Brain Cancer: Epidemiology, TBI, and New Treatments

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Brain Cancer: Epidemiology, TBI, and New Treatments

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Margaret O. Johnson, MD, MPH

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References
  1. Bihn JR, Cioffi G, Waite KA, et al. Brain tumors in United States military veterans.
    Neuro Oncol. 2024;26(2):387-396. doi:10.1093/neuonc/noad182
  2. Stewart IJ, Howard JT, Poltavsky E, et al. Traumatic Brain Injury and Subsequent
    Risk of Brain Cancer in US Veterans of the Iraq and Afghanistan Wars. JAMA Netw
    Open. 2024;7(2):e2354588. doi:10.1001/jamanetworkopen.2023.54588
  3. DoD/USU Brain Tissue Repository. December 15, 2023. Accessed December 11,
    2024. https://researchbraininjury.org/
  4. Munch TN, Gørtz S, Wohlfahrt J, Melbye M. The long-term risk of malignant
    astrocytic tumors after structural brain injury--a nationwide cohort study. Neuro
    Oncol. 2015;17(5):718-724. doi:10.1093/neuonc/nou312
  5. Strowd RE, Dunbar EM, Gan HK, et al. Practical guidance for telemedicine use in
    neuro-oncology. Neurooncol Pract. 2022;9(2):91-104. doi:10.1093/nop/npac002
  6. Parikh DA, Rodgers TD, Passero VA, et al. Teleoncology in the Veterans Health
    Administration: Models of Care and the Veteran Experience. Am Soc Clin Oncol Educ
    Book. 2024;44(e100042. doi:10.1200/EDBK_100042
  7. Batool SM, Escobedo AK, Hsia T, et al. Clinical utility of a blood based assay for
    the detection of IDH1.R132H-mutant gliomas. Nat Commun. 2024;15(1):7074.
    doi:10.1038/s41467-024-51332-7
  8. Mellinghoff IK, van den Bent MJ, Blumenthal DT, et al; INDIGO Trial Investigators.
    Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma. N Engl J Med.
    2023;389(7):589-601. doi:10.1056/NEJMoa2304194
  9. FDA. US Food and Drug Administration. FDA approves vorasidenib for Grade 2
    astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation.
    Accessed December 11, 2024. https://www.fda.gov/drugs/resourcesinformation-
    approved-drugs/fda-approves-vorasidenib-grade-2-astrocytoma-oroligodendroglioma-
    susceptible-idh1-or-idh2-mutation
  10. NIH. National Cancer Institute. Tovorafenib Approved for Some Children with Low-
    Grade Glioma. Accessed December 11, 2024. https://www.cancer.gov/news-events/
    cancer-currents-blog/2024/pediatric-low-grade-glioma-tovorafenib-braf
  11. The Veteran Population. Accessed December 11, 2024. https://www.va.gov/vetdata/
    docs/surveysandstudies/vetpop.pdf
  12. Miller AM, Szalontay L, Bouvier N, et al. Next-generation sequencing of
    cerebrospinal fluid for clinical molecular diagnostics in pediatric, adolescent
    and young adult brain tumor patients. Neuro Oncol. 2022;24(10):1763-1772.
    doi:10.1093/neuonc/noac035
Author and Disclosure Information

Margaret O. Johnson, MD, MPH
Assistant Professor,
Department of Neurosurgery
Duke University School of Medicine;
Staff Physician
Department of Veterans Affairs
National Tele-Oncology Program
Durham, North Carolina


Dr. Johnson has no relevant financial relationships to disclose. 

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Author and Disclosure Information

Margaret O. Johnson, MD, MPH
Assistant Professor,
Department of Neurosurgery
Duke University School of Medicine;
Staff Physician
Department of Veterans Affairs
National Tele-Oncology Program
Durham, North Carolina


Dr. Johnson has no relevant financial relationships to disclose. 

Author and Disclosure Information

Margaret O. Johnson, MD, MPH
Assistant Professor,
Department of Neurosurgery
Duke University School of Medicine;
Staff Physician
Department of Veterans Affairs
National Tele-Oncology Program
Durham, North Carolina


Dr. Johnson has no relevant financial relationships to disclose. 

Click to view more from Cancer Data Trends 2025. 

Click to view more from Cancer Data Trends 2025. 

