Elizabeth M Wells1,2, Nicole J Ullrich3, Kristy Seidel4, Wendy Leisenring5, Charles A Sklar6, Gregory T Armstrong7, Lisa Diller3, Allison King8, Kevin R Krull7,9, Joseph P Neglia10, Marilyn Stovall11, Kimberly Whelan12, Kevin C Oeffinger13, Leslie L Robison7, Roger J Packer1,2. 1. Center for Neuroscience and Behavioral Medicine, Brain Tumor Institute. 2. Division of Neurology, Children's National Health System, Washington, DC. 3. Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, Massachusetts. 4. Clinical Research Division, Fred Hutchinson Cancer Research Center and University of Washington, Seattle, Washington. 5. Programs in Clinical Statistics and Cancer Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington. 6. Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York. 7. Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, Tennessee. 8. Departments of Hematology and Oncology, Occupational Therapy and Pediatrics, Washington University, St Louis, Missouri. 9. Department of Psychology, St Jude Children's Research Hospital, Memphis, Tennessee. 10. Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota. 11. Department of Radiation Physics, Division of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas. 12. Department of Hematology and Oncology, University of Alabama, Birmingham, Alabama. 13. Duke Cancer Institute, Durham, North Carolina.
Abstract
Background: Survivors of childhood central nervous system (CNS) tumors experience high rates of treatment-related neurologic sequelae. Whether survivors continue to be at increased risk for new events as they age is unknown. Methods: Adverse neurologic health conditions in 5-year survivors of CNS tumors from the Childhood Cancer Survivor Study (n = 1876) were evaluated longitudinally at a median 23.0 years from diagnosis (range, 5.1-38.9), median age at last evaluation 30.3 years (range, 6.1-56.4). Multivariable regression estimated hazard ratios (HRs) and 95% CIs. Results: From 5 to 30 years post diagnosis, cumulative incidence increased for seizures from 27% to 41%, motor impairment 21% to 35%, and hearing loss 9% to 23%. Risks were elevated compared with siblings (eg, seizures HR: 12.7; 95% CI: 9.6-16.7; motor impairment HR: 7.6; 95% CI: 5.8-9.9; hearing loss HR: 18.4; 95% CI: 13.1-25.9). Regional brain doses of radiation therapy were associated with development of new deficits (eg, frontal ≥50 Gy and motor impairment HR: 2.0; 95% CI: 1.2-3.4). Increased risk for motor impairment was also associated with tumor recurrence (HR: 2.6; 95% CI: 1.8-3.8), development of a meningioma (HR: 2.3; 95% CI: 0.9-5.4), and stroke (HR: 14.9; 95% CI: 10.4-21.4). Seizure risk was doubled by recurrence (HR: 2.3; 95% CI: 1.6-3.2), meningioma (HR: 2.6; 95% CI: 1.1-6.5), and stroke (HR: 2.0; 95% CI: 1.1-3.4). Conclusions: CNS tumor survivors remain at risk for new-onset adverse neurologic events across their lifespans at a rate greater than siblings. Cranial radiation, stroke, tumor recurrence, and development of meningioma were independently associated with late-onset adverse neurologic sequelae.
Background: Survivors of childhood central nervous system (CNS) tumors experience high rates of treatment-related neurologic sequelae. Whether survivors continue to be at increased risk for new events as they age is unknown. Methods: Adverse neurologic health conditions in 5-year survivors of CNS tumors from the Childhood Cancer Survivor Study (n = 1876) were evaluated longitudinally at a median 23.0 years from diagnosis (range, 5.1-38.9), median age at last evaluation 30.3 years (range, 6.1-56.4). Multivariable regression estimated hazard ratios (HRs) and 95% CIs. Results: From 5 to 30 years post diagnosis, cumulative incidence increased for seizures from 27% to 41%, motor impairment 21% to 35%, and hearing loss 9% to 23%. Risks were elevated compared with siblings (eg, seizures HR: 12.7; 95% CI: 9.6-16.7; motor impairment HR: 7.6; 95% CI: 5.8-9.9; hearing loss HR: 18.4; 95% CI: 13.1-25.9). Regional brain doses of radiation therapy were associated with development of new deficits (eg, frontal ≥50 Gy and motor impairment HR: 2.0; 95% CI: 1.2-3.4). Increased risk for motor impairment was also associated with tumor recurrence (HR: 2.6; 95% CI: 1.8-3.8), development of a meningioma (HR: 2.3; 95% CI: 0.9-5.4), and stroke (HR: 14.9; 95% CI: 10.4-21.4). Seizure risk was doubled by recurrence (HR: 2.3; 95% CI: 1.6-3.2), meningioma (HR: 2.6; 95% CI: 1.1-6.5), and stroke (HR: 2.0; 95% CI: 1.1-3.4). Conclusions: CNS tumor survivors remain at risk for new-onset adverse neurologic events across their lifespans at a rate greater than siblings. Cranial radiation, stroke, tumor recurrence, and development of meningioma were independently associated with late-onset adverse neurologic sequelae.
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