Treatment of Childhood High-Grade Astrocytomas
Treatment of Newly Diagnosed Childhood High-Grade Astrocytomas
Treatment options under clinical evaluation
Treatment of Recurrent Childhood High-Grade Astrocytomas
Treatment options under clinical evaluation
To determine and implement optimum management, treatment is often guided by a multidisciplinary team of cancer specialists who have experience treating childhood brain tumors.Treatment of Newly Diagnosed Childhood High-Grade Astrocytomas
Outcome in high-grade gliomas occurring in childhood may be more favorable than that in adults, but it is not clear whether this difference is caused by biologic variations in tumor characteristics, therapies used, tumor resectability, or other factors that are presently not understood.
The therapy for both children and adults with supratentorial high-grade astrocytoma includes surgery, radiation therapy, and chemotherapy.
Standard treatment options for newly diagnosed childhood high-grade astrocytomas include the following:Surgery
The ability to obtain a complete resection is associated with a better prognosis.[2,3] Among patients treated with surgery, radiation therapy, and nitrosourea (lomustine)-based chemotherapy, 5-year progression-free survival was 19% ± 3%; survival was 40% in those who had total resections. Similarly, in a trial of multiagent chemoradiation therapy and adjuvant chemotherapy in addition to valproic acid, 5-year event-free survival (EFS) was 13%, but for children with a complete resection of their tumor, the EFS was 48%.[Level of evidence: 2A]Adjuvant therapy
Radiation therapy is routinely administered to a field that widely encompasses the entire tumor. The radiation therapy dose to the tumor bed is usually at least 54 Gy. Despite such therapy, overall survival rates remain poor. Similarly poor survival is seen in children with spinal cord primaries and children with thalamic high-grade gliomas.[6,7]; [8,9][Level of evidence: 3iiiA]Chemotherapy
In one trial, children with glioblastoma who were treated on a prospective randomized trial with adjuvant lomustine, vincristine, and prednisone fared better than children treated with radiation therapy alone.
In adults, the addition of temozolomide during and after radiation therapy resulted in improved 2-year EFS as compared with treatment with radiation therapy alone. Adult patients with glioblastoma with a methylated O6-methylguanine-DNA-methyltransferase (MGMT) promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not benefit from temozolomide.[11,12] The role of temozolomide given concurrently with radiation therapy for children with supratentorial high-grade glioma appears comparable to the outcome seen in children treated with nitrosourea-based therapy  and again demonstrated a survival advantage for those children with a methylated MGMT promoter.
Clinical trials that evaluate chemotherapy with or without radiation therapy are ongoing. Information about ongoing clinical trials is available from the NCI Web site.Treatment options under clinical evaluation
The following is an example of a national and/or institutional clinical trial that is currently being conducted or is under analysis. Information about ongoing clinical trials is available from the NCI Web site.
- ACNS0822 (NCT01236560) (Vorinostat, Temozolomide, or Bevacizumab in Combination With Radiation Therapy Followed by Bevacizumab and Temozolomide in Young Patients With Newly Diagnosed High-Grade Glioma): The Children's Oncology Group is conducting a randomized phase II/III study of vorinostat and local radiation therapy, temozolomide and local radiation therapy, or bevacizumab and radiation therapy followed by maintenance bevacizumab and temozolomide in newly diagnosed high-grade glioma.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with childhood high-grade untreated astrocytoma or other tumor of glial origin. 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.Treatment of Recurrent Childhood High-Grade Astrocytomas
Most patients with high-grade astrocytomas or gliomas will eventually have tumor recurrence, usually within 3 years of original diagnosis but perhaps many years after initial treatment. Disease may recur at the primary tumor site, at the margin of the resection/radiation bed, or at noncontiguous central nervous system sites. Systemic relapse is rare but may occur.
At the time of recurrence, a complete evaluation for extent of relapse is indicated for all malignant tumors. 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 following:
- Initial tumor type.
- Length of time between initial treatment and the reappearance of the mass lesion.
- Clinical picture.
