Pediatric Astrocytoma Treatment & Management
- Author: Tobey J MacDonald, MD; Chief Editor: Max J Coppes, MD, PhD, MBA more...
See the list below:
- Treatment of astrocytomas depends on the location and grade of the tumor. Tumor location and associated morbidity may limit resection or render the tumor inoperable.
- Patients who develop significant obstructive hydrocephaly that does not resolve may require the placement of a ventriculoperitoneal shunt.
- Chemotherapy has had a limited role and limited success in the treatment of high-grade astrocytomas.
- For low-grade astrocytomas that are inoperable because of location or have demonstrated early recurrence or progression, chemotherapy with carboplatin and vincristine has been successfully used in prepubertal children in an effort to avoid or delay irradiation. Other drug regimens may also be effective.
- Chemotherapy has little impact on the overall survival of patients with high-grade tumors despite several regimens showing significant tumor response rates. To date, nitrosoureas (ie, bischloroethylnitrosourea [BCNU], cyclohexylchloroethylnitrosurea [CCNU]) and cisplatin show the most efficacy against these tumors. The most recent Children's Oncology Group (COG) study (CCG-9933) showed no benefit in survival for patients with residual postoperative high-grade astrocytomas receiving combinations of these agents in high-dose prior to irradiation. The alkylating agent, temozolomide, shows promising results in recent clinical trials as adjuvant therapy with radiotherapy in some adults with high-grade gliomas, especially those with tumors that have reduced activity of an enzyme (O6 -methylguanine-DNA-methyltransferase), which reverses alkylator-induced damage; pediatric studies have yet to show benefit.
- A completed COG trial suggests that a CCNU, thioguanine, and procarbazine regimen may be as effective.
- Admit for treatment those patients with high-grade astrocytomas who are eligible for available investigational chemotherapy. Investigational chemotherapy for low-grade tumors is currently administered in an outpatient setting.
- Low-grade astrocytoma
- Surgical resection is the primary treatment modality. If feasible, a complete resection is the goal of surgery in order to minimize the risk of local recurrence. However, long-term progression-free intervals may ensue even after partial resection. Low-grade tumors that recur or progress may be re-resected, and patients can undergo observation without further treatment if the risk of neurologic impairment from further growth is low and the tumor has undergone a significant interim period of dormancy.
- Low-grade tumors that (1) are inoperable (diencephalic, brain stem), (2) are partially resected and posing a high risk of neurologic impairment if allowed to regrow, or (3) demonstrate early progression or recurrence may be treated with local radiotherapy to the area of the tumor plus a 2-cm margin. Radiotherapy is relatively contraindicated in children with neurofibromatosis type 1 (NF1) due to risks of radiation-induced secondary high-grade brain tumors, mutagenesis and intracranial vasculopathy. Alternatively, chemotherapy may be used in young children (prepubertal) in whom the clinician wishes to avoid or to delay radiotherapy because of its potential neurologic sequelae in this age group. To date, the most active chemotherapy regimen for these tumors is carboplatin and vincristine. These agents show objective response rates of 50-80% and produce prolonged stable disease. A COG trial suggests that a CCNU, thioguanine, and procarbazine regimen may be as effective.
- High-grade astrocytoma
- Following surgical resection, patients are treated with local irradiation to 50-60 Gy with a 2-cm to 4-cm margin around the area of edema defined by imaging.
- The addition of single-agent or multiple-agent chemotherapy preradiotherapy and postradiotherapy has little or no impact on the overall survival rate (0-30%) in this group of patients, despite of producing response rates as high as 45%. The most recent COG trial is investigating the benefit of irradiation and concurrent temozolomide postoperatively.
- Biologic therapy targeting (molecular markers) in pediatric high-grade astrocytomas, such as tyrosine kinase inhibitors that inhibit epidermal growth factor receptor (EGFR), are also being investigated.
- Adult trials have shown the benefit of bevacizumab and irinotecan in those with recurrent disease; studies are underway in children.
- In infants with varying types of malignant brain tumors in whom irradiation is withheld, promising results have been reported with the use of high-dose chemotherapy, although patients with a histologic diagnosis of malignant astrocytoma make up only a small fraction of this group.
