Retrospective study of diffuse intrinsic pontine glioma in the Belgian population: a 25 year experience

Abstract

Introduction

Diffuse intrinsic pontine glioma is a rare disease with a high mortality. Our primary aim was to determine the incidence of this disease in Belgium. Secondly, we wanted to compare the treatment approach of Belgian pediatric oncology centres, to investigate possibilities for improvement.

Methods

We retrospectively collected and analysed data on DIPG-patients diagnosed between 1994 and 2018 and recorded in the Belgian Cancer Registry. We included patients ≤ 18 years who were followed in one of the eight Belgian pediatric oncology centres.

Results

We included 100 patients. Files were complete in 87 patients. We observed an increase in diagnoses with an incidence of 3.1 per 1,000,000 persons (aged 0–≤ 18) per year over the last 5 years compared to an overall incidence of 1.8. Biopsy was performed at diagnosis in 51.7% of patients. In one fifth this was study-related. Mutation analysis was known in eight patients, of which six showed the H3 K27M-mutation. 58.8% of patients received chemotherapy, without a significant survival benefit. 12.6% of patients were included in a clinical trial. Biopsy rate and the use of chemotherapy differed widely between centres. Mean OS and PFS were 10.49 and 4.87 months respectively. We observed an improved survival over time.

Conclusions

Over the past 25 years, we observed an increase of new DIPG-diagnoses. Outcome in our cohort is comparable with literature findings. We demonstrate an important heterogeneity in treatment approach between different centres and limited inclusion in clinical trials. Therefore, collaboration between centres and inclusion of patients in clinical trials is much needed.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. 1.

    Hargrave D, Bartels U, Bouffet E (2006) Diffuse brainstem glioma in children: critical review of clinical trials. Lancet Oncol 7(3):241–248. https://doi.org/10.1016/S1470-2045(06)70615-5

    Google Scholar 

  2. 2.

    Jansen MH, van Vuurden DG, Vandertop WP, Kaspers GJ (2012) Diffuse intrinsic pontine gliomas: a systematic update on clinical trials and biology. Cancer Treat Rev 38(1):27–35. https://doi.org/10.1016/j.ctrv.2011.06.007

    Google Scholar 

  3. 3.

    Veldhuijzen van Zanten SE, Jansen MH, Sanchez Aliaga E, van Vuurden DG, Vandertop WP, Kaspers GJ (2015) A twenty-year review of diagnosing and treating children with diffuse intrinsic pontine glioma in The Netherlands. Expert Rev Anticancer Ther. 15(2):157–164. https://doi.org/10.1586/14737140.2015.974563

    Google Scholar 

  4. 4.

    Green AL, Kieran MW (2015) Pediatric brainstem gliomas: new understanding leads to potential new treatments for two very different tumors. Curr Oncol Rep 17(3):436. https://doi.org/10.1007/s11912-014-0436-7

    Google Scholar 

  5. 5.

    Robison NJ, Kieran MW (2014) Diffuse intrinsic pontine glioma: a reassessment. J Neurooncol 119(1):7–15. https://doi.org/10.1007/s11060-014-1448-8

    Google Scholar 

  6. 6.

    Vitanza NA, Monje M (2019) Diffuse intrinsic pontine glioma: from diagnosis to next-generation clinical trials. Curr Treat Options Neurol. https://doi.org/10.1007/s11940-019-0577-y

    Google Scholar 

  7. 7.

    Baugh J, Bartels U, Leach J, Jones B, Chaney B, Warren KE et al (2017) The international diffuse intrinsic pontine glioma registry: an infrastructure to accelerate collaborative research for an orphan disease. J Neurooncol. 132(2):323–331. https://doi.org/10.1007/s11060-017-2372-5

    Google Scholar 

  8. 8.

    Puget S, Beccaria K, Blauwblomme T, Roujeau T, James S, Grill J et al (2015) Biopsy in a series of 130 pediatric diffuse intrinsic pontine gliomas. Childs Nerv Syst 31(10):1773–1780. https://doi.org/10.1007/s00381-015-2832-1

    Google Scholar 

  9. 9.

    Gupta N, Goumnerova LC, Manley P, Chi SN, Neuberg D, Puligandla M et al (2018) Prospective feasibility and safety assessment of surgical biopsy for patients with newly diagnosed diffuse intrinsic pontine glioma. Neuro Oncol 20(11):1547–1555. https://doi.org/10.1093/neuonc/noy070al

    Google Scholar 

  10. 10.

    Paugh BS, Qu C, Jones C, Liu Z, Adamowicz-Brice M, Zhang J et al (2010) Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease. J Clin Oncol 28(18):3061–3068. https://doi.org/10.1200/JCO.2009.26.7252

    Google Scholar 

  11. 11.

    Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS, Becksfort J et al (2012) Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44(3):251–253. https://doi.org/10.1038/ng.1102

    Google Scholar 

  12. 12.

    Castel D, Philippe C, Calmon R, Le Dret L, Truffaux N, Boddaert N et al (2015) Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes. Acta Neuropathol 130(6):815–827. https://doi.org/10.1007/s00401-015-1478-0

    Google Scholar 

  13. 13.

