Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jun 1;23(6):1012-1023.
doi: 10.1093/neuonc/noaa276.

Local and systemic therapy of recurrent ependymoma in children and adolescents: short- and long-term results of the E-HIT-REZ 2005 study

Jonas E Adolph  1 , Gudrun Fleischhack  1 , Ruth Mikasch  1 , Julia Zeller  1 , Monika Warmuth-Metz  2 , Brigitte Bison  2 , Martin Mynarek  3 , Stefan Rutkowski  3 , Ulrich Schüller  3 , Katja von Hoff  4 , Denise Obrecht  3 , Torsten Pietsch  5 , Stefan M Pfister  6   7   8 , Kristian W Pajtler  6   7   8 , Olaf Witt  6   7   8 , Hendrik Witt  6   7   8 , Rolf-Dieter Kortmann  9 , Beate Timmermann  10 , Jürgen Krauß  2 , Michael C Frühwald  11 , Andreas Faldum  12 , Robert Kwiecien  12 , Udo Bode  5 , Stephan Tippelt  1
Affiliations

Local and systemic therapy of recurrent ependymoma in children and adolescents: short- and long-term results of the E-HIT-REZ 2005 study

Jonas E Adolph et al. Neuro Oncol. .

Abstract

Background: Survival in recurrent ependymomas in children and adolescents mainly depends on the extent of resection. Studies on repeated radiotherapy and chemotherapy at relapse have shown conflicting results.

Methods: Using data from the German multi-center E-HIT-REZ-2005 study, we examined the role of local therapy and the efficacy of chemotherapy with blockwise temozolomide (TMZ) in children and adolescents with recurrent ependymomas.

Results: Fifty-three patients with a median age of 6.9 years (1.25-25.4) at first recurrence and a median follow-up time of 36 months (2-115) were recruited. Gross- and near-total resection (GTR/NTR) were achieved in 34 (64.2%) patients and associated with a markedly improved 5-year overall survival (OS) of 48.7% vs. 5.3% in less than GTR/NTR. Radiotherapy showed no improvement in OS following complete resection (OS: 70 (CI: 19.9-120.1) vs. 95 (CI: 20.7-169.4) months), but an advantage was found in less than GTR/NTR (OS: 22 (CI: 12.7-31.3) vs. 7 (CI: 0-15.8) months). Following the application of TMZ, disease progression was observed in most evaluable cases (18/21). A subsequent change to oral etoposide and trofosfamide showed no improved response. PF-A EPN were most abundant in relapses (n = 27). RELA-positive EPN (n = 5) had a 5-year OS of 0%.

Conclusion: The extent of resection is the most important predictor of survival at relapse. Focal re-irradiation is a useful approach if complete resection cannot be achieved, but no additional benefit was seen after GTR/NTR. Longer-term disease stabilization (>6 months) mediated by TMZ occurred in a small number of cases (14.3%).

Keywords: chemotherapy; ependymoma; radiotherapy; relapse; tumor resection.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
PFS and OS respectively for (a + b) extent of resection, (c + d) radiotherapy, (e + f) patients with subtotal or no resection stratified by radiotherapy, and (g + h) patients with spinal metastases at first relapse stratified by craniospinal irradiation (CSI) or local irradiation.
Fig. 2
Fig. 2
a) Treatment flowchart of 53 patients included in the E-HIT-REZ-2005 study b) OS (OS) for all patients with known molecular classification at first recurrence.
Fig. 3
Fig. 3
Multivariate Cox proportional hazard regression for OS (OS) at recurrence, concerning the grade of resection, radiotherapy at 1st relapse, time to recurrence >24 months, age at 1st recurrence <4 y, metastases, and sex.
See this image and copyright information in PMC

Comment in

  • Pediatric ependymomas: destined to recur?
    Ritzmann TA, Kilday JP, Grundy RG. Ritzmann TA, et al. Neuro Oncol. 2021 Jun 1;23(6):874-876. doi: 10.1093/neuonc/noab066. Neuro Oncol. 2021. PMID: 33728470 Free PMC article. No abstract available.

References

    1. Zacharoulis S, Ashley S, Moreno L, Gentet JC, Massimino M, Frappaz D. Treatment and outcome of children with relapsed ependymoma: a multi-institutional retrospective analysis. Childs Nerv Syst. 2010;26(7):905–911. - PubMed
    1. Tsang DS, Burghen E, Klimo P Jr, Boop FA, Ellison DW, Merchant TE. Outcomes After Reirradiation for Recurrent Pediatric Intracranial Ependymoma. Int J Radiat Oncol Biol Phys. 2018;100(2):507–515. - PubMed
    1. Messahel B, Ashley S, Saran F, et al. ; Children’s Cancer Leukaemia Group Brain Tumour Committee . Relapsed intracranial ependymoma in children in the UK: patterns of relapse, survival and therapeutic outcome. Eur J Cancer. 2009;45(10):1815–1823. - PubMed
    1. Goldwein JW, Leahy JM, Packer RJ, et al. . Intracranial ependymomas in children. Int J Radiat Oncol Biol Phys. 1990; 19(10):1497–1502. - PubMed
    1. Tihan T, Zhou T, Holmes E, Burger PC, Ozuysal S, Rushing EJ. The prognostic value of histological grading of posterior fossa ependymomas in children: a Children’s Oncology Group study and a review of prognostic factors. Mod Pathol. 2008;21(2):165–177. - PubMed

Publication types