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 language | American English |
|---|---|
| Journal | Neurosurgery Articles |
| Volume | 34 |
| Issue number | 21 |
| State | Published - Jul 20 2016 |
Keywords
- Adolescent
- Adult
- Child
- Preschool
- Cohort Studies
- Combined Modality Therapy
- Cytoreduction Surgical Procedures
- Ependymoma
- Female
- Humans
- Infant
- Infratentorial Neoplasms
- Male
- Retrospective Studies
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In: Neurosurgery Articles, Vol. 34, No. 21, 20.07.2016.
Research output: Contribution to journal › Article › peer-review
}
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 TW
AU - Luu, Betty
AU - Cavalli, Florence MG
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 KH
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 PC
AU - Oba-Shinjo, Sueli M
AU - Marie, Suely KN
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
AU - Vera, Elizabeth
N1 - Ramaswamy V, Hielscher T, Mack SC, Lassaletta A, Lin T, Pajtler KW, Jones DT, Luu B, Cavalli FM, Aldape K, Remke M, Mynarek M, Rutkowski S, Gururangan S, McLendon RE, Lipp ES, Dunham C, Hukin J, Eisenstat DD, Fulton D, van Landeghem FK, Santi M, van Veelen MC, Van Meir EG, Osuka S, Fan X, Muraszko KM, Tirapelli DP, Oba-Shinjo SM, Marie SK, Carlotti CG, Lee JY, Nageswara Rao AA, Giannini C, Faria CC, Nunes S, Mora J, Hamilton RL, Hauser P, Jabado N, Petrecca K, Jung S, Massimi L, Zollo M, Cinalli G, Bognar L, Klekner A, Hortobagyi T, Leary S, Ermoian RP, Olson JM, Leonard JR, Gardner C, Grajkowska WA, 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, Tunon T, Schuller U, Zitterbart K, Sterba J, Chan JA, 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 AM, Pollack IF, Prados M, Robins HI, Soffietti R, Wu J, Metellus P, Tabori U, Bartels U, Bouffet E, Hawkins CE, Rutka JT, Dirks P, Pfister SM, Merchant TE, Gilbert MR, Armstrong TS, Korshunov A, Ellison DW, and Taylor MD. Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: A retrospective multicohort analysis. J Clin Oncol 2016; 34(21):2468-2477.
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 - Adolescent
KW - Adult
KW - Child
KW - Preschool
KW - Cohort Studies
KW - Combined Modality Therapy
KW - Cytoreduction Surgical Procedures
KW - Ependymoma
KW - Female
KW - Humans
KW - Infant
KW - Infratentorial Neoplasms
KW - Male
KW - Retrospective Studies
UR - https://scholarlycommons.henryford.com/neurosurgery_articles/203
UR - http://sfxhosted.exlibrisgroup.com/hfhs?sid=Entrez:PubMed&id=pmid:27269943
M3 - Article
SN - 1527-7755
VL - 34
JO - Neurosurgery Articles
JF - Neurosurgery Articles
IS - 21
ER -