paediatrics Brussels 17

Int. J. Radiation Oncology Biol. Phys., Vol. 46, No. 2, pp. 287–295, 2000 Copyright © 2000 Elsevier Science Inc. Printed in the USA. All rights reserved 0360-3016/00/$–see front matter

PII S0360-3016(99)00414-9

CLINICAL INVESTIGATION

Brain

COMBINED POSTOPERATIVE IRRADIATION AND CHEMOTHERAPY FOR ANAPLASTIC EPENDYMOMAS IN CHILDHOOD: RESULTS OF THE GERMAN PROSPECTIVE TRIALS HIT 88/89 AND HIT 91 B EATE T IMMERMANN , M.D.,* R OLF -D IETER K ORTMANN , M.D.,* J OACHIM K¨ UHL , M.D., † C HRISTOPH M EISNER , M.A., ‡ I RENE S LAVC , M.D., § T HORSTEN P IETSCH , M.D., \ AND M ICHAEL B AMBERG , M.D.* *Department of Radiooncology, University of Tu¨bingen, Tu¨bingen, Germany; † Children’s Hospital, University of Wu¨rzburg, Wu¨rzburg, Germany; ‡ Institute for Medical Information Processing, University of Tu¨bingen, Tu¨bingen, Germany; § Children’s Hospital, General Hospital Vienna, Vienna, Austria; \ Institute of Neuropathology, University of Bonn, Bonn, Germany Purpose: To evaluate the outcome in children with anaplastic ependymomas after surgery, irradiation, and chemotherapy; and to identify prognostic factors for survival. Methods and Materials: Fifty-five children ( n 5 27 girls, 28 boys; median age at diagnosis, 6.2 years) with newly diagnosed anaplastic ependymomas were treated in the multicenter, prospective trials HIT 88/89 and HIT 91. Macroscopic complete resection was achieved in 28 patients; 27 patients underwent incomplete resection. All patients received chemotherapy before ( n 5 40) or after irradiation ( n 5 15). The irradiation volume encom- passed either the neuraxis followed by a boost to the primary tumor site ( n 5 40) or the tumor region only ( n 5 13). No radiotherapy was administered in two patients. Results: Median follow-up was 38 months. The overall survival rate at 3 years after surgery was 75.6%. Disease progression occurred in 25 children with local progression occurring in 20. The median time to disease progression was 45 months. The only significant prognostic factor was the extent of resection (estimated progression-free survival [EPFS] after 3 years was 83.3% after complete resection and 38.5% after incomplete resection) and the presence of metastases at the time of diagnosis (0% vs. 65.8% 3-year EPFS in localized tumors). Age, sex, tumor site, mode of chemotherapy, and irradiation volume did not influence survival. Conclusions: Treatment centers should be meticulous about surgery and diagnostic workup. Because the primary tumor region is the predominant site of failure it is important to intensify local treatment. Dose escalation by hyperfractionation or stereotactic radiotherapy might be a promising approach in macroscopically residual disease. The role of adjuvant chemotherapy requires further study. © 2000 Elsevier Science Inc.

Anaplastic ependymoma, Children, Radiotherapy, Chemotherapy.

INTRODUCTION

neuroradiological imaging, neurosurgical techniques, post- operative care, and the precision of radiotherapy. However, predictive factors are still controversial, and there is no agreement on standard therapy. During the past several decades, prophylactic irradiation of the neuraxis was recommended following surgical resec- tion of the tumor (4–6). Nearly all authors have agreed with the importance of achieving macroscopically complete tu- mor resection (7–10). In contrast, the role of adjuvant che- motherapy in the treatment regimen has not been defined. We present the results from an analysis of patients with anaplastic ependymomas treated in two prospective multi- center trials undertaken to evaluate survival after combined therapy and the validity of prognostic factors for survival.

The incidence of ependymomas in the pediatric age group is low, constituting usually less than 10% of all intracranial tumors, with an incidence of 2.2 to 2.7/100,000 per year (1). Two-thirds of low- and high-grade ependymomas localize infratentorially and about one-third localize supratentori- ally. This tumor carries the risk of meningeal dissemination, which occurs in 2% to 30% of patients (2). Previous series, most of them retrospective, have shown a probability of recurrence after 5 years of 50%, with the majority of failures occurring at the site of the primary disease (3, 4). Over the past 25 years, there has been progressive im- provement in treatment results, stemming from advances in Reprint requests to: Beate Timmermann, M.A., Eberhard-Karls Universita¨t, Klinik fu¨r Strahlentherapie, Hoppe-Seyler-Str. 3, 72076 Tu¨bingen, Germany. E-mail: betimmer@med.uni-tuebingen.de Presented at the 40th Annual Meeting of the American Society for Therapeutic Radiology and Oncology in Phoenix, AZ, October 25–29, 1998.

Acknowledgments— The authors thank Julia Becker and Johanna Kirsch for their continuous support during this study. Accepted for publication 15 June 1999.

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