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 Lipp, Christopher Dunham, Juliette Hukin, David D. Eisenstat, Dorcas Fulton & 95 others Frank 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, S. Marie, Carlos Carlotti, Ji Yeoun Lee, Amulya A Nageswara Rao, Caterina Giannini, Claudia C. Faria, Sofia Nunes, Jaume Mora, Ronald L. Hamilton, P. Hauser, Nada Jabado, Kevin Petrecca, Shin Jung, Luca Massimi, Massimo Zollo, Giuseppe Cinalli, Bognár László, Almos Klekner, Tibor Hortobagyi, Sarah Leary, Ralph P. 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, R. 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, J. Sterba, Jennifer 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, A. M P Omuro, Ian F. Pollack, Michael Prados, H. I. Robins, Riccardo Soffietti, Jing Wu, Phillipe Metellus, Uri Tabori, Ute Bartels, Eric Bouffet, Cynthia Hawkins, James T. Rutka, Peter Dirks, Stefan M. Pfister, Thomas E. Merchant, Mark R. Gilbert, Terri S. Armstrong, Andrey Korshunov, David W. Ellison, M. Taylor

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2468-2477
Number of pages10
JournalJournal of Clinical Oncology
Volume34
Issue number21
DOIs
Publication statusPublished - Jul 20 2016

Fingerprint

Ependymoma
Radiotherapy
Biomarkers
Radiation
Therapeutics
Recurrence
Natural History
Methylation
Disease-Free Survival
Survival Rate
Randomized Controlled Trials
Observation
Demography
Genome

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era : A retrospective multicohort analysis. / 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; Dunham, Christopher; Hukin, Juliette; Eisenstat, David D.; Fulton, Dorcas; van Landeghem, Frank; Santi, Mariarita; van Veelen, Marie Lise C; Van Meir, Erwin G.; Osuka, Satoru; Fan, Xing; Muraszko, Karin M.; Tirapelli, Daniela P C; Oba-Shinjo, Sueli M.; Marie, S.; Carlotti, Carlos; Lee, Ji Yeoun; Rao, Amulya A Nageswara; Giannini, Caterina; Faria, Claudia C.; Nunes, Sofia; Mora, Jaume; Hamilton, Ronald L.; Hauser, P.; Jabado, Nada; Petrecca, Kevin; Jung, Shin; Massimi, Luca; Zollo, Massimo; Cinalli, Giuseppe; László, Bognár; Klekner, Almos; Hortobagyi, Tibor; Leary, Sarah; Ermoian, Ralph P.; Olson, James M.; Leonard, Jeffrey R.; Gardner, Corrine; Grajkowska, Wiesława; Chambless, Lola B.; Cain, Jason; Eberhart, Charles G.; Ahsan, Sama; Massimino, Maura; Giangaspero, Felice; Buttarelli, Francesca Romana; Packer, R. 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; Von Hoff, Katja; Alonso, Marta M.; Tuñon, Teresa; Schüller, Ulrich; Zitterbart, Karel; Sterba, J.; Chan, Jennifer; 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, A. M P; Pollack, Ian F.; Prados, Michael; Robins, H. I.; Soffietti, Riccardo; Wu, Jing; Metellus, Phillipe; Tabori, Uri; Bartels, Ute; Bouffet, Eric; Hawkins, Cynthia; Rutka, James T.; Dirks, Peter; Pfister, Stefan M.; Merchant, Thomas E.; Gilbert, Mark R.; Armstrong, Terri S.; Korshunov, Andrey; Ellison, David W.; Taylor, M.

In: Journal of Clinical Oncology, Vol. 34, No. 21, 20.07.2016, p. 2468-2477.

