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.
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. 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., Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: A retrospective multicohort analysis, <<JOURNAL OF CLINICAL ONCOLOGY>>, 2016; 34 (21): 2468-2477. [doi:10.1200/JCO.2015.65.7825] [http://hdl.handle.net/10807/124194]
Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: A retrospective multicohort analysis
Massimi, Luca;
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.
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