Clinical Investigation
Infant Ependymoma in a 10-Year AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) Experience With Omitted or Deferred Radiotherapy

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Purpose

The protocols of the 1990s omitted or delayed irradiation, using upfront chemotherapy to spare the youngest children with ependymoma the sequelae of radiotherapy (RT). We treated 41 children under the age of 3 years with intracranial ependymoma between 1994 and 2003.

Patients and Methods

After surgery, chemotherapy was given as follows: regimen I with four blocks of vincristine, high-dose methotrexate 5 g/m2, and cyclophosphamide 1.5 g/m2 alternating with cisplatin 90 mg/m2 plus VP16 450 mg/m2 for 14 months; subsequently, regimen II was used: VEC (VCR, VP16 300 mg/m2, and cyclophosphamide 3 g/m2) for 6 months. Radiotherapy was planned for residual tumor after the completion of chemotherapy or for progression.

Results

We treated 23 boys and 18 girls who were a median 22 months old; 14 were given regimen I, 27 were given regimen II; 22 underwent complete resection, 19 had residual tumor. Ependymoma was Grade 2 in 25 patients and Grade 3 in 16; tumors were infratentorial in 37 patients and supratentorial in 4. One child had intracranial metastases; 29 had progressed locally after a median 9 months. Event-free survival was 26% at 3 and 5 years and 23% at 8 years. One child died of sepsis, and another developed a glioblastoma 72 months after RT. Progression-free survival was 27% at 3, 5, and 8 years, and overall survival was 48%, 37%, and 28% at 3, 5, and 8 years, respectively. Of the 13 survivors, 6 never received RT; their intellectual outcome did not differ significantly in those children than in those without RT.

Conclusions

Our results confirm poor rates of event-free survival and overall survival for up-front chemotherapy in infant ependymoma. No better neurocognitive outcome was demonstrated in the few survivors who never received RT.

Introduction

Until 10 years ago, there was strong evidence that younger children with ependymoma had a higher risk of recurrence or adverse outcome, both after tailored treatment, frequently omitting or delaying radiotherapy (RT), and given specific biologic features (1). Nowadays, the cutoff age of 3 years for risk stratification (2), or 4 or 5 years in some studies (3), seems to coincide with undertreatment, more because of earlier concern about RT damaging the developing brain than because of any intrinsically more severe prognostic factors (4).

The protocols of the 1990s aimed to omit or delay RT in favor of upfront chemotherapy to spare surviving children the late effects of radiation 3, 5, 6, 7. Taking this approach, we treated 41 children under 3 years of age at the time of their diagnosis, and their outcome forms the subject of this study.

Section snippets

Patients and Methods

Children with posterior fossa or supratentorial ependymoma were eligible for the study if they met the following criteria: (1) age under 3 years at diagnosis; 2) histologically proven ependymoma; (3) no previous exposure to chemotherapy (except for steroids) or RT; (4) normal cardiac, hepatic, and renal function; (5) a Lansky score exceeding 30. More than one surgical procedure was accepted to maximize resection before adjuvant treatment. The adjuvant chemotherapy protocols were approved by the

Results

From 1994 to 2003, 41 patients—(23 boys and 18 girls, with a median age of 22 months (range, 3–36 months)—were treated at 14 AIEOP centers. At the time of this report, the median follow-up for the surviving children was 100 months (range, 14–181 months). Patients were divided by age at diagnosis into three groups: 4 patients were under 1 year old, 22 were between 1 and 2 years old, and 15 were over 2 years old. Fourteen children were treated with regimen I, and the other 27 children were

Discussion

In the early 1990s, many multiinstitutional clinical trials on malignant brain tumors occurring in children under 3 years old were designed mainly with a view to postponing RT. This approach was prompted by the favorable results reported in 1993, for some histologic subtypes at least, by Duffner et al. (2), who used chemotherapy systematically for malignant brain tumors, deferring any RT until the child reached the age of 3.

The harmful effects of RT, which are particularly severe in young

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    Supported in part by the Associazione Italiana per la Ricerca sul Cancro.

    Conflict of interest: none.

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