References
  1. Bihn JR, Cioffi G, Waite KA, et al. Brain tumors in United States military veterans.
    Neuro Oncol. 2024;26(2):387-396. doi:10.1093/neuonc/noad182
  2. Stewart IJ, Howard JT, Poltavsky E, et al. Traumatic Brain Injury and Subsequent
    Risk of Brain Cancer in US Veterans of the Iraq and Afghanistan Wars. JAMA Netw
    Open. 2024;7(2):e2354588. doi:10.1001/jamanetworkopen.2023.54588
  3. DoD/USU Brain Tissue Repository. December 15, 2023. Accessed December 11,
    2024. https://researchbraininjury.org/
  4. Munch TN, Gørtz S, Wohlfahrt J, Melbye M. The long-term risk of malignant
    astrocytic tumors after structural brain injury--a nationwide cohort study. Neuro
    Oncol. 2015;17(5):718-724. doi:10.1093/neuonc/nou312
  5. Strowd RE, Dunbar EM, Gan HK, et al. Practical guidance for telemedicine use in
    neuro-oncology. Neurooncol Pract. 2022;9(2):91-104. doi:10.1093/nop/npac002
  6. Parikh DA, Rodgers TD, Passero VA, et al. Teleoncology in the Veterans Health
    Administration: Models of Care and the Veteran Experience. Am Soc Clin Oncol Educ
    Book. 2024;44(e100042. doi:10.1200/EDBK_100042
  7. Batool SM, Escobedo AK, Hsia T, et al. Clinical utility of a blood based assay for
    the detection of IDH1.R132H-mutant gliomas. Nat Commun. 2024;15(1):7074.
    doi:10.1038/s41467-024-51332-7
  8. Mellinghoff IK, van den Bent MJ, Blumenthal DT, et al; INDIGO Trial Investigators.
    Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma. N Engl J Med.
    2023;389(7):589-601. doi:10.1056/NEJMoa2304194
  9. FDA. US Food and Drug Administration. FDA approves vorasidenib for Grade 2
    astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation.
    Accessed December 11, 2024. https://www.fda.gov/drugs/resourcesinformation-
    approved-drugs/fda-approves-vorasidenib-grade-2-astrocytoma-oroligodendroglioma-
    susceptible-idh1-or-idh2-mutation
  10. NIH. National Cancer Institute. Tovorafenib Approved for Some Children with Low-
    Grade Glioma. Accessed December 11, 2024. https://www.cancer.gov/news-events/
    cancer-currents-blog/2024/pediatric-low-grade-glioma-tovorafenib-braf
  11. The Veteran Population. Accessed December 11, 2024. https://www.va.gov/vetdata/
    docs/surveysandstudies/vetpop.pdf
  12. Miller AM, Szalontay L, Bouvier N, et al. Next-generation sequencing of
    cerebrospinal fluid for clinical molecular diagnostics in pediatric, adolescent
    and young adult brain tumor patients. Neuro Oncol. 2022;24(10):1763-1772.
    doi:10.1093/neuonc/noac035
References
  1. Bihn JR, Cioffi G, Waite KA, et al. Brain tumors in United States military veterans.
    Neuro Oncol. 2024;26(2):387-396. doi:10.1093/neuonc/noad182
  2. Stewart IJ, Howard JT, Poltavsky E, et al. Traumatic Brain Injury and Subsequent
    Risk of Brain Cancer in US Veterans of the Iraq and Afghanistan Wars. JAMA Netw
    Open. 2024;7(2):e2354588. doi:10.1001/jamanetworkopen.2023.54588
  3. DoD/USU Brain Tissue Repository. December 15, 2023. Accessed December 11,
    2024. https://researchbraininjury.org/
  4. Munch TN, Gørtz S, Wohlfahrt J, Melbye M. The long-term risk of malignant
    astrocytic tumors after structural brain injury--a nationwide cohort study. Neuro
    Oncol. 2015;17(5):718-724. doi:10.1093/neuonc/nou312
  5. Strowd RE, Dunbar EM, Gan HK, et al. Practical guidance for telemedicine use in
    neuro-oncology. Neurooncol Pract. 2022;9(2):91-104. doi:10.1093/nop/npac002
  6. Parikh DA, Rodgers TD, Passero VA, et al. Teleoncology in the Veterans Health
    Administration: Models of Care and the Veteran Experience. Am Soc Clin Oncol Educ
    Book. 2024;44(e100042. doi:10.1200/EDBK_100042
  7. Batool SM, Escobedo AK, Hsia T, et al. Clinical utility of a blood based assay for
    the detection of IDH1.R132H-mutant gliomas. Nat Commun. 2024;15(1):7074.
    doi:10.1038/s41467-024-51332-7
  8. Mellinghoff IK, van den Bent MJ, Blumenthal DT, et al; INDIGO Trial Investigators.
    Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma. N Engl J Med.
    2023;389(7):589-601. doi:10.1056/NEJMoa2304194
  9. FDA. US Food and Drug Administration. FDA approves vorasidenib for Grade 2
    astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation.
    Accessed December 11, 2024. https://www.fda.gov/drugs/resourcesinformation-
    approved-drugs/fda-approves-vorasidenib-grade-2-astrocytoma-oroligodendroglioma-
    susceptible-idh1-or-idh2-mutation
  10. NIH. National Cancer Institute. Tovorafenib Approved for Some Children with Low-
    Grade Glioma. Accessed December 11, 2024. https://www.cancer.gov/news-events/
    cancer-currents-blog/2024/pediatric-low-grade-glioma-tovorafenib-braf
  11. The Veteran Population. Accessed December 11, 2024. https://www.va.gov/vetdata/
    docs/surveysandstudies/vetpop.pdf
  12. Miller AM, Szalontay L, Bouvier N, et al. Next-generation sequencing of
    cerebrospinal fluid for clinical molecular diagnostics in pediatric, adolescent
    and young adult brain tumor patients. Neuro Oncol. 2022;24(10):1763-1772.
    doi:10.1093/neuonc/noac035
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Brain Cancer: Epidemiology, TBI, and New Treatments

