Glioblastoma as an age-related neurological disorder in adults

Miri Kim; Erik Ladomersky; Andreas Mozny; Masha Kocherginsky; Kaitlyn O'shea; Zachary Z. Reinstein; Lijie Zhai; April Bell; Kristen L. Lauing; Lakshmi Bollu; Erik Rabin; Karan Dixit; Priya Kumthekar; Leonidas C. Platanias; Lifang Hou; Yinan Zheng; Jennifer Wu; Bin Zhang; Maya Hrachova; Sarah A. Merrill; Maciej M. Mrugala; Vikram C. Prabhu; Craig Horbinski; Charles David James; Bakhtiar Yamini; Quinn T. Ostrom; Margaret O. Johnson; David A. Reardon; Rimas V. Lukas; Derek A. Wainwright

doi:10.1093/noajnl/vdab125

Glioblastoma as an age-related neurological disorder in adults

Miri Kim, Erik Ladomersky, Andreas Mozny, Masha Kocherginsky, Kaitlyn O'shea, Zachary Z. Reinstein, Lijie Zhai, April Bell, Kristen L. Lauing, Lakshmi Bollu, Erik Rabin, Karan Dixit, Priya Kumthekar, Leonidas C. Platanias, Lifang Hou, Yinan Zheng, Jennifer Wu, Bin Zhang, Maya Hrachova, Sarah A. MerrillMaciej M. Mrugala, Vikram C. Prabhu, Craig Horbinski, Charles David James, Bakhtiar Yamini, Quinn T. Ostrom, Margaret O. Johnson, David A. Reardon, Rimas V. Lukas, Derek A. Wainwright

Neurology

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Advanced age is a major risk factor for the development of many diseases including those affecting the central nervous system. Wild-type isocitrate dehydrogenase glioblastoma (IDHwt GBM) is the most common primary malignant brain cancer and accounts for ≥90% of all adult GBM diagnoses. Patients with IDHwt GBM have a median age of diagnosis at 68-70 years of age, and increasing age is associated with an increasingly worse prognosis for patients with this type of GBM. Methods: The Surveillance, Epidemiology, and End Results, The Cancer Genome Atlas, and the Chinese Glioma Genome Atlas databases were analyzed for mortality indices. Meta-analysis of 80 clinical trials was evaluated for log hazard ratio for aging to tumor survivorship. Results: Despite significant advances in the understanding of intratumoral genetic alterations, molecular characteristics of tumor microenvironments, and relationships between tumor molecular characteristics and the use of targeted therapeutics, life expectancy for older adults with GBM has yet to improve. Conclusions: Based upon the results of our analysis, we propose that age-dependent factors that are yet to be fully elucidated, contribute to IDHwt GBM patient outcomes.

Original language	English (US)
Article number	vdab125
Journal	Neuro-Oncology Advances
Volume	3
Issue number	1
DOIs	https://doi.org/10.1093/noajnl/vdab125
State	Published - Jan 1 2021

Keywords

CD4
IDO
aging
glioma
immunotherapy
senescence

ASJC Scopus subject areas

Clinical Neurology
Oncology
Surgery

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10.1093/noajnl/vdab125

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Kim, M., Ladomersky, E., Mozny, A., Kocherginsky, M., O'shea, K., Reinstein, Z. Z., Zhai, L., Bell, A., Lauing, K. L., Bollu, L., Rabin, E., Dixit, K., Kumthekar, P., Platanias, L. C., Hou, L., Zheng, Y., Wu, J., Zhang, B., Hrachova, M., ... Wainwright, D. A. (2021). Glioblastoma as an age-related neurological disorder in adults. Neuro-Oncology Advances, 3(1), Article vdab125. https://doi.org/10.1093/noajnl/vdab125

Kim, M, Ladomersky, E, Mozny, A, Kocherginsky, M, O'shea, K, Reinstein, ZZ, Zhai, L, Bell, A, Lauing, KL, Bollu, L, Rabin, E, Dixit, K, Kumthekar, P, Platanias, LC, Hou, L, Zheng, Y, Wu, J, Zhang, B, Hrachova, M, Merrill, SA, Mrugala, MM, Prabhu, VC, Horbinski, C, James, CD, Yamini, B, Ostrom, QT, Johnson, MO, Reardon, DA, Lukas, RV & Wainwright, DA 2021, 'Glioblastoma as an age-related neurological disorder in adults', Neuro-Oncology Advances, vol. 3, no. 1, vdab125. https://doi.org/10.1093/noajnl/vdab125

