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Articles
700
http://oncology.thelancet.comVol 8 August 2007
After a central review, 59 (66%) of cases were designated
classic (WHO grade II) ependymoma. The local
histopathological grade was changed in 26 (29%)
tumours—14 cases changed from grade II to III, and
from grade III to II in 12. Cerebrospinal fluid (CSF)
cytology was examined in 37 patients (42%), with no
malignant cells detected.
44 (49%) had a complete resection of the primary
tumour, 41 (46%) had subtotal resection, and biopsy only
was done in three (3%), and one (1%) died perioperatively.
The concordance between the surgical report and central
radiology reviewwith respect to completeness of resection
was 68%.
The median start of chemotherapy was 23 days (range
0–81) after surgery. Five patients had a delay of more than
50 days (range 52–81). One patient had chemotherapy after
delayed second-look surgery. 51 (57%) completed all seven
cycles of chemotherapy. A further ten patients stopped
protocol treatment as they had been on treatment for over
1 year without completing all cycles, ninewere in remission,
and one had stable residual disease. Chemotherapy was
stopped early in 27 patients: 11 had disease progression,
ten had unacceptable toxicity, one had residual disease and
was irradiated, one patient had no tumour on imaging,
whereas for four patients no specific reason was given.
There was one postoperative death. Haematological toxicity
was the most common treatment-related problem, with
either grade 3 or 4 occurring in all patients (table 3). Only
two, one metastatic and one non-metastatic, patients had
grade 4 audiological toxicity.
50 of the 80 patients with non-metastatic disease
progressed, of whom 34 were irradiated for progression
(figure 1); eight were aged less than 3 years), and
16 patients with progressive disease were not irradiated
for reasons determined by the physician or parent. In
addition, two were irradiated (one younger than
2·5 years) despite no progression being reported. Thus,
44 (55%) patients with non-metastatic disease were not
irradiated. All nine patients who had metastatic disease
at diagnosis progressed. Six of these nine patients were
irradiated. As would be anticipated, the radiotherapy rate
was lower in those with a complete tumour resection:
18 of 44 (41%) compared to 24 of 44
(55%) of those not
fully resected.
Given that not all patients who progressed were
irradiated, to reflect more accurately the need for
radiotherapy, we used cumulative incidence methodology
(CIM)
19
to calculate radiotherapy-free survival. For all
89 patients, the 3-year and 5-year cumulative radiotherapy
rates were 44·6% (95% CI 34·5–56·2) and 49·3%
(38·8–61·0), respectively. The median time from surgery
to radiotherapy was 20·3 months (range 7·8–123·6) and
median age at irradiation was 3·6 years (range 1·5–11·9).
In non-metastatic patients, combining all who were
irradiated with those that were eligible for this treatment
modality (but did not receive it) perhaps reflects more
accurately the success of this chemotherapy protocol in
avoiding radiotherapy. The 5-year cumulative incidence
rate of freedom from radiotherapy for non-metastatic
patients was 42% (95% CI 32–53; 1-sum of all the curves in
figure 2).
In total, 59 patients including all nine with metastatic
disease progressed, 37 of whom subsequently died.
47 relapsed locally, four at a metastatic site, six at both local
and metastatic sites, one was unknown, and one child
died during surgery. In all 40 patients who received
radiotherapy for their progression, 23 also had surgery. Of
the remainder
who did not receive radiotherapy, seven
patients underwent surgery alone, two received alternative
chemotherapy, one was treated under a palliative care
regimen, eight had no further treatment, and one died
perioperatively (table 4).
0·25
0·50
0·75
0·00
Event-free survival (%)
1·00
Metastases
9
3
0
0
0
0
No metastases 80
51
34
21
15
9
Event-free survival (years)
Numbers at risk
Metastatic
Non-metastatic
0
2
4
6
8
10
12
··
··
0·25
0·50
0·75
0·00
Overall survival (%)
1·00
Metastases
9
7
3
0
0
0
No metastases
80
72
47
28
17
9
Time from surgery (years)
Numbers at risk
Metastatic
Non-metastatic
0
2
4
6
8
10
··
··
12
Figure 4:
Overall survival by presence or absence of metastases at diagnosis
Figure 3:
Event-free survival by presence or absence of metastases at diagnosis