Annals of Diagnostic Paediatric Pathology

84
of treatment options. In such circumstances the mentioned
factors with potential influence on survival were not independent
verieties, and multivariate analysis could not be performed.
We made a 2-step statistical analysis. First, comparability
of the subgroups of benign and anaplastic ependymomas
was ascertained, according to age, extent of surgery, type
of RT, and use of CHT. Then, we made a few separate comparisons
for comparable subgroups of patients in order to
analyse the potential influence of risk factors on actuarial EFS.
EFS probability curves were drawn, and their stratification
was studied using the log-rank test.
We did not study overall survival (OS), because recurrences
of tumors as well as their treatments were not analysed.
Results
Age of the patients ranged from 5 months to 18 years and 6
months (median 5 years 0 months). In 63 patients ependymomas
were located in the infratentorial space, and in 59 children
supratentorial tumors were found. In 61 patients the tumors
were totally, in 38 subtotally, and in 38 children partially
resected. In the remaining 5 cases only biopsies were
performed. In the years since 1981 thru 1999, the extent of
surgical tumor removal was evaluated on the basis of surgical
reports and postoperative control CTs. Since 1999, the intraoperative
estimation as well as postoperative MRI studies have
been used to determine the extent of surgical resection. All
pathological specimens were reviewed and devided into two
subgroups of 89 benign and 53 malignant (anaplastic) ependymomas.
Anaplastic tumors matched the following critera:
marked nuclear pleomorphism, high mitotic activity, necrosis,
vascular proliferation. 118 patients were treated with radiotherapy.
Radiotherapy significanty changed over the described
period of time, due to the developement of cobalttherapy
and linac technology as well as introduction of new
treatment protocols. To simplify the variety of problems concerning
radiotherapy, for further analysis we defined only two
main subgroups: 1. “local” radiotherapy (29 patients) and 2.
neuroaxis radiotherapy (89 patients). Untill 1996, irrespective
of the extent of surgical resection, all patients underwent
whole neuroaxis irradiation. Since1996 thru 2000, patients
after total removal of benign ependymomas were treated with
“local” radiotherapy. In 2000 the “wait and see” approach was
introduced after total removal of benign tumors. Partial resections
of benign ependymomas were followed by chemotherapy
and “local” RT. Anaplastic ependymomas after surgery were
treated with adjuvant chemotherapy followed by tumor bed
and ventricles irradiation, and maintenance chemotherapy. Two
different treatment approaches were tailored for children under
3 years of age. Total resection of benign ependymoma
was the only treatment modality. The rest of patients below 3
years of age (partial resection of benign tumor and all patients
with anaplastic ependymomas) were treated with 18-months’
chemotherapy without RT. The use of the whole neuroaxis
RT was reserved only for disseminated tumors. Chemotherapy
was used for the treatment of 58 patients. The median followup
period was 3 years and 2 months (ranging from 2 months
to 18 years and 6 months).
In the study group there were no significant differences
between patients with benign and anaplastic tumors according
to age and extent of resection. The use of neuroaxis vs. local RT
were close to the limit of signifficance (Table 1). The entire
study group was devided into 3 age-dependent subgroups. There
were 41 children below 3 years of age. In 75 patients, age ranged
from 3 to 10 years, and 26 patients were older than 10 years.
The list of subsequent comparisons of potential risk factors,
outcomes and statistical analysis are shown in Table 2.
The study revealed that age of patients significantly influenced
EFS.The lower the age, the worse the prognosis (Fig.
1). No differences were found concernig event-free survival
probabillities for the group of 83 patients with infratentorial
tumors vs. 59 patients with supratentorial ependymomas. Primary
tumor location did not influence EFS. Diagnosis of malignant
(anaplastic) ependymoma according to the mentioned
morphologic criteria was a marker of poor prognosis in the study
group (Fig. 2). Event-free survival probability for the group of
99/142 patients after total and subtotal tumor resection was better
than for the group of 43/142 patients after partial resection and
biopsy. Extent of surgical resection significantly influenced EFS
for the entire study group. Extent of surgical removal significantly
influenced EFS for benign tumors. The prognosis was
better for patients after total and subtotal resection of benign
ependymomas (Fig. 3). Event-free survival probability after total
and subtotal resection of grade III ependymomas was slightly
better than after less radical resection, but stratification of survival
curves was not significant. The comparison of EFS probabilities
for benign ependymomas treated with neuroaxis and
“local” RT revealed that EFS was better for the subgroup after
whole neuroaxis irradiation. It is rather confusing, taking into
account everyday clinical practice. Before 1996, all the cases
of intracranial ependymomas irrespective histological malignancy
and extent of surgical resection received whole neuroaxis
RT, whereas after 1996 neuroaxis irradiation was reserved for
disseminated lesions only. There was no statistically significant
difference between EFS probabilities for neuroaxis vs. “local”
(tumor bed or tumor bed + ventricles) RT for the patients
with malignant ependymomas. It was shown that introduction
(1997) of the standardized treatment protocols including: surgery,
adjuvant chemotherapy, tumor bed or tumor bed + ventricles
radiotherapy, and finally maintenance chemotherapy significantly
improved EFS probability for malignant ependymomas
(Fig. 4). Statistically significant stratification of EFS curves
for the patients treated with chemotherapy vs. patients treated
without chemotherapy after total or subtotal tumor removals
indicates that chemotherapy improved control of small tumor
residues (Fig. 5).
Discussion
Identification of clinical and pathological factors influencing
survival has a key role in improvement of treatment outcomes
in children suffering from intracranial ependymomas. Various
risk factors were proposed, and because of relatively small
and heterogenous groups of patients and different treatemt
protocols, the results of numerous studies differ considerably