paediatrics Brussels 17

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skewed towards higher values. The median SRDChemo achieved was 0·97, very close to the protocol ideal of unity, but ranged from 0·59 (a patient receiving cycle 1 only) to 1·46 (a patient receiving all seven cycles who was

Median time to progression for the 59 patients who progressed was 1·6 years (range 0·1–10·2). The 3-year event-free survival for all 89 patients was 42·7% (95% CI 32·2–52·8) and 5-year 37·5% (27·3–47·7) (figure 3). As would be anticipated, event-free survival was poorer for those with metastatic disease (HR 4·1, 95% CI 2·0–8·7, p<0·0001) with all progressing within 3 years. In the non-metastatic patients, the 3-year and 5-year event-free survival was 47·6% (36·2–58·1) and 41·8% (30·7–52·6). No significant difference was seen in event-free survival at 5 years between non-metastatic patients with WHO grades II and III disease: 38·4% (95% CI 26·6–50·0) and 41·7% (15·3–66·5), respectively. For the 51 patients alive at last follow-up, the median follow up was 6·0 years (range 1·5–11·3). 38 patients died: 34 due to tumour, four from post–surgical complications. The 3-year overall survival for the whole group was 76·8% (95% CI 66·4–84·4) and the 5-year overall survival was 60·0% (95% CI 48·4–69·7). As expected, survival was poorer for those with metastatic disease (hazard ratio [HR] 3·0 [95% CI 1·2–7·3], p=0·016) (figure 4). In the non-metastatic patients, the 3-year and 5-year overall survival was 79·3% (95% CI 68·5–86·8) and 63·4% (51·2–73·4), respectively. Although the numbers were small, 14 children, those younger than 1 year at diagnosis, seemed to have the poorest survival, although this was not significant: 44% were alive at 5 years compared with 65% for those aged between 2 and 3 years at diagnosis (HR 1·4 [95% CI 0·9–2·2]; p=0·18; table 5). Whether the patient was male or female did not seem to affect outcome. Tumour location in the supratentorium was associated with a better survival than for patients with infratentorial tumours (83% vs 56%), but this comparison was not significant (HR 3·1 [95% CI 0·8–12·5]; p=0·12; table 5). The 5-year overall survival for grade II disease was 61·5% (95% CI 48·2–72·4) and 66·7% (33·7–86·0) for grade III. Patients with a complete resection, based on neurosurgical review, had better 5-year event-free survival (48·9% [95% CI 33·8–62·8]), than those with partial resection or biopsy alone (25·8% [13·7–39·6]). Importantly, there was a difference in 5-year overall survival (68·1% [51·2–80·2] vs 51·8% [35·6–65·8]) for complete versus incomplete resection, although this is not firmly established with our study sample size (p=0·07; figure 5). Overall survival based on the radiological assessment of residual tumour showed that complete resection did not confer a better outcome (p=0·28). From our analysis neurosurgical rather than radiological assessment of completeness of resection was a more powerful predictor of outcome (data not shown). The actual distribution of the SRDChemo achieved from the combination chemotherapy schedule of table 1 varied according to the total number of cycles received by each patient. There was a tendency towards lower SRDChemo in those who had the fewest cycles, whereas in those who had all seven cycles, the distribution is

N

HR for death (95% CI) p

Age <1 year at diagnosis

14 31 76 30 45 55 32

1·4 (0·9-2·2) 1·1 (0·5-2·1) 3·1 (0·8-12·5) 1·6 (0·8-3·2) 1·8 (0·9-3·6) 1·5 (0·7-3·0) 1·6 (1·0-2·7)

0·18 0·13 0·12 0·15 0·07 0·28 0·04

Female sex

Infratentorial ependymoma

WHO III histology

Partial resection (judged by neurosurgeon) Partial resection (judged by radiological review)

Dose intensity <0·8

Table 5: Risks from different potential prognostic variables

1·00

Less than full total resection Full total resection

0·75

0·50

Overall survival (%)

0·25

0·00

12

0

2

4

6

8

10

Time from surgery (years)

Total resection 44 Partial resection 45 Numbers at risk

41 38

29

17

11

6

·· ··

21

12

7

3

Figure 5: Overall survival based on neurosurgical assessment of the extent of resection at the end of surgery

1·00

0·75

0·50

Overall survival (%)

0·25

RDIChemo <0·79 RDIChemo 0·80–0·94 RDIChemo >0·95

0·00

0

1

2

3

4

5

6

Survival from end of chemotherapy (years)

Numbers at risk

RDIChemo 0·50–0·79 32 RDIChemo 0·80–0·94 33 RDIChemo 0·95–1·41 23

28 31 21

21

15 19 18

12 17 13

8

7

27 19

15 10

14

8

Figure 6: Overall survival from end of chemotherapy by relative dose intensity chemotherapy (RDIChemo) received

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