Ependymoma: lessons from the past, prospects for the future

Abstract

Dear Editor: The invited review from Little et al. sheds a light on the potentially hazardous arbitrary decision-making process physicians may use in the management of intracranial ependymoma [6]. Based on their review of the literature, Little et al. conclude that “deferring adjuvant radiotherapy for low-risk patients with childhood ependymomas who have undergone complete resection is a reasonable treatment option”. This statement is problematic since a significant number of readers may consider it as a take home message and apply this recommendation in their daily practice. Unfortunately, the history of childhood ependymoma has already suffered the consequences of similar arbitrary statements in the early 1980 when Salazar et al., based on a review of autopsy material concluded that patients with high-grade ependymomas (regardless of location) or with low-grade infratentorial tumors with positive CSF or subarachnoid findings of spinal metastases should be treated with craniospinal radiation [9]. More than 20 years later and despite extensive evidence that craniospinal radiation does not improve survival in patients with ependymoma, some institutions still use this approach. This is a devastating example of the long-term implications of statements made by people considered as authorities in the field. In fact, Dr. Little’s conclusion that some children with completely resected ependymoma could be observed rather than irradiated might be right. However, one must first have a clear definition of low-risk ependymoma and how to tease out the subgroup of low-risk patients. The authors cite the work from Epstein reported in two different publications [1, 5]. This series is in reality significantly biased with regard to the age of the patients (median age 6 years old with a range of 3 to 21 years) and the location (50% supratentorial, 50% infratentorial) and this reflects a specific pattern of referral rather than a representative pediatric patient population. Similarly, Little et al. do not provide an overview of their results in their report and only describe a subset of patients successfully managed without radiation. The main challenge in this context is the selection of patients who may benefit from a deferral strategy. It is clear that histopathological criteria cannot be used unless a consensus on grading is achieved. The discrepancy between pathologists is illustrated by a proportion of WHO grade III ependymoma that ranges from 7% to 89% in a review of institutional series published the literature [2]. Other criteria such as the surgeon’s opinion or even the absence of residual tumor on postoperative MRI cannot always be considered as reliable parameters. Certainly the strongest evidence that deferral of radiation may be detrimental can be found in the results of so called “baby-brain experiences”. Groups in the USA, France, and UK used a postoperative chemotherapy approach in infants and children under 3 years of age [3, 4, 12]. These studies reported 5-year event-free survival (EFS) of 12%, 22%, and 47%, respectively. These rates are strikingly lower than the 76.9% 7-year EFS recently reported by Merchant et al. with the use of immediate postoperative radiation [7]. Nevertheless, in these baby-brain studies, 12 to 47% of the patients were successfully treated without postoperative radiation. Identification of these patients may become possible by objective biological risk stratification of pediatric ependymomas. Indeed, the strongest predictor of outcome in two large retrospective studies was the negative staining for human telomere reverse transcriptase (hTERT) [8, 10]. In Childs Nerv Syst (2009) 25:1383–1384 DOI 10.1007/s00381-009-0915-6