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

2016; Lippincott Williams & Wilkins; Volume: 34; Issue: 21 Linguagem: Inglês

10.1200/jco.2015.65.7825

1527-7755

Vijay Ramaswamy, Thomas Hielscher, Stephen C. Mack, Álvaro Lassaletta, Tong Lin, Kristian W. Pajtler, David Jones, Betty Luu, Florence M.G. Cavalli, Kenneth Aldape, Marc Remke, Martin Mynarek, Stefan Rutkowski, Sridharan Gururangan, Roger E. McLendon, Eric Lipp, Christopher Dunham, Juliette Hukin, David D. Eisenstat, Dorcas Fulton, Frank K.H. van Landeghem, Mariarita Santi, Marie‐Lise C. van Veelen, Erwin G. Van Meir, Satoru Osuka, Xing Fan, Karin M. Muraszko, Daniela Pretti da Cunha Tirapelli, Sueli Mieko Oba‐Shinjo, Suely Kazue Nagahashi Marie, Carlos Gilberto Carlotti, Ji Yeoun Lee, Amulya A. Nageswara Rao, Caterina Giannini, Cláudia C. Faria, Sofia Nunes, Jaume Mora, Ronald L. Hamilton, Péter Hauser, Nada Jabado, Kevin Petrecca, Shin Jung, Luca Massimi, Massimo Zollo, Giuseppe Cinalli, László Bognár, Álmos Klekner, Tibor Hortobágyi, Sarah Leary, Ralph Ermoian, James M. Olson, Jeffrey R. Leonard, Corrine Gardner, Wiesława Grajkowska, Lola B. Chambless, Jason Cain, Charles G. Eberhart, Sama Ahsan, Maura Massimino, Felice Giangaspero, Francesca Romana Buttarelli, Roger J. Packer, Lyndsey Emery, William H. Yong, Horacio Soto, Linda M. Liau, Richard G. Everson, Andrew J. Grossbach, Tarek Shalaby, Michael Grotzer, Matthias A. Karajannis, David Zagzag, Helen Wheeler, Katja von Hoff, Marta M. Alonso, T. Tuñón, Ulrich Schüller, Karel Zitterbart, Jaroslav Štěrba, Jennifer A. Chan, Miguel A. Guzmán, Samer K. Elbabaa, Howard Colman, Girish Dhall, Paul G. Fisher, Maryam Fouladi, Amar Gajjar, Stewart Goldman, Eugene Hwang, Marcel Kool, Harshad Ladha, Elizabeth Vera‐Bolanos, Khalida Wani, Frank S. Lieberman, Tom Mikkelsen, Antonio Omuro, Ian F. Pollack, Michael D. Prados, H. Ian Robins, Riccardo Soffietti, Jing Wu, Phillipe Métellus, Uri Tabori, Ute Bartels, Éric Bouffet, Cynthia Hawkins, James T. Rutka, Peter B. Dirks, Stefan M. Pfister, Thomas E. Merchant, Mark R. Gilbert, Terri S. Armstrong, Andrey Korshunov, David W. Ellison, Michael D. Taylor,

Cancer Genomics and Diagnostics

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.