Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis

• Type of Material: Article
• Authors: Vijay Ramaswamy, Hospital for Sick Children; Thomas Hielscher, German Cancer Research Center; Stephen C. Mack, Hospital for Sick Children; Alvaro Lassaletta, Hospital for Sick Children; Tong Lin, St Jude Children's Research Hospital; Kristian W. Pajtler, German Cancer Research Center; David T. W. Jones, German Cancer Research Center; Betty Luu, Hospital for Sick Children; Erwin Van Meir, Emory University; Michael D. Taylor, Hospital for Sick Children
• Language: English
• Date: 2016-07-20
• Publisher: AMER SOC CLINICAL ONCOLOGY
• Publication Version: Final Published Version
• Copyright Statement: © 2016 by American Society of Clinical Oncology.
• Final Published Version (URL): http://dx.doi.org/10.1200/JCO.2015.65.7825
• Title of Journal or Parent Work: JOURNAL OF CLINICAL ONCOLOGY
• Volume: 34
• Issue: 21
• Start Page: 2468
• End Page: +
• Grant/Funding Information: See publication for full funding statement.
• Keywords: CHILDHOOD; Science & Technology; PEDIATRIC-PATIENTS; Oncology; CHILDREN; AGE; Life Sciences & Biomedicine; CRANIAL RADIATION; BRAIN-TUMORS; CHEMOTHERAPY; CONFORMAL RADIATION-THERAPY; NEWLY-DIAGNOSED EPENDYMOMA; PHASE-II TRIAL
• Research Categories: Health Sciences, Oncology; Biology, Radiation

Abstract

Purpose: Posterior fossa ependymoma comprises two distinct molecular variants termed EPN-PFA and EPN-PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known. Methods: Four independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses. Results: Molecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN-PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN-PFA, a substantial proportion of patients with EPN-PFB can be cured with surgery alone, and patients with relapsed EPN-PFB can often be treated successfully with delayed external-beam irradiation. Conclusion: The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN-PFA and EPN-PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN-PFA, even with adjuvant radiation therapy. Patients with EPN-PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence.