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.

Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: A retrospective multicohort analysis

Giannini C.;Giangaspero F.;
2016

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.
2016
Ramaswamy V.; Hielscher T.; Mack S.C.; Lassaletta A.; Lin T.; Pajtler K.W.; Jones D.T.W.; Luu B.; Cavalli F.M.G.; Aldape K.; Remke M.; Mynarek M.; Rutkowski S.; Gururangan S.; McLendon R.E.; Lipp E.S.; Dunham C.; Hukin J.; Eisenstat D.D.; Fulton D.; Van Landeghem F.K.H.; Santi M.; Van Veelen M.-L.C.; Van Meir E.G.; Osuka S.; Fan X.; Muraszko K.M.; Tirapelli D.P.C.; Oba-Shinjo S.M.; Marie S.K.N.; Carlotti C.G.; Lee J.Y.; Rao A.A.N.; Giannini C.; Faria C.C.; Nunes S.; Mora J.; Hamilton R.L.; Hauser P.; Jabado N.; Petrecca K.; Jung S.; Massimi L.; Zollo M.; Cinalli G.; Bognar L.; Klekner A.; Hortobagyi T.; Leary S.; Ermoian R.P.; Olson J.M.; Leonard J.R.; Gardner C.; Grajkowska W.A.; Chambless L.B.; Cain J.; Eberhart C.G.; Ahsan S.; Massimino M.; Giangaspero F.; Buttarelli F.R.; Packer R.J.; Emery L.; Yong W.H.; Soto H.; Liau L.M.; Everson R.; Grossbach A.; Shalaby T.; Grotzer M.; Karajannis M.A.; Zagzag D.; Wheeler H.; Von Hoff K.; Alonso M.M.; Tunon T.; Schuller U.; Zitterbart K.; Sterba J.; Chan J.A.; Guzman M.; Elbabaa S.K.; Colman H.; Dhall G.; Fisher P.G.; Fouladi M.; Gajjar A.; Goldman S.; Hwang E.; Kool M.; Ladha H.; Vera-Bolanos E.; Wani K.; Lieberman F.; Mikkelsen T.; Omuro A.M.; Pollack I.F.; Prados M.; Robins H.I.; Soffietti R.; Wu J.; Metellus P.; Tabori U.; Bartels U.; Bouffet E.; Hawkins C.E.; Rutka J.T.; Dirks P.; Pfister S.M.; Merchant T.E.; Gilbert M.R.; Armstrong T.S.; Korshunov A.; Ellison D.W.; Taylor M.D.
File in questo prodotto:
Eventuali allegati, non sono esposti

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/730592
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 67
  • Scopus 151
  • ???jsp.display-item.citation.isi??? 133
social impact