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What does a non-response to induction chemotherapy imply in high-risk medulloblastomas?

  • Clinical Study
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Abstract

Purpose

High-risk medulloblastomas (HR-MB) may not respond to induction chemotherapy, with either post-induction stable (SD) or progressive disease (PD). There is no consensus regarding their optimal management.

Methods

A retrospective, multicentre study investigated patients with non-responder HR-MB treated according to the PNET HR + 5 protocol (NCT00936156) between 01/01/2009 and 31/12/2018. After two courses of etoposide and carboplatin (induction), patients with SD or PD were analyzed. Upon clinician’s decision, the PNET HR + 5 protocol was either pursued with tandem high-dose chemotherapy (HDCT) and craniospinal irradiation (CSI) (continuation group) or it was modified (switched group).

Results

Forty-nine patients were identified. After induction, 37 patients had SD and 12 had PD. The outcomes were better for the SD group: the 5-y PFS and OS were 52% (95% CI 35–67) and 70% (95% CI 51–83), respectively, in the SD group while the 2-y PFS and OS were 17% (95% CI 3–41) and 25% (95% CI 6–50), respectively, in the PD group (p < 0.0001). The PNET HR + 5 strategy was pursued for 3 patients in the PD group, of whom only one survived. In the SD group, it was pursued for 24/37 patients whereas 13 patients received miscellaneous treatments including a 36 Gy CSI in 12 cases. Despite that continuation and switched group were well-balanced for factors impacting the outcomes, the latter were better in the continuation group than in the switched group: the 5-y PFS were 78% (95% CI 54–90) versus 0% (p < 0.001), and the 5-y OS were 78% (95% CI 54–90) versus 56% (95% CI 23–79) (p = 0.0618) respectively. In the SD group, multivariate analysis revealed that MYC amplification, molecular group 3, and a switched strategy were independent prognostic factors for progression.

Conclusion

Patients with post-induction SD may benefit from HDCT and CSI, whereas patients with early PD will require new therapeutic approaches.

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Acknowledgements

We would like to thank Lila Saidoun, Marianne Roumy, Isabelle Couteau, Cécile Dumesnil-de Maricourt, Céline Icher, and Yaelle Ouldbey for their assistance with various aspects of this study.

Funding

The authors did not receive support from any organization for the submitted work.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Institut d’Hématologie et d’Oncologie pédiatrique, 1 Place Professeur Joseph Renaut, 69008, Lyon, France

    Jihane Adelon & Cécile Faure-Conter

  2. Department of Pediatric and Adolescent Oncology, Gustave Roussy Institute, Villejuif, France

    Christelle Dufour

  3. Biostatistics and Methodology Unit, Department of Clinical Research and Investigation, Gustave Roussy Institute, Villejuif, France

    Stéphanie Foulon

  4. INSERM U830, Laboratory of Translational Research in Pediatric Oncology, SIREDO Pediatric Oncology Center, Curie Institute, Paris, France

    Julien Masliah Planchon

  5. Department of Neuropathology, Institut de Pathologie Est, Hospices civils de Lyon, Lyon, France

    David Meyronnet

  6. SIREDO Pediatric Oncology Center, Curie Institute, Paris, France

    Franck Bourdeaut

  7. Department of Pediatric Hematology-Oncology, Centre Hospitalo-Universitaire de Montpellier, Montpellier, France

    Gilles Palenzuela

  8. Department of Pediatric Oncology, Children’s Hospital, Nancy, France

    Fanny Fouyssac

  9. Pediatric Oncology Unit, Oscar Lambret Comprehensive Cancer Center, Lille, France

    Sandra Raimbault

  10. Department of Pediatric Oncology, University Hospital, Angers, France

    Emilie De Carli

  11. Department of Pediatric Hematology-Oncology, University Hospital, Besançon, France

    Sébastien Klein

  12. Department of Pediatric Immunohematology and Oncology, University Hospital, Grenoble, France

    Anne Pagnier

  13. Department of Pediatric Onco-Hematology, CHU Toulouse, France

    Anne-Isabelle Bertozzi

  14. Department of Pediatric Hematology and Oncology, La Timone Children’s Hospital, Marseille, France

    Angélique Rome

  15. Department of Pediatric Hematology and Oncology Unit, University Hospital of Saint-Étienne, Saint-Étienne, France

    Audrey David

  16. Clinical Research and Innovation Department, Léon Bérard Cancer Centre, Biostatistics Unit, Lyon, France

    Sylvie Chabaud

Authors
  1. Jihane Adelon
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  2. Christelle Dufour
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  3. Stéphanie Foulon
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  13. Anne-Isabelle Bertozzi
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  15. Audrey David
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  17. Cécile Faure-Conter
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Contributions

Conceptualization, methodology, data analysis and interpretation, writing-original draft, review, editing: JA and CF-C. Statistical analysis, data interpretation: SC. Data collection, writing, review: all authors.

Corresponding author

Correspondence to Jihane Adelon.

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Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

Ethics approval was waived by the local Ethics Committee of the Centre Léon Bérard in light of the retrospective nature of the study, and all of the procedures that were performed were part of the routine care. The study was conducted according to the French Reference Methodology MR-004 (Commission Nationale Informatique et Libertés CNIL reference number 2217201v0).

Consent to participate

Written consent was obtained from the parents/guardians of living patients by a letter of non-opposition to study participation that was sent and in which the aims of the study were described and the guarantee that the patient’s personal details would remain anonymous was affirmed.

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Adelon, J., Dufour, C., Foulon, S. et al. What does a non-response to induction chemotherapy imply in high-risk medulloblastomas?. J Neurooncol 153, 425–440 (2021). https://doi.org/10.1007/s11060-021-03777-9

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  • DOI: https://doi.org/10.1007/s11060-021-03777-9

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