paediatrics Brussels 17

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

EATE

IMMERMANN

, M.D.,* R

OLF

-D

IETER

ORTMANN

, M.D.,* J

OACHIM

K¨

UHL

, M.D.,

†

HRISTOPH

EISNER

, M.A.,

‡

RENE

LAVC

, M.D.,

HORSTEN

IETSCH

, M.D.,

AND

ICHAEL

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 (

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 (

40) or after irradiation (

15). The irradiation volume encom-

passed either the neuraxis followed by a boost to the primary tumor site (

40) or the tumor region only (

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

Anaplastic ependymoma, Children, Radiotherapy, Chemotherapy.

INTRODUCTION

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

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.

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.

Int. J. Radiation Oncology Biol. Phys., Vol. 46, No. 2, pp. 287–295, 2000

0360-3016/00/$–see front matter

287