- Astrocytoma of the brain stem
- Surgery has no role in those patients with diffuse pontine lesions (eg, malignant brainstem glioma), the most common brainstem tumor. Surgery is feasible for many patients with exophytic and cystic tumors, and extensive resection may prolong survival even without further treatment. However, a surgical approach to focal midbrain, medulla, and tectal plate regions is hazardous and resections are generally limited.
- Local radiotherapy to 54 Gy is used for patients with inoperable tumors and for those who have high-grade lesions or early recurrence/progression of low-grade tumors. Radiotherapy for diffuse pontine lesions and high-grade tumors usually results in early and significant neurologic improvement, although the overall outlook remains dismal.
- Despite ongoing clinical trials, a chemotherapeutic role in the management of patients with brainstem tumors has yet to be established.
- Trials are underway using radiosensitizing chemotherapy and biologic therapy, concurrent with radiotherapy, in attempts to improve survival.
- Astrocytoma of the visual pathway
- The natural history of visual pathway astrocytomas is erratic. Some patients experience long-term stabilization without treatment, whereas others develop progressive disease with neurologic deterioration culminating in death. This is especially true for children with neurofibromatosis. In contrast to those with chiasmatic lesions, patients with isolated optic nerve tumors rarely die of their disease; therefore, treatment efficacy must be based on visual outcome and freedom from treatment sequelae.
- A period of observation without treatment is recommended in cases without severe proptosis, rapidly progressive visual decline, or extensive chiasmal tumors (with distortion or invasion of optic tracts, hypothalamus, or the third ventricular area).
- Surgery is warranted only in those with chiasmatic or deeper intracranial involvement in order to rule out the possibility of an uncommon high-grade lesion. For these patients and for those with an isolated optic nerve tumor whose clinical characteristics do not meet the criteria above, the preferred treatment is local radiotherapy to 55 Gy. With radiotherapy, as many as 90% of patients show at least stabilization of visual decline and 10-year progression-free survival rates of 70-90%.
- Chemotherapy with carboplatin and vincristine may be used as an initial therapy or to delay irradiation in prepubertal children. This combination chemotherapy has produced complete or partial responses in 45% of newly diagnosed patients. Other regimens may also be effective.
- Intramedullary spinal cord astrocytomas
- Complete surgical resections are difficult in astrocytomas because a distinct tumor-cord interface is often absent; however, nearly 80-90% of resections may be performed in most cases.
- Treatment with radiotherapy is the same as that for other CNS astrocytomas. Lower radiation doses to 50 Gy are used because of radiation intolerance of the spinal cord. Treatment of low-grade tumors with radiotherapy yields 5-year survival rates of 65-70%. Patients with high-grade tumors generally die of their disease within months of diagnosis despite radiation and chemotherapy.
See Brain Cancer Treatment Protocols for summarized information.
See the list below:
- Radiation oncologist for high-grade, recurrent and/or progressive, or visual pathway tumors
- Neuroendocrinologist evaluation
- Occupational and/or physical therapist for rehabilitation
- Regular team members, including the following:
- Pediatric oncologist
See the list below:
- No specific dietary requirements or restrictions are indicated.
- Patients who develop severe anorexia or weight loss as a result of therapy (particularly infants) may need supplemental nutrition to maintain daily requirements.
See the list below:
- No restrictions in activity are indicated unless dictated by underlying neurological deficits.
- Patients with ventriculoperitoneal shunts may be restricted from high-impact sports, such as diving.
Hales RK, Shokek O, Burger PC, Paynter NP, Chaichana KL, Quiñones-Hinojosa A, et al. Prognostic factors in pediatric high-grade astrocytoma: the importance of accurate pathologic diagnosis. J Neurooncol. 2010 Aug. 99(1):65-71. [Medline].
Tihan T, Ersen A, Qaddoumi I, Sughayer MA, Tolunay S, Al-Hussaini M, et al. Pathologic characteristics of pediatric intracranial pilocytic astrocytomas and their impact on outcome in 3 countries: a multi-institutional study. Am J Surg Pathol. 2012 Jan. 36(1):43-55. [Medline].
