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radiotherapy Six of the total 15 children had anaplastic
histology and no further specific clinical parameters were
listed separately for ependymoma patients. In the series of
White et al., 5/14 children younger than 4 years of age with
ependymomas survived after receiving a VETOPEC-based
early chemotherapy . All patients had M0 stage though,
and information about the proportions of anaplastic tumors
and irradiated patients is missing in the report. Radiotherapy
was reserved for relapse in the report of Ater et al., who
administered MOPP-Chemotherapy to infants less than 3
years of age . Five ependymomas were included, two
survived; one of them received salvage radiotherapy.
Local control is the most important aspect of treatment
in ependymomas; most treatment failures occur locally.
Several trials have shown that complete surgery is a strong
prognostic factor in these tumors .
In Children’s Cancer Group (CCG) Protocol 921, patients with
gross total resection had a 5-year progression free survival of
66%, compared to 11% for those with residual disease In
the analysis of the German HIT trials for children with
anaplastic ependymoma above 3 years of age, a 3-year PFS of
83.3% could be achieved after complete resection,
compared to only 38.5% after incomplete surgery . In
our analysis, babies and infants receiving complete surgery
also show an advantage, with 3-year PFS of 41.2%, compared
to only 12.5% after incomplete resection. Still, the
importance of the operative procedure is very clear and
there have been groups reporting successful treatment of
intracranial ependymoma with surgery alone . Palma et
al. reported that six out of 12 children survived without any
adjuvant therapy; only one child experienced late recur-
rence In young children omission of adjuvant, therapy
could significantly reduce the risk of late morbidity, thus,
potentially favoring an attempt to remove remaining tumor
at second surgery. On the other hand, the risks of aggressive
surgery are high in young children and the role of surgery
without adjuvant radiation is still uncertain. Ependymomas
have not been supposed to be very chemo-responsive in the
past. In a randomized CCG trial for children over 3 years of
age, vincristine and lomustine were found to be of no benefit
for ependymoma . In the CCG trial for infants, including
five children with measurable postoperative disease, no
child with intracranial ependymoma achieved complete or
even partial response after receiving chemotherapy .
Response rates reported in other retrospective studies range
from 0 to 48% In the Australia–New Zealand trial,
seven children were evaluable for response to chemother-
apy, and six achieved either complete or partial response,
but only five of 14 children with ependymoma survived, none
of those with initial dissemination Duffner et al.
concluded from her re-analysis of the Baby-POG I trial that
ependymoma might be chemo-sensitive, but not chemo-
curable, because long delay of radiotherapy reduced survival
rates despite intensive interposed chemotherapy . In our
series, only three out of 13 children treated with
chemotherapy alone survived.
Historically, surgery alone resulted in 5-year survival
rates of less than 30%, comprising all ranges of histological
grade and degree of surgery After employing adjuvant
irradiation routinely, survival could be improved signifi-
cantly, with survival rates of up to 60% in older children
. The irradiation volume encompassed the
whole neuraxis in most of the children, which led to
significant late sequelae Later trials
attempted to delay or omit radiation therapy in infants.
The Baby-POG I trial treated 48 children with intracranial
ependymoma under the age of 3 years. First analysis resulted
in promising 3-year overall survival rates of 61.8% These
findings did not persist. The children developed late
recurrences and new analysis revealed the benefit of not
delaying radiotherapy for any longer than 1 year, with 5-year
overall survival rates of 63.3%. When radiotherapy was
delayed for 2 years, 5-year overall survival rate was only
25.7% They concluded that delay of radiotherapy of
more than 1 year adversely affected survival. Several trials
tried to delay or avoid radiotherapy: the CCG trial by
administering postoperatively the ‘eight-in-one’ regimen,
the M.D. Anderson Cancer Center study MOPP chemother-
apy, and the Australia–New Zealand study by giving
Vincristine, etoposide and intensive cyclophosphamide. But
all of these studies included only 5–15 children and could not
lead to strong conclusions regarding radiotherapy .
In our trial, the 3-year overall survival rate of 21 children
who were irradiated was 66.7%, compared to only 38.5% for
those receiving no radiotherapy. We failed to answer the
question if radiotherapy can be delayed until recurrence.
However, only two of nine children receiving radiotherapy
after developing progression survived without any further
progression. Nowadays, the irradiation of intracranial
ependymoma without dissemination has changed signifi-
cantly. Most of the brain tumor groups recommend
encompassing the tumor bed only, because as with our
findings, no benefit could be detected of irradiating the
whole CNS of patients with non-disseminated ependymoma
. This reduction of irradiated central nervous tissue
will lead to reduction of the risk of late sequelae. The
efficacy of chemotherapy is still unclear and the predomi-
nance of local failures indicates the need for local treatment
approaches. Therefore, we feel that the avoidance or long
delay of local radiotherapy even in young children with
ependymoma is not yet justified. This is in accordance with
the current Children’s Oncology Group trial (COG ACNS0121)
implementing RT even for very young children with localized
ependymoma . Regarding the optimal doses for radio-
therapy, we cannot draw any conclusion from our analysis
because of the small group and inhomogeneous treatments.
Retrospective series indicate that total doses greater than
45 Gy must be delivered to the tumor site Merchant
et al. studied anaplastic ependymoma and found a positive
influence of increasing the local dose
There is consensus that local relapse is the major cause of
failure in ependymoma . In accord-
ance in our analysis, all children failed locally and, in 76% of
the cases, the site of failure was solely local.
Age at diagnosis was found to be an important prognostic
factor for ependymomas. In previous studies, children below
3–6 years had a lower survival rate than older patients
There is little data concerning the impact of age
in the subgroup of infants and babies. Duffner et al. revealed
a significant difference between the two age groups (A: 0–24
months vs. B: 24–36 months) with 5-year survival rates of
25.7% compared to 63.3%, but the younger children had a
B. Timmermann et al. / Radiotherapy and Oncology 77 (2005) 278–285 283