinical or imaging progression may provide opportunity for...

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Autores principales: Miller, Alexandra, Szalontay, Luca, Bouvier, Nancy, Ahmed, Hamza, Hill, Katherine, Rafailov, Johnathan, Lee, Alex, Rodriguez-Sanchez, Irene, Yildirim, Onur, Patel, Arti, Bale, Tejus, Benayed, Ryma, Arcila, Maria, Donzelli, Maria, Dunkel, Ira, Gilheeney, Stephen, Khakoo, Yasmin, Kramer, Kim, Sait, Sameer F, Greenfield, Jeffrey, Souweidane, Mark, Haque, Sofia, Mauguen, Audrey, Berger, Michael, Mellinghoff, Ingo, Karajannis, Matthias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168217/
http://dx.doi.org/10.1093/neuonc/noab090.207
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author Miller, Alexandra
Szalontay, Luca
Bouvier, Nancy
Ahmed, Hamza
Hill, Katherine
Rafailov, Johnathan
Lee, Alex
Rodriguez-Sanchez, Irene
Yildirim, Onur
Patel, Arti
Bale, Tejus
Benayed, Ryma
Arcila, Maria
Donzelli, Maria
Dunkel, Ira
Gilheeney, Stephen
Khakoo, Yasmin
Kramer, Kim
Sait, Sameer F
Greenfield, Jeffrey
Souweidane, Mark
Haque, Sofia
Mauguen, Audrey
Berger, Michael
Mellinghoff, Ingo
Karajannis, Matthias
author_facet Miller, Alexandra
Szalontay, Luca
Bouvier, Nancy
Ahmed, Hamza
Hill, Katherine
Rafailov, Johnathan
Lee, Alex
Rodriguez-Sanchez, Irene
Yildirim, Onur
Patel, Arti
Bale, Tejus
Benayed, Ryma
Arcila, Maria
Donzelli, Maria
Dunkel, Ira
Gilheeney, Stephen
Khakoo, Yasmin
Kramer, Kim
Sait, Sameer F
Greenfield, Jeffrey
Souweidane, Mark
Haque, Sofia
Mauguen, Audrey
Berger, Michael
Mellinghoff, Ingo
Karajannis, Matthias
author_sort Miller, Alexandra
collection PubMed
description PURPOSE: Pediatric central nervous system tumors remain a leading cause of cancer-related death in children and adolescents. Safe sampling of tumor tissue for diagnostic purposes may be challenging. Subclinical detection of disease prior to clinical or imaging progression may provide opportunity for earlier intervention and ultimately improve overall survival. Additionally, our understanding of molecular evolution in response to therapy remains limited, given the rarity of serial sampling of tumor tissue. METHODS: We report our experience with minimally invasive molecular diagnostics using a validated next generation sequencing assay for sequencing of cerebrospinal fluid (CSF) cell-free DNA (cfDNA) obtained at the time of surgery, by intraventricular catheter or lumbar puncture. All CSF samples were collected as part of clinical care, and results reported to both clinicians and patients/families. RESULTS: We analyzed 64 CSF samples from 45 pediatric and adolescent and young adult (AYA) patients (pediatric=25; AYA=20) with primary and recurrent brain tumors across 12 histopathological subtypes including high-grade glioma (n=10), medulloblastoma (n=10), pineoblastoma (n=5), low grade glioma (n=4), diffuse leptomeningeal glioneuronal tumor (DLGNT) (n=4), metastatic retinoblastoma (n=4), ependymoma (n=3), and other (n=5). Somatic alterations were detected in 28/64 samples (44.4%) and in at least one sample per unique patient in 22/45 patients (48.8%). CSF cfDNA positivity was strongly associated with the presence of disseminated disease at the time of collection (86.3%). No association was seen between CSF cfDNA positivity and the timing of CSF collection during the patient’s disease course. CONCLUSION: We identified four general categories where CSF cfDNA testing provided additional relevant diagnostic, prognostic, and/or therapeutic information, impacting clinical assessment and decision making: 1) diagnosis; 2) identification of actionable alterations; 3) track response to therapy; and 4) monitoring tumor evolution. Our findings support broader implementation of clinical CSF cfDNA testing in this population that may improve care.
