Journal of Neuro-Oncology

, Volume 114, Issue 3, pp 339–344 | Cite as

Clinico-radiologic characteristics of long-term survivors of diffuse intrinsic pontine glioma

  • Sadhana Jackson
  • Zoltan Patay
  • Robyn Howarth
  • Atmaram S. Pai Panandiker
  • Arzu Onar-Thomas
  • Amar Gajjar
  • Alberto Broniscer
Clinical Study


Diffuse intrinsic pontine glioma (DIPG) is the deadliest central nervous system tumor in children. The survival of affected children has remained poor despite treatment with radiation therapy (RT) with or without chemotherapy. We reviewed the medical records of all surviving patients with DIPG treated at our institution between October 1, 1992 and May 31, 2011. Blinded central radiologic review of the magnetic resonance imaging at diagnosis of all surviving patients and 15 controls with DIPG was performed. All surviving patients underwent neurocognitive assessment during follow-up. Five (2.6 %) of 191 patients treated during the study period were surviving at a median of 9.3 years from their diagnosis (range 5.3–13.2 years). Two patients were younger than 3 years, one lacked signs of pontine cranial nerve involvement, and three had longer duration of symptoms at diagnosis. One patient had a radiologically atypical tumor and one had a tumor originating in the medulla. All five patients received RT. Chemotherapy was variable among these patients. Neurocognitive assessments were obtained after a median interval of 7.1 years. Three of four patients who underwent a detailed evaluation showed cognitive function in the borderline or mental retardation range. Two patients experienced disease progression at 8.8 and 13 years after diagnosis. A minority of children with DIPG experienced long-term survival with currently available therapies. These patients remained at high risk for tumor progression even after long follow-ups. Four of our long-term survivors had clinical and radiologic characteristics at diagnosis associated with improved outcome.


