Treatment Options Under Clinical Evaluation
Current Clinical Trials

Treatment options should be considered not only to improve survival but also to stabilize visual function. Children with isolated optic nerve tumors have a better prognosis than those with lesions that involve the chiasm or that extend along the visual pathway.[1-3] Children with neurofibromatosis type 1 (NF-1) also have a better prognosis, especially when the tumor is found in asymptomatic patients at the time of screening.[1] Observation is an option for patients with NF-1 or nonprogressive masses.[1,2,4] Spontaneous regressions of optic pathway gliomas have been reported in children both with and without NF-1.[5,6] For children with isolated optic nerve lesions and progressive symptoms, complete surgical resection or local radiation therapy may result in prolonged progression-free survival.[1]

Radiation therapy results in long-term disease control for most children with chiasmatic and posterior pathway chiasmatic gliomas, but may also result in substantial intellectual and endocrinologic sequelae, cerebrovascular damage, and possibly an increased risk of secondary tumors.[1,3,7,8] An alternative to immediate radiation therapy is subtotal surgical resection, but it is unclear how many patients will have stable disease and for how long.[7] 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.[9-11]

Chemotherapy may result in objective tumor shrinkage and will delay the need for radiation therapy in most patients.[4,12-15] The most widely used regimen to treat progression or symptomatic nonresectable, low-grade gliomas is a combination of carboplatin and vincristine.[4,15] Other chemotherapy approaches have been employed to treat children with progressive optic pathway gliomas, including multiagent platinum-based regimens [12,16] and nitrosourea-based regimens.[13]

Reported 5-year progression-free survival rates have ranged from approximately 35% to 60% for children receiving platinum-based chemotherapy for optic pathway gliomas,[12,15] but most patients ultimately require further treatment. Among children receiving chemotherapy for optic pathway gliomas, those without NF-1 have higher rates of disease progression than those with NF-1, and infants have higher rates of disease progression than do children older than 1 year.[12,15,16] Given the side effects associated with radiation therapy, chemotherapy may be particularly appropriate for patients with NF-1 and for younger children. Younger children are at higher risk for radiation-associated intellectual and endocrinologic sequelae. Children with NF-1 are at higher risk for radiation-associated secondary tumors and morbidity due to vascular changes.[17] Chemotherapy has been shown to shrink tumors in children with hypothalamic gliomas and the diencephalic syndrome, resulting in weight gain in those who respond to treatment.[18]

The Children's Oncology Group (COG) completed a randomized phase III trial (COG-A9952) that treated children younger than 10 years with low-grade chiasmatic/hypothalamic gliomas on one of two regimens: carboplatin and vincristine or thioguanine (6-thioguanine), lomustine, and procarbazine hydrochloride given with vincristine. Children with NF-1 were only treated on the carboplatin and vincristine arm. Study results are pending.

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 COG is also conducting a group-wide pilot study of vincristine, carboplatin, and temozolomide for children younger than 10 years with newly diagnosed disease (without NF-1).

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with untreated childhood visual pathway and hypothalamic 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. Jenkin D, Angyalfi S, Becker L, et al.: Optic glioma in children: surveillance, resection, or irradiation? Int J Radiat Oncol Biol Phys 25 (2): 215-25, 1993.  [PUBMED Abstract]
   
   
2. Kovalic JJ, Grigsby PW, Shepard MJ, et al.: Radiation therapy for gliomas of the optic nerve and chiasm. Int J Radiat Oncol Biol Phys 18 (4): 927-32, 1990.  [PUBMED Abstract]
   
   
3. Tao ML, Barnes PD, Billett AL, et al.: Childhood optic chiasm gliomas: radiographic response following radiotherapy and long-term clinical outcome. Int J Radiat Oncol Biol Phys 39 (3): 579-87, 1997.  [PUBMED Abstract]
   
   
4. 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]
   
   
5. Schmandt SM, Packer RJ, Vezina LG, et al.: Spontaneous regression of low-grade astrocytomas in childhood. Pediatr Neurosurg 32 (3): 132-6, 2000.  [PUBMED Abstract]
   
   
6. Parsa CF, Hoyt CS, Lesser RL, et al.: Spontaneous regression of optic gliomas: thirteen cases documented by serial neuroimaging. Arch Ophthalmol 119 (4): 516-29, 2001.  [PUBMED Abstract]
   
   
7. Wisoff JH, Abbott R, Epstein F: Surgical management of exophytic chiasmatic-hypothalamic tumors of childhood. J Neurosurg 73 (5): 661-7, 1990.  [PUBMED Abstract]
   
   
8. Khafaga Y, Hassounah M, Kandil A, et al.: Optic gliomas: a retrospective analysis of 50 cases. Int J Radiat Oncol Biol Phys 56 (3): 807-12, 2003.  [PUBMED Abstract]
   
   
9. 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]
   
   
10. 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]
    
    
11. Combs SE, Schulz-Ertner D, Moschos D, et al.: Fractionated stereotactic radiotherapy of optic pathway gliomas: tolerance and long-term outcome. Int J Radiat Oncol Biol Phys 62 (3): 814-9, 2005.  [PUBMED Abstract]
    
    
12. 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]
    
    
13. 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]
    
    
14. 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]
    
    
15. 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]
    
    
16. Massimino M, Spreafico F, Cefalo G, et al.: High response rate to cisplatin/etoposide regimen in childhood low-grade glioma. J Clin Oncol 20 (20): 4209-16, 2002.  [PUBMED Abstract]
    
    
17. 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]
    
    
18. Gropman AL, Packer RJ, Nicholson HS, et al.: Treatment of diencephalic syndrome with chemotherapy: growth, tumor response, and long term control. Cancer 83 (1): 166-72, 1998.  [PUBMED Abstract]
    
    

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