Journal of Neuro-Oncology

, Volume 106, Issue 2, pp 391–397 | Cite as

Treatment of recurrent diffuse intrinsic pontine glioma: the MD Anderson Cancer Center experience

  • Johannes E. Wolff
  • Michael E. Rytting
  • Tribhawan S. Vats
  • Peter E. Zage
  • Joann L. Ater
  • Shiao Woo
  • John Kuttesch
  • Leena Ketonen
  • Anita Mahajan
Clinical Study – Patient Study


Recurrent diffuse intrinsic pontine gliomas (DIPG) are traditionally treated with palliative care since no effective treatments have been described for these tumors. Recently, clinical studies have been emerging, and individualized treatment is attempted more frequently. However, an informative way to compare the treatment outcomes has not been established, and historical control data are missing for recurrent disease. We conducted a retrospective chart review of patients with recurrent DIPG treated between 1998 and 2010. Response progression-free survival and possible influencing factors were evaluated. Thirty-one patients were identified who were treated in 61 treatment attempts using 26 treatment elements in 31 different regimens. The most frequently used drugs were etoposide (14), bevacizumab (13), irinotecan (13), nimotuzumab (13), and valproic acid (13). Seven patients had repeat radiation therapy to the primary tumor. Response was recorded after 58 treatment attempts and was comprised of 0 treatment attempts with complete responses, 7 with partial responses, 20 with stable diseases, and 31 with progressive diseases The median progression-free survival after treatment start was 0.16 years (2 months) and was found to be correlated to the prior time to progression but not to the number of previous treatment attempts. Repeat radiation resulted in the highest response rates (4/7), and the longest progression-free survival. These data provide a basis to plan future clinical trials for recurrent DIPG. Repeat radiation therapy should be tested in a prospective clinical study.


