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Childhood Brain Stem Glioma Treatment (PDQ®)

  • Last Modified: 01/28/2014

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Newly Diagnosed Childhood Brain Stem Glioma Treatment

Standard Treatment Options for Diffuse Intrinsic Pontine Gliomas (DIPGs)
        Radiation therapy
        Chemotherapy only (infants)
        Treatment options under clinical evaluation
Standard Treatment Options for Focal or Low-Grade Brain Stem Gliomas
        Surgical resection (with or without radiation therapy and chemotherapy)
        Observation (with or without cerebrospinal fluid diversion)
        Radiation therapy, chemotherapy, and alternative approaches for inoperable focal or low-grade tumors
Current Clinical Trials



Standard Treatment Options for Diffuse Intrinsic Pontine Gliomas (DIPGs)

While numerous clinical trials are available for children with newly diagnosed DIPGs, the utility of any therapy besides radiation therapy in the treatment of patients with newly diagnosed DIPG remains unproven.[1-6]; [7,8][Level of evidence: 2A]; [9][Level of evidence: 3iiiA]

Currently, no chemotherapeutic strategy—including neoadjuvant, concurrent, postradiation therapy, or immunotherapy—when added to radiation therapy has led to long-term survival for children with DIPGs.[10-12]; [13][Level of evidence: 2A] This includes studies utilizing high-dose, marrow-ablative chemotherapy with autologous hematopoietic stem cell rescue, which have also been ineffective in extending survival.[14]

Standard treatment options for newly diagnosed DIPGs include the following:

  1. Radiation therapy.
Radiation therapy

Conventional treatment for children with DIPGs is radiation therapy to involved areas. The conventional dose of radiation ranges between 54 Gy and 60 Gy given locally to the primary tumor site in single daily fractions. Such treatment will result in transient benefit for most patients, but more than 90% of patients will die within 18 months of diagnosis.[15]

Radiation-induced changes may occur a few months after the completion of radiation therapy and may mimic tumor progression. When considering the efficacy of additional treatment, care needs to be taken to separate radiation-induced change from progressive disease.[16]

Research studies evaluating the efficacy of hyperfractionated and hypofractionated radiation therapy and radiosensitizers have not demonstrated improved outcomes using these radiation techniques.

  1. Hyperfractionated (twice daily) radiation therapy techniques have been used to deliver a higher dose, and studies using doses as high as 78 Gy have been completed. Evidence demonstrates that these increased radiation therapy doses do not improve the duration or rate of survival for patients with DIPGs, whether given alone [1,17] or in combination with chemotherapy.[3]

  2. Hypofractionated radiation therapy results in survival rates comparable to conventional fractionated radiation therapy techniques, possibly with less treatment burden.[15,18][Level of evidence: 2A]

  3. Studies evaluating the efficacy of various radiosensitizers as a means for enhancing the therapeutic effect of radiation therapy have been undertaken but to date have failed to show any significant improvement in outcome.[1,3-5,19,20]

Chemotherapy only (infants)

Similar to the treatment of other brain tumors, radiation therapy is often omitted for infants with DIPGs, and chemotherapy-only approaches are utilized. However, published data supporting the utility of this approach is lacking.

Treatment options under clinical evaluation

Early-phase therapeutic trials may be available for selected patients. These trials may be available via Children’s Oncology Group phase I institutions, the Pediatric Brain Tumor Consortium, or other entities.

Standard Treatment Options for Focal or Low-Grade Brain Stem Gliomas

Standard treatment options for newly diagnosed focal or low-grade brain stem gliomas include the following:

  1. Surgical resection (with or without radiation therapy and chemotherapy).
  2. Observation (with or without cerebrospinal fluid diversion).
  3. Radiation therapy, chemotherapy, and alternative approaches for inoperable focal or low-grade tumors.
Surgical resection (with or without radiation therapy and chemotherapy)

In general, maximal surgical resection is attempted.[21,22]

Patients with residual tumor may be candidates for additional therapy, including 3-dimensional conformal radiation therapy approaches, with or without adjuvant chemotherapy.

