Purpose of This PDQ Summary
General Information
Cellular Classification
Stage Information
Treatment Option Overview
Untreated Childhood Visual Pathway and Hypothalamic Glioma

Treatment Options Under Clinical Evaluation Current Clinical Trials

Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Current Clinical Trials

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Changes to This Summary (04/07/2008)
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Purpose of This PDQ Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood visual pathway and hypothalamic glioma. This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board ¹.

Information about the following is included in this summary:

• Cellular classification.
• Stage information.
• Treatment options.

This summary is intended as a resource to inform and assist clinicians and other health professionals who care for pediatric cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

In the summary, treatments are described as “standard” or “conventional” and “under clinical evaluation.” These designations should not be used as a basis for reimbursement determinations.

This summary is also available in a patient version ², which is written in less-technical language, and in Spanish ³.  [Note: The PDQ childhood brain tumor treatment summaries are in the process of being substantially revised. This revision process was prompted by changes in the nomenclature and classification for pediatric central nervous system tumors. New PDQ childhood brain tumor treatment summaries will be added and some existing summaries will be replaced or their content combined with other PDQ childhood brain tumor treatment summaries in the near future.]

General Information

The National Cancer Institute provides the PDQ pediatric cancer treatment information summaries as a public service to increase the availability of evidence-based cancer information to health professionals, patients, and the public.

In recent decades, dramatic improvements in survival have been achieved for children and adolescents with cancer. Childhood and adolescent cancer survivors require close follow-up because cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ Late Effects of Treatment for Childhood Cancer ⁴ summary for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)

Primary brain tumors are a diverse group of diseases that together constitute the most common solid tumor of childhood. Brain tumors are classified according to histology, but tumor location and extent of spread are important factors that affect treatment and prognosis. Immunohistochemical analysis, cytogenetic and molecular genetic findings, and measures of mitotic activity are increasingly used in the tumor diagnosis and classification.

Refer to the PDQ Childhood Brain and Spinal Cord Tumors Treatment ⁵ summary for information about the general classification of childhood brain and spinal cord tumors.

Cellular Classification

Childhood visual pathway and hypothalamic gliomas are usually low-grade (grades 1 and 2) astrocytomas. Both pilocytic astrocytomas and fibrillary astrocytomas may occur. The pilomyxoid variant of pilocytic astrocytoma occurs in the visual pathway and may be a more aggressive variant and more likely to disseminate.[1] Visual pathway gliomas include astrocytic tumors of the optic nerve, optic chiasm, and optic tract. Because of the infiltrative nature of such lesions, separation of visual pathway and hypothalamic gliomas from thalamic tumors is often difficult and arbitrary. Malignant gliomas of the visual pathway are rare. Visual pathway gliomas occur at an increased incidence in patients with neurofibromatosis type 1 (NF-1); approximately 20% of all patients with NF-1 will develop a visual pathway glioma. In these patients, the tumor may be found on screening evaluations when the child is asymptomatic or has apparent static neurologic and/or visual deficits. Pathologic confirmation is frequently not obtained in asymptomatic patients, and when biopsies have been performed, these tumors have been found to be predominantly pilocytic (grade 1) rather than fibrillary (grade 2) astrocytomas.[2-5]

References

1. Komotar RJ, Burger PC, Carson BS, et al.: Pilocytic and pilomyxoid hypothalamic/chiasmatic astrocytomas. Neurosurgery 54 (1): 72-9; discussion 79-80, 2004.  [PUBMED Abstract]
   
   
2. Kleihues P, Cavenee WK, eds.: Pathology and Genetics of Tumours of the Nervous System. Lyon, France: International Agency for Research on Cancer, 2000. 
   
   
3. Listernick R, Darling C, Greenwald M, et al.: Optic pathway tumors in children: the effect of neurofibromatosis type 1 on clinical manifestations and natural history. J Pediatr 127 (5): 718-22, 1995.  [PUBMED Abstract]
   
   
4. Burger PC, Scheithauer BW: Tumors of the Central Nervous System. Washington, DC: Armed Forces Institute of Pathology,1994. 
   
   
5. Allen JC: Initial management of children with hypothalamic and thalamic tumors and the modifying role of neurofibromatosis-1. Pediatr Neurosurg 32 (3): 154-62, 2000.  [PUBMED Abstract]
   
   

Stage Information

There is no universally accepted staging system for visual pathway and hypothalamic gliomas. They are low-grade astrocytomas that grow slowly and may occur anywhere along the optic tracts. Visual pathway gliomas are found with increased frequency in patients with neurofibromatosis. The major clinical symptoms are visual. Tumors may also arise in the hypothalamus; in large infiltrating lesions, distinctions between optic and hypothalamic tumors are often artificial and of little clinical importance. In infants and young children, hypothalamic gliomas may result in the diencephalic syndrome, which is manifested by failure to thrive in an emaciated, seemingly euphoric child. Such children may have little in the way of other neurologic findings, but can have macrocephaly, intermittent lethargy, and visual impairment.[1] Because the location of these tumors makes a surgical approach difficult, biopsies are not always done. This is especially true in patients with neurofibromatosis type 1 (NF-1).[2] Visual pathway and hypothalamic gliomas usually spread contiguously, though subarachnoid dissemination has been reported.[1,3] Evaluation should include neuro-ophthalmological testing to carefully monitor the patient for the visual effects of tumor progression that may not be evident using computed tomography or magnetic resonance imaging. Visual-evoked responses have not, as yet, been shown to be more sensitive than clinical examination in patients with visual pathway gliomas, even in young children.

