Long-term outcomes among adult survivors of childhood central nervous system malignancies in the Childhood Cancer Survivor Study

Abstract

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.

Figure 1

Mortality experience of 5-year survivors of childhood central nervous system (CNS) malignancies. A) All-cause and sex-specific mortality among 5-year survivors of CNS malignancies compared with the age-adjusted US population. B) All-cause mortality by primary diagnosis. C) Cumulative cause-specific mortality. D) Cumulative mortality attributable to recurrence by sex. PNET = primitive neuroectodermal tumor, SMN = second malignant neoplasm.

Figure 2

Subsequent neoplasms in 5-year survivors of central nervous system (CNS) malignancies. A) Cumulative incidence of subsequent neoplasms (SN) with death as competing risk. B) Cumulative incidence of detected meningioma conditioned on meningioma-free survival at 5, 10, 15, 20, and 25 years. C) Cumulative incidence of CNS second neoplasms by cranial radiation therapy dose. NMSC = nonmelanoma skin cancer.