Patients for whom initial treatment fails may benefit from additional treatment. High-dose, marrow-ablative chemotherapy with hematopoietic stem cell transplant may be effective in a subset of patients with minimal residual disease at time of recurrence.; [Level of evidence: 3iiiA] Such patients should also be considered for entry into trials of novel therapeutic approaches.Treatment options under clinical evaluation
Early-phase therapeutic trials may be available for selected patients. These trials may be available via the Children's Oncology Group, the Pediatric Brain Tumor Consortium, or other entities. Information about ongoing clinical trials is available from the NCI Web site.Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent childhood astrocytoma or other tumor of glial origin. 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
- Rasheed BK, McLendon RE, Herndon JE, et al.: Alterations of the TP53 gene in human gliomas. Cancer Res 54 (5): 1324-30, 1994. [PUBMED Abstract]
- Wisoff JH, Boyett JM, Berger MS, et al.: Current neurosurgical management and the impact of the extent of resection in the treatment of malignant gliomas of childhood: a report of the Children's Cancer Group trial no. CCG-945. J Neurosurg 89 (1): 52-9, 1998. [PUBMED Abstract]
- Yang T, Temkin N, Barber J, et al.: Gross total resection correlates with long-term survival in pediatric patients with glioblastoma. World Neurosurg 79 (3-4): 537-44, 2013 Mar-Apr. [PUBMED Abstract]
- Fouladi M, Hunt DL, Pollack IF, et al.: Outcome of children with centrally reviewed low-grade gliomas treated with chemotherapy with or without radiotherapy on Children's Cancer Group high-grade glioma study CCG-945. Cancer 98 (6): 1243-52, 2003. [PUBMED Abstract]
- Wolff JE, Driever PH, Erdlenbruch B, et al.: Intensive chemotherapy improves survival in pediatric high-grade glioma after gross total resection: results of the HIT-GBM-C protocol. Cancer 116 (3): 705-12, 2010. [PUBMED Abstract]
- Kramm CM, Butenhoff S, Rausche U, et al.: Thalamic high-grade gliomas in children: a distinct clinical subset? Neuro Oncol 13 (6): 680-9, 2011. [PUBMED Abstract]
- Tendulkar RD, Pai Panandiker AS, Wu S, et al.: Irradiation of pediatric high-grade spinal cord tumors. Int J Radiat Oncol Biol Phys 78 (5): 1451-6, 2010. [PUBMED Abstract]
- Wolff B, Ng A, Roth D, et al.: Pediatric high grade glioma of the spinal cord: results of the HIT-GBM database. J Neurooncol 107 (1): 139-46, 2012. [PUBMED Abstract]
- Ononiwu C, Mehta V, Bettegowda C, et al.: Pediatric spinal glioblastoma multiforme: current treatment strategies and possible predictors of survival. Childs Nerv Syst 28 (5): 715-20, 2012. [PUBMED Abstract]
- Sposto R, Ertel IJ, Jenkin RD, et al.: The effectiveness of chemotherapy for treatment of high grade astrocytoma in children: results of a randomized trial. A report from the Childrens Cancer Study Group. J Neurooncol 7 (2): 165-77, 1989. [PUBMED Abstract]
- Stupp R, Mason WP, van den Bent MJ, et al.: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352 (10): 987-96, 2005. [PUBMED Abstract]
- Hegi ME, Diserens AC, Gorlia T, et al.: MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352 (10): 997-1003, 2005. [PUBMED Abstract]
- Cohen KJ, Pollack IF, Zhou T, et al.: Temozolomide in the treatment of high-grade gliomas in children: a report from the Children's Oncology Group. Neuro Oncol 13 (3): 317-23, 2011. [PUBMED Abstract]
- 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]
- Duffner PK, Krischer JP, Burger PC, et al.: Treatment of infants with malignant gliomas: the Pediatric Oncology Group experience. J Neurooncol 28 (2-3): 245-56, 1996 May-Jun. [PUBMED Abstract]
- Dufour C, Grill J, Lellouch-Tubiana A, et al.: High-grade glioma in children under 5 years of age: a chemotherapy only approach with the BBSFOP protocol. Eur J Cancer 42 (17): 2939-45, 2006. [PUBMED Abstract]
- Warren KE, Gururangan S, Geyer JR, et al.: A phase II study of O6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brainstem gliomas: a Pediatric Brain Tumor Consortium study. J Neurooncol 106 (3): 643-9, 2012. [PUBMED Abstract]
- McCowage GB, Friedman HS, Moghrabi A, et al.: Activity of high-dose cyclophosphamide in the treatment of childhood malignant gliomas. Med Pediatr Oncol 30 (2): 75-80, 1998. [PUBMED Abstract]
- Finlay JL, Dhall G, Boyett JM, et al.: Myeloablative chemotherapy with autologous bone marrow rescue in children and adolescents with recurrent malignant astrocytoma: outcome compared with conventional chemotherapy: a report from the Children's Oncology Group. Pediatr Blood Cancer 51 (6): 806-11, 2008. [PUBMED Abstract]