References

1. Perilongo G, Carollo C, Salviati L, et al.: Diencephalic syndrome and disseminated juvenile pilocytic astrocytomas of the hypothalamic-optic chiasm region. Cancer 80 (1): 142-6, 1997.  [PUBMED Abstract]
   
   
2. Pollack IF, Mulvihill JJ: Special issues in the management of gliomas in children with neurofibromatosis 1. J Neurooncol 28 (2-3): 257-68, 1996 May-Jun.  [PUBMED Abstract]
   
   
3. Mamelak AN, Prados MD, Obana WG, et al.: Treatment options and prognosis for multicentric juvenile pilocytic astrocytoma. J Neurosurg 81 (1): 24-30, 1994.  [PUBMED Abstract]
   
   

Treatment Option Overview

Many of the improvements in survival in childhood cancer have been made as a result of clinical trials that have attempted to improve upon the best available, accepted therapy. Clinical trials in pediatrics are designed to compare new therapy with therapy that is currently accepted as standard. This comparison may be done in a randomized study of two treatment arms, or by evaluating a single new treatment and comparing the results with previously obtained results using existing standard therapy.

Because of the relative rarity of cancer in children, all patients with brain tumors should be considered for entry into a clinical trial. To determine and implement optimum treatment, treatment planning by a multidisciplinary team of cancer specialists who have experience treating childhood brain tumors is required. Radiation therapy of pediatric brain tumors is technically very demanding and should be carried out in centers with experience in that area in order to ensure optimal results.

Debilitating effects on growth and neurologic development have frequently been observed following radiation therapy, especially in younger children.[1-3] There are also other less common complications of radiation therapy, including cerebrovascular accidents.[4] For this reason, the role of chemotherapy in allowing a delay in the administration of radiation therapy is under study, and preliminary results suggest that chemotherapy can be used to delay, and sometimes obviate, the need for radiation therapy in children with benign and malignant lesions.[5] Long-term management of these patients is complex and requires a multidisciplinary approach.

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

References

1. Packer RJ, Sutton LN, Atkins TE, et al.: A prospective study of cognitive function in children receiving whole-brain radiotherapy and chemotherapy: 2-year results. J Neurosurg 70 (5): 707-13, 1989.  [PUBMED Abstract]
   
   
2. Johnson DL, McCabe MA, Nicholson HS, et al.: Quality of long-term survival in young children with medulloblastoma. J Neurosurg 80 (6): 1004-10, 1994.  [PUBMED Abstract]
   
   
3. Packer RJ, Sutton LN, Goldwein JW, et al.: Improved survival with the use of adjuvant chemotherapy in the treatment of medulloblastoma. J Neurosurg 74 (3): 433-40, 1991.  [PUBMED Abstract]
   
   
4. Bowers DC, Mulne AF, Reisch JS, et al.: Nonperioperative strokes in children with central nervous system tumors. Cancer 94 (4): 1094-101, 2002.  [PUBMED Abstract]
   
   
5. Duffner PK, Horowitz ME, Krischer JP, et al.: Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med 328 (24): 1725-31, 1993.  [PUBMED Abstract]
   
   

Untreated Childhood Visual Pathway and Hypothalamic Glioma

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 ⁶) 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 ⁷.

• COG-ACNS0223 ⁸ : 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 ⁹. 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 ⁷.

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]
    
    

Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Recurrence may take place in both benign and malignant childhood visual pathway and hypothalamic gliomas, and may develop many years after initial treatment. Recurrent disease is usually at the primary tumor site, though widely disseminated disease to other intracranial sites and to the spinal leptomeninges has been documented.[1] At the time of recurrence, a complete evaluation to determine the extent of the relapse is indicated. Biopsy or surgical resection may be necessary for confirmation of relapse because other entities, such as secondary tumor and treatment-related brain necrosis, may be clinically indistinguishable from tumor recurrence. The need for surgical intervention must be individualized on the basis of the initial tumor type, the length of time between initial treatment and the reappearance of the mass lesion, and the clinical picture.

If patients have not received radiation therapy, local radiation therapy is the usual treatment.[2] 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.[3,4] In patients treated with surgery alone whose disease progresses, however, chemotherapy and radiation therapy are options. If recurrence takes place after irradiation, chemotherapy should be considered. Chemotherapy may result in relatively long-term disease control.[5,6] Entry into studies of novel therapeutic approaches should be considered for patients with recurrent brain tumors.[7,8] Information about ongoing clinical trials is available from the NCI Web site ¹⁰.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent childhood visual pathway and hypothalamic glioma ¹¹. 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 ⁷.

References

1. Perilongo G, Carollo C, Salviati L, et al.: Diencephalic syndrome and disseminated juvenile pilocytic astrocytomas of the hypothalamic-optic chiasm region. Cancer 80 (1): 142-6, 1997.  [PUBMED Abstract]
   
   
2. 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]
   
   
3. 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]
   
   
4. 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]
   
   
5. Packer RJ, Lange B, Ater J, et al.: Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood. J Clin Oncol 11 (5): 850-6, 1993.  [PUBMED Abstract]
   
   
6. 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]
   
   
7. Chamberlain MC, Grafe MR: Recurrent chiasmatic-hypothalamic glioma treated with oral etoposide. J Clin Oncol 13 (8): 2072-6, 1995.  [PUBMED Abstract]
   
   
8. Gaynon PS, Ettinger LJ, Baum ES, et al.: Carboplatin in childhood brain tumors. A Children's Cancer Study Group Phase II trial. Cancer 66 (12): 2465-9, 1990.  [PUBMED Abstract]
   
   

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Changes to This Summary (04/07/2008)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Editorial changes were made to this summary.

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