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. 2021 Nov;155(2):193-202.
doi: 10.1007/s11060-021-03867-8. Epub 2021 Oct 16.

Systemic chemotherapy of pediatric recurrent ependymomas: results from the German HIT-REZ studies

Jonas E Adolph  1 , Gudrun Fleischhack  1 , Christine Gaab  1 , Ruth Mikasch  1 , Martin Mynarek  2 , Stefan Rutkowski  2 , Ulrich Schüller  2   3   4 , Stefan M Pfister  5   6   7 , Kristian W Pajtler  5   6   7 , Till Milde  5   6   7   8 , Olaf Witt  5   6   7   8 , Brigitte Bison  9 , Monika Warmuth-Metz  10 , Rolf-Dieter Kortmann  11 , Stefan Dietzsch  11   12 , Torsten Pietsch  13 , Beate Timmermann  12 , Stephan Tippelt  14 ; German GPOH HIT-Network
Affiliations

Systemic chemotherapy of pediatric recurrent ependymomas: results from the German HIT-REZ studies

Jonas E Adolph et al. J Neurooncol. 2021 Nov.

Abstract

Purpose: Survival in recurrent ependymoma (EPN) depends mainly on the extent of resection achieved. When complete resection is not feasible, chemotherapy is often used to extend progression-free and overall survival. However, no consistent effect of chemotherapy on survival has been found in patients with recurrent EPN.

Methods: Systemic chemotherapeutic treatment of 138 patients enrolled in the German HIT-REZ-studies was analyzed. Survival depending on the use of chemotherapy, disease-stabilization rates (RR), duration of response (DOR) and time to progression (TTP) were estimated.

Results: Median age at first recurrence was 7.6 years (IQR: 4.0-13.6). At first recurrence, median PFS and OS were 15.3 (CI 13.3-20.0) and 36.9 months (CI 29.7-53.4), respectively. The Hazard Ratio for the use of chemotherapy in local recurrences in a time-dependent Cox-regression analysis was 0.99 (CI 0.74-1.33). Evaluable responses for 140 applied chemotherapies were analyzed, of which sirolimus showed the best RR (50%) and longest median TTP [11.51 (CI 3.98; 14.0) months] in nine patients, with the strongest impact found when sirolimus was used as a monotherapy. Seven patients with progression-free survival > 12 months after subtotal/no-resection facilitated by chemotherapy were found. No definitive survival advantage for any drug in a specific molecularly defined EPN type was found.

Conclusion: No survival advantage for the general use of chemotherapy in recurrent EPN was found. In cases with incomplete resection, chemotherapy was able to extend survival in individual cases. Sirolimus showed the best RR, DOR and TTP out of all drugs analyzed and may warrant further investigation.

Keywords: Chemotherapy; Children; Ependymoma; Recurrence; Sirolimus.

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Conflict of interest statement

Authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Patients with subtotal or no resection at any recurrence and a PFS of over 12 months. Ongoing response denoted at date of last follow-up. Patient (P) 1: 1st recurrence, Vincristine + Cyclophosphamide + Carboplatin + Etoposide (HIT-SKK); P2: 3rd recurrence, Etoposide + Trofosfamide (HIT-REZ 2005); P3: 1st recurrence, HIT-SKK then Actinomycin D + Etoposide + Trofosfamide; P4: 5th recurrence, 5-FU; P5: 1st recurrence, Etoposide + Trofosfamide (HIT-REZ 2005); P6: 1st recurrence, Temozolomide, P7: 2nd recurrence, Temozolomide (HIT-REZ 2005)
See this image and copyright information in PMC

References

    1. Byer L, Kline CN, Coleman C, Allen IE, Whitaker E, Mueller S. A systematic review and meta-analysis of outcomes in pediatric, recurrent ependymoma. J Neurooncol. 2019;144:445–452. doi: 10.1007/s11060-019-03255-3. - DOI - PubMed
    1. Ritzmann TA, Rogers HA, Paine SML, Storer LCD, Jacques TS, Chapman RJ, Ellison D, Donson AM, Foreman NK, Grundy RG. A retrospective analysis of recurrent pediatric ependymoma reveals extremely poor survival and ineffectiveness of current treatments across central nervous system locations and molecular subgroups. Pediatr Blood Cancer. 2020;67:e28426. doi: 10.1002/pbc.28426. - DOI - PubMed
    1. Massimino M, Barretta F, Modena P, Witt H, Minasi S, Pfister SM, Pajtler KW, Antonelli M, Gandola L, Luisa Garre M, Bertin D, Mastronuzzi A, Mascarin M, Quaglietta L, Viscardi E, Sardi I, Ruggiero A, Pollo B, Buccoliero A, Boschetti L, Schiavello E, Chiapparini L, Erbetta A, Morra I, Gessi M, Donofrio V, Patriarca C, Giangaspero F, Johann P, Buttarelli FR. Second series by the Italian association of pediatric hematology and oncology of children and adolescents with intracranial ependymoma: an integrated molecular and clinical characterization with a long-term follow-up. Neuro Oncol. 2021;23:848–857. doi: 10.1093/neuonc/noaa257. - DOI - PMC - PubMed
    1. Junger ST, Mynarek M, Wohlers I, Dorner E, Muhlen AZ, Velez-Char N, von Hoff K, Rutkowski S, Warmuth-Metz M, Kortmann RD, Timmermann B, Rahmann S, Klein-Hitpass L, von Bueren AO, Pietsch T. Improved risk-stratification for posterior fossa ependymoma of childhood considering clinical, histological and genetic features—a retrospective analysis of the HIT ependymoma trial cohort. Acta Neuropathol Commun. 2019;7:181. doi: 10.1186/s40478-019-0820-5. - DOI - PMC - PubMed
    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;26:905–911. doi: 10.1007/s00381-009-1067-4. - DOI - PubMed