Advertisement

Journal of Neuro-Oncology

, Volume 137, Issue 1, pp 111–118 | Cite as

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

  • M. J. Lobon-Iglesias
  • G. Giraud
  • D. Castel
  • C. Philippe
  • M. A. Debily
  • C. Briandet
  • F. Fouyssac
  • E. de Carli
  • C. Dufour
  • D. Valteau-Couanet
  • C. Sainte-Rose
  • T. Blauwblomme
  • K. Beccaria
  • M. Zerah
  • S. Puget
  • R. Calmon
  • N. Boddaert
  • S. Bolle
  • P. Varlet
  • J. Grill
Clinical Study

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.

Keywords

Brainstem glioma H3K27M mutation Midline infiltrative glioma Steroid-independence 

Notes

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.

Supplementary material

11060_2017_2702_MOESM1_ESM.pdf (60 kb)
Supplementary material 1 (PDF 60 KB)

References

  1. 1.
    Vanan MI, Eisenstat DD (2015) DIPG in children: what can we learn from the past? Front Oncol 5:237CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Puget S, Beccaria K, Blauwblomme T, Roujeau T, James S, Grill J, Zerah M, Varlet P, Sainte-Rose C (2015) Biopsy in a series of 130 pediatric diffuse intrinsic pontine gliomas. Child’s Nerv Syst 31:1773–1780CrossRefGoogle Scholar
  3. 3.
    Kieran MW (2015) Time to rethink the unthinkable: upfront biopsy of children with newly diagnosed diffuse intrinsic pontine glioma (DIPG). Pediatr Blood Cancer 62(1):3–4CrossRefPubMedGoogle Scholar
  4. 4.
    Kieran MW, Goumnerova LC, Prados M, Gupta N (2016) Biopsy for diffuse intrinsic pontine glioma: a reappraisal. J Neurosurg Pediatr 18:390–391CrossRefPubMedGoogle Scholar
  5. 5.
    Walker DA, Liu J, Kieran M, Jabado N, Picton S, Packer R, St. Rose C (2013) A multi-disciplinary consensus statement concerning surgical approaches to low-grade, high-grade astrocytomas and diffuse intrinsic pontine gliomas in childhood (CPN Paris 2011) using the Delphi method. Neuro Oncol 15:462–468CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131:803–820CrossRefPubMedGoogle Scholar
  7. 7.
    Frappaz D, Schell M, Thiesse P et al (2008) Preradiation chemotherapy may improve survival in pediatric diffuse intrinsic brainstem gliomas: final results of BSG 98 prospective trial. Neuro Oncol 10:599–607CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Warren KE (2012) Diffuse intrinsic pontine glioma: poised for progress. Front Oncol 2:205CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Jansen MH, Van Zanten SEV, Aliaga ES et al (2015) Survival prediction model of children with diffuse intrinsic pontine glioma based on clinical and radiological criteria. Neuro Oncol 17:160–166CrossRefPubMedGoogle Scholar
  10. 10.
    Massimino M, Biassoni V, Miceli R et al (2014) Results of nimotuzumab and vinorelbine, radiation and re-irradiation for diffuse pontine glioma in childhood. J Neurooncol 118:305–312PubMedGoogle Scholar
  11. 11.
    Castel D, Philippe C, Calmon R et al (2015) Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes. Acta Neuropathol 130:815–827CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Steffen-Smith EA, Baker EH, Venzon D, Shandilya S, Bent RS, Warren KE (2014) Measurements of the pons as a biomarker of progression for pediatric DIPG. J Neurooncol 116:127–133CrossRefPubMedGoogle Scholar
  13. 13.
    Dhermain FG, Hau P, Lanfermann H, Jacobs AH, van den Bent MJ (2010) Advanced MRI and PET imaging for assessment of treatment response in patients with gliomas. Lancet Neurol 9:906–920CrossRefPubMedGoogle Scholar
  14. 14.
    Chassot A, Canale S, Varlet P et al (2012) Radiotherapy with concurrent and adjuvant temozolomide in children with newly diagnosed diffuse intrinsic pontine glioma. J Neurooncol 106:399–407CrossRefPubMedGoogle Scholar
  15. 15.