Diffuse intrinsic pontine glioma Chemotherapy Radiation Biomathematics 


  1. 1.
    Rubin G, Michowitz S, Horev G et al (1998) Pediatric brain stem gliomas: an update. Childs Nerv Syst 14:167–173PubMedCrossRefGoogle Scholar
  2. 2.
    Broniscer A, Gajjar A, Bhargava R et al (1997) Brain stem involvement in children with neurofibromatosis type 1: role of magnetic resonance imaging and spectroscopy in the distinction from diffuse pontine glioma. Neurosurgery 40:331–337, discussion 37–38PubMedCrossRefGoogle Scholar
  3. 3.
    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 113:566–572PubMedCrossRefGoogle Scholar
  4. 4.
    Mauffrey C (2006) Paediatric brainstem gliomas: prognostic factors and management. J Clin Neurosci 13:431–437PubMedCrossRefGoogle Scholar
  5. 5.
    Hargrave D, Chuang N, Bouffet E (2008) Conventional MRI cannot predict survival in childhood diffuse intrinsic pontine glioma. J Neurooncol 86:313–319PubMedCrossRefGoogle Scholar
  6. 6.
    Giussani C, Poliakov A, Ferri RT et al (2010) DTI fiber tracking to differentiate demyelinating diseases from diffuse brain stem glioma. Neuroimage 52:217–223PubMedCrossRefGoogle Scholar
  7. 7.
    Chen X, Weigel D, Ganslandt O, Buchfelder M, Nimsky C (2007) Diffusion tensor imaging and white matter tractography in patients with brainstem lesions. Acta Neurochir (Wien) 149:1117–1131, discussion 31CrossRefGoogle Scholar
  8. 8.
    Leach PA, Estlin EJ, Coope DJ, Thorne JA, Kamaly-Asl ID (2008) Diffuse brainstem gliomas in children: should we or shouldn’t we biopsy? Br J Neurosurg 22:619–624PubMedCrossRefGoogle Scholar
  9. 9.
    Wagner S, Warmuth-Metz M, Emser A et al (2006) Treatment options in childhood pontine gliomas. J Neurooncol 79:281–287PubMedCrossRefGoogle Scholar
  10. 10.
    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
  11. 11.
    Freeman CR, Krischer JP, Sanford RA et al (1993) Final results of a study of escalating doses of hyperfractionated radiotherapy in brain stem tumors in children: a pediatric oncology group study. Int J Radiat Oncol Biol Phys 27:197–206PubMedGoogle Scholar
  12. 12.
    Packer RJ, Boyett JM, Zimmerman RA et al (1993) Hyperfractionated radiation therapy (72 Gy) for children with brain stem gliomas. A childrens cancer group phase I/II trial. Cancer 72:1414–1421PubMedCrossRefGoogle Scholar
  13. 13.
    Farmer JP, Montes JL, Freeman CR, Meagher-Villemure K, Bond MC, O’Gorman AM (2001) Brainstem gliomas. A 10-year institutional review. Pediatr Neurosurg 34:206–214PubMedCrossRefGoogle Scholar
  14. 14.
    Freeman CR, Farmer JP (1998) Pediatric brain stem gliomas: a review. Int J Radiat Oncol Biol Phys 40:265–271PubMedCrossRefGoogle Scholar
  15. 15.
    Fangusaro J (2009) Pediatric high-grade gliomas and diffuse intrinsic pontine gliomas. J Child Neurol 24:1409–1417PubMedCrossRefGoogle Scholar
  16. 16.
    Wagner S, Reinert C, Schmid HJ et al High-dose methotrexate prior to simultaneous radiochemotherapy in children with malignant high-grade gliomas. Anticancer Res 252583–7Google Scholar
  17. 17.
    Finlay JL, Zacharoulis S (2005) The treatment of high grade gliomas and diffuse intrinsic pontine tumors of childhood and adolescence: a historical-and futuristic-perspective. J Neurooncol 75:253–266PubMedCrossRefGoogle Scholar
  18. 18.
    Bouffet E, Khelfaoui F, Philip I, Biron P, Brunat-Mentigny M, Philip T (1997) High-dose carmustine for high-grade gliomas in childhood. Cancer Chemother Pharmacol 39:376–379PubMedCrossRefGoogle Scholar
  19. 19.
    Wolff JE, Westphal S, Molenkamp G et al (2002) Treatment of paediatric pontine glioma with oral trophosphamide and etoposide. Br J Cancer 87:945–949PubMedCrossRefGoogle Scholar
  20. 20.
    Wolff JE, Molenkamp G, Westphal S et al (2000) Oral trofosfamide and etoposide in pediatric patients with glioblastoma multiforme. Cancer 89:2131–2137PubMedCrossRefGoogle Scholar
  21. 21.
    Zhang M, Segerer F, Ketonen L, Mahajan A, Wolff J (2008) Prediction of tumour regrowth of pontine glioma using a two-term model. Anticancer Res 28:741–9Google Scholar
  22. 22.
    Fontanilla HP, Pinnix CC, Ketonen LM et al (2011) Palliative reirradiation for progressive diffuse intrinsic pontine glioma. Am J Clin Oncol (in press)Google Scholar
  23. 23.
    Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481CrossRefGoogle Scholar
  24. 24.
    Mantel N (1966) Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50:163–170PubMedGoogle Scholar
  25. 25.
    Cox C (1988) Multinomial regression models based on continuation ratios. Stat Med 7:435–441PubMedCrossRefGoogle Scholar
  26. 26.
    Massimino M, Bode U, Biassoni V, Fleischhack G (2011) Nimotuzumab for pediatric diffuse intrinsic pontine gliomas. Expert Opin Biol Ther 11:247–256PubMedCrossRefGoogle Scholar
  27. 27.
    Wolff JE, Driever PH, Erdlenbruch B et al (2010) Intensive chemotherapy improves survival in pediatric high-grade glioma after gross total resection: results of the HIT-GBM-C protocol. Cancer 116:705–712PubMedCrossRefGoogle Scholar
  28. 28.
    Wagner S, Benesch M, Berthold F et al (2006) Secondary dissemination in children with high-grade malignant gliomas and diffuse intrinsic pontine gliomas. Br J Cancer 95:991–997PubMedCrossRefGoogle Scholar
  29. 29.
    Liu AK, Macy ME, Foreman NK (2009) Bevacizumab as therapy for radiation necrosis in four children with pontine gliomas. Int J Radiat Oncol Biol Phys 75:1148–1154PubMedCrossRefGoogle Scholar
  30. 30.
    Roujeau T, Machado G, Garnett MR et al (2007) Stereotactic biopsy of diffuse pontine lesions in children. J Neurosurg 107(1 Suppl):1–4PubMedGoogle Scholar
  31. 31.
    Perez-Gomez JL, Rodriguez-Alvarez CA, Marhx-Bracho A, Rueda-Franco F (2010) Stereotactic biopsy for brainstem tumors in pediatric patients. Childs Nerv Syst 26:29–34PubMedCrossRefGoogle Scholar
  32. 32.
    Donaldson SS, Laningham F, Fisher PG (2006) Advances toward an understanding of brainstem gliomas. J Clin Oncol 24:1266–1272PubMedCrossRefGoogle Scholar
  33. 33.
    Wolff JE, Classen CF, Wagner S et al (2008) Subpopulations of malignant gliomas in pediatric patients: analysis of the HIT-GBM database. J Neurooncol 87:155–164PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Johannes E. Wolff
    • 1
    • 2
    • 3
  • Michael E. Rytting
    • 1
  • Tribhawan S. Vats
    • 1
  • Peter E. Zage
    • 1
    • 4
  • Joann L. Ater
    • 1
  • Shiao Woo
    • 5
  • John Kuttesch
    • 6
  • Leena Ketonen
    • 7
  • Anita Mahajan
    • 8
  1. 1.Department of PediatricsThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  2. 2.Department of BiostatisticsM. D. Anderson Cancer CenterHoustonUSA
  3. 3.Department of PediatricsTufts Medical CenterBostonUSA
  4. 4.Department of Pediatric OncologyTexas Children’s HospitalHoustonUSA
  5. 5.Department of Radiation OncologyKosair Children’s Hospital/Norton Healthcare University of Louisville School of MedicineLouisvilleUSA
  6. 6.Pediatrics/Hematology/Oncology—H085Penn State Hershey Children’s HospitalHersheyUSA
  7. 7.Department of Diagnostic ImagingM. D. Anderson Cancer CenterHoustonUSA
  8. 8.Department of Radiation OncologyM. D. Anderson Cancer CenterHoustonUSA

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