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Clinical Investigation
Critical Combinations of Radiation Dose
and Volume Predict Intelligence Quotient
and Academic Achievement Scores After
Craniospinal Irradiation in Children
With Medulloblastoma
Thomas E. Merchant, DO, PhD
, *Jane E. Schreiber, PhD,
y
Shengjie Wu, MS,
z
Renin Lukose, MS
, *Xiaoping Xiong, PhD,
z
and Amar Gajjar, MD
x
*Division of Radiation Oncology, and Departments of
y
Psychology,
z
Biostatistcs, and
x
Oncology,
St. Jude Children’s Research Hospital, Memphis, Tennessee
Received Jan 19, 2014, and in revised form Apr 16, 2014. Accepted for publication Jun 21, 2014.
Summary
The effects of radiation dose
and volume in patients with
medulloblastoma are largely
understood in terms of the
prescribed dose to the
neuraxis. This research
demonstrates an association
between radiation dose to
specific subvolumes of the
brain and decline in longitu-
dinal cognitive scores,
supporting the need to
further reduce radiation dose
and volume or modify the
distribution of dose in these
patients.
Purpose:
To prospectively follow children treated with craniospinal irradiation to
determine critical combinations of radiation dose and volume that would predict for
cognitive effects.
Methods and Materials:
Between 1996 and 2003, 58 patients (median age 8.14 years,
range 3.99-20.11 years) with medulloblastoma received risk-adapted craniospinal irra-
diation followed by dose-intense chemotherapy and were followed longitudinally with
multiple cognitive evaluations (through 5 years after treatment) that included intelli-
gence quotient (estimated intelligence quotient, full-scale, verbal, and performance)
and academic achievement (math, reading, spelling) tests. Craniospinal irradiation
consisted of 23.4 Gy for average-risk patients (nonmetastatic) and 36-39.6 Gy for
high-risk patients (metastatic or residual disease
>
1.5 cm
2
). The primary site was
treated using conformal or intensity modulated radiation therapy using a 2-cm clinical
target volume margin. The effect of clinical variables and radiation dose to different
brain volumes were modeled to estimate cognitive scores after treatment.
Results:
A decline with time for all test scores was observed for the entire cohort. Sex,
race, and cerebrospinal fluid shunt status had a significant impact on baseline scores.
Age and mean radiation dose to specific brain volumes, including the temporal lobes
and hippocampi, had a significant impact on longitudinal scores. Dichotomized dose
distributions at 25 Gy, 35 Gy, 45 Gy, and 55 Gy were modeled to show the impact
Reprint requests to: Thomas E. Merchant, DO, PhD, Division of
Radiation Oncology, St. Jude Children’s Research Hospital, 262 Danny
Thomas Place, Memphis, TN 38105. Tel: (901) 595-3604; E-mail:
thomas. merchant@stjude.orgSupported in part by the American Lebanese Syrian Associated
Charities.
Conflict of interest: none.
Supplementary material for this article can be found at
www.redjournal.org .Int J Radiation Oncol Biol Phys, Vol. 90, No. 3, pp. 554
e
561, 2014
0360-3016/$ - see front matter 2014 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.ijrobp.2014.06.058RadiationOncology
International Journal of
biology physics
www.redjournal.org