Molecular biomarker-defined brain tumors: Epidemiology, validity, and completeness in the United States

J. Bryan Iorgulescu; Chuxuan Sun; Corey Neff; Gino Cioffi; Catherine Gutierrez; Carol Kruchko; Jennifer Ruhl; Kristin A. Waite; Serban Negoita; Jim Hofferkamp; Tarik Tihan; Roger McLendon; Daniel J. Brat; Quinn T. Ostrom; Jill S. Barnholtz-Sloan

doi:10.1093/neuonc/noac113

Molecular biomarker-defined brain tumors: Epidemiology, validity, and completeness in the United States

J. Bryan Iorgulescu^*, Chuxuan Sun, Corey Neff, Gino Cioffi, Catherine Gutierrez, Carol Kruchko, Jennifer Ruhl, Kristin A. Waite, Serban Negoita, Jim Hofferkamp, Tarik Tihan, Roger McLendon, Daniel J. Brat, Quinn T. Ostrom^*, Jill S. Barnholtz-Sloan

^*Corresponding author for this work

Pathology

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

34 Scopus citations

Abstract

Background: Selected molecular biomarkers were incorporated into the US cancer registry reporting for patients with brain tumors beginning in 2018. We investigated the completeness and validity of these variables and described the epidemiology of molecularly defined brain tumor types. Methods: Brain tumor patients with histopathologically confirmed diagnosis in 2018 were identified within the Central Brain Tumor Registry of the United States and NCI's Surveillance, Epidemiology, and End Results Incidence databases. The brain molecular markers (BMM) site-specific data item was assessed for coding completeness and validity. 1p/19q status, MGMT promoter methylation, WHO grade data items, and new ICD-O-3 codes were additionally evaluated. These data were used to profile the characteristics and age-adjusted incidence rates per 100 000 population of molecularly defined brain tumors with 95% confidence intervals (95% CI). Results: BMM completeness across the applicable tumor types was 75%-92% and demonstrated favorable coding validity. IDH-wildtype glioblastomas' incidence rate was 1.74 (95% CI: 1.69-1.78), as compared to 0.14 for WHO grade 2 (95% CI: 0.12-0.15), 0.15 for grade 3 (95% CI: 0.14-0.16), and 0.07 for grade 4 (95% CI: 0.06-0.08) IDH-mutant astrocytomas. Irrespective of WHO grade, IDH mutation prevalence was highest in adolescent and young adult patients, and IDH-mutant astrocytomas were more frequently MGMT promoter methylated. Among pediatric-type tumors, the incidence rate was 0.06 for H3K27M-mutant diffuse midline gliomas (95% CI: 0.05-0.07), 0.03 for SHH-activated/TP53-wildtype medulloblastomas (95% CI: 0.02-0.03), and <0.01 for both C19MC-altered embryonal tumor with multilayered rosettes and RELA-fusion ependymomas. Conclusions: Our findings illustrate the success of developing a dedicated, integrated diagnosis variable, which provides critical molecular information about brain tumors related to accurate diagnosis.

Original language	English (US)
Pages (from-to)	1989-2000
Number of pages	12
Journal	Neuro-oncology
Volume	24
Issue number	11
DOIs	https://doi.org/10.1093/neuonc/noac113
State	Published - Nov 1 2022

Funding

Funding CBTRUS has been funded by the Centers for Disease Control and Prevention under Contract No. 75D30119C06056 Amendment/Modification No: 00002, the American Brain Tumor Association, Novocure, the Musella Foundation, The Sontag Foundation, National Brain Tumor Society, the Pediatric Brain Tumor Foundation, the Uncle Kory Foundation, and the Zelda Dorin Tetenbaum Memorial Fund, and private and in-kind donations. J.B.I. acknowledges support from the National Cancer Institute (NCI; K12CA090354) and Conquer Cancer Foundation/ Sontag Foundation. The research services of J.S.B.-S., K.W., and G.C. were provided by the Division of Cancer Epidemiology and Genetics of the NCI. Contents are solely the responsibility of the authors and do not necessarily represent the official views of either the CDC or the NCI.

