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Articles

262

www.thelancet.com/oncology

Vol 10 March 2009

of brainstem ischaemia on postoperative T2-weighted

MRI, required tracheostomy, and had postoperative

hypertension needing medication. Two of the three also

had a history of a postoperative seizures. There were no

other cases of necrosis and no other patients had a

similar constellation of clinical signs and symptoms

before or during radiotherapy. Including all three cases

of necrosis, the cumulative incidence of brainstem

necrosis at 7 years was 2·5% (95% CI 0·0–5·2);

excluding the patient who died after a seizure, it was

1·6% (0·0–4·0).

Seizure disorders required chronic medication in five

patients with supratentorial tumour location. Two needed

surgery for epilepsy and were able to reduce or stop

medication. There was one case of radiation-related

cerebral vasculopathy in a patient with infratentorial

tumour location that required revascularisation surgery.

The patient was aged 12 months at the time of irradiation

and the high-dose volume encompassed the Circle of

Willis.

7-year estimates of local control, EFS, and overall survival

were 87·3% (95% CI 77·5–97·1), 69·1% (56·9–81·3), and

81·0% (71·0–91·0), respectively (figure 2). Median time to

progression was 22·5 months (range 5·0–90·9) from

diagnosis and 20·3 months (3·1–75·4) from the start of

conformal radiotherapy.

Univariate analyses of overall survival by various clinical

variables are presented in table 2. Multiple regression

analysis showed overall survival was affected by tumour

grade, extent of resection, and ethnic origin: gross-total

resection was associated with a lower risk of death from

any cause than was near-total or subtotal resection

(HR 0·16 [95% CI 0·07–0·37]; p<0·0001), while the risk of

death was greater in patients with anaplastic tumours

than in those with differentiated tumours (HR 3·98

[1·51–10·48]; p=0·0052) and in non-white patients versus

white patients (HR 3·0 [1·21–7·44]; p=0·018). However,

death from necrosis accounted for the lower overall

survival in non-white patients, compared with white

patients: when we excluded the two patients who died of

necrosis, the comparison of ethnic origin was not

significant for overall survival (HR 2·1 [0·8–5·7]; p=0·16

by univariate analysis). The use of chemotherapy before

conformal radiotherapy was associated with a lower overall

N Event-free survival (%)

Overall survival (%)

5 years (95% CI)

7 years (95% CI)

HR (95% CI)

p

5 years (95% CI)

7 years (95% CI)

HR (95% CI)

p

Tumour grade

Differentiated

68 86·4 (76·8–96·0)

79·2 (66·1–92·3)

1·0

0·005 91·9 (84·3–99·5)

89·4 (79·6–99·2)

1·0

0·006

Anaplastic

85

61·3 (46·4–76·2)

61·3 (38·8–83·8)

2·58 (1·30–5·12)

··

78·3 (66·3–90·3)

71·8 (52·6–91·0)

3·56 (1·37–9·22)

··

Tumour location

Infratentorial

122

71·1 (60·5–81·7)

65·8 (52·7–78·9)

1·0

0·16 84·0 (75·6–92·4)

80·5 (69·5–91·5)

1·0

0·6

Supratentorial

31

82·9 (66·6–99·2)

82·9 (57·6–100·0)

0·52 (0·20–1·32)

··

89·5 (76·8–100·0)

83·1 (59·4–100·0) 0·75 (0·25–2·22)

··

Ethnic origin

White

126 75·5 (66·3–84·7)

70·4 (57·7–83·1)

1·0

0·26 87·7 (80·6–94·8)

84·5 (74·7–94·3)

1·0

0·017

Other

27

64·5 (30·8–98·2)

64·5 (30·8–98·2)

1·55 (0·71–3·38)

··

72·9 (44·9–100·0)

60·7 (27·4–94·0)

2·84 (1·16–6·92)

··

Sex

Female

58 84·7 (73·9–95·5)

81·0 (66·3–95·7)

1·0

0·018 91·8 (83·8–99·8)

88·6 (76·8–100·0) 1·0

0·091

Male

95

66·7 (53·4–80·0)

61·0 (43·4–78·6)

2·40 (1·13–5·06)

··

81·1 (70·1–92·1)

76·0 (61·1–90·9)

2·20 (0·86–5·61)

··

Age at CRT (years)

≥3

75

79·0 (66·8–91·2)

69·4 (52·2–86·6)

1·0

0·37

90·1 (81·1–99·1)

81·7 (68·0–95·4)

1·0

0·46

<3

78 68·6 (55·7–81·5)

68·6 (52·1–85·1)

1·34 (0·71–2·52)

··

80·4 (69·8–91·0)

80·4 (66·1–94·7)

1·37 (0·60–3·12)

··

Total dose (Gy)

54

22

80·7 (61·5–99·9)

70·6 (44·1–97·1)

1·0

0·67

85·4 (68·9–100·0)

77·7 (53·8–100·0) 1·0

0·82

59·4

131

72·4 (62·4–82·4)

68·8 (55·5–82·1)

1·04 (0·87–1·24)

··

85·0 (77·0–93·0)

81·6 (70·8–92·4)

0·98 (0·80–1·19)

··

Number of surgical procedures

1

87

79·7 (69·3–90·1)

74·4 (60·3–88·5)

0·55 (0·29–1·02)

0·056 90·1 (82·7–97·5)

83·9 (72·3–95·5)

0·56 (0·24–1·26)

0·15

2–4

66 65·6 (49·5–81·7)

62·0 (41·2–82·8)

1·0

··

78·4 (64·5–92·3)

78·4 (60·6–96·2)

1·0

··

Surgical extent

GTR

125

81·5 (72·7–90·3)

77·3 (65·0–89·6)

0·21 (0·11–0·40)

<0·

0001 93·0 (87·3–98·7)

88·0 (78·8–97·2)

0·16 (0·07–0·36)

<0·0001

NTR or STR

28 41·0 (17·7–64·3)

34·2 (12·1–56·3)

1·0

··

52·4 (25·5–79·3)

52·4 (25·5–79·3)

1·0

··

Pre-CRT chemotherapy

Yes

35

59·4 (39·6–79·2)

48·7 (26·0–71·4)

1·0

0·008 73·6 (55·6–91·6)

66·9 (43·0–90·8)

1·0

0·038

No

118 78·1 (68·3–87·9)

75·9 (62·8–89·0)

0·43 (0·22–0·81)

··

88·6 (81·3–95·9)

85·3 (75·1–95·5)

0·42 (0·18–0·98)

··

HR=hazard ratio. CRT=conformal radiotherapy. GTR=gross-total resection. NTR=near-total resection. STR=subtotal resection.

Table 2:

Univariate analysis of event-free survival and overall survival according to different variables