Prognostic factors that increase the risk for reduced white matter volumes and deficits in attention and learning for survivors of childhood cancers.
OBJECTIVE
In children, CNS-directed cancer therapy is thought to result in decreased cerebral white matter volumes (WMV) and subsequent neurocognitive deficits. This study was designed as a prospective validation of the purported reduction in WMV, associated influential factors, and its relationship to neurocognitive deficits in a very large cohort of both acute lymphoblastic leukemia (ALL) and malignant brain tumors (BT) survivors in comparison to an age similar cohort of healthy sibling controls.


METHODS
The effects of host characteristics and CNS treatment intensity on WMV were investigated in 383 childhood cancer survivors (199 ALL, 184 BT) at least 12 months post-completion of therapy and 67 healthy siblings that served as a control group. t-Tests and multiple variable linear models were used to assess cross-sectional WMV and its relation with neurocognitive function.


RESULTS
BT survivors had lower WMV than ALL survivors, who had less than the control group. Increased CNS treatment intensity, younger age at treatment, and greater time since treatment were significantly associated with lower WMV. Additionally, cancer survivors did not perform as well as the control group on neurocognitive measures of intelligence, attention, and academic achievement. Reduced WMV had a larger impact on estimated IQ among females and children treated at a younger age.


CONCLUSIONS
Survivors of childhood cancer that have undergone higher intensity therapy at a younger age have significantly less WMV than their peers and this difference increases with time since therapy. Decreased WMV is associated with significantly lower scores in intelligence, attention, and academic performance in survivors.
Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee.
Wilburn E
WE
Reddick
Delaram J
DJ
Taghipour
John O
JO
Glass
Jason
J
Ashford
Xiaoping
X
Xiong
Shengjie
S
Wu
Melanie
M
Bonner
Raja B
RB
Khan
Heather M
HM
Conklin
D000367:Age Factors; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001288:Attention; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D001925:Brain Damage, Chronic / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology / Q000473:pathology; D001932:Brain Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000532:radiotherapy; D002648:Child; D002675:Child, Preschool; D016371:Cranial Irradiation / Q000009:adverse effects*; D003430:Cross-Sectional Studies; D004522:Educational Status; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007278:Injections, Spinal; D007360:Intelligence; D007859:Learning Disabilities / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D056784:Leukoencephalopathies / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use; D009483:Neuropsychological Tests; D009929:Organ Size; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000188:drug therapy / Q000532:radiotherapy; D011379:Prognosis; D011446:Prospective Studies; D011832:Radiation Injuries / Q000453:epidemiology / Q000209:etiology / Q000523:psychology; D012306:Risk; D017741:Survivors / Q000523:psychology
D000970:Antineoplastic Agents; D008774:Methylphenidate
cancer survivors; childhood ALL; computer-assisted image analysis; magnetic resonance imaging; malignant primary brain tumors; neuropsychology