1597 / 1708
experimental chemotherapy was recommended to follow,
and radiotherapy was recommended for children older than
18 months.
Radiotherapy
Infratentorial and metastatic tumors were to be treated
by irradiation of the neuraxis, followed by a boost to the
posterior fossa. For supratentorial ependymoma, treatment
volume should encompass the primary tumor site only,
unless the tumor was involving the ventricular system.
The prescribed total dose for the neuraxis covering the
whole subarachnoidal space was 35.2 Gy (1.6 Gy per
fraction, five times weekly). The posterior fossa was to
receive a boost dose of 20.0 Gy (2.0 Gy per fraction, five
times per week). For local radiotherapy, the prescribed total
dose was 54.0 Gy (2.0 Gy per fraction). The PTV should
encompass the primary tumour volume plus additionally a
2 cm safety margin. For children without any residual
disease or dissemination, total dose to the neuraxis was
allowed to be reduced to 24.0 Gy. The choice was at the
discretion of the local radiotherapist.
At the time of onset of the HIT-SKK trial no further
detailed guidelines for radiotherapy were included. In 1991,
the guidelines were specified and a quality assurance
program was integrated. Methods and results have been
published already elsewhere
[25,26]Statistical considerations
The data of children with anaplastic ependymoma, as
confirmed by the institutional pathologists, included in the
HIT-SKK87 and 92 trials served as basis for statistical
evaluation of prognostic factors and survival. Patients
were treated in 23 centers.
Documentation of disease was performed by the treating
centers. The clinical data was monitored at the Children’s
Hospital, University of Wu¨rzburg, Germany. Additional data
on radiotherapy was collected and monitored by the
Department of Radio-Oncology, University of Tu¨bingen,
Germany.
The follow-up period was defined as extending from the
date of surgery to the latest patient contact or event. The
length of survival was calculated from the date of surgery.
Terminal events were defined as date of death from any
cause (overall survival) or the date of first progression or
relapse after surgery (progression-free survival (PFS)). For
all patients alive without events, the length of survival was
censored for the statistical analysis as the last date of
documented contact with the patient. Data for patients who
died without evidence of progression was censored.
The Kaplan–Meier method was used to estimate overall
survival, and the log-rank test was applied for statistical
comparison of survival estimates. Data is presented with
nominal two-tailed p-values and 95% confidence intervals.
All analysis was carried out with the SAS Institute system for
Windows, version 8 software (SAS Institute, Cary, NC).
Results
Patient population
Thirty-four children with ependymoma were eligible
(median age, 20.5 months). Histopathologic findings were
MTX
5g/m2
CF-rescue
Procarbazine
100 mg/m2/d
VCR
1.5mg/m2
Day 1 (= 57) 8
14 15
29
43
Maintenance Chemotherapy
until RT
Induction Chemotherapy
before Maintenance
Procarbazine
100mg/d x 10
Ifosfamide
3g/m2/d x 3
Mesna
3g/m2/d x 5
Etoposide
150mg/m2/d x 3
MTX
5g/m2
CF-rescue
Cisplatin
40mg/m2/d x 3
Cytarabine
400mg/m2/ d x 3
Weeks 1
3
5
7
9
2
12
14
16
18
VCR
1.5mg/m2
VCR
1.5mg/m2
VCR
1.5mg/m2
VCR
1.5mg/m2
MTX
5g/m2
CF-rescue
MTX
5g/m2
CF-rescue
MTX
5g/m2
CF-rescue
Postoperative Chemotherapy
MTX
intraventricular
2mg/d1-4
Cyclophosphamide
i.v. 800 mg/m2/d1-3
VCR i.v.
1.5 mg/m2/d1
MTX
intraventricular
2mg/d1-2
MTX i.v. /24h
5 g/m2/d 1
VCR i.v.
1.5 mg/m2/d1
MTX
intraventricular
2mg/d1-2
MTX i.v. /24h
5 g/m2/d 1
VCR i.v.
1.5 mg/m2/d1
MTX
Intraventricular
2mg/d1-4
Carboplatin i.v.
200 mg/m2/d1-3
Etoposid i.v.
150 mg/m2/d1-3
Weeks 1 (= 10 = 19) 3
5
7
HIT
-
SKK
92
HIT
-
SKK
87
HIT
-
SKK
87
Fig. 2. Chemotherapy schedules.
Ependymomas in babies and infants
280