Title

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

Authors

Vijay Ramaswamy
Thomas Hielscher
Stephen C. Mack
Alvaro Lassaletta
Tong Lin
Kristian W. Pajtler
David TW Jones
Betty Luu
Florence MG 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 KH van Landeghem
Mariarita Santi
Marie-Lise C. van Veelen
Erwin G. Van Meir
Satoru Osuka
Xing Fan
Karin M. Muraszko
Daniela PC Tirapelli
Sueli M. Oba-Shinjo
Suely KN 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

Document Type

Article

Publication Date

7-20-2016

Publication Title

Journal of clinical oncology

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.

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

PubMed ID

27269943

Volume

34

Issue

21

First Page

2468

Last Page

2477

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