paediatrics Brussels 17

Radiotherapy and Oncology 77 (2005) 278–285 www.thegreenjournal.com

Phase II trial

Role of radiotherapy in anaplastic ependymoma in children under age of 3 years: Results of the prospective German brain tumor trials HIT-SKK 87 and 92 * Beate Timmermann a,b, * , Rolf-Dieter Kortmann a , Joachim Ku¨hl c , Stefan Rutkowski c , Karin Dieckmann e , Christof Meisner d , Michael Bamberg a a Department of Radiooncology, University of Tu¨bingen, Tu¨bingen, Germany , b Division of Radiation Medicine, Paul Scherrer Institute, Villigen, Switzerland , c Children’s Hospital, University of Wu¨rzburg, Wu¨rzburg, Germany , d Institute of Medical Information Processing, University of Tu¨bingen, Tu¨bingen, Germany , e Department of Radiooncology, General Hospital, Vienna, Austria Background and purpose : To evaluate the outcome of very young children with anaplastic ependymoma after delayed or omitted radiotherapy (RT). Materials and methods : Children under age of 3 years with anaplastic ependymoma were enrolled in the HIT-SKK 87 trial from 1987. After surgery, low-risk patients (R0, M0) received maintenance chemotherapy until elective RT at age of three. In high-risk patients (R C , M C ) intensive induction chemotherapy was followed by maintenance chemotherapy and subsequently delayed RT. If there was, progression radiotherapy started immediately. In the HIT-SKK 92, trial MTX-based chemotherapy was applied. RT was administered in non-responders only. Results : Thirty-four children with anaplastic ependymoma were eligible (age 1.0–33.0 months). All children received chemotherapy. In 13 children, no RT was administered. Preventive RT after chemotherapy was given in nine, and salvage RT in 12 children. OS and PFS rates after 3-year were 55.9 and 27.3%, respectively. Twenty-five children relapsed. Positive impact on survival was observed in children with higher age, M0-stage, complete resection, and treatment with radiotherapy. Without RT only 3/13, children survived. Conclusion : Delaying RT jeopardizes survival even after intensive chemotherapy. Predominant site of failure is the primary tumor site. RT of the neuraxis should be omitted in localized disease. q 2006 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 77 (2005) 278–285. Abstract

Keywords: Very young children; Ependymomas; Radiation therapy; Chemotherapy

Ependymomas comprise between 5 and 10% of childhood brain tumors [37] . The peak incidence is in the first 3 years of life, where ependymoma account for up to 30% of childhood brain tumors [27,49] . In children, therapy requires a careful balance between toxicity and efficacy. In younger children, the developing brain is very sensitive to any insult. This may lead to severe late sequelae [6,16,19,22,23,32,42] . On the other hand, the prognosis in very young children is particularly poor [7,11,45] . Many attempts have been made to increase survival while reducing adverse side effects. Surgical resection of brain tumors in babies and infants is often difficult [5] . The risk of side effects of radiotherapy correlates inversely to the age of the child [42,43] . In the past postoperative radiotherapy of

the whole central nervous system was standard treatment for ependymoma [27,40] . In 1985, van Eys et al. reported the use of postoperative chemotherapy to avoid radiotherapy for infants [46] . Even though their results were not very promising, many study groups started to delay radiation therapy by early administration of chemotherapy. We present an analysis of infants and babies enrolled in prospective trials with postoperative chemotherapy. The purpose of the report is to present the disease control results for the very young children treated prospectively with postoperative chemotherapy in an effort to delay or avoid irradiation.

Materials and methods In 1987, the German Pediatric Society for Hematology and Oncology (GPOH) initiated a cooperative multi-institutional

* Presented at ECCO 12, Copenhagen, Denmark, 21–25.09.03.

0167-8140/$ - see front matter q 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.radonc.2005.10.016