Elsevier

The Lancet Oncology

Volume 10, Issue 3, March 2009, Pages 258-266
The Lancet Oncology

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Conformal radiotherapy after surgery for paediatric ependymoma: a prospective study

https://doi.org/10.1016/S1470-2045(08)70342-5Get rights and content

Summary

Background

Therapy for ependymoma includes aggressive surgical intervention and radiotherapy administered by use of methods that keep the risk of side-effects to a minimum. We extended this treatment approach to include children under the age of 3 years with the aim of improving tumour control.

Methods

Between July 11, 1997, and Nov 18, 2007, 153 paediatric patients (median age 2·9 years [range 0·9–22·9 months]) with localised ependymoma were treated. 85 patients had anaplastic ependymoma; the tumours of 122 were located in the infratentorial region, and 35 had received previous chemotherapy. Patients received conformal radiotherapy after definitive surgery (125 patients had undergone gross total, 17 near total, and 11 subtotal resection). Doses of 59·4 Gy (n=131) or 54·0 Gy (n=22) were prescribed to a 10 mm margin around the target volume. Disease control, patterns of failure, and complications were recorded for patients followed over 10 years. Overall survival, event-free survival (EFS), cumulative incidence of local recurrences, and cumulative incidence of distant recurrences were assessed. Variables considered included tumour grade, tumour location, ethnic origin, sex, age when undergoing conformal radiotherapy, total radiotherapy dose, number of surgical procedures, surgery extent, and preradiotherapy chemotherapy.

Findings

After a median follow-up of 5·3 years (range 0·4–10·4), 23 patients had died and tumour progression noted in 36, including local (n=14), distant (n=15), and combined failure (n=7). 7-year 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. The cumulative incidences of local and distant failure were 16·3% (9·6–23·0) and 11·5% (5·9–17·1), respectively. In the 107 patients treated with immediate postoperative conformal radiotherapy (without delay or chemotherapy), 7-year local control, EFS, and overall survival were 88·7% (77·9–99·5), 76·9% (63·4–90·4), and 85·0% (74·2–95·8), respectively; the cumulative incidence of local and distant failure were 12·6% (5·1–20·1), and 8·6% (2·8–14·3), respectively. The incidence of secondary malignant brain tumour at 7 years was 2·3% (0–5·6) and brainstem necrosis 1·6% (0–4·0). Overall survival was affected by tumour grade (anaplastic vs differentiated: HR 3·98 [95% CI 1·51–10·48]; p=0·0052), extent of resection (gross total vs near total or subtotal: 0·16 [0·07–0·37]; p<0·0001), and ethnic origin (non-white vs white: 3·0 [1·21–7·44]; p=0·018). EFS was affected by tumour grade (anaplastic vs differentiated: 2·52 [1·27–5·01]; p=0·008), extent of resection (gross total vs near total or subtotal: 0·20 [0·11–0·39]; p<0·0001]), and sex (male vs female: 2·19 [1·03–4·66]; p=0·042). Local failure was affected by extent of resection (gross total vs near total or subtotal: 0·16 [0·067–0·38]; p<0·0001), sex (male vs female: 3·85 [1·10–13·52]; p=0·035), and age (<3 years vs ≥3 years: 3·25 [1·30–8·16]; p=0·012). Distant recurrence was only affected by tumour grade (anaplastic vs differentiated: 4·1 [1·2–14·0]; p=0·017).

Interpretation

Treatment of ependymoma should include surgery with the aim of gross-total resection and conformal, high-dose, postoperative irradiation. Future trials might consider treatment stratification based on sex and age.

Funding

American Cancer Society and American Lebanese Syrian Associated Charities (ALSAC).

Introduction

Newer methods of delivering radiotherapy combined with advances in neurosurgery have increased tumour control and reduced side-effects in paediatric patients with localised ependymoma. Preliminary findings from contemporary series using conformal, intensity-modulated, and proton-beam radiotherapy support this conclusion, with reduced side-effects and improved rates of local tumour control, event-free survival (EFS), and overall survival.1, 2, 3, 4 These results are especially relevant because ependymoma is commonly diagnosed in young patients and radiotherapy avoidance has had limited success.5, 6, 7 Fear of radiation-related side-effects has driven radiotherapy avoidance and the use of chemotherapy in young children. Recent data suggest that 42% of patients might avoid irradiation for up to 5 years after diagnosis by use of chemotherapy.5 Others suggest that fewer than 22% might benefit from this approach6 and that the role of chemotherapy is unproven.8 At stake is overall survival and functional outcome; patients treated with postoperative radiotherapy have better EFS and overall survival than those treated with chemotherapy.

Improved disease control provides a new opportunity to assess prognostic factors, patterns of failure, and late effects of treatment. We previously reported on the use of conformal radiotherapy for ependymoma in a prospective trial that included 88 paediatric patients treated by use of a 10 mm margin around the target volume with a median follow-up of 38 months.4 The 3-year EFS estimate was 74·7% (95% CI 63·5–85·9), median age at irradiation was 3 years (range 1·1–22·9), and few side-effects were noted. In the current report, we describe our findings with extended follow-up of these original patients and extend our single-institution series to now include a total of 153 patients.

Section snippets

Patients

Between July 11, 1997, and Nov 18, 2007, 153 patients were treated with conformal or intensity-modulated radiotherapy, with written informed consent from a parent or guardian. The data presented were current on April 20, 2008. The initial 88 patients were prospectively treated in a phase II trial, approved by the institutional review board (IRB), between July 11, 1997, and Feb 5, 2003. The study was amended, with IRB approval, to included similarly treated patients who were enrolled for

Results

Clinical and treatment characteristics are shown in table 1. All patients were treated with postoperative conformal radiotherapy. 35 of 153 patients (22·9%) received chemotherapy before conformal radiotherapy and 11 of 153 patients (7·2%) had a delay before treatment of more than 4·4 months because of complications, parental indecision, or planned observation. Two patients treated with chemotherapy and two observed after first surgery had local progression and underwent resection before

Discussion

This study highlights the long-term benefits—in terms of local tumour control, EFS, and overall survival—of gross-total resection (including undergoing second surgery as a requisite for patients with macroscopically incomplete resection after initial surgery) and high-dose postoperative radiotherapy for the treatment of children with localised ependymoma, even for those who are younger than 3 years. Although it is important to understand the pitfalls that limit a comparison between this and

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