Prognostic factors in intracranial ependymomas in children

Object. The occurrence of intracranial ependymomas in children is relativel y infrequent, and their prognostic factors are still controversial, especia lly regarding histological composition. Methods. A retrospective study was conducted of 37 children treated during the last 20 years for intracranial ependymomas at the Hopital de la Timone. Both univariate and multivariate statistical analyses were performed to as sess the prognostic relevance of patient age and sex, extent of tumor remov al, location of the tumor (supratentorial compared with infratentorial, med ian compared with lateral), tumor histological composition, and adjuvant th erapies in affecting the 5 year progression-free survival (PFS) rate and ov erall survival (OS) rate. The following histopathological features, either alone or in combination, were analyzed: endothelial proliferation, necrosis , loss of differentiating structures (present compared with absent), the nu mber of mitotic figures per 10 hpf, and cellularity (number of nuclei/5 hpf ). In addition, immunohistochemical detection of Ki-67 antigen was performe d and the Ki-67 labeling index (LI) evaluated in all cases. The 5-year OS and PFS rates were 45% and 25%, respectively (median follow u p 34 months). Four patients died of disease without remission (median 163 d ays) and disease in 21 patients relapsed: 18 in situ and three both in situ and distantly. On univariate analysis total surgical resection and median infratentorial location were associated with a better outcome (p < 0.002) f or both OS and PFS. Loss of differentiating structures was associated with poor prognosis (p < 0.008) and the combination of necrosis, endothelial pro liferation, and mitotic index greater than 5 was also a negative predictive factor for both OS (p < 0.002) and PFS (p = 0.02). The PFS time was shorte r in patients younger than 4 years of age and in patients in whom a Ki-67 L I greater than 1 was found (p = 0.03 and 0.006, respectively). Adjuvant rad iotherapy and chemotherapy were not relevant to prognosis. Moreover, among the 15 patients in whom total excision was achieved, OS was better in those who did not receive adjuvant therapies. In contrast, adjuvant therapies si gnificantly enhanced PFS time in patients in whom tumor excision was incomp lete. Conclusions. This study and analysis of the literature further highlight th at total tumor removal is the treatment of choice for ependymomas in childr en. Postoperative measurement of residual tumor is required, especially bec ause a subgroup of patients might be treated by surgery alone. Median infra tentorial ependymomas have to be distinguished from the lateral type. Appro priate and reproducible histological parameters and Ki-67 LI are of interes t as predictors of outcome.