@article{60c0d15a5b15495aaa828b44c598a6a5,
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.",
keywords = "Adolescent, Adult, Child, Preschool, Cohort Studies, Combined Modality Therapy, Cytoreduction Surgical Procedures, Ependymoma, Female, Humans, Infant, Infratentorial Neoplasms, Male, Retrospective Studies",
author = "Vijay Ramaswamy and Thomas Hielscher and Mack, \{Stephen C\} and Alvaro Lassaletta and Tong Lin and Pajtler, \{Kristian W\} and Jones, \{David TW\} and Betty Luu and Cavalli, \{Florence MG\} and Kenneth Aldape and Marc Remke and Martin Mynarek and Stefan Rutkowski and Sridharan Gururangan and McLendon, \{Roger E\} and Lipp, \{Eric S\} and Christopher Dunham and Juliette Hukin and Eisenstat, \{David D\} and Dorcas Fulton and \{van Landeghem\}, \{Frank KH\} and Mariarita Santi and \{van Veelen\}, \{Marie-Lise C\} and \{Van Meir\}, \{Erwin G\} and Satoru Osuka and Xing Fan and Muraszko, \{Karin M\} and Tirapelli, \{Daniela PC\} and Oba-Shinjo, \{Sueli M\} and Marie, \{Suely KN\} and Carlotti, \{Carlos G\} and Ji-Yeoun Lee and Rao, \{Amulya A Nageswara\} and Caterina Giannini and Faria, \{Claudia C\} and Sofia Nunes and Jaume Mora and Hamilton, \{Ronald L\} and Peter Hauser and Nada Jabado and Kevin Petrecca and Shin Jung and Luca Massimi and Massimo Zollo and Giuseppe Cinalli and L{\'a}szl{\'o} Bogn{\'a}r and Almos Klekner and Tibor Hortob{\'a}gyi and Sarah Leary and Ermoian, \{Ralph P\} and Olson, \{James M\} and Leonard, \{Jeffrey R\} and Corrine Gardner and Grajkowska, \{Wieslawa A\} and Chambless, \{Lola B\} and Jason Cain and Eberhart, \{Charles G\} and Sama Ahsan and Maura Massimino and Felice Giangaspero and Buttarelli, \{Francesca R\} and Packer, \{Roger J\} and Lyndsey Emery and Yong, \{William H\} and Horacio Soto and Liau, \{Linda M\} and Richard Everson and Andrew Grossbach and Tarek Shalaby and Michael Grotzer and Karajannis, \{Matthias A\} and David Zagzag and Helen Wheeler and \{von Hoff\}, Katja and Alonso, \{Marta M\} and Teresa Tu{\~n}on and Ulrich Sch{\"u}ller and Karel Zitterbart and Jaroslav Sterba and Chan, \{Jennifer A\} and Miguel Guzman and Elbabaa, \{Samer K\} and Howard Colman and Girish Dhall and Fisher, \{Paul G\} and Maryam Fouladi and Amar Gajjar and Stewart Goldman and Eugene Hwang and Marcel Kool and Harshad Ladha and Elizabeth Vera-Bolanos and Khalida Wani and Frank Lieberman and Tom Mikkelsen and Omuro, \{Antonio M\} and Pollack, \{Ian F\} and Michael Prados and Robins, \{H Ian\} and Riccardo Soffietti and Jing Wu and Phillipe Metellus and Uri Tabori and Ute Bartels and Eric Bouffet and Hawkins, \{Cynthia E\} and Rutka, \{James T\} and Peter Dirks and Pfister, \{Stefan M\} and Merchant, \{Thomas E\} and Gilbert, \{Mark R\} and Armstrong, \{Terri S\} and Andrey Korshunov and Ellison, \{David W\} and Taylor, \{Michael D\} and Elizabeth Vera",
note = "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.",
year = "2016",
month = jul,
day = "20",
language = "American English",
volume = "34",
journal = "Neurosurgery Articles",
issn = "1527-7755",
number = "21",
}