Observation (with or without cerebrospinal fluid diversion)

Patients with small tectal lesions and hydrocephalus but no other neurological deficits may be treated with cerebrospinal fluid diversion alone and have follow-up with sequential neuroradiographic studies unless there is evidence of progressive disease.[21]

A period of observation may be indicated before instituting any treatment for patients with neurofibromatosis type 1.[23] Brain stem gliomas in these children may be indolent and may require no specific treatment for years.[24]

Radiation therapy, chemotherapy, and alternative approaches for inoperable focal or low-grade tumors

In selected circumstances, adjuvant therapy in the form of radiation therapy or chemotherapy can be considered in a child with a newly diagnosed focal or low-grade brain stem glioma.[25,26][Level of evidence: 3iDi] Decisions regarding the need for such therapy depend on the age of the child, the extent of resection obtainable, and associated neurologic deficits.

Alternative approaches for the treatment of inoperable brain stem gliomas include the following:

  • Stereotactic iodine I-125 brachytherapy approaches, with or without adjuvant chemotherapy.[27]

  • The use of BRAF inhibitors for tumors harboring a V600E mutation.[28]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with untreated childhood brain stem glioma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References
  1. Mandell LR, Kadota R, Freeman C, et al.: There is no role for hyperfractionated radiotherapy in the management of children with newly diagnosed diffuse intrinsic brainstem tumors: results of a Pediatric Oncology Group phase III trial comparing conventional vs. hyperfractionated radiotherapy. Int J Radiat Oncol Biol Phys 43 (5): 959-64, 1999.  [PUBMED Abstract]

  2. Jennings MT, Sposto R, Boyett JM, et al.: Preradiation chemotherapy in primary high-risk brainstem tumors: phase II study CCG-9941 of the Children's Cancer Group. J Clin Oncol 20 (16): 3431-7, 2002.  [PUBMED Abstract]

  3. Allen J, Siffert J, Donahue B, et al.: A phase I/II study of carboplatin combined with hyperfractionated radiotherapy for brainstem gliomas. Cancer 86 (6): 1064-9, 1999.  [PUBMED Abstract]

  4. Broniscer A, Leite CC, Lanchote VL, et al.: 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 (6): 1246-53, 2000.  [PUBMED Abstract]

  5. Doz F, Neuenschwander S, Bouffet E, et al.: Carboplatin before and during radiation therapy for the treatment of malignant brain stem tumours: a study by the Société Française d'Oncologie Pédiatrique. Eur J Cancer 38 (6): 815-9, 2002.  [PUBMED Abstract]

  6. Wolff JE, Westphal S, Mölenkamp G, et al.: Treatment of paediatric pontine glioma with oral trophosphamide and etoposide. Br J Cancer 87 (9): 945-9, 2002.  [PUBMED Abstract]

  7. Korones DN, Fisher PG, Kretschmar C, et al.: Treatment of children with diffuse intrinsic brain stem glioma with radiotherapy, vincristine and oral VP-16: a Children's Oncology Group phase II study. Pediatr Blood Cancer 50 (2): 227-30, 2008.  [PUBMED Abstract]

  8. Cohen KJ, Heideman RL, Zhou T, et al.: Temozolomide in the treatment of children with newly diagnosed diffuse intrinsic pontine gliomas: a report from the Children's Oncology Group. Neuro Oncol 13 (4): 410-6, 2011.  [PUBMED Abstract]

  9. Jalali R, Raut N, Arora B, et al.: Prospective evaluation of radiotherapy with concurrent and adjuvant temozolomide in children with newly diagnosed diffuse intrinsic pontine glioma. Int J Radiat Oncol Biol Phys 77 (1): 113-8, 2010.  [PUBMED Abstract]

  10. Frappaz D, Schell M, Thiesse P, et al.: Preradiation chemotherapy may improve survival in pediatric diffuse intrinsic brainstem gliomas: final results of BSG 98 prospective trial. Neuro Oncol 10 (4): 599-607, 2008.  [PUBMED Abstract]

  11. Frazier JL, Lee J, Thomale UW, et al.: Treatment of diffuse intrinsic brainstem gliomas: failed approaches and future strategies. J Neurosurg Pediatr 3 (4): 259-69, 2009.  [PUBMED Abstract]

  12. Hargrave D, Bartels U, Bouffet E: Diffuse brainstem glioma in children: critical review of clinical trials. Lancet Oncol 7 (3): 241-8, 2006.  [PUBMED Abstract]

