1588 / 1708
Hospital, University of Wu¨rzburg, Wu¨rzburg, Germany.
Additional data about radiotherapy were collected and mon-
itored by the Department of Radiooncology, University of
Tu¨bingen, Tu¨bingen, Germany. The follow-up period was
defined as extending from the date of surgery to the date of
last patient contact or last event. The length of survival was
calculated from the date of surgery. Terminal events were
defined as the date of death from any cause (overall surviv-
al), the date of progression (progression-free survival), or
the date of diagnosis, progression, or death (event-free
survival). For all patients alive without events, the length of
survival for the statistical analysis was considered the last
date of the documented contact with the patient. Data for
patients who died without evidence of progression were
censored.
The Kaplan-Meier method was used to estimate survival,
and the log-rank test was used for the statistical comparison
of survival estimates. We planned to perform a multivariate
analysis (Cox regression) only if more than one of the
potential prognostic factors showed a remarkable influence
in the univariate analysis (
p
,
0.1) and a minimum of 10%
of the patients had one of these risk factors. All statistical
analyses in this study were done for descriptive purposes.
Data are presented with nominal two-tailed
p
values (unad-
justed for multiple comparisons) and 95% confidence inter-
vals. All analyses were carried out with the SAS system for
Windows 6.1 software (SAS Institute, Cary, NC).
RESULTS
Patient population
Seventy-one children were treated for anaplastic
ependymoma. Pathologic findings were reviewed in 51
(71.8%) children. Sixteen children were excluded from
evaluation because the pathologic results of the review
committee revealed low-grade ependymoma (
n
5
1),
ependymoblastoma (
n
5
5), primitive neuroectodermal
tumor (
n
5
2), astrocytoma (
n
5
1), medulloblastoma
(
n
5
5), or glioblastoma (
n
5
2). Of 55 patients eligible
for the study (27 females and 28 males; age range 3.0 –
16.6 years; median, 6.2 years), pathologic review was
performed in 35 children. In 26 patients, the tumor site
was supratentorial (47.3%); in 29 children, the tumor site
was infratentorial (52.7%) (Table 1).
In 20 patients, leptomeningeal dissemination was evalu-
ated by CSF cytologic studies at presentation. Four patients
had positive CSF cytology findings; in 35 children, no CSF
findings were available, but the children underwent cranio-
spinal MRI. Metastases to the central nervous system (CNS)
were found in 2 children: 1 child had a spinal tumor in the
lumbosacral region, and the other child had cerebral dis-
semination as well as positive CSF findings. No metastases
outside the CNS were found (Table 2).
Treatment
Surgery.
All children underwent surgery. The extent of
resection was assessed by postoperative CT/MRI and was
considered macroscopically complete in 28 children and
incomplete in 27.
Chemotherapy.
Eighteen children in HIT 88/89 and 37
children in HIT 91 were treated. In the HIT 91 trial, 81% of
the patients were randomized; the parents of 7 children
refused randomization. All patients received adjuvant che-
motherapy; maintenance chemotherapy was performed in
15 children and sandwich chemotherapy in 40 children.
Radiotherapy.
Thirteen children were irradiated at the
primary tumor site only. The median total dose was 54.0 Gy
(1 patient received a dose of 55.8 Gy). The median dose per
fraction was 2.0 Gy (range, 1.8–2.0 Gy).
Forty children received craniospinal irradiation with an
additional boost to the posterior fossa. The median total
dose to the neuraxis was 35.2 Gy (range, 24.0–39.6 Gy);
15.0% of the patients received a dose of less than 30.0 Gy.
Table 1. Characteristics of 55 children with anaplastic
ependymomas treated in Germany and Austria, 1988–1997
Characteristic
No. of
patients
Percentage
Median age (range): 6.2 years (3–16)
Sex
Male
28
50.9
Female
27
49.1
Site
Infratentorial
29
52.7
Supratentorial
26
47.3
Metastases
M0
50
91.0
M1
3
5.4
M2/3
2
3.6
Surgery
Incomplete resection
27
49.1
Complete resection
28
50.9
HIT
88/89
18
32.7
91
37
67.3
Chemotherapy
Maintenance
15
27.3
Sandwich
40
72.7
Radiotherapy*
CSI
40
72.7
Local field
13
23.6
CSI
5
craniospinal irradiation.
* 2 children received no irradiation.
Table 2. Pattern of dissemination at time of diagnosis in 5
children
Age (years),
sex
Primary tumor
site
CSF
positive
Distant
metastases
M
stage
3.4, F
Infratentorial
Yes
No
M1
5.3, F
Supratentorial
Yes
No
M1
4.0, F
Infratentorial
Yes
No
M1
7.9, M Infratentorial
Yes
Cerebral
M2
8.7, M Infratentorial
Unknown Lumbosacral M3
CSF
5
cytologic analysis of cerebrospinal fluid.
289
Anaplastic ependymomas in childhood
●
B. T
IMMERMANN
et al.