LAUSR

AbstractOBJECTIVETo examine longitudinal neuropsychological functioning in children receiving treatment for medulloblastoma on COG clinical trial ACNS0331.METHODSChildren aged 3 and older diagnosed with medulloblastoma participated in neuropsychological testing as part of the original study design or in conjunction with COG protocol ALTE07C1. Children under 8 were randomized to receive craniospinal irradiation (CSI) of either 18 Gy (reduced dose) or 23.4 Gy (standard dose); all children aged 8+ received 23.4 Gy. All children received either a 54 Gy boost to the entire posterior fossa (standard boost) or tumor bed (reduced volume boost), plus standard chemotherapy. Intellectual functioning (IQ) of children was evaluated an average of 0.67 (+0.21) and 2.99 (+0.59) years post-diagnosis.RESULTSOf 464 eligible and evaluable patients enrolled on ACNS0331, 337 (72.6%) completed intellectual testing at one or both timepoints (mean age at diagnosis=9.1 [SD=4.06], range 3-19 years; 65.3% male; 83.1% white). Mean estimated IQ was in the average range at both timepoints (mean IQ T1=95.7 + 15.14; mean IQ T2=94.4 + 14.21), and declined an average of 2.2 (+ 9.98) points over time. Among children aged 3-7 at diagnosis, those randomized to standard dose CSI exhibited greater IQ declines over time than those in the lower-dose group (-7.2 vs. -0.4, respectively; p= .04). Among all ages, younger children (p <.01) and those who received a standard boost volume (p=.01) exhibited lower IQ at T2.CONCLUSIONSResults of this prospective, randomized clinical trial suggest that children receiving a boost to the whole posterior fossa experience steeper declines in intellectual functioning over time. In addition, reducing whole-brain dose for younger children was also associated with less decline. Results suggest that strategies to limit the CSI dose and/or boost volume in children treated for medulloblastoma may improve neuropsychological outcomes. These approaches need to be weighed against the possible impact on disease control.