  13. Warren K, Bent R, Wolters PL, et al.: A phase 2 study of pegylated interferon α-2b (PEG-Intron(®)) in children with diffuse intrinsic pontine glioma. Cancer 118 (14): 3607-13, 2012.  [PUBMED Abstract]

  14. Bouffet E, Raquin M, Doz F, et al.: Radiotherapy followed by high dose busulfan and thiotepa: a prospective assessment of high dose chemotherapy in children with diffuse pontine gliomas. Cancer 88 (3): 685-92, 2000.  [PUBMED Abstract]

  15. Janssens GO, Jansen MH, Lauwers SJ, et al.: Hypofractionation vs conventional radiation therapy for newly diagnosed diffuse intrinsic pontine glioma: a matched-cohort analysis. Int J Radiat Oncol Biol Phys 85 (2): 315-20, 2013.  [PUBMED Abstract]

  16. Liu AK, Macy ME, Foreman NK: Bevacizumab as therapy for radiation necrosis in four children with pontine gliomas. Int J Radiat Oncol Biol Phys 75 (4): 1148-54, 2009.  [PUBMED Abstract]

  17. Freeman CR, Krischer JP, Sanford RA, et al.: 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 (2): 197-206, 1993.  [PUBMED Abstract]

  18. Negretti L, Bouchireb K, Levy-Piedbois C, et al.: Hypofractionated radiotherapy in the treatment of diffuse intrinsic pontine glioma in children: a single institution's experience. J Neurooncol 104 (3): 773-7, 2011.  [PUBMED Abstract]

  19. Freeman CR, Kepner J, Kun LE, et al.: A detrimental effect of a combined chemotherapy-radiotherapy approach in children with diffuse intrinsic brain stem gliomas? Int J Radiat Oncol Biol Phys 47 (3): 561-4, 2000.  [PUBMED Abstract]

  20. Bradley KA, Zhou T, McNall-Knapp RY, et al.: Motexafin-gadolinium and involved field radiation therapy for intrinsic pontine glioma of childhood: a children's oncology group phase 2 study. Int J Radiat Oncol Biol Phys 85 (1): e55-60, 2013.  [PUBMED Abstract]

  21. Vandertop WP, Hoffman HJ, Drake JM, et al.: Focal midbrain tumors in children. Neurosurgery 31 (2): 186-94, 1992.  [PUBMED Abstract]

  22. Kestle J, Townsend JJ, Brockmeyer DL, et al.: Juvenile pilocytic astrocytoma of the brainstem in children. J Neurosurg 101 (1 Suppl): 1-6, 2004.  [PUBMED Abstract]

  23. Bilaniuk LT, Molloy PT, Zimmerman RA, et al.: Neurofibromatosis type 1: brain stem tumours. Neuroradiology 39 (9): 642-53, 1997.  [PUBMED Abstract]

  24. Molloy PT, Bilaniuk LT, Vaughan SN, et al.: Brainstem tumors in patients with neurofibromatosis type 1: a distinct clinical entity. Neurology 45 (10): 1897-902, 1995.  [PUBMED Abstract]

  25. Klimo P Jr, Pai Panandiker AS, Thompson CJ, et al.: Management and outcome of focal low-grade brainstem tumors in pediatric patients: the St. Jude experience. J Neurosurg Pediatr 11 (3): 274-81, 2013.  [PUBMED Abstract]

  26. Ronghe M, Hargrave D, Bartels U, et al.: Vincristine and carboplatin chemotherapy for unresectable and/or recurrent low-grade astrocytoma of the brainstem. Pediatr Blood Cancer 55 (3): 471-7, 2010.  [PUBMED Abstract]

  27. Ruge MI, Kickingereder P, Simon T, et al.: Stereotactic iodine-125 brachytherapy for treatment of inoperable focal brainstem gliomas of WHO grades I and II: feasibility and long-term outcome. J Neurooncol 109 (2): 273-83, 2012.  [PUBMED Abstract]

  28. Rush S, Foreman N, Liu A: Brainstem ganglioglioma successfully treated with vemurafenib. J Clin Oncol 31 (10): e159-60, 2013.  [PUBMED Abstract]