@article{8b0a034cb4944d24bba406099eba26bd,

title = "Glioblastoma as an age-related neurological disorder in adults",

abstract = "Background: Advanced age is a major risk factor for the development of many diseases including those affecting the central nervous system. Wild-type isocitrate dehydrogenase glioblastoma (IDHwt GBM) is the most common primary malignant brain cancer and accounts for ≥90% of all adult GBM diagnoses. Patients with IDHwt GBM have a median age of diagnosis at 68-70 years of age, and increasing age is associated with an increasingly worse prognosis for patients with this type of GBM. Methods: The Surveillance, Epidemiology, and End Results, The Cancer Genome Atlas, and the Chinese Glioma Genome Atlas databases were analyzed for mortality indices. Meta-analysis of 80 clinical trials was evaluated for log hazard ratio for aging to tumor survivorship. Results: Despite significant advances in the understanding of intratumoral genetic alterations, molecular characteristics of tumor microenvironments, and relationships between tumor molecular characteristics and the use of targeted therapeutics, life expectancy for older adults with GBM has yet to improve. Conclusions: Based upon the results of our analysis, we propose that age-dependent factors that are yet to be fully elucidated, contribute to IDHwt GBM patient outcomes.",

keywords = "CD4, IDO, aging, glioma, immunotherapy, senescence",

author = "Miri Kim and Erik Ladomersky and Andreas Mozny and Masha Kocherginsky and Kaitlyn O'shea and Reinstein, {Zachary Z.} and Lijie Zhai and April Bell and Lauing, {Kristen L.} and Lakshmi Bollu and Erik Rabin and Karan Dixit and Priya Kumthekar and Platanias, {Leonidas C.} and Lifang Hou and Yinan Zheng and Jennifer Wu and Bin Zhang and Maya Hrachova and Merrill, {Sarah A.} and Mrugala, {Maciej M.} and Prabhu, {Vikram C.} and Craig Horbinski and James, {Charles David} and Bakhtiar Yamini and Ostrom, {Quinn T.} and Johnson, {Margaret O.} and Reardon, {David A.} and Lukas, {Rimas V.} and Wainwright, {Derek A.}",

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s). Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.",

year = "2021",

month = jan,

day = "1",

doi = "10.1093/noajnl/vdab125",

language = "English (US)",

volume = "3",

journal = "Neuro-Oncology Advances",

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T1 - Glioblastoma as an age-related neurological disorder in adults

AU - Kim, Miri

AU - Ladomersky, Erik

AU - Mozny, Andreas

AU - Kocherginsky, Masha

AU - O'shea, Kaitlyn

AU - Reinstein, Zachary Z.

AU - Zhai, Lijie

AU - Bell, April

AU - Lauing, Kristen L.

AU - Bollu, Lakshmi

AU - Rabin, Erik

AU - Dixit, Karan

AU - Kumthekar, Priya

AU - Platanias, Leonidas C.

AU - Hou, Lifang

AU - Zheng, Yinan

AU - Wu, Jennifer

AU - Zhang, Bin

AU - Hrachova, Maya

AU - Merrill, Sarah A.

AU - Mrugala, Maciej M.

AU - Prabhu, Vikram C.

AU - Horbinski, Craig

AU - James, Charles David

AU - Yamini, Bakhtiar

AU - Ostrom, Quinn T.

AU - Johnson, Margaret O.

AU - Reardon, David A.

AU - Lukas, Rimas V.

AU - Wainwright, Derek A.

PY - 2021/1/1

Y1 - 2021/1/1

N2 - Background: Advanced age is a major risk factor for the development of many diseases including those affecting the central nervous system. Wild-type isocitrate dehydrogenase glioblastoma (IDHwt GBM) is the most common primary malignant brain cancer and accounts for ≥90% of all adult GBM diagnoses. Patients with IDHwt GBM have a median age of diagnosis at 68-70 years of age, and increasing age is associated with an increasingly worse prognosis for patients with this type of GBM. Methods: The Surveillance, Epidemiology, and End Results, The Cancer Genome Atlas, and the Chinese Glioma Genome Atlas databases were analyzed for mortality indices. Meta-analysis of 80 clinical trials was evaluated for log hazard ratio for aging to tumor survivorship. Results: Despite significant advances in the understanding of intratumoral genetic alterations, molecular characteristics of tumor microenvironments, and relationships between tumor molecular characteristics and the use of targeted therapeutics, life expectancy for older adults with GBM has yet to improve. Conclusions: Based upon the results of our analysis, we propose that age-dependent factors that are yet to be fully elucidated, contribute to IDHwt GBM patient outcomes.

AB - Background: Advanced age is a major risk factor for the development of many diseases including those affecting the central nervous system. Wild-type isocitrate dehydrogenase glioblastoma (IDHwt GBM) is the most common primary malignant brain cancer and accounts for ≥90% of all adult GBM diagnoses. Patients with IDHwt GBM have a median age of diagnosis at 68-70 years of age, and increasing age is associated with an increasingly worse prognosis for patients with this type of GBM. Methods: The Surveillance, Epidemiology, and End Results, The Cancer Genome Atlas, and the Chinese Glioma Genome Atlas databases were analyzed for mortality indices. Meta-analysis of 80 clinical trials was evaluated for log hazard ratio for aging to tumor survivorship. Results: Despite significant advances in the understanding of intratumoral genetic alterations, molecular characteristics of tumor microenvironments, and relationships between tumor molecular characteristics and the use of targeted therapeutics, life expectancy for older adults with GBM has yet to improve. Conclusions: Based upon the results of our analysis, we propose that age-dependent factors that are yet to be fully elucidated, contribute to IDHwt GBM patient outcomes.

KW - CD4

KW - IDO

KW - aging

KW - glioma

KW - immunotherapy

KW - senescence

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DO - 10.1093/noajnl/vdab125

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JO - Neuro-Oncology Advances

JF - Neuro-Oncology Advances

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M1 - vdab125

ER -

Glioblastoma as an age-related neurological disorder in adults

Abstract

Keywords

ASJC Scopus subject areas

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