paediatrics Brussels 17

VOLUME 22 NUMBER 15 AUGUST 1 2004

J OURNAL OF C LINICAL O NCOLOGY

O R I G I N A L R E P O R T

Preliminary Results From a Phase II Trial of Conformal Radiation Therapy and Evaluation of Radiation-Related CNS Effects for Pediatric Patients With Localized Ependymoma Thomas E. Merchant, Raymond K. Mulhern, Matthew J. Krasin, Larry E. Kun, Tani Williams, Chenghong Li, Xiaoping Xiong, Raja B. Khan, Robert H. Lustig, Frederick A. Boop, and Robert A. Sanford Purpose We conducted a phase II trial of conformal radiation therapy (CRT) for localized childhood ependymoma to determine whether the irradiated volume could be reduced to decrease CNS-related side effects without diminishing the rate of disease control. Patients and Methods Between July 1997 and January 2003, 88 pediatric patients (median age, 2.85 4.5 years) received CRT in which doses (59.4 Gy to 73 patients or 54.0 Gy after gross-total resection to 15 patients younger than 18 months) were administered to the gross tumor volume and a margin of 10 mm. Patients were categorized according to extent of resection (underwent gross total resection, n 74; near-total resection, n 6; subtotal resection, n 8), prior chemotherapy (n 16), tumor grade (anaplastic, n 35), and tumor location (infratentorial, n 68). An age-appropriate neurocognitive battery was administered before and serially after CRT. Results The median length of follow-up was 38.2 months ( 16.4 months); the 3-year progression-free survival estimate was 74.7% 5.7%. Local failure occurred in eight patients, distant failure in eight patients, and both in four patients. The cumulative incidence of local failure as a component of failure at 3 years was 14.8% 4.0%. Mean scores on all neurocognitive outcomes were stable and within normal limits, with more than half the cohort tested at or beyond 24 months. Conclusion Limited-volume irradiation achieves high rates of disease control in pediatric patients with ependymoma and results in stable neurocognitive outcomes. A B S T R A C T

From the Division of Radiation Oncol- ogy, Department of Biostatistics, Divi- sion of Behavioral Medicine, St Jude Children’s Research Hospital; Semmes- Murphey Neurologic and Spine Insti- tute; and Division of Pediatric Neurosurgery, University of Tennessee, College of Medicine, Memphis, TN; and Division of Pediatric Endocrinology, Uni- versity of California San Francisco, San Francisco, CA. Submitted November 24, 2003; accepted May 8, 2004. Supported in part by Cancer Center Support grant No. CA21765 from the National Cancer Institute, by Research Project grant No. RPG-99-252-01-CCE from the American Cancer Society, and by the American Lebanese Syrian Associated Charities. Authors’ disclosures of potential con- flicts of interest are found at the end of this article. Address reprint requests to Thomas E. Merchant, DO, PhD, Division of Radia- tion Oncology, St Jude Children’s Re- search Hospital, 332 N Lauderdale St, Memphis, TN 38105-2794; e-mail: thomas.merchant@stjude.org. © 2004 by American Society of Clinical Oncology

J Clin Oncol 22:3156-3162. © 2004 by American Society of Clinical Oncology

ominous for those who are very young at the time of treatment, has motivated investiga- tors to test strategies to delay or avoid the use of radiation in young children. However, cooperative group trials testing the use of chemotherapy to delay irradiation have met with limited success, reporting results inferior to those achieved for patients treated with im- mediate postoperative radiation therapy. 3-5 Conformal radiation therapy (CRT) is a spectrum of radiation treatment planning and delivery techniques developed to focus radiation and limit the highest doses to the

INTRODUCTION Ependymoma is a rare brain tumor that oc- curs in very young children: fewer than 150 cases per year occur in the United States among persons younger than 14 years. 1 Sur- gery and postoperative radiation therapy are essential to the successful management of ependymoma, but those who receive radia- tion therapy are at risk of side effects that negatively affect cognitive, endocrine, and neurologic function. 2 The specter of radiation-related side effects, which is most

0732-183X/04/2215-3156/$20.00 DOI: 10.1200/JCO.2004.11.142

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