Neurocognitive consequences of risk-adapted therapy for childhood medulloblastoma.
OBJECTIVE
This prospective, longitudinal study examined the effects of risk-adapted craniospinal irradiation (CSI) dose and the interactions of dose with age and time from diagnosis on intelligence quotient (IQ) and academic achievement (reading, spelling, and math) among patients treated for medulloblastoma (MB).


METHODS
Patients received serial neurocognitive testing spanning from 0 to 6.03 years after diagnosis (median, 3.14 years). The multi-institutional study included 111 patients, who were 3 to 20 years of age at diagnosis (median age, 7.4 years), treated for MB with risk-adapted CSI followed by four cycles of high-dose chemotherapy (cyclophosphamide, cisplatin, and vincristine) with stem-cell support. High-risk patients (HR; n = 37) received CSI to 36 to 39.6 Gy and conformal boost treatment of the primary site to 55.8 to 59.4 Gy. Average-risk patients (AR; n = 74) received CSI to 23.4 Gy and conformal boost treatment of the posterior fossa to 36.0 Gy and primary site to 55.8 Gy.


RESULTS
Multivariate modeling revealed statistically significant declines in mean IQ (-1.59 points/yr; P = .006), reading (-2.95 points/yr; P < .0001), spelling (-2.94 points/yr; P < .0001), and math (-1.87 points/yr; P = .003) scores for the entire group. The effects of risk-adapted radiation therapy on IQ, reading, and spelling were moderated by age, with the greatest rates of decline observed for the HR patients who were younger (< 7 years old) at diagnosis.


CONCLUSIONS
Young age at diagnosis was the most prominent risk factor for neurocognitive deficits among survivors of MB despite reductions in CSI dosing and efforts to limit the boost volume. Younger patients exhibited substantial problems with the development of reading skills.
Mulhern
Raymond K
RK
Division of Behavioral Medicine, Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.
Palmer
Shawna L
SL
Merchant
Thomas E
TE
Wallace
Dana
D
Kocak
Mehmet
M
Brouwers
Pim
P
Krull
Kevin
K
Chintagumpala
Murali
M
Stargatt
Robyn
R
Ashley
David M
DM
Tyc
Vida L
VL
Kun
Larry
L
Boyett
James
J
Gajjar
Amar
A
D000124:Achievement; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002528:Cerebellar Neoplasms / Q000523:psychology* / Q000628:therapy*; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000209:etiology*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007360:Intelligence; D008137:Longitudinal Studies; D008297:Male; D008527:Medulloblastoma / Q000523:psychology* / Q000628:therapy*; D011446:Prospective Studies; D013997:Time Factors