Primary postoperative chemotherapy without radiotherapy for intracranial ependymoma in children

Abstract

Introduction: Intracranial ependymomas are the third most common histologic subtype of childhood brain tumor. Although ependymomas may occur at any age, about 50% are diagnosed in children younger than 5 years of age. In adults, most ependymomas are cortical, but 70% to 80% of the tumors that arise in children involve posterior fossa structures [1]. Ependymomas are often laterally placed, involving the brainstem and cerebellar peduncles, with contiguous involvement of multiple cranial nerves. The intramixture of the tumor with the cranial nerves and portions of the brainstem makes surgical resections diffi cult, and there is often a quandary as to whether to attempt a gross total resection, given the potential morbidity. This decision is made even more diffi cult because many studies suggest that patients who undergo total resections are more likely to have long-term disease control [1–3]. The histologic grading of ependymomas has been variably related to outcome, with most but not all studies demonstrating poorer survival for anaplastic tumors [1–3]. Most reports conclude that less than 5% of ependymomas are disseminated at the time of diagnosis. Thus, stratifi cation based on the extent of disease at the time of diagnosis is usually not particularly helpful. Similarly, robust prospective biologic predictors of outcome have yet to be identifi ed. Recent reports have demonstrated excellent 3to 5-year survival rates in children with totally resected ependymomas of the posterior fossa who receive postoperative radiotherapy to the primary tumor site [2]. Conformal radiotherapy techniques result in excellent disease control, with the caveat that many posterior fossa ependymomas extend to the lower brainstem or upper cervical cord, and these regions may need to be included in the radiation portal [2–4]. Somewhat reassuringly, neurocognitive outcome has been reported to be relatively unimpaired by the radiotherapy delivered, although this assumption must be considered somewhat preliminary [5]. The benefi t of chemotherapy for children with ependymomas is far from proven. Early studies suggested no benefi t from the addition of adjuvant chemotherapy when given during and after radiotherapy. Recently, other studies have suggested that chemotherapy given prior to radiation therapy may be of benefi t, especially in patients with anaplastic tumors. One of the rationales for the use of chemotherapy is to couple it with radiotherapy to improve survival. Another is to use chemotherapy to try to delay the need for radiotherapy, especially in patients thought to be most vulnerable to the deleterious long-term effects of radiotherapy—primarily children with large cortical lesions or younger children with lesions anywhere in the neuroaxis. There is no consensus on the age at which radiotherapy, including conformal radiotherapy, is safe. Some studies have used conformal radiotherapy in children as young as 1 year of age, and others have suggested the use of chemotherapy in order to delay radiation therapy until the child is at least 3 years old [2].