Publication details

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

Authors	RAMASWAMY Vijay HIELSCHER Thomas MACK Stephen C. LASSALETTA Alvaro LIN Tong PAJTLER Kristian W. JONES David T.W. LUU Betty CAVALLI Florence M.G. ALDAPE Kenneth REMKE Marc MYNAREK Martin RUTKOWSKI Stefan GURURANGAN Sridharan MCLENDON Roger E. LIPP Eric S. DUNHAM Christopher HUKIN Juliette EISENSTAT David D. FULTON Dorcas LANDEGHEM Frank K. H. van SANTI Mariarita VEELEN Marie-Lise C. van VAN MEIR Erwin G. OSUKA Satoru FAN Xing MURASZKO Karin M. TIRAPELLI Daniela P.C. OBA-SHINJO Sueli M. MARIE Suely K.N. CARLOTTI Carlos G. LEE Ji Yeoun RAO Amulya A. Nagesware GIANNINI Caterina FARIA Claudia C. NUNES Sofia MORA Jaume HAMILTON Ronald L. HAUSER Peter JABADO Nada PETRECCA Kevin JUNG Shin MASSIMI Luca ZOLLO Massimo CINALLI Giuseppe BOGNÁR László KLEKNER Almos HORTOBÁGYI Tibor LEARY Sarah ERMOIAN Ralph P. OLSON James M. LEONARD Jeffrey R. GARDNER Corrine GRAJKOWSKA Wieslawa A. CHAMBLESS Lola B. CAIN Jason EBERHART Charles G. AHSAN Sama MASSIMINO Maura GIANGASPERO Felice BUTTARELLI Francesca R. PACKER Roger J. EMERY Lyndsey YONG William H. SOTO Horacio LIAU Linda M. EVERSON Richard GROSSBACH Andrew SHALABY Tarek GROTZER Michael KARAJANNIS Matthias A. ZAGZAG David WHEELER Helen HOFF Katja von ALONSO Marta M. TUON Teresa SCHÜLLER Ulrich ZITTERBART Karel ŠTĚRBA Jaroslav CHAN Jennifer A. GUZMAN Miguel ELBABAA Samer K. COLMAN Howard DHALL Girish FISHER Paul G. FOULADI Maryam GAJJAR Amar GOLDMAN Stewart HWANG Eugene KOOL Marcel LADHA Harshad VERA-BOLANOS Elizabeth WANI Khalida LIEBERMAN Frank MIKKELSEN Tom OMURO Antonio M. POLLACK Ian F. PRADOS Michael ROBINS H. Ian SOFFIETTI Riccardo WU Jing METELLUS Phillipe TABORI Uri BARTELS Ute BOUFFET Eric HAWKINS Cynthia E. RUTKA James T. DIRKS Peter PFISTER Stefan M. MERCHANT Thomas E. GILBERT Mark R. ARMSTRONG Terri S. KORSHUNOV Andrey ELLISON David W. TAYLOR Michael D.
Year of publication	2016
Type	Article in Periodical
Magazine / Source	Journal of Clinical Oncology
MU Faculty or unit	Faculty of Medicine
Citation
Doi	http://dx.doi.org/10.1200/JCO.2015.65.7825
Field	Oncology and hematology
Keywords	CONFORMAL RADIATION-THERAPY; NEWLY-DIAGNOSED EPENDYMOMA; PHASE-II TRIAL; BRAIN-TUMORS; PEDIATRIC-PATIENTS; CRANIAL RADIATION; CHILDREN; CHILDHOOD; CHEMOTHERAPY; AGE
Description	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.MethodsFour 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.