Leroy HA, Baroncini M, Delestret I, Florent V, Vinchon M. Anorexia: an early sign of fourth ventricle astrocytoma in children. Childs Nerv Syst. 2014 Dec. 30(12):2089-95. [Medline].
Belirgen M, Berrak SG, Ozdag H, Bozkurt SU, Eksioglu-Demiralp E, Ozek MM. Biologic tumor behavior in pilocytic astrocytomas. Childs Nerv Syst. 2012 Mar. 28(3):375-89. [Medline].
Chintagumpala MM, Friedman HS, Stewart CF, et al. A phase II window trial of procarbazine and topotecan in children with high-grade glioma: a report from the children's oncology group. J Neurooncol. 2006 Apr. 77(2):193-8. [Medline].
Geyer JR, Sposto R, Jennings M, et al. Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children's Cancer Group. J Clin Oncol. 2005 Oct 20. 23(30):7621-31. [Medline].
Pollack IF, Hamilton RL, Sobol RW, et al. O6-methylguanine-DNA methyltransferase expression strongly correlates with outcome in childhood malignant gliomas: results from the CCG-945 Cohort. J Clin Oncol. 2006 Jul 20. 24(21):3431-7. [Medline].
Akyüz C, Demir HA, Varan A, Yalçin B, Kutluk T, Büyükpamukçu M. Temozolomide in relapsed pediatric brain tumors: 14 cases from a single center. Childs Nerv Syst. 2012 Jan. 28(1):111-5. [Medline].
Ait Khelifa-Gallois N, Laroussinie F, Puget S, Sainte-Rose C, Dellatolas G. Long-term functional outcome of patients with cerebellar pilocytic astrocytoma surgically treated in childhood. Brain Inj. 2014 Nov 10. 1-8. [Medline].
Chen L, Du C, Wang L, Yang C, Zhang JR, Li N, et al. Human positive coactivator 4 (PC4) is involved in the progression and prognosis of astrocytoma. J Neurol Sci. 2014 Sep 19. [Medline].
Bouffet E, Jakacki R, Goldman S, et al. Phase II Study of weekly vinblastine in recurrent/refractory pediatric low-grade gliomas. Neuro-Oncology. 2008. 10(3):450.
Bredel M, Pollack IF, Hamilton RL, James CD. Epidermal growth factor receptor expression and gene amplification in high-grade non-brainstem gliomas of childhood. Clin Cancer Res. 1999 Jul. 5(7):1786-92. [Medline].
Cokgor I, Friedman AH, Friedman HS. Gliomas. Eur J Cancer. 1998 Nov. 34(12):1910-5; discussion 1916-8. [Medline].
Fernandez C, Figarella-Branger D, Girard N, et al. Pilocytic astrocytomas in children: prognostic factors--a retrospective study of 80 cases. Neurosurgery. 2003 Sep. 53(3):544-53; discussion 554-5. [Medline].
Finlay JL, Boyett JM, Yates AJ, et al. Randomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-1-day regimen. Childrens Cancer Group. J Clin Oncol. 1995 Jan. 13(1):112-23. [Medline].
Finlay JL, Wisoff JH. The impact of extent of resection in the management of malignant gliomas of childhood. Childs Nerv Syst. 1999 Nov. 15(11-12):786-8. [Medline].
Gilbertson RJ, Hill DA, Hernan R, et al. ERBB1 is amplified and overexpressed in high-grade diffusely infiltrative pediatric brain stem glioma. Clin Cancer Res. 2003 Sep 1. 9(10 Pt 1):3620-4. [Medline].
Grill J, Couanet D, Cappelli C, et al. Radiation-induced cerebral vasculopathy in children with neurofibromatosis and optic pathway glioma. Ann Neurol. 1999 Mar. 45(3):393-6. [Medline].
Gururangan S, Fisher MJ, Allen JC, Herndon JE 2nd, Quinn JA, Reardon DA, et al. Temozolomide in children with progressive low-grade glioma. Neuro Oncol. 2007 Apr. 9(2):161-8. [Medline].
Guthrie BL, Laws ER Jr. Supratentorial low-grade gliomas. Neurosurg Clin N Am. 1990 Jan. 1(1):37-48. [Medline].