Research output: Contribution to journalArticle

Ramaswamy, V, Hielscher, T, Mack, SC, Lassaletta, A, Lin, T, Pajtler, KW, Jones, DTW, Luu, B, Cavalli, FMG, Aldape, K, Remke, M, Mynarek, M, Rutkowski, S, Gururangan, S, McLendon, RE, Lipp, E, Dunham, C, Hukin, J, Eisenstat, DD, Fulton, D, van Landeghem, F, Santi, M, van Veelen, MLC, Van Meir, EG, Osuka, S, Fan, X, Muraszko, KM, Tirapelli, DPC, Oba-Shinjo, SM, Marie, S, Carlotti, C, Lee, JY, Rao, AAN, Giannini, C, Faria, CC, Nunes, S, Mora, J, Hamilton, RL, Hauser, P, Jabado, N, Petrecca, K, Jung, S, Massimi, L, Zollo, M, Cinalli, G, László, B, Klekner, A, Hortobagyi, T, Leary, S, Ermoian, RP, Olson, JM, Leonard, JR, Gardner, C, Grajkowska, W, Chambless, LB, Cain, J, Eberhart, CG, Ahsan, S, Massimino, M, Giangaspero, F, Buttarelli, FR, Packer, RJ, Emery, L, Yong, WH, Soto, H, Liau, LM, Everson, R, Grossbach, A, Shalaby, T, Grotzer, M, Karajannis, MA, Zagzag, D, Wheeler, H, Von Hoff, K, Alonso, MM, Tuñon, T, Schüller, U, Zitterbart, K, Sterba, J, Chan, J, Guzman, M, Elbabaa, SK, Colman, H, Dhall, G, Fisher, PG, Fouladi, M, Gajjar, A, Goldman, S, Hwang, E, Kool, M, Ladha, H, Vera-Bolanos, E, Wani, K, Lieberman, F, Mikkelsen, T, Omuro, AMP, Pollack, IF, Prados, M, Robins, HI, Soffietti, R, Wu, J, Metellus, P, Tabori, U, Bartels, U, Bouffet, E, Hawkins, C, Rutka, JT, Dirks, P, Pfister, SM, Merchant, TE, Gilbert, MR, Armstrong, TS, Korshunov, A, Ellison, DW & Taylor, M 2016, 'Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: A retrospective multicohort analysis', Journal of Clinical Oncology, vol. 34, no. 21, pp. 2468-2477. https://doi.org/10.1200/JCO.2015.65.7825
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 ; Dunham, Christopher ; Hukin, Juliette ; Eisenstat, David D. ; Fulton, Dorcas ; van Landeghem, Frank ; Santi, Mariarita ; van Veelen, Marie Lise C ; Van Meir, Erwin G. ; Osuka, Satoru ; Fan, Xing ; Muraszko, Karin M. ; Tirapelli, Daniela P C ; Oba-Shinjo, Sueli M. ; Marie, S. ; Carlotti, Carlos ; Lee, Ji Yeoun ; Rao, Amulya A Nageswara ; Giannini, Caterina ; Faria, Claudia C. ; Nunes, Sofia ; Mora, Jaume ; Hamilton, Ronald L. ; Hauser, P. ; Jabado, Nada ; Petrecca, Kevin ; Jung, Shin ; Massimi, Luca ; Zollo, Massimo ; Cinalli, Giuseppe ; László, Bognár ; Klekner, Almos ; Hortobagyi, Tibor ; Leary, Sarah ; Ermoian, Ralph P. ; Olson, James M. ; Leonard, Jeffrey R. ; Gardner, Corrine ; Grajkowska, Wiesława ; Chambless, Lola B. ; Cain, Jason ; Eberhart, Charles G. ; Ahsan, Sama ; Massimino, Maura ; Giangaspero, Felice ; Buttarelli, Francesca Romana ; Packer, R. 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 ; Von Hoff, Katja ; Alonso, Marta M. ; Tuñon, Teresa ; Schüller, Ulrich ; Zitterbart, Karel ; Sterba, J. ; Chan, Jennifer ; 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, A. M P ; Pollack, Ian F. ; Prados, Michael ; Robins, H. I. ; Soffietti, Riccardo ; Wu, Jing ; Metellus, Phillipe ; Tabori, Uri ; Bartels, Ute ; Bouffet, Eric ; Hawkins, Cynthia ; Rutka, James T. ; Dirks, Peter ; Pfister, Stefan M. ; Merchant, Thomas E. ; Gilbert, Mark R. ; Armstrong, Terri S. ; Korshunov, Andrey ; Ellison, David W. ; Taylor, M. / Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era : A retrospective multicohort analysis. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 21. pp. 2468-2477.
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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.",
author = "Vijay Ramaswamy and Thomas Hielscher and Mack, {Stephen C.} and Alvaro Lassaletta and Tong Lin and Pajtler, {Kristian W.} and Jones, {David T W} and Betty Luu and Cavalli, {Florence M G} and Kenneth Aldape and Marc Remke and Martin Mynarek and Stefan Rutkowski and Sridharan Gururangan and McLendon, {Roger E.} and Eric Lipp and Christopher Dunham and Juliette Hukin and Eisenstat, {David D.} and Dorcas Fulton and {van Landeghem}, Frank and Mariarita Santi and {van Veelen}, {Marie Lise C} and {Van Meir}, {Erwin G.} and Satoru Osuka and Xing Fan and Muraszko, {Karin M.} and Tirapelli, {Daniela P C} and Oba-Shinjo, {Sueli M.} and S. Marie and Carlos Carlotti and Lee, {Ji Yeoun} and Rao, {Amulya A Nageswara} and Caterina Giannini and Faria, {Claudia C.} and Sofia Nunes and Jaume Mora and Hamilton, {Ronald L.} and P. Hauser and Nada Jabado and Kevin Petrecca and Shin Jung and Luca Massimi and Massimo Zollo and Giuseppe Cinalli and Bogn{\'a}r L{\'a}szl{\'o} and Almos Klekner and Tibor Hortobagyi and Sarah Leary and Ermoian, {Ralph P.} and Olson, {James M.} and Leonard, {Jeffrey R.} and Corrine Gardner and Wiesława Grajkowska and Chambless, {Lola B.} and Jason Cain and Eberhart, {Charles G.} and Sama Ahsan and Maura Massimino and Felice Giangaspero and Buttarelli, {Francesca Romana} and Packer, {R. J.} and Lyndsey Emery and Yong, {William H.} and Horacio Soto and Liau, {Linda M.} and Richard Everson and Andrew Grossbach and Tarek Shalaby and Michael Grotzer and Karajannis, {Matthias A.} and David Zagzag and Helen Wheeler and {Von Hoff}, Katja and Alonso, {Marta M.} and Teresa Tu{\~n}on and Ulrich Sch{\"u}ller and Karel Zitterbart and J. Sterba and Jennifer Chan and Miguel Guzman and Elbabaa, {Samer K.} and Howard Colman and Girish Dhall and Fisher, {Paul G.} and Maryam Fouladi and Amar Gajjar and Stewart Goldman and Eugene Hwang and Marcel Kool and Harshad Ladha and Elizabeth Vera-Bolanos and Khalida Wani and Frank Lieberman and Tom Mikkelsen and Omuro, {A. M P} and Pollack, {Ian F.} and Michael Prados and Robins, {H. I.} and Riccardo Soffietti and Jing Wu and Phillipe Metellus and Uri Tabori and Ute Bartels and Eric Bouffet and Cynthia Hawkins and Rutka, {James T.} and Peter Dirks and Pfister, {Stefan M.} and Merchant, {Thomas E.} and Gilbert, {Mark R.} and Armstrong, {Terri S.} and Andrey Korshunov and Ellison, {David W.} and M. Taylor",
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month = "7",
day = "20",
doi = "10.1200/JCO.2015.65.7825",
language = "English",
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TY - JOUR

