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


Vijay Ramaswamy
Thomas Hielscher
Stephen C Mack
Alvaro Lassaletta
Tong Lin
Kristian W Pajtler
David T W Jones
Betty Luu
Florence M G Cavalli
Kenneth Aldape
Marc Remke
Martin Mynarek
Stefan Rutkowski
Sridharan Gururangan
Roger E McLendon
Eric S 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 P C Tirapelli
Sueli M Oba-Shinjo
Suely K N Marie
Carlos G Carlotti
Ji Yeoun Lee
Amulya A Nageswara Rao
Caterina Giannini
Claudia C Faria
Sofia Nunes
Jaume Mora
Ronald L Hamilton
Peter Hauser
Nada Jabado
Kevin Petrecca
Shin Jung
Luca Massimi
Massimo Zollo
Giuseppe Cinalli
László Bognár
Almos Klekner
Tibor Hortobágyi
Sarah Leary
Ralph P Ermoian
James M Olson
Jeffrey R Leonard
Corrine Gardner
Wieslawa A Grajkowska
Lola B Chambless
Jason Cain
Charles G Eberhart
Sama Ahsan
Maura Massimino
Felice Giangaspero
Francesca R Buttarelli
Roger J Packer
Lyndsey Emery
William H Yong
Horacio Soto
Linda M Liau
Richard Everson
Andrew Grossbach
Tarek Shalaby
Michael Grotzer
Matthias A Karajannis
David Zagzag
Helen Wheeler
Katja von Hoff
Marta M Alonso
Teresa Tuñon
Ulrich Schüller
Karel Zitterbart
Jaroslav Sterba
Jennifer A Chan
Miguel Guzman
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 Lieberman
Tom Mikkelsen, Henry Ford Health SystemFollow
Antonio M Omuro
Ian F Pollack
Michael Prados
H Ian Robins
Riccardo Soffietti
Jing Wu
Phillipe Metellus
Uri Tabori
Ute Bartels
Eric Bouffet
Cynthia E Hawkins
James T Rutka
Peter Dirks
Stefan M Pfister
Thomas E Merchant
Mark R Gilbert
Terri S Armstrong
Andrey Korshunov
David W Ellison
Michael D Taylor

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Journal of clinical oncology


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.

Medical Subject Headings

Adolescent; Adult; Child; Child, Preschool; Cohort Studies; Combined Modality Therapy; Cytoreduction Surgical Procedures; Ependymoma; Female; Humans; Infant; Infratentorial Neoplasms; Male; Retrospective Studies

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