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Brain Cancer: Epidemiology, TBI, and New Treatments

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Brain cancer represents a notable health challenge for veterans. The first large-scale study on brain tumors in US veterans showed that the most frequently diagnosed tumors were nonmalignant pituitary tumors, nonmalignant meningiomas, and glioblastomas.1 Exposure to combat-related traumatic brain injuries (TBIs) may contribute to the risk for brain tumors, and further research is ongoing.2,3 A 2024 study demonstrated that veterans with moderate/severe and penetrating TBIs had an increased risk of brain cancer, but previous research in civilians has not echoed these findings.2,4 

As our understanding of the connection between TBI and brain cancer evolves, health care initiatives and new research are aiming to serve the veteran population most at risk. Telehealth is being used throughout the VA to help veterans, especially those in rural locations, receive neuro-oncology care.5,6 In terms of research, the DoD and Uniformed Services University have established a Brain Tissue Repository. This program may be better able to explore the TBI/brain cancer connection through veteran brain tissue donation.3

New assays are also being developed to help identify brain cancer faster. Liquid biopsy techniques focused on IDH1 have shown promise.7 In terms of treatment, the IDH1/IDH2 inhibitor vorasidenib prolonged progression free survival in grade 2 IDH-mutant gliomas in clinical trials and was approved by the FDA in 2024.8,9 Although not pertaining directly to the veteran population, a new treatment for pediatric brain tumors also was approved by the FDA in 2024.10 These milestones reflect an encouraging trend in precision medicine, opening doors for more targeted brain tumor therapies and tools across various patient groups.

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New Classifications and Emerging Treatments in Brain Cancer

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New Classifications and Emerging Treatments in Brain Cancer
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Margaret O. Johnson, MD, MPH

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References
  1. Sokolov AV et al. Pharmacol Rev. 2021;73(4):1-32. doi:10.1124/pharmrev.121.000317
  2. Louis DN et al. Neuro Oncol. 2021;23(8):1231-1251. doi:10.1093/neuonc/noab106
  3. Mellinghoff IK et al. Clin Cancer Res. 2021;27(16):4491-4499. doi:10.1158/1078-0432.CCR-21-0611
  4. Woo C et al. JCO Clin Cancer Inform. 2021;5:985-994. doi:10.1200/CCI.21.00052
  5. Study of vorasidenib (AG-881) in participants with residual or recurrent grade 2 glioma with an IDH1 or IDH2 mutation (INDIGO). ClinicalTrials.gov. Updated May 17, 2022. Accessed December 8, 2022. https://clinicaltrials.gov/ct2/show/NCT04164901
  6. Servier's pivotal phase 3 indigo trial investigating vorasidenib in IDH-mutant low-grade glioma meets primary endpoint of progression-free survival (PFS) and key secondary endpoint of time to next intervention (TTNI) (no date) Servier US. March 14, 2023. Accessed March 20, 2023. https://www.servier.us/serviers-pivotal-phase-3-indigo-trial-meets-primary-endpoint
  7. Nehra M et al. J Control Release. 2021;338:224-243. doi:10.1016/j.jconrel.2021.08.027
  8. Hersh AM et al. Cancers (Basel). 2022;14(19):4920. doi:10.3390/cancers14194920
  9. Shoaf ML, Desjardins A. Neurotherapeutics. 2022;19(6):1818-1831. doi:10.1007/s13311-022-01256-1
  10. Bagley SJ, O’Rourke DM. Pharmacol Ther. 2020;205:107419. doi:10.1016/j.pharmthera.2019.107419
  11. Batich KA et al. Clin Cancer Res. 2020;26(20):5297-5303. doi:10.1158/1078-0432.CCR-20-1082
  12. Lin J et al. Cancer. 2020;126(13):3053-3060. doi:10.1002/cncr.32884
  13. Barth SK et al. Cancer Epidemiol. 2017;50(pt A):22-29. doi:10.1016/j.canep.2017.07.012
  14. VA and partners hope APOLLO program will be leap forward for precision oncology. US Department of Veteran Affairs. May 1, 2019. Accessed December 8, 2022. https://www.research.va.gov/currents/0519-VA-and-partners-hope-APOLLO-program-will-be-leap-forward-for-precision-oncology.cfm
  15. Konteatis Z et al. ACS Med Chem Lett. 2020;11(2):101-107. doi:10.1021/acsmedchemlett.9b00509
Author and Disclosure Information