Huncharek M, Wheeler L, McGarry R, Geschwind JF. Chemotherapy response rates in recurrent/progressive pediatric glioma; results of a systematic review. ALYSIS. 1999 Jul-Aug. 19(4C):3569-74. [Medline].
Jacobson DM. Gliomas of the anterior visual pathways. Neurosurg Clin N Am. 1999 Oct. 10(4):683-98, ix. [Medline].
Khatua S, Peterson KM, Brown KM, et al. Overexpression of the EGFR/FKBP12/HIF-2alpha pathway identified in childhood astrocytomas by angiogenesis gene profiling. Cancer Res. 2003 Apr 15. 63(8):1865-70. [Medline].
Khaw SL, Coleman LT, Downie PA, Heath JA, Ashley DM. Temozolomide in pediatric low-grade glioma. Pediatr Blood Cancer. 2007 Nov. 49(6):808-11. [Medline].
Komotar RJ, Mocco J, Carson BS, et al. Pilomyxoid astrocytoma: a review. MedGenMed. 2004. 6(4):42. [Medline].
Kuo DJ, Weiner HL, Wisoff J, et al. Temozolomide is active in childhood, progressive, unresectable, low-grade gliomas. J Pediatr Hematol Oncol. 2003 May. 25(5):372-8. [Medline].
Lafay-Cousin L, Holm S, Qaddoumi I, et al. Weekly vinblastine in pediatric low-grade glioma patients with carboplatin allergic reaction. Cancer. 2005 Jun 15. 103(12):2636-42. [Medline].
MacDonald TJ, Arenson EB, Ater J, et al. Phase II study of high-dose chemotherapy before radiation in children with newly diagnosed high-grade astrocytoma: final analysis of Children's Cancer Group Study 9933. Cancer. 2005 Dec 15. 104(12):2862-71. [Medline].
Nadkarni TD, Rekate HL. Pediatric intramedullary spinal cord tumors. Critical review of the literature. Childs Nerv Syst. 1999 Jan. 15(1):17-28. [Medline].
Nicholson HS, Krailo M, Ames MM, et al. Phase I study of temozolomide in children and adolescents with recurrent solid tumors: a report from the Children's Cancer Group. J Clin Oncol. 1998 Sep. 16(9):3037-43. [Medline].
Packer RJ. Brain tumors in children. Arch Neurol. 1999 Apr. 56(4):421-5. [Medline].
Pencalet P, Maixner W, Sainte-Rose C, et al. Benign cerebellar astrocytomas in children. J Neurosurg. 1999 Feb. 90(2):265-73. [Medline].
Pollack IF. The role of surgery in pediatric gliomas. J Neurooncol. 1999 May. 42(3):271-88. [Medline].
Pollack IF, Boyett JM, Finlay JL. Chemotherapy for high-grade gliomas of childhood. Childs Nerv Syst. 1999 Oct. 15(10):529-44. [Medline].
Pollack IF, Finkelstein SD, Woods J, et al. Expression of p53 and prognosis in children with malignant gliomas. N Engl J Med. 2002 Feb 7. 346(6):420-7. [Medline].
Prados MD, Edwards MS, Rabbitt J, Lamborn K, Davis RL, Levin VA. Treatment of pediatric low-grade gliomas with a nitrosourea-based multiagent chemotherapy regimen. J Neurooncol. 1997 May. 32(3):235-41. [Medline].
Reddy AT, Packer RJ. Chemotherapy for low-grade gliomas. Childs Nerv Syst. 1999 Oct. 15(10):506-13. [Medline].
Rubin G, Michowitz S, Horev G, et al. Pediatric brain stem gliomas: an update. Childs Nerv Syst. 1998 Apr-May. 14(4-5):167-73. [Medline].
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. 2006 Jun 1. 24(16):2570-5. [Medline].
Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10. 352(10):987-96. [Medline].
Thorarinsdottir HK, Rood B, Kamani N, et al. Outcome for children 111111111111111111Pediatr Blood Cancer</i>. 2006 Feb 2. [Medline].
Vredenburgh JJ, Desjardins A, Herndon JE 2nd, et al. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol. 2007 Oct 20. 25(30):4722-9. [Medline].
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. 1998 Jul. 89(1):52-9. [Medline].