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spelling pubmed-81682172021-06-02 EPCT-21. NEXT-GENERATION SEQUENCING OF CEREBROSPINAL FLUID FOR CLINICAL MOLECULAR DIAGNOSTICS IN ADOLESCENT AND YOUNG ADULT (AYA) BRAIN TUMOR PATIENTS Miller, Alexandra Szalontay, Luca Bouvier, Nancy Ahmed, Hamza Hill, Katherine Rafailov, Johnathan Lee, Alex Rodriguez-Sanchez, Irene Yildirim, Onur Patel, Arti Bale, Tejus Benayed, Ryma Arcila, Maria Donzelli, Maria Dunkel, Ira Gilheeney, Stephen Khakoo, Yasmin Kramer, Kim Sait, Sameer F Greenfield, Jeffrey Souweidane, Mark Haque, Sofia Mauguen, Audrey Berger, Michael Mellinghoff, Ingo Karajannis, Matthias Neuro Oncol Translational/Early Phase Clinical Trials PURPOSE: Pediatric central nervous system tumors remain a leading cause of cancer-related death in children and adolescents. Safe sampling of tumor tissue for diagnostic purposes may be challenging. Subclinical detection of disease prior to clinical or imaging progression may provide opportunity for earlier intervention and ultimately improve overall survival. Additionally, our understanding of molecular evolution in response to therapy remains limited, given the rarity of serial sampling of tumor tissue. METHODS: We report our experience with minimally invasive molecular diagnostics using a validated next generation sequencing assay for sequencing of cerebrospinal fluid (CSF) cell-free DNA (cfDNA) obtained at the time of surgery, by intraventricular catheter or lumbar puncture. All CSF samples were collected as part of clinical care, and results reported to both clinicians and patients/families. RESULTS: We analyzed 64 CSF samples from 45 pediatric and adolescent and young adult (AYA) patients (pediatric=25; AYA=20) with primary and recurrent brain tumors across 12 histopathological subtypes including high-grade glioma (n=10), medulloblastoma (n=10), pineoblastoma (n=5), low grade glioma (n=4), diffuse leptomeningeal glioneuronal tumor (DLGNT) (n=4), metastatic retinoblastoma (n=4), ependymoma (n=3), and other (n=5). Somatic alterations were detected in 28/64 samples (44.4%) and in at least one sample per unique patient in 22/45 patients (48.8%). CSF cfDNA positivity was strongly associated with the presence of disseminated disease at the time of collection (86.3%). No association was seen between CSF cfDNA positivity and the timing of CSF collection during the patient’s disease course. CONCLUSION: We identified four general categories where CSF cfDNA testing provided additional relevant diagnostic, prognostic, and/or therapeutic information, impacting clinical assessment and decision making: 1) diagnosis; 2) identification of actionable alterations; 3) track response to therapy; and 4) monitoring tumor evolution. Our findings support broader implementation of clinical CSF cfDNA testing in this population that may improve care. Oxford University Press 2021-06-01 /pmc/articles/PMC8168217/ http://dx.doi.org/10.1093/neuonc/noab090.207 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Translational/Early Phase Clinical Trials
Miller, Alexandra
Szalontay, Luca
Bouvier, Nancy
Ahmed, Hamza
Hill, Katherine
Rafailov, Johnathan
Lee, Alex
Rodriguez-Sanchez, Irene
Yildirim, Onur
Patel, Arti
Bale, Tejus
Benayed, Ryma
Arcila, Maria
Donzelli, Maria
Dunkel, Ira
Gilheeney, Stephen
Khakoo, Yasmin
Kramer, Kim
Sait, Sameer F
Greenfield, Jeffrey
Souweidane, Mark
Haque, Sofia
Mauguen, Audrey
Berger, Michael
Mellinghoff, Ingo
Karajannis, Matthias
EPCT-21. NEXT-GENERATION SEQUENCING OF CEREBROSPINAL FLUID FOR CLINICAL MOLECULAR DIAGNOSTICS IN ADOLESCENT AND YOUNG ADULT (AYA) BRAIN TUMOR PATIENTS
title EPCT-21. NEXT-GENERATION SEQUENCING OF CEREBROSPINAL FLUID FOR CLINICAL MOLECULAR DIAGNOSTICS IN ADOLESCENT AND YOUNG ADULT (AYA) BRAIN TUMOR PATIENTS
title_full EPCT-21. NEXT-GENERATION SEQUENCING OF CEREBROSPINAL FLUID FOR CLINICAL MOLECULAR DIAGNOSTICS IN ADOLESCENT AND YOUNG ADULT (AYA) BRAIN TUMOR PATIENTS
title_fullStr EPCT-21. NEXT-GENERATION SEQUENCING OF CEREBROSPINAL FLUID FOR CLINICAL MOLECULAR DIAGNOSTICS IN ADOLESCENT AND YOUNG ADULT (AYA) BRAIN TUMOR PATIENTS
title_full_unstemmed EPCT-21. NEXT-GENERATION SEQUENCING OF CEREBROSPINAL FLUID FOR CLINICAL MOLECULAR DIAGNOSTICS IN ADOLESCENT AND YOUNG ADULT (AYA) BRAIN TUMOR PATIENTS
title_short EPCT-21. NEXT-GENERATION SEQUENCING OF CEREBROSPINAL FLUID FOR CLINICAL MOLECULAR DIAGNOSTICS IN ADOLESCENT AND YOUNG ADULT (AYA) BRAIN TUMOR PATIENTS
title_sort epct-21. next-generation sequencing of cerebrospinal fluid for clinical molecular diagnostics in adolescent and young adult (aya) brain tumor patients
topic Translational/Early Phase Clinical Trials
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168217/
http://dx.doi.org/10.1093/neuonc/noab090.207
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