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Ependymomas in babies and infants

Table 2 Univariate analysis of the correlation between patient and treatment parameters and estimated PFS in 34 children with ependymoma

Table 3 Univariate analysis of the correlation between radiotherapy parameters and overall survival

Parameter of radiotherapy

No. of patients

3-Year OS rate (%)

95% CI

P -value

Parameter

No. of patients ( n Z 34)

3-Year PFS rate (%)

95% CI

P -value

Given

21 13

66.7 38.5 66.7 66.7 54.5 80.0

46.5–86.8

Not given

12.0–64.9 0.21

Age

Preventive 12

40.0–93.3

! 18 months 13 O 18 months 21

16.8 33.3

0–37.9

0.23

Salvage

9

35.9–97.5 0.62

13.2–53.5

CSI C boost

11

25.1–83.9

Sex

Local fields 10

55.2–100 0.69

Male

18 16

17.7 37.5

0–35.9

0.26

Female

13.8–61.2

Metastases a M0

19

33.4

11.6–55.2 0.11

M1/2/3

5

0

0–0

in spite of salvage irradiation; one is living with local recurrence and is receiving salvage chemotherapy. Target volume of radiotherapy was not found to impact survival either. However, in the six children with dissemination during or after chemotherapy, none received craniospinal radiotherapy before dissemination; two failed after local irradiation. In 13 children, radiotherapy was omitted and only chemotherapy was given; three of them survived. In these 13 children even after progression in nine children either parents had refused treatment or, responsible clinicians stated that general condition contradicted further treatment. In metastatic ependymoma ( n Z 5), two received craniospinal irradiation, one local radiotherapy, and in two children no irradiation was administered. Only one child survived, who received craniospinal radiotherapy. Discussion Ependymomas in childhood are rare. However, ependy- moma has a peak incidence in infants and babies [27] . Only a few large series refer to ependymoma in early infancy. As in the German HIT trials, in most of the previous series all malignant brain tumors were treated with the same strategy. Different cut-off ages were chosen in those series and no analysis focused on anaplastic ependymoma in infancy only. In the HIT trials only anaplastic ependymomas were included. The current gold standard for treating ependymoma in early infancy is hard to define. Until the early eighties standard treatment was surgery followed by craniospinal or focal radiotherapy [4,5,11,40] . Because of severe adverse effects that may occur when irradiating the central nervous system in young children [6,42,43] , alternative treatment approaches have been introduced by adding intensive chemotherapy in order to delay or omit radiotherapy [20,46] . Treatment results have been disappointing with survival rates between 20 and 50% [12,28,49] . Our strategy, including early postoperative chemother- apy and selective radiotherapy when appropriate, resulted in 3-year overall survival and PFS rates of 55.9 and 27.3%, respectively, for all patients. These results are similar to those previously reported. Geyer et al. observed a 3-year PFS rate of 26% in 15 infants less than 18 months with ependymomas after postoperative ‘eight-in-one’ chemo- therapy with a subset of about 20% not receiving

Resection

Complete 18 Incomplete 16

41.2 12.5

17.8–64.6 0.07

0–28.7

Schedule SKK 87

15 19

40.0 16.7

15.2–64.8 0.15

SKK 92

0–33.9

Histology

Reviewed 17

25.0 29.4

3.8–46.2 0.84

Not rev.

17

7.7–51.1

a Children without CSF examination were excluded from this analysis.

Prognostic factors Treatment related and clinical variables, which correlate with overall survival and PFS, are listed in Table 2 . Among the factors associated with PFS, younger age, male gender, incomplete resection ( Fig. 4 ) and the presence of metastases at time of diagnosis showed a negative trend, which did not reach statistical significance. The children treated according to HIT-SKK 87 fared better than those included in HIT-SKK 92. Among the factors associated with overall survival, admin- istration of radiotherapy showed a positive trend without statistical significance ( Table 3 ). Administering radiotherapy for prevention or salvage did not show correlation with overall survival either. Nine children received radiotherapy after progression or recurrence had occurred; only two of them survived without further progression. Six children died

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 Probability

Complete res. ( n = 18) Incomplete res. ( n = 16 )

p = 0.07

0

20 40 Progression free survival (months)

Fig. 4. Extent of resection and PFS.