paediatrics Brussels 17

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Results 89 patients with a diagnosis of intracranial ependymoma from 21 participating centres were registered to the study between Dec 1, 1992, and April 31, 2003. Of these, 80 (90%) presented without metastatic disease and nine (10%) with imaging evidence of primary dissemination. Of the children with metastatic disease, three had nodular spinal leptomeningeal dissemination (M3), three had cerebral nodules (M2), and three had cranial and spinal disease (M3) present on pre-operative MRI images. Table 2 shows patients’ characteristics. The children were predominantly male (58 [66%]). 76 (85%) had infratentorial tumours. Pre-chemotherapy assessment was done consistent with a Lansky play scale of 70–90%.

proportion of the cumulative dose of the chemotherapy regimen actually received relative to that defined in the protocol (table 1). These proportions were then averaged over all patients receiving the regimen. The relative dose intensity (RDIChemo) adjusted the individual patient SRDChemo by the ratio of the time the regimen took to be given, divided by the corresponding protocol-defined time. These are then averaged for all patients to give the regimen RDIChemo. After surgery, patients were classified into four groups: those who (A) continue to be alive without progression and without radiotherapy; (B) have disease progression, or die without progression first being documented, but who do not receive radiotherapy; (C) receive elective radiotherapy without documentation of progression; or (D) receive radiotherapy after progression. Of the corresponding survival times in these groups, those in A were censored for all events, whereas those for B, C, and D represent times to competing events. A competing event is one which, if it occurs, prevents another event from being observed. In the presence of competing risks, the cumulative incidence method 19 estimates the cumulative probability for each cause of failure for B, C, or D in the presence of all risks to the patients concerned. If the radiotherapy-free survival (RADFS) rate is calculated, which adds all the event types together, then (1–RADFS) is the sum of the three separate cumulative incidences. Event-free survival was defined as the time from date of surgery to the date of the first event—ie, a recurrence or death. When death followed recurrence, the event was the recurrence. Overall survival was calculated as the time from the date of surgery to death from any cause. Patients still alive were censored at the date last seen. Survival probabilities were calculated using the Kaplan-Meier method. The hazard ratios and 95% CIs for comparing metastatic and non-metastatic patients were estimated using the Cox proportional hazards model. The potential influences of age, sex, histology, tumour site, and extent of resection on the hazard ratio were also investigated with the Cox model. 20 The effect of the RDIChemo was assessed by calculating the residual overall survival time from 1-year after the start of chemotherapy. 21 The protocol of this trial is currently under review to ensure it complies with good clinical practice, and the revised protocol will be registered in a publicly accessible database upon completion. Role of the funding source The sponsor of the study had no role in the study design, conduct of the study, data collection, data management, data analysis, data interpretation, preparation of the report, review of the report, or approval of the report. RGG, SAW, CLW, KR, JI, TC, WKC, NT, DWE, and DM had full access to all of the raw data and RGG had final responsibility to submit for publication.

0·6

Elective radiotherapy but no progression (C) Radiotherapy after progression (D) No radiotherapy despite progression (B)

0·4

0·2

Event-free survival (%)

0·0

12

0

2

4

6

8

10

Event-free survival (years)

Numbers at risk of competing events

79

51

33

20

12

9

··

Figure 2: Competing risks analysis for patients with non-metastatic ependymoma

Number of relapses (n=59)

5-year overall survival from the date of relapse (95% CI)

Relapse site Local relapse site

47

26 (13-41)

Local and metastatic relapse

6 4

Too early to tell Too early to tell

Metastatic relapse only

Unknown

1 1

0 0

Perioperative death

WHO grade WHO primary tumour grade II WHO primary tumour grade III

37 22

30 (13-48) 25 (8-47)

Surgery No surgery after relapse Surgery after relapse

28 30

24 (8-44) 31 (13-51)

Perioperative death

1

0

Radiotherapy No radiotherapy after relapse Radiotherapy without surgery Radiotherapy with surgery

18 17 23

Too early to tell

20 (5-43) 32 (11-55)

Perioperative death

1

0

Table 4 : Outcome in patients with a first relapse after primary treatment

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