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Diffuse intrinsic pontine gliomas (DIPG) at recurrence: is there a window to test new therapies in some patients?

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Abstract

Children with diffuse intrinsic pontine glioma (DIPG) need new and more efficient treatments. They can be developed at relapse or at diagnosis, but therefore they must be combined with radiotherapy. Survival of children after recurrence and its predictors were studied to inform the possibility to design early phase clinical trials for DIPG at this stage. Among 142 DIPG patients treated between 1998 and 2014, 114 had biopsy-proven DIPG with histone H3 status available for 83. We defined as long survivors’ patients who survived more than 3 months after relapse which corresponds to the minimal life expectancy requested for phase I/II trials. Factors influencing post-relapse survival were accordingly compared between short and long-term survivors after relapse. Fifty-seven percent of patients were considered long survivors and 70% of them had a Lansky Play Scale (LPS) above 50% at relapse. Patients who became steroids-independent after initial treatment for at least 2 months had better survival after relapse (3.7 versus 2.6 months, p = 0.001). LPS above 50% at relapse was correlated with better survival after relapse (3.8 versus 1.8 months, p < 0.001). Patients with H3.1 mutation survived longer after relapse (4.9 versus 2.7 months, p = 0.007). Patients who received a second radiotherapy at the time of relapse had an improved survival (7.5 versus 4 months, p = 0.001). In the two-way ANOVA analysis, steroid-independence and LPS predicted survival best and the type of histone H3 (H3.1 or H3.3) mutated did not improve prediction. Survival of many DIPG patients after relapse over 3 months would make possible to propose specific trials for this condition. Steroid-independence, H3 mutation status and LPS should be considered to predict eligibility.

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Acknowledgements

We thank the Swedish Children Cancer Foundation for supporting Dr Giraud fellowship in Gustave Roussy Cancer Campus, Marianne Raquin for her precious help with the databases, All the patients and the medical crew who made possible the documentation of medical history.

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Author notes

  1. M. J. Lobon-Iglesias and G. Giraud have contributed equally to the work.

Authors and Affiliations

  1. Department of Pediatric and Adolescent Oncology, Gustave Roussy and University Paris-Saclay, Villejuif, France

    M. J. Lobon-Iglesias, G. Giraud, D. Castel, C. Dufour, D. Valteau-Couanet & J. Grill

  2. Team “Target Identification and Innovative Anticancer Therapies in Pediatric Cancers”, Unite Mixte de Recherche 8203 du Centre National de la Recherche Scientifique (CNRS) and University Paris-Saclay, Villejuif, France

    M. J. Lobon-Iglesias, D. Castel, C. Philippe, M. A. Debily, C. Dufour, K. Beccaria & J. Grill

  3. Neuro-Oncology Team, Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden

    G. Giraud

  4. University of Evry-Val d’Essone, Evry, France

    M. A. Debily

  5. Department of Pediatrics, University Hospital of Dijon, Dijon, France

    C. Briandet

  6. Department of Pediatric Oncology, University Hospital of Nancy-Brabois, Nancy, France

    F. Fouyssac

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

    E. de Carli

  8. Department of Neurosurgery, Necker Sick Children’s University Hospital and Paris Descartes University, Paris, France

    C. Sainte-Rose, T. Blauwblomme, K. Beccaria, M. Zerah & S. Puget

  9. Department of Radiology, Necker Sick Children’s University Hospital and Paris Descartes University, Paris, France

    R. Calmon & N. Boddaert

  10. Imagine Institute and Unité 1163 de l’Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France

    R. Calmon & N. Boddaert

  11. Department of Radiotherapy, Gustave Roussy, Villejuif, France

    S. Bolle

  12. Department of Neuropathology, Sainte-Anne Hospital and Paris Descartes University, Paris, France

    P. Varlet

Authors
  1. M. J. Lobon-Iglesias
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  2. G. Giraud
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  3. D. Castel
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  4. C. Philippe
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  5. M. A. Debily
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  6. C. Briandet
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  7. F. Fouyssac
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  8. E. de Carli
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  9. C. Dufour
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  10. D. Valteau-Couanet
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  11. C. Sainte-Rose
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  12. T. Blauwblomme
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  13. K. Beccaria
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  14. M. Zerah
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  15. S. Puget
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  16. R. Calmon
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  17. N. Boddaert
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  18. S. Bolle
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  19. P. Varlet
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  20. J. Grill
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Corresponding author

Correspondence to J. Grill.

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Lobon-Iglesias, M.J., Giraud, G., Castel, D. et al. Diffuse intrinsic pontine gliomas (DIPG) at recurrence: is there a window to test new therapies in some patients?. J Neurooncol 137, 111–118 (2018). https://doi.org/10.1007/s11060-017-2702-7

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  • DOI: https://doi.org/10.1007/s11060-017-2702-7

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