Longitudinal assessment of late-onset neurologic conditions in survivors of childhood central nervous system tumors: A Childhood Cancer Survivor Study report

Elizabeth M. Wells, Nicole J. Ullrich, Kristy Seidel, Wendy Leisenring, Charles A. Sklar, Gregory T. Armstrong, Lisa DIller, Allison King, Kevin R. Krull, Joseph P. Neglia, Marilyn Stovall, Kimberly Whelan, Kevin C. Oeffinger, Leslie L. Robison, Roger J. Packer

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)132-142
Number of pages11
JournalNeuro-Oncology
Volume20
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Central Nervous System Neoplasms
Nervous System
Meningioma
Seizures
Stroke
Neoplasms
Hearing Loss
Recurrence
Radiotherapy
Radiation
Incidence
Health
Brain

Keywords

  • childhood central nervous system tumor survivors
  • late effects
  • neurologic outcomes

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Cite this

Longitudinal assessment of late-onset neurologic conditions in survivors of childhood central nervous system tumors : A Childhood Cancer Survivor Study report. / Wells, Elizabeth M.; Ullrich, Nicole J.; Seidel, Kristy; Leisenring, Wendy; Sklar, Charles A.; Armstrong, Gregory T.; DIller, Lisa; King, Allison; Krull, Kevin R.; Neglia, Joseph P.; Stovall, Marilyn; Whelan, Kimberly; Oeffinger, Kevin C.; Robison, Leslie L.; Packer, Roger J.

In: Neuro-Oncology, Vol. 20, No. 1, 01.01.2018, p. 132-142.

Research output: Contribution to journalArticle

Wells, EM, Ullrich, NJ, Seidel, K, Leisenring, W, Sklar, CA, Armstrong, GT, DIller, L, King, A, Krull, KR, Neglia, JP, Stovall, M, Whelan, K, Oeffinger, KC, Robison, LL & Packer, RJ 2018, 'Longitudinal assessment of late-onset neurologic conditions in survivors of childhood central nervous system tumors: A Childhood Cancer Survivor Study report', Neuro-Oncology, vol. 20, no. 1, pp. 132-142. https://doi.org/10.1093/neuonc/nox148
Wells, Elizabeth M. ; Ullrich, Nicole J. ; Seidel, Kristy ; Leisenring, Wendy ; Sklar, Charles A. ; Armstrong, Gregory T. ; DIller, Lisa ; King, Allison ; Krull, Kevin R. ; Neglia, Joseph P. ; Stovall, Marilyn ; Whelan, Kimberly ; Oeffinger, Kevin C. ; Robison, Leslie L. ; Packer, Roger J. / Longitudinal assessment of late-onset neurologic conditions in survivors of childhood central nervous system tumors : A Childhood Cancer Survivor Study report. In: Neuro-Oncology. 2018 ; Vol. 20, No. 1. pp. 132-142.
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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.",
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T1 - Longitudinal assessment of late-onset neurologic conditions in survivors of childhood central nervous system tumors

T2 - A Childhood Cancer Survivor Study report

AU - Wells, Elizabeth M.

AU - Ullrich, Nicole J.

AU - Seidel, Kristy

AU - Leisenring, Wendy

AU - Sklar, Charles A.

AU - Armstrong, Gregory T.

AU - DIller, Lisa

AU - King, Allison

AU - Krull, Kevin R.

AU - Neglia, Joseph P.

AU - Stovall, Marilyn

AU - Whelan, Kimberly

AU - Oeffinger, Kevin C.

AU - Robison, Leslie L.

AU - Packer, Roger J.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - childhood central nervous system tumor survivors

KW - late effects

KW - neurologic outcomes

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