Diffuse Glioma Long-term Neurocognitive Pontine Survivors 



This work was supported by the US National Institutes of Health Cancer Center Support (CORE) Grant P30 CA21765 and by the American Lebanese Syrian Associated Charities (ALSAC). All procedures described in this manuscript were performed in compliance with clinical research regulations in the United States.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Hargrave D, Bartels U, Bouffet E (2006) Diffuse brainstem glioma in children: critical review of clinical trials. Lancet Oncol 7:241–248PubMedCrossRefGoogle Scholar
  2. 2.
    Puget S, Philippe C, Bax DA et al (2012) Mesenchymal transition and PDGFRA amplification/mutation are key distinct oncogenic events in pediatric diffuse intrinsic pontine gliomas. PLoS One 7:e30313PubMedCrossRefGoogle Scholar
  3. 3.
    Monje M, Mitra SS, Freret ME et al (2011) Hedgehog-responsive candidate cell of origin for diffuse intrinsic pontine glioma. Proc Natl Acad Sci USA 108:4453–4458PubMedCrossRefGoogle Scholar
  4. 4.
    Broniscer A, Leite CC, Lanchote VL, Machado TM, Cristófani LM (2000) Radiation therapy and high-dose tamoxifen in the treatment of patients with diffuse brainstem gliomas: results of a Brazilian cooperative study. Brainstem Glioma Cooperative Group. J Clin Oncol 18:1246–1253PubMedGoogle Scholar
  5. 5.
    Greenberg ML, Fisher PG, Freeman C et al (2005) Etoposide, vincristine, and cyclosporin A with standard-dose radiation therapy in newly diagnosed diffuse intrinsic brainstem gliomas: a Pediatric Oncology Group phase I study. Pediatr Blood Cancer 45:644–648PubMedCrossRefGoogle Scholar
  6. 6.
    Wagner S, Warmuth-Metz M, Emser A et al (2006) Treatment options in childhood pontine gliomas. J Neurooncol 79:281–287PubMedCrossRefGoogle Scholar
  7. 7.
    Massimino M, Spreafico F, Biassoni V et al (2008) Diffuse pontine gliomas in children: changing strategies, changing results? a mono-institutional 20-year experience. J Neurooncol 87:355–361PubMedCrossRefGoogle Scholar
  8. 8.
    Broniscer A, Baker JN, Tagen M et al (2010) Phase I study of vandetanib during and after radiotherapy in children with diffuse intrinsic pontine glioma. J Clin Oncol 28:4762–4768PubMedCrossRefGoogle Scholar
  9. 9.
    Haas-Kogan DA, Banerjee A, Poussaint TY et al (2011) Phase II trial of tipifarnib and radiation in children with newly diagnosed diffuse intrinsic pontine gliomas. Neuro Oncol 13:298–306PubMedCrossRefGoogle Scholar
  10. 10.
    Pollack IF, Stewart CF, Kocak M et al (2011) A phase II study of gefitinib and irradiation in children with newly diagnosed brainstem gliomas: a report from the pediatric brain tumor consortium. Neuro Oncol 13:290–297PubMedCrossRefGoogle Scholar
  11. 11.
    Freeman CR, Bourgouin PM, Sanford RA, Cohen ME, Friedman HS, Kun LE (1996) Long term survivors of childhood brain stem gliomas treated with hyperfractionated radiotherapy. Clinical characteristics and treatment related toxicities. The Pediatric Oncology Group. Cancer 77:555–562PubMedCrossRefGoogle Scholar
  12. 12.
    Allen J, Siffert J, Donahue B et al (1999) A phase I/II study of carboplatin combined with hyperfractionated radiotherapy for brainstem gliomas. Cancer 86:1064–1069PubMedCrossRefGoogle Scholar
  13. 13.
    Hargrave D, Chuang N, Bouffet E (2008) Conventional MRI cannot predict survival in childhood diffuse intrinsic pontine glioma. J Neurooncol 86:313–319PubMedCrossRefGoogle Scholar
  14. 14.
    Warren K, Bent R, Wolters PL et al (2012) A phase 2 study of pegylated interferon α-2b (PEG-Intron(®)) in children with diffuse intrinsic pontine glioma. Cancer 118:3607–3613PubMedCrossRefGoogle Scholar
  15. 15.
    Barkovich AJ, Krischer J, Kun LE et al (1990/1991) Brain stem gliomas: a classification system based on magnetic resonance imaging. Pediatr Neurosurg 16:73–83CrossRefGoogle Scholar
  16. 16.
    Fischbein NJ, Prados MD, Wara W, Russo C, Edwards MS, Barkovich AJ (1996) Radiologic classification of brain stem tumors: correlation of magnetic resonance imaging appearance with clinical outcome. Pediatr Neurosurg 24:9–23PubMedCrossRefGoogle Scholar
  17. 17.
    Wechsler D (2003) Wechsler intelligence scale for children. The Psychological Corporation, San AntonioGoogle Scholar
  18. 18.