T1 - Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era

T2 - 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

AU - Dunham, Christopher

AU - Hukin, Juliette

AU - Eisenstat, David D.

AU - Fulton, Dorcas

AU - van Landeghem, Frank

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, S.

AU - Carlotti, Carlos

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, P.

AU - Jabado, Nada

AU - Petrecca, Kevin

AU - Jung, Shin

AU - Massimi, Luca

AU - Zollo, Massimo

AU - Cinalli, Giuseppe

AU - László, Bognár

AU - Klekner, Almos

AU - Hortobagyi, Tibor

AU - Leary, Sarah

AU - Ermoian, Ralph P.

AU - Olson, James M.

AU - Leonard, Jeffrey R.

AU - Gardner, Corrine

AU - Grajkowska, Wiesława

AU - Chambless, Lola B.

AU - Cain, Jason

AU - Eberhart, Charles G.

AU - Ahsan, Sama

AU - Massimino, Maura

AU - Giangaspero, Felice

AU - Buttarelli, Francesca Romana

AU - Packer, R. 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, J.

AU - Chan, Jennifer

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, A. M P

AU - Pollack, Ian F.

AU - Prados, Michael

AU - Robins, H. I.

AU - Soffietti, Riccardo

AU - Wu, Jing

AU - Metellus, Phillipe

AU - Tabori, Uri

AU - Bartels, Ute

AU - Bouffet, Eric

AU - Hawkins, Cynthia

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, M.

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.

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UR - http://www.scopus.com/inward/citedby.url?scp=84978701824&partnerID=8YFLogxK

U2 - 10.1200/JCO.2015.65.7825

DO - 10.1200/JCO.2015.65.7825

M3 - Article

VL - 34

SP - 2468

EP - 2477

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 21

ER -