Revised: June 2005

The most important prognostic variables for survival of patients with malignant astrocytoma are age (less than or greater than 50 years), performance status (KPS greater or less than 70) and tumour grade (grade III or grade IV)(1).

Younger patients with a good performance status have a median survival of 59 months with grade III tumours and 18 months with grade IV tumours. Older patients with a good performance status have a median survival of 37 months with grade III tumours and 11 months with grade IV tumours(1).

Patients over 50 years with a poor performance status have a median survival of only 18 months with grade III tumours and 5 months with grade IV tumours(1).

All patients with suspected malignant astrocytoma, based on medical imaging, who are fit for biopsy should have tumour tissue obtained to confirm the diagnosis.

Patients who, after treatment with dexamethasone, are unfit for biopsy are unlikely to benefit from any further treatment because of their very short expected survival.

Tumours suitable for surgery should receive maximal surgical debulking(2).

Prospective randomized controlled trials have confirmed the benefit of postoperative radiation treatment for patients with malignant gliomas, which extends the median survival from 14 weeks to 36 weeks compared to surgery alone(3). The usual course of radiation extends over 6 weeks.

Non-randomized prospective studies in grade IV astrocytoma have shown that older patients, or patients with poor performance status (KPS = 50), achieve equivalent survival benefit with shorter courses of radiation treatment.

A meta-analysis of 16 randomized trials of chemotherapy, in addition to radiation treatment for malignant gliomas, has shown a survival benefit at one year of 17% for grade III astrocytomas and 7% for grade IV astrocytomas, compared to treatment with radiation alone(5).

For grade III astrocytomas, a small prospective study of combination chemotherapy with procarbazine, CCNU and vincristine (PCV) has shown superiority over single agent chemotherapy with BCNU(6).  However, review of RTOG trials of PCV in anaplastic astrocytoma has failed to show a benefit to the combination treatment over single agent nitrosoureas(10).  Similarly, a recent European trial of PCV in malignant glioma showed no benefit over RT alone for either grade III or Grade IV tumors(11).

For grade IV astrocytomas, no combination of chemotherapy agents has demonstrated significant superiority over single agent BCNU (7).  Randomized trials have not clearly shown benefit in Grade IV astrocytoma over RT alone.  Two meta-analyses of chemotherapy-based randomized trials have suggested a small benefit for adjuvant nitrosourea-based chemotherapy in malignant glioma(5,9).  These benefits are small (6-10% increase in 1 year survival) and chemotherapy remains an option for young patients (<60 yrs) with good performance status.

The randomized  study by Stupp reported [in the New Journal England of Medicine. 352;10:987-97 in March 2005,] comparing radiation alone to RT with concurrent Temozolamide, followed by 6 months fo Temozolomide, showed a 3 month survival benefit.  The 2 year survival improved from 10% to 26.5%. Grade 3/4 toxicity was 7%.

Patients with good performance status and residual tumour after radiotherapy and/or chemotherapy may benefit from a second surgical resection(8).

For management of recurrent tumours follow this link. 

References: 

1. Curran WJ, Scott CB, Horton J et al. Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group Malignant glioma trials. J Nat Cancer Inst 85(9):704-710, 1993.     
2. Wood JR, Green SB, Shapiro WR. The prognostic importance of tumour size in malignant gliomas: a computed tomographic scan study by the Brain Tumour Cooperative Group. J Clin Oncol 6(2): 338-43, 1988.     
3. Walker MD, Alexander E, Hunt WE et al. Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. J Neurosurg 49(3): 333-43, 1978.     
4. Bauman GS, Gaspar LE, Fisher BJ et al. A prospective study of short course radiotherapy in poor prognosis glioblastoma multiforme. Int J Rad Onc Biol Phys 29(4): 835-9, 1994.     
5. Fine HA, Dear KB, Loeffler JS et al. Meta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults. Cancer 71(8): 2585-2597, 1993.     
6. Levin VA, Silver P, Hannigan J et al. Superiority of post-radiation adjuvant chemotherapy with CCNU, procarbazine, and Vincristine (PCV) over BCNU for anaplastic gliomas. NCOC 6G61 Final Report. Int J Rad Onc Biol Phys 18(2): 321-323, 1990.     
7. Rodriguez LA, Levin VA. Does chemotherapy benefit the patient with a central nervous system glioma? Oncology 1(9): 29-36, 1987.     
8. Young B, Oldfield EH, Markesbery WR et al. Reoperation for glioblastoma. J Neurosurg 55(6): 917-21, 1981.
9. Glioma Meta-analysis Trialists Group.  Chemotherapy in adult high grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomized trials.  Lancet 359: 1011-18, 2002.
10. Prados MD, Scott C, Curran WJ, et al.  Procarbazine, lomustine, and vincristine (PCV) chemotherapy for anaplastic astrocytoma: a retrospective review of Radiation Therapy Oncology Group protocols comparing survival with carmustine or PCV adjuvant chemotherapy.  J Clin Oncol 17:3389-95, 1999.
11. Medical Research Council Brain Tumour Working Party.  Randomized trial of procarbazine, lomustine and vincristine in the adjuvant treatment of high grade astrocytoma: a Medical Research Council trial.  J Clin Oncol 19:509-18, 2001.