Chemotherapy for intracranial ependymoma in adults

Abstract

BackgroundEpendymal tumors in adults are rare, accounting for less than 4 % of primary tumors of the central nervous system in this age group. The low prevalence of intracranial ependymoma in adults limits the ability to perform clinical trials. Therefore, treatment decisions are based on small, mostly retrospective studies and the role of chemotherapy has remained unclear.MethodsWe performed a retrospective study on 17 adult patients diagnosed with intracranial World Health Organisation grade II or III ependymoma, who were treated with chemotherapy at any time during the disease course. Benefit from chemotherapy was estimated by applying Macdonald criteria. Progression-free (PFS) and overall survival (OS) were calculated from start of chemotherapy, using the Kaplan-Meier method.ResultsEleven patients had supratentorial and 6 infratentorial tumors. Ten patients were treated with temozolomide (TMZ), 3 with procarbazine/lomustine/vincristine (PCV), 3 with platinum-based chemotherapy and 1 patient received epirubicin/ifosfamide. Response rates were as follows: TMZ 8/10 stable disease; PCV 3/3 stable disease; platinum-based chemotherapy 1/3 partial response; epirubicin/ifosfamide 1/1 complete response. PFS rates at 6, 12 and 24 months were 52.9, 35.3 and 23.5 %. OS rates at 6, 12 and 24 months were 82.4, 82.4 and 70.1 %. There was no indication for a favourable prognostic role of O6-methylguanyl-DNA-methyltransferase (MGMT) promoter methylation which was detected in 3/12 investigated tumors.ConclusionsSurvival outcomes in response to chemotherapy in adult intracranial ependymoma patients vary substantially, but individual patients may respond to any kind of chemotherapy. There were too few patients to compare survival data between chemotherapeutic subgroups.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2323-0) contains supplementary material, which is available to authorized users.

The current consensus on the clinical management of intracranial ependymoma and its distinct molecular variants

“…Cohorts of pediatric or adult patients in which the role of chemotherapy was retrospectively analyzed either failed to demonstrate a survival advantage or showed substantial variation between individual patients [3, 13, 28]. Two international randomized trials in children are currently comparing post-irradiation chemotherapy to observation only, SIOP Ependymoma II (Europe) and ACNS0831 (USA).…”

Ependymoma

“…Retrospective analyses of pediatric and adult cohorts, in which chemotherapy was part of the treatment of ependymoma patients, either failed to demonstrate survival advantages linked to chemotherapy or showed substantial variation between individual patients. [26][27][28] In children, the two international randomized trials described in the following, Children's Oncology Group (COG) ACNS0831 and International Society for Pediatric Oncology (SIOP) Ependymoma II, are currently comparing postirradiation chemotherapy to observation only. Intracranial ependymomas mainly present with locally invasive growth patterns but low metastatic potential (<10% at the time of first diagnosis).…”

“…The percentage of patients alive at 6 and 24 months was 82.4 and 70.1%, respectively, but the retrospective approach and small numbers prevent any conclusions favoring one regimen over another. 27 Temozolomide has been evaluated in a retrospective study of grade II and III ependymomas, and median PFS and median OS were reported as 9.69 and 30.55 months, respectively. 65 In two small studies, there was no correlation with MGMT methylation status and response to temozolomide .…”

“…65 In two small studies, there was no correlation with MGMT methylation status and response to temozolomide . 27,65 The Collaborative Ependymoma Research Network (CERN) has completed an uncontrolled phase II trial in unselected, recurrent ependymoma of temozolomide and lapatinib (to target the known expression of EGFR), but the final results have not been published (NCT00826241).…”

Classificação molecular de ependimomas pediátricos

“…E até o momento não há agentes quimioterápicos que podem ser rotineiramente recomendados(JUNG et al, 2018).A maioria dos estudos são retrospectivos, e regimes de quimioterapia baseados em Cisplatina têm sido empregados e parecem resultar em melhor resposta clínica, porém sem prolongar a SG e ou SLE(BRANDES et al, 2005). A temozolomida (TMZ), tratamento padrão para muitos tumores do SNC, apresentou eficácia em pacientes com EPN intracranianos recorrentes refratários à Cisplatina, todavia os estudos que mostram avaliações retrospectivas em pacientes grau II e III de que receberam TMZ são limitados(CHAMBERLAIN & JOHNSTON, 2009;GRAMATZKI et al, 2016;RUDÀ et al, 2018). O bevacizumab, um anticorpo monoclonal que tem como alvo o VEGF têm sido explorado em um estudo retrospectivo em EPNs recorrentes, demonstrando progressão de 6,4 meses e mediana de SG de 9,4 meses(GREEN et al, 2009).…”