1599 / 1708
Prognostic factors
Treatment related and clinical variables, which correlate
with overall survival and PFS, are listed in
Table 2. Among
the factors associated with PFS, younger age, male gender,
incomplete resection (
Fig. 4) and the presence of metastases
at time of diagnosis showed a negative trend, which did not
reach statistical significance. The children treated according
to HIT-SKK 87 fared better than those included in HIT-SKK 92.
Among the factors associated with overall survival, admin-
istration of radiotherapy showed a positive trend without
statistical significance (
Table 3 ). Administering radiotherapy
for prevention or salvage did not show correlation with
overall survival either. Nine children received radiotherapy
after progression or recurrence had occurred; only two of
them survived without further progression. Six children died
in spite of salvage irradiation; one is living with local
recurrence and is receiving salvage chemotherapy. Target
volume of radiotherapy was not found to impact survival
either. However, in the six children with dissemination
during or after chemotherapy, none received craniospinal
radiotherapy before dissemination; two failed after local
irradiation. In 13 children, radiotherapy was omitted and
only chemotherapy was given; three of them survived. In
these 13 children even after progression in nine children
either parents had refused treatment or, responsible
clinicians stated that general condition contradicted further
treatment. In metastatic ependymoma (
n
Z
5), two received
craniospinal irradiation, one local radiotherapy, and in two
children no irradiation was administered. Only one child
survived, who received craniospinal radiotherapy.
Discussion
Ependymomas in childhood are rare. However, ependy-
moma has a peak incidence in infants and babies
[27] .Only a
few large series refer to ependymoma in early infancy. As in
the German HIT trials, in most of the previous series all
malignant brain tumors were treated with the same
strategy. Different cut-off ages were chosen in those series
and no analysis focused on anaplastic ependymoma in
infancy only. In the HIT trials only anaplastic ependymomas
were included.
The current gold standard for treating ependymoma in
early infancy is hard to define. Until the early eighties
standard treatment was surgery followed by craniospinal or
focal radiotherapy
[4,5,11,40] .Because of severe adverse
effects that may occur when irradiating the central nervous
system in young children
[6,42,43] ,alternative treatment
approaches have been introduced by adding intensive
chemotherapy in order to delay or omit radiotherapy
[20,46]. Treatment results have been disappointing with
survival rates between 20 and 50%
[12,28,49] .Our strategy, including early postoperative chemother-
apy and selective radiotherapy when appropriate, resulted
in 3-year overall survival and PFS rates of 55.9 and 27.3%,
respectively, for all patients. These results are similar to
those previously reported. Geyer et al. observed a 3-year
PFS rate of 26% in 15 infants less than 18 months with
ependymomas after postoperative ‘eight-in-one’ chemo-
therapy with a subset of about 20% not receiving
Table 2
Univariate analysis of the correlation between patient and
treatment parameters and estimated PFS in 34 children with
ependymoma
Parameter
No. of
patients
(
n
Z
34)
3-Year PFS
rate (%)
95% CI
P
-value
Age
!
18 months 13
16.8
0–37.9
0.23
O
18 months 21
33.3
13.2–53.5
Sex
Male
18
17.7
0–35.9
0.26
Female
16
37.5
13.8–61.2
Metastases
a
M0
19
33.4
11.6–55.2 0.11
M1/2/3
5
0
0–0
Resection
Complete 18
41.2
17.8–64.6 0.07
Incomplete 16
12.5
0–28.7
Schedule
SKK 87
15
40.0
15.2–64.8 0.15
SKK 92
19
16.7
0–33.9
Histology
Reviewed 17
25.0
3.8–46.2 0.84
Not rev.
17
29.4
7.7–51.1
a
Children without CSF examination were excluded from this
analysis.
0
20
40
Progression free survival (months)
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
Probability
Complete res. ( n = 18)
Incomplete res. ( n = 16 )
p = 0.07
Fig. 4. Extent of resection and PFS.
Table 3
Univariate analysis of the correlation between radiotherapy
parameters and overall survival
Parameter of
radiotherapy
No. of
patients
3-Year OS
rate (%)
95% CI
P
-value
Given
21
66.7
46.5–86.8
Not given
13
38.5
12.0–64.9 0.21
Preventive 12
66.7
40.0–93.3
Salvage
9
66.7
35.9–97.5 0.62
CSI
C
boost
11
54.5
25.1–83.9
Local fields 10
80.0
55.2–100 0.69
Ependymomas in babies and infants
282