Margaret O. Johnson, MD, MPH
Neuro-oncologist, National TeleOncology and National Precision Oncology Program
Veterans Health Administration
Assistant Professor of Neurosurgery,
Preston Robert Tisch Brain Tumor Center,
Duke University School of Medicine
Durham, NC

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Margaret O. Johnson, MD, MPH
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Margaret O. Johnson, MD, MPH
Neuro-oncologist, National TeleOncology and National Precision Oncology Program
Veterans Health Administration
Assistant Professor of Neurosurgery,
Preston Robert Tisch Brain Tumor Center,
Duke University School of Medicine
Durham, NC

Author and Disclosure Information

Margaret O. Johnson, MD, MPH
Neuro-oncologist, National TeleOncology and National Precision Oncology Program
Veterans Health Administration
Assistant Professor of Neurosurgery,
Preston Robert Tisch Brain Tumor Center,
Duke University School of Medicine
Durham, NC

Click to view more from Cancer Data Trends 2023.

Click to view more from Cancer Data Trends 2023.

References
  1. Sokolov AV et al. Pharmacol Rev. 2021;73(4):1-32. doi:10.1124/pharmrev.121.000317
  2. Louis DN et al. Neuro Oncol. 2021;23(8):1231-1251. doi:10.1093/neuonc/noab106
  3. Mellinghoff IK et al. Clin Cancer Res. 2021;27(16):4491-4499. doi:10.1158/1078-0432.CCR-21-0611
  4. Woo C et al. JCO Clin Cancer Inform. 2021;5:985-994. doi:10.1200/CCI.21.00052
  5. Study of vorasidenib (AG-881) in participants with residual or recurrent grade 2 glioma with an IDH1 or IDH2 mutation (INDIGO). ClinicalTrials.gov. Updated May 17, 2022. Accessed December 8, 2022. https://clinicaltrials.gov/ct2/show/NCT04164901
  6. Servier's pivotal phase 3 indigo trial investigating vorasidenib in IDH-mutant low-grade glioma meets primary endpoint of progression-free survival (PFS) and key secondary endpoint of time to next intervention (TTNI) (no date) Servier US. March 14, 2023. Accessed March 20, 2023. https://www.servier.us/serviers-pivotal-phase-3-indigo-trial-meets-primary-endpoint
  7. Nehra M et al. J Control Release. 2021;338:224-243. doi:10.1016/j.jconrel.2021.08.027
  8. Hersh AM et al. Cancers (Basel). 2022;14(19):4920. doi:10.3390/cancers14194920
  9. Shoaf ML, Desjardins A. Neurotherapeutics. 2022;19(6):1818-1831. doi:10.1007/s13311-022-01256-1
  10. Bagley SJ, O’Rourke DM. Pharmacol Ther. 2020;205:107419. doi:10.1016/j.pharmthera.2019.107419
  11. Batich KA et al. Clin Cancer Res. 2020;26(20):5297-5303. doi:10.1158/1078-0432.CCR-20-1082
  12. Lin J et al. Cancer. 2020;126(13):3053-3060. doi:10.1002/cncr.32884
  13. Barth SK et al. Cancer Epidemiol. 2017;50(pt A):22-29. doi:10.1016/j.canep.2017.07.012
  14. VA and partners hope APOLLO program will be leap forward for precision oncology. US Department of Veteran Affairs. May 1, 2019. Accessed December 8, 2022. https://www.research.va.gov/currents/0519-VA-and-partners-hope-APOLLO-program-will-be-leap-forward-for-precision-oncology.cfm
  15. Konteatis Z et al. ACS Med Chem Lett. 2020;11(2):101-107. doi:10.1021/acsmedchemlett.9b00509
References
  1. Sokolov AV et al. Pharmacol Rev. 2021;73(4):1-32. doi:10.1124/pharmrev.121.000317
  2. Louis DN et al. Neuro Oncol. 2021;23(8):1231-1251. doi:10.1093/neuonc/noab106
  3. Mellinghoff IK et al. Clin Cancer Res. 2021;27(16):4491-4499. doi:10.1158/1078-0432.CCR-21-0611
  4. Woo C et al. JCO Clin Cancer Inform. 2021;5:985-994. doi:10.1200/CCI.21.00052
  5. Study of vorasidenib (AG-881) in participants with residual or recurrent grade 2 glioma with an IDH1 or IDH2 mutation (INDIGO). ClinicalTrials.gov. Updated May 17, 2022. Accessed December 8, 2022. https://clinicaltrials.gov/ct2/show/NCT04164901
