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these tumours may be similar to low-grade gliomas, where
no untoward impact on overall survival has been observed
following a ‘wait and see’ policy following surgery n
the other hand, no data about the impact of delaying RT on
tumour control and survival are available for adult patients
with totally resected low-grade ependymomas, and thus the
best postoperative policy remains controversial. The option
of a close observation and delaying irradiation until tumour
progression seems appropriate for individual clinical use on
type Rbasis for selected subsets of patients, such as thosewith
totally resected low-grade tumours. The standard treatment
volume should be defined according to modern conforma-
tional techniques and is limited to the pre-surgical tumour bed
with an added margin of 1–2 cm n a type C basis
in all low-grade lesions and on a type R
basis in high-grade supratentorial lesions
Craniospinal irradiation should be reserved for patients with
evidence of cranio-spinal seeding nd is suitable
for individual clinical use on type R basis in high-grade
infratentorial lesions based on their
high potential of tumour spread into the ventricular sys-
tem and into the spinal subarachnoid space] However,
prophylactic spinal irradiation did not seem to modify pat-
terns of failure or high-grade
lesions, which disseminated into the spine in 8–9.4% of
patients treated with and in 6.6–10% without craniospinal
irradiation Moreover, local recurrence is the pre-
dominant pattern of failure for both low-grade and high-grade
ependymomas and the lack of local con-
trol represents the main risk factor for subarachnoid seeding
which rises from 3.3–5% to 8.5–10% based on either
the absence or presence of local recurrence inally,
no survival advantage has been demonstrated for cranio-
spinal irradiation nd the rate of spinal seeding
among high-grade tumours may be overestimated since
most authors have not excluded ependymoblastomas, and
treatment-related toxicity remains a serious concern, espe-
cially in small children Little is known about the
optimal radiation schedules dose to be employed. Doses
>45 Gy r >50 Gy ave been shown
to be superior to lower doses. Other authors did not observe
differences in outcome using doses of 40–50 Gy or of
50–55 Gy standard dose, on type Rbasis, of 54–60 Gy,
should be delivered to the tumour bed. Whenever possible,
the dose to the optic chiasm should be limited to 55.8 Gy, to
the upper cervical spinal cord to 54 Gy and to the optic nerves
to 50.4 Gy ecently, the issue of treatment duration was
addressed in a series of 34 patients collected over e period of
33 years he authors concluded that treatment duration
was the most important prognostic factor.
6.3. Chemotherapy
Information concerning the activity of chemotherapy in
ependymoma is very limited. The role of postoperative
chemotherapy has been assessed in a randomised phase III
trial of childrenwith infratentorial ependymoma, without evi-
dence of survival benefit urrently, there is no proof that
the addition of chemotherapy to radiotherapy improves out-
come and application of adjuvant chemotherapy should not be
recommended as standard treatment and should be restricted
to investigational trials
6.4. Treatment of recurrent disease
A standard salvage therapy for recurrent ependymoma
has not been identified. Second surgery and re-irradiation
can be suitable for individual clinical use. Patients with
ependymoma failure provide an important opportunity for
prospective investigation of potentially effective drugs, and
their inclusion in investigational multi-centre clinical trials
should strongly be encouraged. Cisplatin and carboplatin are
the most extensively tested single agents, showing response
rates of 31% and 13%, respectively, in a total of about 30
patients Therefore, chemotherapy including cisplatin
may be suitable for individual clinical use. Among the other
few agents which have been assessed in 10 cases or more,
are ifosfamide, thiotepa, arizidinybenzoquinone, dibromod-
ulcitol, idarubicin and PCNU. None of these has achieved a
better than 10% response rate Anecdotal experiences
with procarbazine, vincristine and cytarabine have not been
encouraging, while etoposide achieved two responses in nine
cases A few combinations of agents have been investi-
gated, mainly in infants and young children. There are only a
few trials including more than 20 cases, in which 48% of 25
children, under 3 years of age responded to a combination of
vincristine and cyclophosphamide nd 55% of 21 cases
responded to a combination of procarbazine, ifosfamide,
etoposide, high-dose methotrexate, cisplatin and cytarabine
High-dose chemotherapy has also undergone limited
clinical investigation in children, without proven benefits and
up to 33% treatment-related fatal toxicities To
date this approach should be considered not recommended.
6.5. New active drugs and therapeutic options
Since the inability to eradicate the primary tumour in
both low- and high-grade ependymomas is the single most
important factor of treatment failure more aggres-
sive local therapies are being assessed in clinical trials to
improve tumour control. Stereotactic radiosurgery has given
favourable results in small series as a first-line nd
as a salvage treatment nd deserves further evalua-
tion. Conformational radiotherapy as hyperfractionated dose
schedules have also been explored, and may help decreas-
ing local failure rate in subtotally resected patients
Among the new drugs, topotecan and paclitaxel have been
investigated, however without evidence of activity hile
preliminary experience with temozolomide, as reported in
abstract form, seems somewhat more encouraging The
use of temozolomide should be further examined in the con-
text of a clinical trial.