Resection and radiotherapy for intracranial ependymoma: a multiinstitutional 50-year experience

View More View Less
  • 1 Division of Neurosurgery, University Health Network, University of Toronto, Ontario, Canada;
  • | 2 Department of Radiation Oncology, Peggy and Charles Stephenson Oklahoma Cancer Center,
  • | 3 Department of Neurosurgery, and
  • | 4 Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma;
  • | 5 Department of Radiation Oncology, The Ottawa Hospital, University of Ottawa, Ontario, Canada; and
  • | 6 Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $515.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $612.00
USD  $45.00
USD  $515.00
USD  $612.00
Print or Print + Online Sign in

OBJECTIVE

Maximal safe resection is the standard-of-care treatment for adults with intracranial ependymoma. The value of adjuvant radiotherapy remains unclear as these tumors are rare and current data are limited to a few retrospective cohort studies. In this study, the authors assembled a cohort of patients across multiple international institutions to assess the utility of adjuvant radiotherapy in this patient population.

METHODS

Adults with intracranial ependymoma managed surgically at the University Health Network in Toronto, Canada, the University of Oklahoma Health Sciences Center in Oklahoma City, Oklahoma, and The Ottawa Hospital in Ottawa, Canada, were included in this study. The primary end points were progression-free survival (PFS) and overall survival (OS). Clinicopathological variables were assessed in univariate and multivariate Cox proportional hazard models for prognostic significance of PFS and OS.

RESULTS

A total of 122 patients diagnosed between 1968 and 2019 were identified for inclusion. The majority of patients had grade II ependymomas on histopathology (78%) that were infratentorially located (71%), underwent gross-total (GTR) or near-total resection (NTR; 55%), and were treated with adjuvant radiotherapy (67%). A volumetric analysis of the extent of resection in 49 patients with available tumor volume data supported the accuracy of the categorical GTR, NTR, and subtotal resection (STR) groups utilized. Independent statistically significant predictors of poorer PFS in the multivariate analysis included STR or biopsy (vs GTR/NTR; HR 5.4, 95% confidence interval [CI] 2.4–11.0, p < 0.0001) and not receiving adjuvant radiotherapy; cranial (HR 0.5, 95% CI 0.2–1.1) and craniospinal (HR 0.2, 95% CI 0.04–0.5) adjuvant radiotherapy regimens improved PFS (p = 0.0147). Predictors of poorer OS in the multivariate analysis were grade III histopathology (vs grade II: HR 5.7, 95% CI 1.6–20.2, p = 0.0064) and undergoing a biopsy/STR (vs GTR/NTR: HR 9.8, 95% CI 3.2–30.1, p = 0.0001).

CONCLUSIONS

The results of this 50-year experience in treating adult intracranial ependymomas confirm an important role for maximal safe resection (ideally GTR or NTR) and demonstrate that adjuvant radiotherapy improves PFS. This work will guide future studies as testing for molecular ependymoma alterations become incorporated into routine clinical practice.

ABBREVIATIONS

CI = confidence interval; EOR = extent of resection; GTR = gross-total resection; HR = hazard ratio; NTR = near-total resection; OS = overall survival; PFS = progression-free survival; STR = subtotal resection.

Images from Minchev et al. (pp 479–488).

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $515.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $612.00
USD  $515.00
USD  $612.00
  • 1

    Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, Barnholtz-Sloan JS. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2012-2016. Neuro Oncol. 2019;21(5)(suppl 5):v1v100.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Delgado-López PD, Corrales-García EM, Alonso-García E, García-Leal R, González-Rodrigálvarez R, Araus-Galdós E, Martín-Alonso J. Central nervous system ependymoma: clinical implications of the new molecular classification, treatment guidelines and controversial issues. Clin Transl Oncol. 2019;21(11):14501463.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Zapotocky M, Beera K, Adamski J, Laperierre N, Guger S, Janzen L, et al. Survival and functional outcomes of molecularly defined childhood posterior fossa ependymoma: cure at a cost. Cancer. 2019;125(11):18671876.

    • Search Google Scholar
    • Export Citation
  • 4

    Merchant TE, Bendel AE, Sabin ND, Burger PC, Shaw DW, Chang E, et al. Conformal radiation therapy for pediatric ependymoma, chemotherapy for incompletely resected ependymoma, and observation for completely resected, supratentorial ependymoma. J Clin Oncol. 2019;37(12):974983.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Reni M, Brandes AA, Vavassori V, Cavallo G, Casagrande F, Vastola F, et al. A multicenter study of the prognosis and treatment of adult brain ependymal tumors. Cancer. 2004;100(6):12211229.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Metellus P, Barrie M, Figarella-Branger D, Chinot O, Giorgi R, Gouvernet J, et al. Multicentric French study on adult intracranial ependymomas: prognostic factors analysis and therapeutic considerations from a cohort of 152 patients. Brain. 2007;130(Pt 5):13381349.

