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J Clin Oncol. 2016 Jul 20;34(21):2468-77. doi: 10.1200/JCO.2015.65.7825. Epub 2016 Jun 6.

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

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Vijay Ramaswamy, Stephen C. Mack, Alvaro Lassaletta, Betty Luu, Florence M.G. Cavalli, Uri Tabori, Ute Bartels, Eric Bouffet, Cynthia E. Hawkins, James T. Rutka, Peter Dirks, and Michael D. Taylor, The Hospital for Sick Children; Vijay Ramaswamy, Kenneth Aldape, James T. Rutka, and Michael D. Taylor, University of Toronto; Kenneth Aldape, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario; Christopher Dunham and Juliette Hukin, British Columbia Children's Hospital; Juliette Hukin, University of British Columbia, Vancouver, British Columbia; David D. Eisenstat, Dorcas Fulton, and Frank K.H. van Landeghem, University of Alberta, Edmonton; Jennifer A. Chan, University of Calgary, Calgary, Alberta; Nada Jabado and Kevin Petrecca, McGill University, Montreal, Quebec, Canada; Thomas Hielscher, Kristian W. Pajtler, David T.W. Jones, Marcel Kool, Stefan M. Pfister, and Andrey Korshunov, German Cancer Research Center; Stefan M. Pfister, University Hospital Heidelberg, Heidelberg; Marc Remke, University Hospital Düsseldorf, Düsseldorf; Martin Mynarek, Stefan Rutkowski, and Katja von Hoff, University Medical Center Hamburg-Eppendorf, Hamburg; Ulrich Schüller, Ludwig-Maximilians-Universität, Munich, Germany; Stephen C. Mack, Cleveland Clinic Foundation, Cleveland; Maryam Fouladi, University of Cincinnati, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Tong Lin, Amar Gajjar, Thomas E. Merchant, and David W. Ellison, St Jude Children's Research Hospital, Memphis; Lola B. Chambless, Vanderbilt Medical Center, Nashville, TN; Sridharan Gururangan, Roger E. McLendon, and Eric S. Lipp, Duke University, Durham; Jing Wu, University of North Carolina at Chapel Hill, Chapel Hill, NC; Mariarita Santi, Children's Hospital of Philadelphia; Lyndsey Emery, Hospital of the University of Pennsylvania, Philadelphia; Ronald L. Hamilton and Ian F. Pollack, University of Pittsburgh School of Medicine; Frank Lieberman, University of Pittsburgh Medical Cen



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.


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.


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.


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.

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