Radiation Dose Escalation for Localized Ependymoma

Abstract

Ependymomas are glial tumors most often diagnosed in the pediatric population. World Health Organization (WHO) grade II and III histologies are treated with surgery and radiation therapy (RT) as standard of care. Prospective studies have shown delivery of doses up to 59.4 Gy is safe and feasible in the pediatric population with impressive treatment outcomes(1). Currently, no randomized studies exist evaluating the effect of dose escalation above 54.0 Gy on survival in localized ependymoma, and higher doses may pose a greater risk of brainstem toxicity. In this study, we seek to evaluate the effect of radiation dose escalation on overall survival in patients with localized ependymoma using data from the National Cancer Data Base (NCDB). Patients with localized WHO grade II and III ependymoma treated from 2010 to 2014 were identified from the NCDB. Overall survival (OS) between those patients receiving 54.0 Gy or ≥59.4 Gy was compared using Cox proportional hazards regression and propensity score matching. Factors associated with receipt of high dose RT were assessed using multivariable logistic regression analysis. A total of 554 patients were included. Of these, 281 (51%) were ≤18 years of age and 264 (48%) had WHO grade III disease. Gross total resection was performed in 339 cases (61%), subtotal resection in 133 (24%), and biopsy only in 82 (15%). Chemotherapy was given in 105 cases (19%). Patients received 54.0 Gy (n=224, 46%) or ≥59.4 Gy (n=330, 54%). On multivariable analysis, WHO grade III histology and tumor size >4 cm were associated with receipt of high-dose RT. Multivariate analysis revealed no significant difference in OS between patients receiving 54.0 Gy and those receiving ≥59.4 Gy (hazard ratio (HR)=1.00, 95% CI: 0.56-1.78, p=0.98). Propensity score matching confirmed the absence of a statistically significant difference in OS between the dose levels. In this national cohort, dose escalation ≥59.4 Gy did not result in improved OS among patients with localized high-grade ependymoma. A significant limitation of this study is the inability to evaluate local control outcomes based on dose, which may be improved with dose escalation. Further prospective study of the role of dose escalation in localized ependymoma is warranted. 1. Merchant TE, Li C, Xiong X, et al. Conformal radiotherapy after surgery for paediatric ependymoma: a prospective study. Lancet Oncol. 2009;10:258–266.