Keywords

CBTRUS
IDH
biomarkers
brain tumor
molecular epidemiology

ASJC Scopus subject areas

Clinical Neurology
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/neuonc/noac113

Cite this

Iorgulescu, J. B., Sun, C., Neff, C., Cioffi, G., Gutierrez, C., Kruchko, C., Ruhl, J., Waite, K. A., Negoita, S., Hofferkamp, J., Tihan, T., McLendon, R., Brat, D. J., Ostrom, Q. T., & Barnholtz-Sloan, J. S. (2022). Molecular biomarker-defined brain tumors: Epidemiology, validity, and completeness in the United States. Neuro-oncology, 24(11), 1989-2000. https://doi.org/10.1093/neuonc/noac113

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title = "Molecular biomarker-defined brain tumors: Epidemiology, validity, and completeness in the United States",

abstract = "Background: Selected molecular biomarkers were incorporated into the US cancer registry reporting for patients with brain tumors beginning in 2018. We investigated the completeness and validity of these variables and described the epidemiology of molecularly defined brain tumor types. Methods: Brain tumor patients with histopathologically confirmed diagnosis in 2018 were identified within the Central Brain Tumor Registry of the United States and NCI's Surveillance, Epidemiology, and End Results Incidence databases. The brain molecular markers (BMM) site-specific data item was assessed for coding completeness and validity. 1p/19q status, MGMT promoter methylation, WHO grade data items, and new ICD-O-3 codes were additionally evaluated. These data were used to profile the characteristics and age-adjusted incidence rates per 100 000 population of molecularly defined brain tumors with 95% confidence intervals (95% CI). Results: BMM completeness across the applicable tumor types was 75%-92% and demonstrated favorable coding validity. IDH-wildtype glioblastomas' incidence rate was 1.74 (95% CI: 1.69-1.78), as compared to 0.14 for WHO grade 2 (95% CI: 0.12-0.15), 0.15 for grade 3 (95% CI: 0.14-0.16), and 0.07 for grade 4 (95% CI: 0.06-0.08) IDH-mutant astrocytomas. Irrespective of WHO grade, IDH mutation prevalence was highest in adolescent and young adult patients, and IDH-mutant astrocytomas were more frequently MGMT promoter methylated. Among pediatric-type tumors, the incidence rate was 0.06 for H3K27M-mutant diffuse midline gliomas (95% CI: 0.05-0.07), 0.03 for SHH-activated/TP53-wildtype medulloblastomas (95% CI: 0.02-0.03), and <0.01 for both C19MC-altered embryonal tumor with multilayered rosettes and RELA-fusion ependymomas. Conclusions: Our findings illustrate the success of developing a dedicated, integrated diagnosis variable, which provides critical molecular information about brain tumors related to accurate diagnosis.",

keywords = "CBTRUS, IDH, biomarkers, brain tumor, molecular epidemiology",

author = "Iorgulescu, {J. Bryan} and Chuxuan Sun and Corey Neff and Gino Cioffi and Catherine Gutierrez and Carol Kruchko and Jennifer Ruhl and Waite, {Kristin A.} and Serban Negoita and Jim Hofferkamp and Tarik Tihan and Roger McLendon and Brat, {Daniel J.} and Ostrom, {Quinn T.} and Barnholtz-Sloan, {Jill S.}",

note = "Publisher Copyright: {\textcopyright} 2022 Published by Oxford University Press on behalf of the Society for Neuro-Oncology.",

year = "2022",

month = nov,

day = "1",

doi = "10.1093/neuonc/noac113",

language = "English (US)",

volume = "24",

pages = "1989--2000",

journal = "Neuro-oncology",

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Iorgulescu, JB, Sun, C, Neff, C, Cioffi, G, Gutierrez, C, Kruchko, C, Ruhl, J, Waite, KA, Negoita, S, Hofferkamp, J, Tihan, T, McLendon, R, Brat, DJ, Ostrom, QT & Barnholtz-Sloan, JS 2022, 'Molecular biomarker-defined brain tumors: Epidemiology, validity, and completeness in the United States', Neuro-oncology, vol. 24, no. 11, pp. 1989-2000. https://doi.org/10.1093/neuonc/noac113

TY - JOUR

T1 - Molecular biomarker-defined brain tumors

T2 - Epidemiology, validity, and completeness in the United States

AU - Iorgulescu, J. Bryan

AU - Sun, Chuxuan

AU - Neff, Corey

AU - Cioffi, Gino

AU - Gutierrez, Catherine

AU - Kruchko, Carol

AU - Ruhl, Jennifer

AU - Waite, Kristin A.

AU - Negoita, Serban

AU - Hofferkamp, Jim

AU - Tihan, Tarik

AU - McLendon, Roger

AU - Brat, Daniel J.

AU - Ostrom, Quinn T.

AU - Barnholtz-Sloan, Jill S.

