Revised: June 2014

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).  Additionally, molecular markers of good survival include MGMT promoter methylation and IDH1 mutations (2,3).

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(4).

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(5). The usual course of radiation extends over 6 weeks.

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(6).

A multicentre EORTC/NCIC-sponsored randomized clinical trial comparing radiotherapy alone to radiotherapy with concurrent and adjuvant temozolomide improved median survival by 2.5 months and 2 year survival by 16% (7).  Further follow-up revealed the 5 year survival to be improved by 10% with the addition of temozolomide chemotherapy (8).  Therefore, the current standard of care for glioblastoma in patients under 70 with acceptable performance status, consists of 60 Gy partial brain RT with concurrent temozolomide and 6 cycles of adjuvant temozolomide.

The role of chemotherapy in elderly patients with GBM is less certain.  Two European elderly trials looking at single agent temozolomide vs RT alone for patients with glioblastoma over age 65 showed equivalent outcomes (9,10).  Interestingly, in both trials, there was a difference in outcome depending on MGMT methylation status of the tumours.  MGMT methylated tumours showed a better outcome with Temozolomide whereas unmethylated patients survived longer with RT.  The role of combination of RT + TMZ is being explored with clinical trials in the elderly.

Currently the role for concurrent chemoradiotherapy in the treatment of grade 3 astrocytomas is unknown pending ongoing clinical trials.  In the absence of data, centres have adopted either single modality radiotherapy or radiotherapy combined with temozolomide as utilized in glioblastoma.

Patients with good performance status and residual tumour after radiotherapy and/or chemotherapy may benefit from a second surgical resection(11).

For management of recurrent tumours see Cerebral Metastasis. 

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. Hegi ME, Diserens AC, Gorila T, et al.  MGMT gene silencing and benefit from temozolomide in glioblastoma.  N Engl J Med 352(10): 997-1003, 2005.

3. Yan H, Parsons DW, Jin G, et al.  IDH1 and IDH2 mutations in gliomas.  N Engl J Med 360(8): 765-73, 2009.

4. 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.     

5. 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.

6. Keime-Guibert F, Chinot O, Taillandier L, et al.  Radiotherapy for glioblastoma in the elderly. N Engl J Med 356(15):1527-35, 2007.   

7. 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.  

8. Stupp R, Hegi ME, Mason WP, et al.  Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomized phase III study: 5-year analysis of the EORTC-NCIC trial.  Lancet Oncol 10(5):459-66, 2009.

9. Malmstrom A, Gronberg BH, Marosi C, et al.  Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma:  the Nordic randomized, phase 3 trial.  Lancet Oncol 13(9):916-26, 2012.

10. Wick W, Platten M, Meisner C, et al.  Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial.  Lancet Oncol 13(7):707-15, 2012.

11. Young B, Oldfield EH, Markesbery WR et al. Reoperation for glioblastoma. J Neurosurg 55(6): 917-21, 1981.