paediatrics Brussels 17

RadiationOncology International Journal of biology physics

www.redjournal.org

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

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

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.

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.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.2014.06.058

Supported 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 .