paediatrics Brussels 17

RadiationOncology International Journal of biology physics

www.redjournal.org

Clinical Investigation

Effect of Cerebellum Radiation Dosimetry on Cognitive Outcomes in Children With Infratentorial Ependymoma Thomas E. Merchant, DO, PhD, * Shelly Sharma, MD, * Xiaoping Xiong, PhD, y Shengjie Wu, MS, y and Heather Conklin, PhD z

*Division of Radiation Oncology and Departments of y Biostatistics and z Psychology, St. Jude Children’s Research Hospital, Memphis, Tennessee

Received Dec 21, 2013, and in revised form Mar 28, 2014. Accepted for publication Jun 18, 2014.

Summary This study associates longi- tudinal deficits in intelli- gence quotient (IQ) and academic achievement with collateral irradiation of the posterior cerebellum in chil- dren with infratentorial ependymoma. To further reduce cerebellum-linked neurocognitive deficits, radi- ation dose to the posterior cerebellum should be avoi- ded in treatment planning and delivery. Advanced methods of radiation therapy may be used to further opti- mize treatment of these patients.

Purpose: Cognitive decline is a recognized effect of radiation therapy (RT) in children treated for brain tumors. The importance of the cerebellum and its contribution to cognition have been recognized; however, the effect of RT on cerebellum-linked neu- rocognitive deficits has yet to be explored. Methods and Materials: Seventy-six children (39 males) at a median 3.3 years of age (range, 1-17 years old) were irradiated for infratentorial ependymoma from 1997 to 2008. The total prescribed dose was 54 to 59.4 Gy administered to the postoperative tumor bed with 5- or 10-mm clinical target volume margin. Age-appropriate cognitive and academic testing was performed prior to the start of RT and was then repeated at 6 months and annually throughout 5 years. The anterior and posterior cerebellum and other normal brain volumes were contoured on postcontrast, T1-weighted postopera- tive magnetic resonance images registered to treatment planning computed tomogra- phy images. Mean doses were calculated and used with time after RT and other clinical covariates to model their effect on neurocognitive test scores. Results: Considering only the statistically significant rates in longitudinal changes for test scores and models that included mean dose, there was a correlation between mean infratentorial dose and intelligence quotient (IQ; 0.190 patients/Gy/year; P Z .001), math ( 0.164 patients/Gy/year; P Z .010), reading ( 0.137 patients/Gy/year; P Z .011), and spelling scores ( 0.147 patients/Gy/year; P Z .012), where Gy was measured as the difference between the mean dose received by an individual patient and the mean dose received by the patient group. There was a correlation between mean anterior cerebellum dose and IQ scores ( 0.116 patients/Gy/year; P Z .042) and mean posterior cerebellum dose and IQ ( 0.150 patients/Gy/year; P Z .002), math

Reprint requests to: Thomas E. Merchant, DO, PhD, Division of Ra- diation Oncology, St. Jude Children’s Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105-3678. Tel: (901) 595-3604; E-mail: thomas.merchant@stjude.org This work was supported in part by National Cancer Institute Cancer Center grant CA21765 and American Cancer Society research project Int J Radiation Oncol Biol Phys, Vol. 90, No. 3, pp. 547 e 553, 2014 0360-3016/$ - see front matter 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ijrobp.2014.06.043

grant RPG-99-252-01-CCE and the American Lebanese Syrian and Associated Charities. Supplementary material for this article can be found at www.redjournal.org .