Treatment Options Under Clinical Evaluation
Current Clinical Trials

To determine and implement optimum treatment, treatment planned by a multidisciplinary team of cancer specialists who have experience treating childhood brain tumors is required.

The usual treatment for low-grade supratentorial astrocytoma is determined by location. Hemispheric tumors are often amenable to complete surgical resection.[1,2] Low-grade diencephalic tumors can also be aggressively resected, with resultant long-term disease control;[3,4] however, such resection may result in significant neurologic sequelae, especially in children younger than 2 years at diagnosis.[3] Because of the infiltrative nature of some deep-seeded lesions, extensive surgical resection may not be appropriate and biopsy followed by either radiation or chemotherapy should be considered. Treatment options for patients with incompletely resected tumor must be individualized and may include observation, re-resection, chemotherapy, and radiation.

Radiation therapy is often reserved until progressive disease is documented,[1,5] and its use may be further delayed through the use of chemotherapy, a strategy that is commonly employed in young children.[6,7] Debilitating effects on growth and neurologic development have frequently been observed following radiation therapy, especially in younger children with extensive lesions. For those children with low-grade glioma for whom radiation therapy is indicated, conformal radiotherapeutic approaches appear effective and offer the potential for reducing the acute and long-term toxicities associated with this modality.[8,9]

Evaluation with detailed electroencephalographic mapping and surgery designed to remove the tumor and adjacent epileptic foci has been recommended for those patients with low-grade tumor and seizures.[2] Excellent results in tumor and seizure control, however, have been reported with magnetic resonance-based total tumor resection.[10] Chemotherapy can be used to delay, and sometimes obviate, the need for radiation therapy in children with benign lesions.[6] The most widely used regimen to treat progressive or symptomatic nonresectable, low-grade gliomas is a combination of carboplatin and vincristine.[6,7] The 3-year progressive-free survival for children younger than 5 years is 74%, but most patients ultimately require further treatment. Other chemotherapeutic regimens have also been shown to be effective.[11-13]

Radiation and alkylating agents are used as a last resort for patients with NF-1, given the increased risk of inducing neurotoxicity and second malignancy in this population.[14,15]

The following is an example of a national and/or institutional clinical trial that is currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.

• COG-ACNS0223 : The Children’s Oncology Group (COG) is conducting a limited-institution phase I/II study of carboplatin, temozolomide, and vincristine for children with newly diagnosed low-grade gliomas.

The designations in PDQ that treatments are “standard” or “under clinical evaluation” are not to be used as a basis for reimbursement determinations.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with childhood low-grade cerebral astrocytoma. 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. Pollack IF, Claassen D, al-Shboul Q, et al.: Low-grade gliomas of the cerebral hemispheres in children: an analysis of 71 cases. J Neurosurg 82 (4): 536-47, 1995.  [PUBMED Abstract]
   
   
2. Berger MS, Ghatan S, Haglund MM, et al.: Low-grade gliomas associated with intractable epilepsy: seizure outcome utilizing electrocorticography during tumor resection. J Neurosurg 79 (1): 62-9, 1993.  [PUBMED Abstract]
   
   
3. Wisoff JH, Abbott R, Epstein F: Surgical management of exophytic chiasmatic-hypothalamic tumors of childhood. J Neurosurg 73 (5): 661-7, 1990.  [PUBMED Abstract]
   
   
4. Albright AL: Feasibility and advisability of resections of thalamic tumors in pediatric patients. J Neurosurg 100 (5 Suppl Pediatrics): 468-72, 2004.  [PUBMED Abstract]
   
   
5. Fisher BJ, Leighton CC, Vujovic O, et al.: Results of a policy of surveillance alone after surgical management of pediatric low grade gliomas. Int J Radiat Oncol Biol Phys 51 (3): 704-10, 2001.  [PUBMED Abstract]
   
   
6. Packer RJ, Ater J, Allen J, et al.: Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas. J Neurosurg 86 (5): 747-54, 1997.  [PUBMED Abstract]
   
   
7. Gnekow AK, Kortmann RD, Pietsch T, et al.: Low grade chiasmatic-hypothalamic glioma-carboplatin and vincristin chemotherapy effectively defers radiotherapy within a comprehensive treatment strategy -- report from the multicenter treatment study for children and adolescents with a low grade glioma -- HIT-LGG 1996 -- of the Society of Pediatric Oncology and Hematology (GPOH). Klin Padiatr 216 (6): 331-42, 2004 Nov-Dec.  [PUBMED Abstract]
   
   
8. Merchant TE, Zhu Y, Thompson SJ, et al.: Preliminary results from a Phase II trail of conformal radiation therapy for pediatric patients with localised low-grade astrocytoma and ependymoma. Int J Radiat Oncol Biol Phys 52 (2): 325-32, 2002.  [PUBMED Abstract]
   
   
9. Marcus KJ, Goumnerova L, Billett AL, et al.: Stereotactic radiotherapy for localized low-grade gliomas in children: final results of a prospective trial. Int J Radiat Oncol Biol Phys 61 (2): 374-9, 2005.  [PUBMED Abstract]
   
   
10. Packer RJ, Sutton LN, Patel KM, et al.: Seizure control following tumor surgery for childhood cortical low-grade gliomas. J Neurosurg 80 (6): 998-1003, 1994.  [PUBMED Abstract]
    
    
11. Laithier V, Grill J, Le Deley MC, et al.: Progression-free survival in children with optic pathway tumors: dependence on age and the quality of the response to chemotherapy--results of the first French prospective study for the French Society of Pediatric Oncology. J Clin Oncol 21 (24): 4572-8, 2003.  [PUBMED Abstract]
    
    
12. Prados MD, Edwards MS, Rabbitt J, et al.: Treatment of pediatric low-grade gliomas with a nitrosourea-based multiagent chemotherapy regimen. J Neurooncol 32 (3): 235-41, 1997.  [PUBMED Abstract]
    
    
13. Gururangan S, Cavazos CM, Ashley D, et al.: Phase II study of carboplatin in children with progressive low-grade gliomas. J Clin Oncol 20 (13): 2951-8, 2002.  [PUBMED Abstract]
    
    
14. Grill J, Couanet D, Cappelli C, et al.: Radiation-induced cerebral vasculopathy in children with neurofibromatosis and optic pathway glioma. Ann Neurol 45 (3): 393-6, 1999.  [PUBMED Abstract]
    
    
15. Sharif S, Ferner R, Birch JM, et al.: Second primary tumors in neurofibromatosis 1 patients treated for optic glioma: substantial risks after radiotherapy. J Clin Oncol 24 (16): 2570-5, 2006.  [PUBMED Abstract]
    
    

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