  6. Servier's pivotal phase 3 indigo trial investigating vorasidenib in IDH-mutant low-grade glioma meets primary endpoint of progression-free survival (PFS) and key secondary endpoint of time to next intervention (TTNI) (no date) Servier US. March 14, 2023. Accessed March 20, 2023. https://www.servier.us/serviers-pivotal-phase-3-indigo-trial-meets-primary-endpoint
  7. Nehra M et al. J Control Release. 2021;338:224-243. doi:10.1016/j.jconrel.2021.08.027
  8. Hersh AM et al. Cancers (Basel). 2022;14(19):4920. doi:10.3390/cancers14194920
  9. Shoaf ML, Desjardins A. Neurotherapeutics. 2022;19(6):1818-1831. doi:10.1007/s13311-022-01256-1
  10. Bagley SJ, O’Rourke DM. Pharmacol Ther. 2020;205:107419. doi:10.1016/j.pharmthera.2019.107419
  11. Batich KA et al. Clin Cancer Res. 2020;26(20):5297-5303. doi:10.1158/1078-0432.CCR-20-1082
  12. Lin J et al. Cancer. 2020;126(13):3053-3060. doi:10.1002/cncr.32884
  13. Barth SK et al. Cancer Epidemiol. 2017;50(pt A):22-29. doi:10.1016/j.canep.2017.07.012
  14. VA and partners hope APOLLO program will be leap forward for precision oncology. US Department of Veteran Affairs. May 1, 2019. Accessed December 8, 2022. https://www.research.va.gov/currents/0519-VA-and-partners-hope-APOLLO-program-will-be-leap-forward-for-precision-oncology.cfm
  15. Konteatis Z et al. ACS Med Chem Lett. 2020;11(2):101-107. doi:10.1021/acsmedchemlett.9b00509
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Brain cancer remains a tremendous challenge in oncology, often with the worst prognosis and fewest approved treatment options.1 Classifying, treating, and identifying the causes in both the general population and in veterans have been challenging; but recently, there has been progress.2-4 In 2021, the World Health Organization (WHO) updated the classification system for primary brain and spinal cord tumors.2 Most importantly, the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5) updates included the importance of molecular diagnostic techniques to ensure appropriate diagnoses.2 

Along with the progress in tumor classification, treatment advances are also showing promise with the use of new targeted therapies.3 A multi-site phase 3 clinical trial investigating an isocitrate dehydrogenase (IDH) inhibitor, vorasidenib, in patients with residual or recurrent IDH mutant low-grade glioma met its primary endpoint of PFS in March 2023.5,6 In addition to brain-penetrant targeted therapies, advances in drug administration and delivery have also emerged to circumvent the blood-brain barrier using nanotechnology, focused ultrasound, oncolytic viruses, vaccines, and CAR T-cell therapies.7-11

Many unanswered questions remain regarding the rates and outcomes for veterans with brain cancer. However, investigations and initiatives are ongoing to better understand the role of military service and exposures that may be associated with an increased risk of developing brain tumors.4,12,13 In addition, efforts are in place to improve molecular characterization and personalized treatments for brain cancer through the Applied Proteogenomics Organizational Learning and Outcomes (APOLLO) and NPOP.14 Despite the complexity of brain cancer, with its numerous challenges and unknowns, there have been recent advances in classification and potential treatments. Understanding the causes and improving treatments for brain cancer in the veteran population is paramount.

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