paediatrics Brussels 17

In children >5 years of age at diagnosis, the standard post-

operative treatment includes local RT. The rationale is that

more than one-half of EP patients relapse locally

(14)

. Major

debates are ongoing concerning the type of RT (

e.g.,

stan-

dard, conformational, hyperfractionated), the fields (local,

craniospinal) and doses to be used. Craniospinal RT is no

longer advocated for localized EP, unlike for medulloblas-

toma

(21–23)

. A dose–effect relationship has been suggested

by a retrospective analysis

(23) .

A consensus for delivering

doses >50 Gy is emerging

(14)

. HFRT involves giving

a smaller dose per fraction, with RT fractions administered

at least twice each day. The total radiation dose is increased

and the total treatment duration remains approximately the

same. Small doses given more than once a day, usually 6–8 h

apart, produce a redistribution of proliferating tumor cells,

with some cells entering a radiosensitive stage. Other nonpro-

liferating or dose-limiting tissues, such as normal brain, will

potentially be spared by this effect of redistribution. HFRT

exploits the differences in repair capacity between tumor

and late-responding normal tissues. To maintain an isoeffect

in tissues, owing to the sparing effect of smaller fractions (the

molecular mechanism of which is still hypothetical), the total

dose must be increased

(24)

. The efficacy of HFRT has been

shown in medulloblastoma

(5)

, and the results of the random-

ized primitive neuroectodermal tumor IV study are pending.

HFRT has never been reported as the sole treatment of EP.

Most series have used it in combination with chemotherapy

(6, 16, 25)

. Encouraging results have been reported by

Needle

et al.

(6)

for a short series of 19 children >5 years

of age. The 5-year PFS rate was 74% when chemotherapy

Table 4. Comparison of six different treatment strategies for intracranial EP after surgery

Investigator

Patients (

)

Complete resection

(%)

Median age (y)

Radiation dose and

type (

)

Adjuvant

chemotherapy (

)

PFS

Timmermann

et al.

(21)

55 (5)

6.2

54 Gy conventional

and focal (13)

3 y, 76% 3 y, 59%

35 Gy CSI + 20 Gy

focal boost (40)

Not irradiated (2)

Merchant

et al.

(26)

88 (0)

2.8

59.4 Gy conformal

and focal (NI)

NA 3 y, 75%

54 Gy for children

<18 mo (NI)

Massimino

et al.

(16)

63 (1)

NA 70 Gy bifractionated

and focal (46)

5 y, 75% 5 y, 56%

54 Gy conventional

and focal (12)

35 Gy CSI +

bifractionated

boost (1)

Not irradiated (4)

Needle

et al.

(6)

19 (0)

7.5

70.7 Gy

bifractionated and

focal (14)

NA 5 y, 74%

35 Gy bifractionated

CSI + 35 Gy boost

(2)

45 Gy conventional

and focal (1)

36 Gy CSI + 18 Gy

focal boost (1)

36 Gy WBI + 18 Gy

focal boost (1)

Agaoglu

et al.

(27)

40 (7)

5.5

54 Gy conventional

and focal (15)

5 y, 65% 5 y, 51%

35 Gy CSI + 20 Gy

focal boost (23)

Not irradiated (2)

Present study

24 (0)

60 Gy bifractionated

and focal (18)

None

3 y, 79.2% 3 y, 62.5%

60 Gy bifractionated

and focal + 6 Gy

focal boost (5)

5 y, 74% 5 y, 54.2%

54 Gy bifractionated

and focal (1)

Abbreviations:

EP = ependymoma; OS = overall survival; PFS = progression-free survival; CSI = craniospinal irradiation; NI = no informa-

tion; WBI = whole brain irradiation; NA = not available.

1540

I. J. Radiation Oncology

Biology

Physics

Volume 74, Number 5, 2009