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 | English (US) |
|---|---|
| Pages (from-to) | 2468-2477 |
| Number of pages | 10 |
| Journal | Journal of Clinical Oncology |
| Volume | 34 |
| Issue number | 21 |
| DOIs | |
| State | Published - Jul 20 2016 |
Funding
M.D.T. is supported by funds from the Garron Family Chair in Childhood Cancer Research at the Hospital for Sick Children and the University of Toronto and operating funds from the Pediatric Brain Tumor Foundation,Meagan'sWalk, the Rally Foundation, the National Institutes of Health (NIH; Grants No. R01CA159859 and R01CA148699), and the Canadian Institutes of Health Research (CIHR). V.R. is supported by a CIHR fellowship, an Alberta Innovates-Health Solutions Clinical Fellowship, a Collaborative Ependymoma Research Network (CERN) Foundation fellowship, and an Alex's Lemonade Stand Young Investigator Award. E.B. and V.R. acknowledge support from b.r.a.i.n.child. S.G., R.E.M., and D.B. are supported by the Pediatric Brain Tumor Foundation. M.R. is supported by a fellowship from the Mildred Scheel Cancer Foundation. S.M.P. is supported by a grant from the Deutsche Kinderkrebsstiftung. M.A.K. and D.Z. are supported by the NYU Langone Human Specimen Resource Center, Laura and Isaac Perlmutter Cancer Center, and Clinical and Translational Science Institute (CTSI), which were partially supported by the Cancer Center Support Grant P30CA016087 and a grant from the National Center for the Advancement of Translational Science (NCATS) (UL 1 TR000038), NIH, and grants from The Making Headway Foundation. A.K. was supported by the Hungarian Brain Research Program (Grant No. KTIA-13-NAP-A-V/3), the TAMOP- 4.2.2.A-11/1/KONV-2012-0025 project, and Janos Bolyai Scholarship of the Hungarian Academy of Sciences. K.Z. acknowledges the support of an Institutional Research Project grant to junior researchers from the Faculty ofMedicine, Masaryk University. E.V.M. is funded by NIH Grants No. R01 CA163722 and NS096236, St Baldrick's Foundation, and the Cure Childhood Cancer Foundation. M.D.T., V.R., K.A., T.S.A., and M.R.G. are supported by the CERN Foundation.
ASJC Scopus subject areas
- Oncology
- Cancer Research
