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

TY - JOUR

T1 - Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis

AU - Ramaswamy, Vijay

AU - Hielscher, Thomas

AU - Mack, Stephen C

AU - Lassaletta, Alvaro

AU - Lin, Tong

AU - Pajtler, Kristian W

AU - Jones, David T W

AU - Luu, Betty

AU - Cavalli, Florence M G

AU - Aldape, Kenneth

AU - Remke, Marc

AU - Mynarek, Martin

AU - Rutkowski, Stefan

AU - Gururangan, Sridharan

AU - McLendon, Roger E

AU - Lipp, Eric S

AU - Dunham, Christopher

AU - Hukin, Juliette

AU - Eisenstat, David D

AU - Fulton, Dorcas

AU - van Landeghem, Frank K H

AU - Santi, Mariarita

AU - van Veelen, Marie-Lise C

AU - Van Meir, Erwin G

AU - Osuka, Satoru

AU - Fan, Xing

AU - Muraszko, Karin M

AU - Tirapelli, Daniela P C

AU - Oba-Shinjo, Sueli M

AU - Marie, Suely K N

AU - Carlotti, Carlos G

AU - Lee, Ji Yeoun

AU - Rao, Amulya A Nageswara

AU - Giannini, Caterina

AU - Faria, Claudia C

AU - Nunes, Sofia

AU - Mora, Jaume

AU - Hamilton, Ronald L

AU - Hauser, Peter

AU - Jabado, Nada

AU - Petrecca, Kevin

AU - Jung, Shin

AU - Massimi, Luca

AU - Zollo, Massimo

AU - Cinalli, Giuseppe

AU - Bognár, László

AU - Klekner, Almos

AU - Hortobágyi, Tibor

AU - Leary, Sarah

AU - Ermoian, Ralph P

AU - Olson, James M

AU - Leonard, Jeffrey R

AU - Gardner, Corrine

AU - Grajkowska, Wieslawa A

AU - Chambless, Lola B

AU - Cain, Jason

AU - Eberhart, Charles G

AU - Ahsan, Sama

AU - Massimino, Maura

AU - Giangaspero, Felice

AU - Buttarelli, Francesca R

AU - Packer, Roger J

AU - Emery, Lyndsey

AU - Yong, William H

AU - Soto, Horacio

AU - Liau, Linda M

AU - Everson, Richard

AU - Grossbach, Andrew

AU - Shalaby, Tarek

AU - Grotzer, Michael

AU - Karajannis, Matthias A

AU - Zagzag, David

AU - Wheeler, Helen

AU - von Hoff, Katja

AU - Alonso, Marta M

AU - Tuñon, Teresa

AU - Schüller, Ulrich

AU - Zitterbart, Karel

AU - Sterba, Jaroslav

AU - Chan, Jennifer A

AU - Guzman, Miguel

AU - Elbabaa, Samer K

AU - Colman, Howard

AU - Dhall, Girish

AU - Fisher, Paul G

AU - Fouladi, Maryam

AU - Gajjar, Amar

AU - Goldman, Stewart

AU - Hwang, Eugene

AU - Kool, Marcel

AU - Ladha, Harshad

AU - Vera-Bolanos, Elizabeth

AU - Wani, Khalida

AU - Lieberman, Frank

AU - Mikkelsen, Tom

AU - Omuro, Antonio M

AU - Pollack, Ian F

AU - Prados, Michael

AU - Robins, H Ian

AU - Soffietti, Riccardo

AU - Wu, Jing

AU - Metellus, Phillipe

AU - Tabori, Uri

AU - Bartels, Ute

AU - Bouffet, Eric

AU - Hawkins, Cynthia E

AU - Rutka, James T

AU - Dirks, Peter

AU - Pfister, Stefan M

AU - Merchant, Thomas E

AU - Gilbert, Mark R

AU - Armstrong, Terri S

AU - Korshunov, Andrey

AU - Ellison, David W

AU - Taylor, Michael D

N1 - © 2016 by American Society of Clinical Oncology.

PY - 2016/7/20

Y1 - 2016/7/20

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1200/JCO.2015.65.7825

DO - 10.1200/JCO.2015.65.7825

M3 - SCORING: Journal article

C2 - 27269943

VL - 34

SP - 2468

EP - 2477

JO - J CLIN ONCOL

JF - J CLIN ONCOL

SN - 0732-183X

IS - 21

ER -