Journal of the National Cancer Institute Advance Access originally published online on June 17, 2009
JNCI Journal of the National Cancer Institute 2009 101(13):946-958; doi:10.1093/jnci/djp148
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© The Author 2009. Published by Oxford University Press.
ARTICLES |
Long-Term Outcomes Among Adult Survivors of Childhood Central Nervous System Malignancies in the Childhood Cancer Survivor Study
Affiliations of authors: Department of Epidemiology and Cancer Control and Department of Oncology, St Jude Children's Research Hospital, Memphis, TN (GTA, KKN, MMH, KRK, LLR, SH); Department of Public Health Sciences, University of Alberta, Edmonton, AB (QL, YY); Department of Clinical Statistics and Cancer Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA (WL); Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA (SSD); Program in Occupational Therapy and Department of Pediatrics, Washington University, St Louis, MO (AAK); Department of Radiation Physics, University of Texas, M. D. Anderson Cancer Center, Houston, TX (MS); Department of Pediatrics and Department of Neurology, Brain Tumor Institute, Children's National Medical Center and George Washington University, Washington, DC (RJP)
Correspondence to: Gregory T. Armstrong, MD, MSCE, Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 735, Memphis, TN 38105 (e-mail: greg.armstrong{at}stjude.org).
Background: Adult survivors of childhood central nervous system (CNS) malignancies are at high risk for long-term morbidity and late mortality. However, patterns of late mortality, the long-term risks of subsequent neoplasms and debilitating medical conditions, and sociodemographic outcomes have not been comprehensively characterized for individual diagnostic and treatment groups.
Methods: We collected information on treatment, mortality, chronic medical conditions, and neurocognitive functioning of adult 5-year survivors of CNS malignancies diagnosed between 1970 and 1986 within the Childhood Cancer Survivor Study. Using competing risk framework, we calculated cumulative mortality according to cause of death and cumulative incidence of subsequent neoplasms according to exposure and dose of cranial radiation therapy (RT). Neurocognitive impairment and socioeconomic outcomes were assessed with respect to dose of CNS radiotherapy to specific brain regions. Cumulative incidence of chronic medical conditions was compared between survivors and siblings using Cox regression models. All tests of statistical significance were two-sided.
Results: Among all eligible 5-year survivors (n = 2821), cumulative late mortality at 30 years was 25.8% (95% confidence interval [CI] = 23.4% to 28.3%), due primarily to recurrence and/or progression of primary disease. Patients who received cranial RT of 50 Gy or more (n = 813) had a cumulative incidence of a subsequent neoplasm within the CNS of 7.1% (95% CI = 4.5% to 9.6%) at 25 years from diagnosis compared with 1.0% (95% CI = 0% to 2.3%) for patients who had no RT. Survivors had higher risk than siblings of developing new endocrine, neurological, or sensory complications 5 or more years after diagnosis. Neurocognitive impairment was high and proportional to radiation dose for specific tumor types. There was a dose-dependent association between RT to the frontal and/or temporal lobes and lower rates of employment, and marriage.
Conclusions: Survivors of childhood CNS malignancies are at high risk for late mortality and for developing subsequent neoplasms and chronic medical conditions. Care providers should be informed of these risks so they can provide risk-directed care and develop screening guidelines.
| CONTEXT AND CAVEATS Prior knowledge The long-term health of those treated as children for malignancies of the central nervous system (CNS) had been incompletely characterized. Study design Retrospective cohort study relying on a questionnaire, medical records, and the National Death Index for information. Siblings were selected randomly to serve as control subjects where appropriate. Cumulative mortality and incidence of subsequent neoplasms were analyzed using competing risk models. Contribution This study provided a comprehensive assessment of the long-term risks of mortality, subsequent medical complications, and neurocognitive impairment in survivors of pediatric malignancies of the CNS, and how radioactive treatment was associated with these risks. Implications Due to high risks of mortality, subsequent cancers, and other medical conditions, survivors of CNS malignancies will need specialized care and screening. Limitations Treatment of pediatric cancers has changed considerably since the time when the patients in this cohort were treated; the results of this analysis may not be applicable to future survivors. From the Editors
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Manuscript received November 24, 2008; revised April 7, 2009; accepted May 1, 2009.
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J Natl Cancer Inst 2009 101: 901.