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Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis.

Publication ,  Journal Article
Ramaswamy, V; Hielscher, T; Mack, SC; Lassaletta, A; Lin, T; Pajtler, KW; Jones, DTW; Luu, B; Cavalli, FMG; Aldape, K; Remke, M; Mynarek, M ...
Published in: J Clin Oncol
July 20, 2016

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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Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

July 20, 2016

Volume

34

Issue

21

Start / End Page

2468 / 2477

Location

United States

Related Subject Headings

  • Retrospective Studies
  • Oncology & Carcinogenesis
  • Male
  • Infratentorial Neoplasms
  • Infant
  • Humans
  • Female
  • Ependymoma
  • Cytoreduction Surgical Procedures
  • Combined Modality Therapy
 

Citation

APA
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MLA
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Ramaswamy, V., Hielscher, T., Mack, S. C., Lassaletta, A., Lin, T., Pajtler, K. W., … Taylor, M. D. (2016). Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis. J Clin Oncol, 34(21), 2468–2477. https://doi.org/10.1200/JCO.2015.65.7825
Ramaswamy, Vijay, Thomas Hielscher, Stephen C. Mack, Alvaro Lassaletta, Tong Lin, Kristian W. Pajtler, David T. W. Jones, et al. “Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis.J Clin Oncol 34, no. 21 (July 20, 2016): 2468–77. https://doi.org/10.1200/JCO.2015.65.7825.
Ramaswamy V, Hielscher T, Mack SC, Lassaletta A, Lin T, Pajtler KW, et al. Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis. J Clin Oncol. 2016 Jul 20;34(21):2468–77.
Ramaswamy, Vijay, et al. “Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis.J Clin Oncol, vol. 34, no. 21, July 2016, pp. 2468–77. Pubmed, doi:10.1200/JCO.2015.65.7825.
Ramaswamy V, Hielscher T, Mack SC, Lassaletta A, Lin T, Pajtler KW, Jones DTW, Luu B, Cavalli FMG, Aldape K, Remke M, Mynarek M, Rutkowski S, Gururangan S, McLendon RE, Lipp ES, Dunham C, Hukin J, Eisenstat DD, Fulton D, van Landeghem FKH, Santi M, van Veelen M-LC, Van Meir EG, Osuka S, Fan X, Muraszko KM, Tirapelli DPC, Oba-Shinjo SM, Marie SKN, Carlotti CG, Lee JY, Rao AAN, Giannini C, Faria CC, Nunes S, Mora J, Hamilton RL, Hauser P, Jabado N, Petrecca K, Jung S, Massimi L, Zollo M, Cinalli G, Bognár L, Klekner A, Hortobágyi 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, Tuñon T, Schüller 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, 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 Jul 20;34(21):2468–2477.

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

July 20, 2016

Volume

34

Issue

21

Start / End Page

2468 / 2477

Location

United States

Related Subject Headings

  • Retrospective Studies
  • Oncology & Carcinogenesis
  • Male
  • Infratentorial Neoplasms
  • Infant
  • Humans
  • Female
  • Ependymoma
  • Cytoreduction Surgical Procedures
  • Combined Modality Therapy