PY - 2022/11/1

Y1 - 2022/11/1

N2 - Background: Selected molecular biomarkers were incorporated into the US cancer registry reporting for patients with brain tumors beginning in 2018. We investigated the completeness and validity of these variables and described the epidemiology of molecularly defined brain tumor types. Methods: Brain tumor patients with histopathologically confirmed diagnosis in 2018 were identified within the Central Brain Tumor Registry of the United States and NCI's Surveillance, Epidemiology, and End Results Incidence databases. The brain molecular markers (BMM) site-specific data item was assessed for coding completeness and validity. 1p/19q status, MGMT promoter methylation, WHO grade data items, and new ICD-O-3 codes were additionally evaluated. These data were used to profile the characteristics and age-adjusted incidence rates per 100 000 population of molecularly defined brain tumors with 95% confidence intervals (95% CI). Results: BMM completeness across the applicable tumor types was 75%-92% and demonstrated favorable coding validity. IDH-wildtype glioblastomas' incidence rate was 1.74 (95% CI: 1.69-1.78), as compared to 0.14 for WHO grade 2 (95% CI: 0.12-0.15), 0.15 for grade 3 (95% CI: 0.14-0.16), and 0.07 for grade 4 (95% CI: 0.06-0.08) IDH-mutant astrocytomas. Irrespective of WHO grade, IDH mutation prevalence was highest in adolescent and young adult patients, and IDH-mutant astrocytomas were more frequently MGMT promoter methylated. Among pediatric-type tumors, the incidence rate was 0.06 for H3K27M-mutant diffuse midline gliomas (95% CI: 0.05-0.07), 0.03 for SHH-activated/TP53-wildtype medulloblastomas (95% CI: 0.02-0.03), and <0.01 for both C19MC-altered embryonal tumor with multilayered rosettes and RELA-fusion ependymomas. Conclusions: Our findings illustrate the success of developing a dedicated, integrated diagnosis variable, which provides critical molecular information about brain tumors related to accurate diagnosis.

AB - Background: Selected molecular biomarkers were incorporated into the US cancer registry reporting for patients with brain tumors beginning in 2018. We investigated the completeness and validity of these variables and described the epidemiology of molecularly defined brain tumor types. Methods: Brain tumor patients with histopathologically confirmed diagnosis in 2018 were identified within the Central Brain Tumor Registry of the United States and NCI's Surveillance, Epidemiology, and End Results Incidence databases. The brain molecular markers (BMM) site-specific data item was assessed for coding completeness and validity. 1p/19q status, MGMT promoter methylation, WHO grade data items, and new ICD-O-3 codes were additionally evaluated. These data were used to profile the characteristics and age-adjusted incidence rates per 100 000 population of molecularly defined brain tumors with 95% confidence intervals (95% CI). Results: BMM completeness across the applicable tumor types was 75%-92% and demonstrated favorable coding validity. IDH-wildtype glioblastomas' incidence rate was 1.74 (95% CI: 1.69-1.78), as compared to 0.14 for WHO grade 2 (95% CI: 0.12-0.15), 0.15 for grade 3 (95% CI: 0.14-0.16), and 0.07 for grade 4 (95% CI: 0.06-0.08) IDH-mutant astrocytomas. Irrespective of WHO grade, IDH mutation prevalence was highest in adolescent and young adult patients, and IDH-mutant astrocytomas were more frequently MGMT promoter methylated. Among pediatric-type tumors, the incidence rate was 0.06 for H3K27M-mutant diffuse midline gliomas (95% CI: 0.05-0.07), 0.03 for SHH-activated/TP53-wildtype medulloblastomas (95% CI: 0.02-0.03), and <0.01 for both C19MC-altered embryonal tumor with multilayered rosettes and RELA-fusion ependymomas. Conclusions: Our findings illustrate the success of developing a dedicated, integrated diagnosis variable, which provides critical molecular information about brain tumors related to accurate diagnosis.

KW - CBTRUS

KW - IDH

KW - biomarkers

KW - brain tumor

KW - molecular epidemiology

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UR - http://www.scopus.com/inward/citedby.url?scp=85131708321&partnerID=8YFLogxK

U2 - 10.1093/neuonc/noac113

DO - 10.1093/neuonc/noac113

M3 - Article

C2 - 35460555

AN - SCOPUS:85131708321

SN - 1522-8517

VL - 24

SP - 1989

EP - 2000

JO - Neuro-oncology

JF - Neuro-oncology

IS - 11

ER -

Molecular biomarker-defined brain tumors: Epidemiology, validity, and completeness in the United States

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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