paediatrics Brussels 17

I. J. Radiation Oncology d Biology d Physics

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Volume 74, Number 5, 2009

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

Complete resection (%)

Radiation dose and type ( n )

Adjuvant chemotherapy ( n )

Patients ( n )

Investigator

Median age (y)

OS

PFS

Timmermann et al. (21)

55 (5)

51

6.2

54 Gy conventional and focal (13) 35 Gy CSI + 20 Gy focal boost (40) Not irradiated (2) 59.4 Gy conformal and focal (NI) 54 Gy for children <18 mo (NI) 54 Gy conventional and focal (12) 35 Gy CSI + bifractionated boost (1) Not irradiated (4) 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) 54 Gy conventional and focal (15) 35 Gy CSI + 20 Gy focal boost (23) Not irradiated (2) 60 Gy bifractionated and focal (18) 60 Gy bifractionated and focal + 6 Gy focal boost (5) 54 Gy bifractionated and focal (1) 70.7 Gy bifractionated and focal (14)

55

3 y, 76% 3 y, 59%

Merchant et al. (26)

88 (0)

84

2.8

5

NA 3 y, 75%

Massimino et al. (16)

63 (1)

73

NA 70 Gy bifractionated and focal (46)

14

5 y, 75% 5 y, 56%

Needle et al. (6)

19 (0)

47

7.5

16

NA 5 y, 74%

Agaoglu et al. (27)

40 (7)

50

5.5

22

5 y, 65% 5 y, 51%

Present study

24 (0)

67

9

None

3 y, 79.2% 3 y, 62.5%

5 y, 74% 5 y, 54.2%

Abbreviations: EP = ependymoma; OS = overall survival; PFS = progression-free survival; CSI = craniospinal irradiation; NI = no informa- tion; WBI = whole brain irradiation; NA = not available.

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

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,