    Wechsler D (2008) Wechsler adult intelligence scale. The Psychological Corporation, San AntonioGoogle Scholar
  19. 19.
    Woodcock RW, McGrew KS, Mather N (2001) Woodcock–Johnson tests of achievement III. Riverside Publishing, ItascaGoogle Scholar
  20. 20.
    Wechsler D (2002) Wechsler individual achievement test. The Psychological Corporation, San AntonioGoogle Scholar
  21. 21.
    Bryant BR, Wiederholt L, Bryant DP (2004) Gray diagnostic reading tests. PRO-ED Inc., AustinGoogle Scholar
  22. 22.
    Gioia GA, Isquith PK, Guy SC, Kenworthy L (2000) Behavior rating inventory of executive function. Psychological Assessment Resources Inc., OdessaGoogle Scholar
  23. 23.
    Sanford RA, Freeman CR, Burger P, Cohen ME (1988) Prognostic criteria for experimental protocols in pediatric brainstem gliomas. Surg Neurol 30:276–280PubMedCrossRefGoogle Scholar
  24. 24.
    Fisher PG, Breiter S, Carson BS et al (2000) A clinicopathologic reappraisal of brain stem tumor classification. Identification of pilocytic astrocytoma and fibrillary astrocytoma as distinct entities. Cancer 89:1569–1576PubMedCrossRefGoogle Scholar
  25. 25.
    Pollack IF, Jakacki RI, Blaney SM et al (2007) Phase I trial of imatinib in children with newly diagnosed brainstem and recurrent malignant gliomas: a pediatric brain tumor consortium report. Neuro Oncol 9:145–160PubMedCrossRefGoogle Scholar
  26. 26.
    Adams DM, Zhou T, Berg SL, Bernstein M, Neville K, Blaney SM (2008) Children’s Oncology Group. phase 1 trial of O6-benzylguanine and BCNU in children with CNS tumors: a Children’s Oncology Group study. Pediatr Blood Cancer 50:549–553PubMedCrossRefGoogle Scholar
  27. 27.
    Kieran MW, Packer RJ, Onar A et al (2007) Phase I and pharmacokinetic study of the oral farnesyltransferase inhibitor lonafarnib administered twice daily to pediatric patients with advanced central nervous system tumors using a modified continuous reassessment method: a pediatric brain tumor consortium study. J Clin Oncol 25:3137–3143PubMedCrossRefGoogle Scholar
  28. 28.
    Broniscer A, Iacono L, Chintagumpala M et al (2005) Role of temozolomide after radiotherapy for newly diagnosed diffuse brainstem glioma in children: results of a multiinstitutional study (SJHG-98). Cancer 103:133–139PubMedCrossRefGoogle Scholar
  29. 29.
    Cohen KJ, Heideman RL, Zhou T et al (2011) Temozolomide in the treatment of children with newly diagnosed diffuse intrinsic pontine gliomas: a report from the Children’s Oncology Group. Neuro Oncol 13:410–416PubMedCrossRefGoogle Scholar
  30. 30.
    Lezak MD, Howieson DB, Loring DW (2004) Neuropsychological assessment. Oxford University Press, New YorkGoogle Scholar
  31. 31.
    Garrard P, Bradshaw D, Jäger HR, Thompson AJ, Losseff N, Playford D (2002) Cognitive dysfunction after isolated brain stem insult. An underdiagnosed cause of long term morbidity. J Neurol Neurosurg Psychiatry 73:191–194PubMedCrossRefGoogle Scholar
  32. 32.
    Hoffmann M, Watts A (1998) Cognitive dysfunction in isolated brainstem stroke: a neuropsychological and SPECT study. J Stroke Cerebrovasc Dis 7:24–31PubMedCrossRefGoogle Scholar
  33. 33.
    Hoffmann M, Schmitt F (2004) Cognitive impairment in isolated subtentorial stroke. Acta Neurol Scand 109:14–24PubMedCrossRefGoogle Scholar
  34. 34.
    Wu G, Broniscer A, McEachron TA et al (2012) Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44:251–253PubMedCrossRefGoogle Scholar
  35. 35.
    Khuong-Quang DA, Buczkowicz P, Rakopoulos P et al (2012) K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas. Acta Neuropathol 124:439–447PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Sadhana Jackson
    • 1
  • Zoltan Patay
    • 2
  • Robyn Howarth
    • 3
  • Atmaram S. Pai Panandiker
    • 2
  • Arzu Onar-Thomas
    • 4
  • Amar Gajjar
    • 1
    • 5
  • Alberto Broniscer
    • 1
    • 5
  1. 1.Department of OncologySt. Jude Children’s Research HospitalMemphisUSA
  2. 2.Department of Radiological SciencesSt. Jude Children’s Research HospitalMemphisUSA
  3. 3.Department of PsychologySt. Jude Children’s Research HospitalMemphisUSA
  4. 4.Department of BiostatisticsSt. Jude Children’s Research HospitalMemphisUSA
  5. 5.Department of PediatricsUniversity of Tennessee Health Sciences CenterMemphisUSA

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