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Molecular alterations associated with improved outcome in patients with glioblastoma treated with Tumor-Treating Fields
BACKGROUND: The genomic and overall biologic landscape of glioblastoma (GB) has become clearer over the past 2 decades, as predictive and prognostic biomarkers of both de novo and transformed forms of GB have been identified. The oral chemotherapeutic agent temozolomide (TMZ) has been integral to st...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9270729/ https://www.ncbi.nlm.nih.gov/pubmed/35821680 http://dx.doi.org/10.1093/noajnl/vdac096 |
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author | Pandey, Manjari Xiu, Joanne Mittal, Sandeep Zeng, Jia Saul, Michelle Kesari, Santosh Azadi, Amir Newton, Herbert Deniz, Karina Ladner, Katherine Sumrall, Ashley Korn, W Michael Lou, Emil |
author_facet | Pandey, Manjari Xiu, Joanne Mittal, Sandeep Zeng, Jia Saul, Michelle Kesari, Santosh Azadi, Amir Newton, Herbert Deniz, Karina Ladner, Katherine Sumrall, Ashley Korn, W Michael Lou, Emil |
author_sort | Pandey, Manjari |
collection | PubMed |
description | BACKGROUND: The genomic and overall biologic landscape of glioblastoma (GB) has become clearer over the past 2 decades, as predictive and prognostic biomarkers of both de novo and transformed forms of GB have been identified. The oral chemotherapeutic agent temozolomide (TMZ) has been integral to standard-of-care treatment for nearly 2 decades. More recently, the use of non-pharmacologic interventions, such as application of alternating electric fields, called Tumor-Treating Fields (TTFields), has emerged as a complementary treatment option that increases overall survival (OS) in patients with newly diagnosed GB. The genomic factors associated with improved or lack of response to TTFields are unknown. METHODS: We performed comprehensive genomic analysis of GB tumors resected from 55 patients who went on to receive treatment using TTFields, and compared results to 57 patients who received standard treatment without TTFields. RESULTS: We found that molecular driver alterations in NF1, and wild-type PIK3CA and epidermal growth factor receptor (EGFR), were associated with increased benefit from TTFields as measured by progression-free survival (PFS) and OS. There were no differences when stratified by TP53 status. When NF1, PIK3CA, and EGFR status were combined as a Molecular Survival Score, the combination of the 3 factors significantly correlated with improved OS and PFS in TTFields-treated patients compared to patients not treated with TTFields. CONCLUSIONS: These results shed light on potential driver and passenger mutations in GB that can be validated as predictive biomarkers of response to TTFields treatment, and provide an objective and testable genomic-based approach to assessing response. |
format | Online Article Text |
id | pubmed-9270729 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-92707292022-07-11 Molecular alterations associated with improved outcome in patients with glioblastoma treated with Tumor-Treating Fields Pandey, Manjari Xiu, Joanne Mittal, Sandeep Zeng, Jia Saul, Michelle Kesari, Santosh Azadi, Amir Newton, Herbert Deniz, Karina Ladner, Katherine Sumrall, Ashley Korn, W Michael Lou, Emil Neurooncol Adv Basic and Translational Investigations BACKGROUND: The genomic and overall biologic landscape of glioblastoma (GB) has become clearer over the past 2 decades, as predictive and prognostic biomarkers of both de novo and transformed forms of GB have been identified. The oral chemotherapeutic agent temozolomide (TMZ) has been integral to standard-of-care treatment for nearly 2 decades. More recently, the use of non-pharmacologic interventions, such as application of alternating electric fields, called Tumor-Treating Fields (TTFields), has emerged as a complementary treatment option that increases overall survival (OS) in patients with newly diagnosed GB. The genomic factors associated with improved or lack of response to TTFields are unknown. METHODS: We performed comprehensive genomic analysis of GB tumors resected from 55 patients who went on to receive treatment using TTFields, and compared results to 57 patients who received standard treatment without TTFields. RESULTS: We found that molecular driver alterations in NF1, and wild-type PIK3CA and epidermal growth factor receptor (EGFR), were associated with increased benefit from TTFields as measured by progression-free survival (PFS) and OS. There were no differences when stratified by TP53 status. When NF1, PIK3CA, and EGFR status were combined as a Molecular Survival Score, the combination of the 3 factors significantly correlated with improved OS and PFS in TTFields-treated patients compared to patients not treated with TTFields. CONCLUSIONS: These results shed light on potential driver and passenger mutations in GB that can be validated as predictive biomarkers of response to TTFields treatment, and provide an objective and testable genomic-based approach to assessing response. Oxford University Press 2022-06-21 /pmc/articles/PMC9270729/ /pubmed/35821680 http://dx.doi.org/10.1093/noajnl/vdac096 Text en © The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Basic and Translational Investigations Pandey, Manjari Xiu, Joanne Mittal, Sandeep Zeng, Jia Saul, Michelle Kesari, Santosh Azadi, Amir Newton, Herbert Deniz, Karina Ladner, Katherine Sumrall, Ashley Korn, W Michael Lou, Emil Molecular alterations associated with improved outcome in patients with glioblastoma treated with Tumor-Treating Fields |
title | Molecular alterations associated with improved outcome in patients with glioblastoma treated with Tumor-Treating Fields |
title_full | Molecular alterations associated with improved outcome in patients with glioblastoma treated with Tumor-Treating Fields |
title_fullStr | Molecular alterations associated with improved outcome in patients with glioblastoma treated with Tumor-Treating Fields |
title_full_unstemmed | Molecular alterations associated with improved outcome in patients with glioblastoma treated with Tumor-Treating Fields |
title_short | Molecular alterations associated with improved outcome in patients with glioblastoma treated with Tumor-Treating Fields |
title_sort | molecular alterations associated with improved outcome in patients with glioblastoma treated with tumor-treating fields |
topic | Basic and Translational Investigations |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9270729/ https://www.ncbi.nlm.nih.gov/pubmed/35821680 http://dx.doi.org/10.1093/noajnl/vdac096 |
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