    Geoerger B, Hargrave D, Thomas F et al (2011) Innovative therapies for children with cancer pediatric phase I study of erlotinib in brainstem glioma and relapsing/refractory brain tumors. Neuro Oncol 13:109–118CrossRefPubMedGoogle Scholar
  16. 16.
    Bernier-Chastagner V, Grill J, Doz F et al (2005) Topotecan as a radiosensitizer in the treatment of children with malignant diffuse brainstem gliomas: Results of a French Society of Paediatric Oncology Phase II Study. Cancer 104:2792–2797CrossRefPubMedGoogle Scholar
  17. 17.
    Stupp R et al (2014) Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071–22072 study): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 15:1100–1108CrossRefPubMedGoogle Scholar
  18. 18.
    Dufour C et al (2006) High-grade glioma in children under 5 years of age: a chemotherapy only approach with the BBSFOP protocol. Eur J Cancer 42(17):2939–2945 42:2939–2945CrossRefGoogle Scholar
  19. 19.
    Hargrave D, Bartels U, Bouffet E (2006) Diffuse brainstem glioma in children: critical review of clinical trials. Lancet Oncol 7:241–248CrossRefPubMedGoogle Scholar
  20. 20.
    Cohen KJ, Jabado N, Grill J (2017) Diffuse intrinsic pontine gliomas—current management and new biologic insights. Is there a glimmer of hope? Neuro Oncol 19:1025–1034CrossRefPubMedGoogle Scholar
  21. 21.
    Wolff JE, Rytting ME, Vats TS, Zage PE, Ater JL, Woo S, Kuttesch J, Ketonen L, Mahajan A (2012) Treatment of recurrent diffuse intrinsic pontine glioma: the MD Anderson Cancer Center experience. J Neurooncol 106:391–397CrossRefPubMedGoogle Scholar
  22. 22.
    Green AL, Kieran MW (2015) Pediatric brainstem gliomas: new understanding leads to potential new treatments for two very different tumors. Curr Oncol Rep.  https://doi.org/10.1007/s11912-014-0436-7 PubMedGoogle Scholar
  23. 23.
    Janssens GO, Gandola L, Bolle S 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 73:38–47CrossRefPubMedGoogle Scholar
  24. 24.
    Carceller F, Fowkes LA, Khabra K et al (2016) Pseudoprogression in children, adolescents and young adults with non-brainstem high grade glioma and diffuse intrinsic pontine glioma. J Neurooncol 129:109–121CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • M. J. Lobon-Iglesias
    • 1
    • 2
  • G. Giraud
    • 1
    • 3
  • D. Castel
    • 1
    • 2
  • C. Philippe
    • 2
  • M. A. Debily
    • 2
    • 4
  • C. Briandet
    • 5
  • F. Fouyssac
    • 6
  • E. de Carli
    • 7
  • C. Dufour
    • 1
    • 2
  • D. Valteau-Couanet
    • 1
  • C. Sainte-Rose
    • 8
  • T. Blauwblomme
    • 8
  • K. Beccaria
    • 2
    • 8
  • M. Zerah
    • 8
  • S. Puget
    • 8
  • R. Calmon
    • 9
    • 10
  • N. Boddaert
    • 9
    • 10
  • S. Bolle
    • 11
  • P. Varlet
    • 12
  • J. Grill
    • 1
    • 2
  1. 1.Department of Pediatric and Adolescent OncologyGustave Roussy and University Paris-SaclayVillejuifFrance
  2. 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-SaclayVillejuifFrance
  3. 3.Neuro-Oncology Team, Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck LaboratoryUppsala UniversityUppsalaSweden
  4. 4.University of Evry-Val d’EssoneEvryFrance
  5. 5.Department of PediatricsUniversity Hospital of DijonDijonFrance
  6. 6.Department of Pediatric OncologyUniversity Hospital of Nancy-BraboisNancyFrance
  7. 7.Department of Pediatric OncologyUniversity Hospital of AngersAngersFrance
  8. 8.Department of NeurosurgeryNecker Sick Children’s University Hospital and Paris Descartes UniversityParisFrance
  9. 9.Department of RadiologyNecker Sick Children’s University Hospital and Paris Descartes UniversityParisFrance
  10. 10.Imagine Institute and Unité 1163 de l’Institut National de la Santé et de la Recherche Médicale (INSERM)ParisFrance
  11. 11.Department of RadiotherapyGustave RoussyVillejuifFrance
  12. 12.Department of NeuropathologySainte-Anne Hospital and Paris Descartes UniversityParisFrance

Personalised recommendations