    • Search Google Scholar
    • Export Citation
  • 7

    Vitanovics D, Bálint K, Hanzély Z, Banczerowski P, Afra D. Ependymoma in adults: surgery, reoperation and radiotherapy for survival. Pathol Oncol Res. 2010;16(1):9399.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Vera-Bolanos E, Aldape K, Yuan Y, Wu J, Wani K, Necesito-Reyes MJ, et al. Clinical course and progression-free survival of adult intracranial and spinal ependymoma patients. Neuro Oncol. 2015;17(3):440447.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Nuño M, Yu JJ, Varshneya K, Alexander J, Mukherjee D, Black KL, Patil CG. Treatment and survival of supratentorial and posterior fossa ependymomas in adults. J Clin Neurosci. 2016;28:2430.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Song SW, Dho YS, Kim JW, Kim YH, Paek SH, Kim DG, et al. Recursive partitioning analysis for disease progression in adult intracranial ependymoma patients. J Clin Neurosci. 2017;46:7278.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Deng X, Zhang X, Yang L, Lu X, Fang J, Yu L, et al. Personalizing age-specific survival prediction and risk stratification in intracranial grade II/III ependymoma. Cancer Med. 2020;9(2):615625.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Wee CW, Kim IH, Park CK, Lim DH, Nam DH, Yoon HI, et al. Postoperative radiotherapy for WHO grade II-III intracranial ependymoma in adults: an intergroup collaborative study (KROG 18-06/KNOG 18-01). Radiother Oncol. 2020;150:411.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Achey RL, Vo S, Cioffi G, Gittleman H, Schroer J, Khanna V, et al. Ependymoma, NOS and anaplastic ependymoma incidence and survival in the United States varies widely by patient and clinical characteristics, 2000-2016. Neurooncol Pract. 2020;7(5):549558.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Pajtler KW, Witt H, Sill M, Jones DT, Hovestadt V, Kratochwil F, et al. Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. Cancer Cell. 2015;27(5):728743.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Pajtler KW, Mack SC, Ramaswamy V, Smith CA, Witt H, Smith A, et al. The current consensus on the clinical management of intracranial ependymoma and its distinct molecular variants. Acta Neuropathol. 2017;133(1):512.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Baroni LV, Sundaresan L, Heled A, Coltin H, Pajtler KW, Lin T, et al. Ultra high-risk PFA ependymoma is characterized by loss of chromosome 6q. Neuro Oncol. 2021;23(8):13601370.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Lester A, McDonald KL. Intracranial ependymomas: molecular insights and translation to treatment. Brain Pathol. 2020;30(1):312.

  • 18

    Sreenivasan SA, Madhugiri VS, Sasidharan GM, Kumar RV. Measuring glioma volumes: a comparison of linear measurement based formulae with the manual image segmentation technique. J Cancer Res Ther. 2016;12(1):161168.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Shuster JJ. Median follow-up in clinical trials. J Clin Oncol. 1991;9(1):191192.

  • 20

    Cavalli FMG, Hübner JM, Sharma T, Luu B, Sill M, Zapotocky M, et al. Heterogeneity within the PF-EPN-B ependymoma subgroup. Acta Neuropathol. 2018;136(2):227237.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Ellison DW, Kocak M, Figarella-Branger D, Felice G, Catherine G, Pietsch T, et al. Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts. J Negat Results Biomed. 2011;10:7.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Merchant TE, Kun LE, Wu S, Xiong X, Sanford RA, Boop FA. Phase II trial of conformal radiation therapy for pediatric low-grade glioma. J Clin Oncol. 2009;27(22):35983604.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Massimino M, Miceli R, Giangaspero F, Boschetti L, Modena P, Antonelli M, et al. Final results of the second prospective AIEOP protocol for pediatric intracranial ependymoma. Neuro Oncol. 2016;18(10):14511460.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Wu J, Armstrong TS, Gilbert MR. Biology and management of ependymomas. Neuro Oncol. 2016;18(7):902913.

Metrics

All Time Past Year Past 30 Days
Abstract Views 715 715 73
Full Text Views 140 140 31
PDF Downloads 172 172 47
EPUB Downloads 0 0 0