J Bryan Iorgulescu1,2, Chuxuan Sun3, Corey Neff4,5, Gino Cioffi4,6, Catherine Gutierrez1,2, Carol Kruchko4, Jennifer Ruhl7, Kristin Waite4,6, Serban Negoita7, Jim Hofferkamp8, Tarik Tihan9, Roger McLendon10,11,12, Daniel J Brat13, Quinn T Ostrom4,5,11,12, Jill S Barnholtz-Sloan4,6,14. 1. Department of Pathology, Brigham and Women's Hospital, Harvard Medical School. 2. Department of Medical Oncology, Dana-Farber Cancer Institute. 3. Department of Biostatistics, Duke University School of Medicine. 4. Central Brain Tumor Registry of the United States. 5. Department of Neurosurgery, Duke University School of Medicine. 6. Trans Divisional Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute. 7. Surveillance, Epidemiology, and End Results program, National Cancer Institute. 8. North American Association of Central Cancer Registries. 9. Division of Neuropathology, Department of Pathology, University of California San Francisco. 10. Department of Pathology, Duke University School of Medicine. 11. The Preston Robert Tisch Brain Tumor Center, Duke University School of Medicine. 12. Duke Cancer Institute, Duke University Medical Center. 13. Department of Pathology, Northwestern University Feinberg School of Medicine. 14. Center for Biomedical Informatics & Information Technology, National Cancer Institute.
Abstract
BACKGROUND: Selected molecular biomarkers were incorporated into U.S. 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, and 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 & 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 ETMRs 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. Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.
BACKGROUND: Selected molecular biomarkers were incorporated into U.S. 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, and 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 & 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 ETMRs 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. Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.