    Janssens GO, Jansen MH, Lauwers SJ, Nowak PJ, Oldenburger FR, Bouffet E et al (2013) Hypofractionation vs conventional radiation therapy for newly diagnosed diffuse intrinsic pontine glioma: a matched-cohort analysis. Int J Radiat Oncol Biol Phys 85(2):315–320. https://doi.org/10.1016/j.ijrobp.2012.04.006

    Google Scholar 

  14. 14.

    Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK et al (2016) The 2016 world health organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131(6):803–820. https://doi.org/10.1007/s00401-016-1545-1

    Google Scholar 

  15. 15.

    El-Khouly FE, Veldhuijzen van Zanten SEM, Santa-Maria Lopez V, Hendrikse NH, Kaspers GJL, Loizos G et al (2019) Diagnostics and treatment of diffuse intrinsic pontine glioma: where do we stand? J Neurooncol. 145(1):177–184. https://doi.org/10.1007/s11060-019-03287-9

    Google Scholar 

  16. 16.

    Cage TA, Samagh SP, Mueller S, Nicolaides T, Haas-Kogan D, Prados M et al (2013) Feasibility, safety, and indications for surgical biopsy of intrinsic brainstem tumors in children. Childs Nerv Syst 29(8):1313–1319. https://doi.org/10.1007/s00381-013-2101-0

    Google Scholar 

  17. 17.

    Gallitto M, Lazarev S, Wasserman I, Stafford JM, Wolden SL, Terezakis SA et al (2019) Role of radiation therapy in the management of diffuse intrinsic pontine glioma: a systematic review. Adv Radiat Oncol 30(4):12. https://doi.org/10.1016/j.adro.2019.03.009

    Google Scholar 

  18. 18.

    Freese C, Takiar V, Fouladi M, DeWire M, Breneman J, Pater L (2017) Radiation and subsequent reirradiation outcomes in the treatment of diffuse intrinsic pontine glioma and a systematic review of the reirradiation literature. Pract Radiat Oncol. 7(2):86–92. https://doi.org/10.1016/j.prro.2016.11.005

    Google Scholar 

  19. 19.

    Janssens GO, Gandola L, Bolle S, Mandeville H, Ramos-Albiac M, van Beek K et al (2017) Survival benefit for patients with diffuse intrinsic pontine glioma (DIPG) undergoing re-irradiation at first progression: a matched-cohort analysis on behalf of the SIOP-E-HGG/DIPG working group. Eur J Cancer 73:38–47. https://doi.org/10.1016/j.ejca.2016.12.007

    Google Scholar 

  20. 20.

    Patil N, Kelly ME, Yeboa DN, Buerki RA, Cioffi G, Balaji S et al (2020) Epidemiology of brainstem high-grade gliomas in children and adolescents in the United States 2000–2017. Neuro Oncol. https://doi.org/10.1093/neuonc/noaa295

    Google Scholar 

  21. 21.

    Mathew RK, Rutka JT (2018) Diffuse intrinsic pontine glioma : clinical features, molecular genetics, and novel targeted therapeutics. J Korean Neurosurg Soc 61(3):343–351. https://doi.org/10.3340/jkns.2018.0008

    Google Scholar 

  22. 22.

    Lu VM, Power EA, Zhang L, Daniels DJ (2019) Liquid biopsy for diffuse intrinsic pontine glioma: an update. J Neurosurg Pediatr 6:1–8. https://doi.org/10.3171/2019.6.PEDS19259

    Google Scholar 

  23. 23.

    Huang TY, Piunti A, Lulla RR, Qi J, Horbinski CM, Tomita T et al (2017) Detection of histone H3 mutations in cerebrospinal fluid-derived tumor DNA from children with diffuse midline glioma. Acta Neuropathol Commun 5(1):28. https://doi.org/10.1186/s40478-017-0436-6

    Google Scholar 

  24. 24.

    Broniscer A, Laningham FH, Sanders RP, Kun LE, Ellison DW, Gajjar A (2008) Young age may predict a better outcome for children with diffuse pontine glioma. Cancer 113(3):566–572. https://doi.org/10.1002/cncr.23584

    Google Scholar 

  25. 25.

    Guillamo JS, Monjour A, Taillandier L, Devaux B, Varlet P, Haie-Meder C et al (2001) Brainstem gliomas in adults: prognostic factors and classification. Brain 124(Pt 12):2528–2539. https://doi.org/10.1093/brain/124.12.2528

    Google Scholar 

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Acknowledgements

We thank Morgan Collin, Caroline De Schepper, Annouschka Laenen, Caroline Martin, An Michiels, Wiert Robberechts, Catherine Sondag, Sam Van Gerwen, Merry Van Puyvelde, Michel Vanden Eynden and Nancy Van Damme for their contribution to this study.

Funding

No funds, grants, or other support was received.

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Authors

Contributions

All authors contributed to the study conception and design. Data collection was performed by DR, data analysis was performed by DR and JM. The first draft of the manuscript was written by DR and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Dries Ruttens.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committees of the different centres.

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Ruttens, D., Messiaen, J., Ferster, A. et al. Retrospective study of diffuse intrinsic pontine glioma in the Belgian population: a 25 year experience. J Neurooncol (2021). https://doi.org/10.1007/s11060-021-03766-y

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Keywords

  • Diffuse intrinsic pontine glioma
  • Brainstem glioma
  • Diffuse midline glioma
  • Biopsy
  • Radiotherapy
  • Chemotherapy