Diffuse Intrinsic Pontine Gliomas
        Treatment options under clinical evaluation
Focal or Low-grade Brain Stem Gliomas
Neurofibromatosis
Current Clinical Trials

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Conventional treatment for children with diffuse intrinsic pontine glioma (DIPG) is radiation therapy to involved areas. Such treatment will result in transient benefit for most patients, but over 90% of patients will die within 18 months of diagnosis. The conventional dose of radiation therapy ranges between 54 Gy and 60 Gy given locally to the primary tumor site in single daily fractions.

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 DIPG whether given alone,[1,2] or in combination with chemotherapy.[3] Studies evaluating the efficacy of various radiosensitizers as a means for enhancing the therapeutic effect of this modality are under study but to date have failed to show significant improvement in outcome.[2-6]

The utility of chemotherapy in the treatment of patients with newly diagnosed DIPG is unproven.[2,3,5-11][Level of evidence: 2A] To date, neither adjuvant or neoadjuvant chemotherapy, nor immunotherapy when added to radiation therapy has been demonstrated to improve survival for children with DIPG. Similarly, studies utilizing high-dose therapy with stem cell rescue have been ineffective in extending survival.[12] Studies using new anticancer agents with alternative mechanisms of actions and brain stem radiation are ongoing.

• The Children's Oncology Group (COG) trial (COG-ACNS0222) is a phase II study of motexafin, gadolinium and concomitant radiation therapy.



• The Pediatric Brain Tumor Consortium (PBTC) is conducting a phase I study of capecitabine and concomitant radiation therapy (PBTC-021). It is planned that this study will become a phase II trial once the phase I portion of the trial is complete.

In general, maximal surgical resection should be attempted.[13,14] Patients with residual tumors may be candidates for additional therapy including radiation or adjuvant therapy including three-dimensional conformal approaches. Information about ongoing clinical trials is available from the NCI Web site.

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.[13]

Children with neurofibromatosis type I and brain stem gliomas may have a different prognosis than other patients who have intrinsic lesions. Patients with neurofibromatosis may present with a long history of symptoms or be identified on screening tests; a period of observation may be indicated before instituting any treatment.[15] Brain stem gliomas in these children may be indolent and may require no specific treatment for years.[16]

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry 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. 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]
   
   
2. 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]
   
   
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. 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]
   
   
5. 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]
   
   
6. 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]
   
   
7. Jenkin RD, Boesel C, Ertel I, et al.: Brain-stem tumors in childhood: a prospective randomized trial of irradiation with and without adjuvant CCNU, VCR, and prednisone. A report of the Childrens Cancer Study Group. J Neurosurg 66 (2): 227-33, 1987.  [PUBMED Abstract]
   
   
8. Blaney SM, Phillips PC, Packer RJ, et al.: Phase II evaluation of topotecan for pediatric central nervous system tumors. Cancer 78 (3): 527-31, 1996.  [PUBMED Abstract]
   
   
9. 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]
   
   
10. 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]
    
    
11. 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]
    
    
12. 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]
    
    
13. Vandertop WP, Hoffman HJ, Drake JM, et al.: Focal midbrain tumors in children. Neurosurgery 31 (2): 186-94, 1992.  [PUBMED Abstract]
    
    
14. 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]
    
    
15. Bilaniuk LT, Molloy PT, Zimmerman RA, et al.: Neurofibromatosis type 1: brain stem tumours. Neuroradiology 39 (9): 642-53, 1997.  [PUBMED Abstract]
    
    
16. 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]
    
    

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