| Authors: |
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.; Bognár, L.; Klekner, A.; Hortobágyi, 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.; Tuñon, T.; Schüller, 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. |
| Article Title: |
Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: A retrospective multicohort analysis |
| 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 by American Society of Clinical Oncology. |
| Journal Title: |
Journal of Clinical Oncology
|
| Volume: |
34 |
| Issue: |
21 |
| ISSN: |
0732-183X |
| Publisher: |
American Society of Clinical Oncology
|
| Date Published: |
2016-07-20 |
| Start Page: |
2468 |
| End Page: |
2477 |
| Language: |
English |
| DOI: |
10.1200/jco.2015.65.7825
|
| PROVIDER: |
scopus
|
| PUBMED: |
27269943
|
| PMCID: |
PMC4962737
|
| DOI/URL: |
|
| Notes: |
Article -- Export Date: 2 August 2016 -- Source: Scopus |
