Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

For patients with glioblastoma (World Health Organization grade IV), the cure rate is very low with standard local treatment. These patients are appropriate candidates for clinical trials designed to improve local control by adding newer forms of treatment to standard treatment. (Refer to the Glioblastoma section in the Classification section of this summary for more information.)

STANDARD TREATMENT OPTIONS:

1. Surgery plus radiation therapy and chemotherapy.[1,2,3,4,5] A randomized cooperative study showed no additional benefit from brachytherapy added to external-beam radiation therapy (EBRT) and carmustine (BCNU).[6][Level of evidence: 1iiA] A randomized study of patients 60 years and older compared 60 Gy administered over the course of 6 weeks (standard course) with 40 Gy in 15 fractions administered over the course of 3 weeks (short course).[7] Karnofsky performance status scores were similar. Overall survival was similar in the two groups in this underpowered study (lower-bound 95% confidence interval, -13.7%).[7][Level of evidence: 1iiA]
2. Surgery plus radiation therapy.
3. BCNU-impregnated polymer (Gliadel wafer) implanted during initial surgery. A randomized double-blinded controlled trial with 240 patients with high-grade glioma showed a survival advantage for patients who had BCNU-impregnated polymer placed intraoperatively at the time of initial surgery when they were compared with the placebo-treated group. The median survival was 13.9 months in the treated group and 11.6 months in the control group (overall survival, P = .03).[8][Level of evidence: 1iA]
4. A randomized study of radiation therapy versus radiation therapy plus temozolomide followed by 6 months of adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme demonstrated a statistically significant increase in median survival of 3 months in the combination-treated group.[9] The 2-year survival rate was 26.5% in the combination group compared with only 10.4% in the radiation-only group. The treatment is relatively safe and well tolerated.[9,10,11,12][Level of evidence: 1iiA]

TREATMENT OPTIONS UNDER CLINICAL EVALUATION:

• Patients with brain tumors that are either infrequently curable or unresectable should be considered candidates for clinical trials that evaluate hyperfractionated radiation therapy, accelerated-fraction radiation therapy, stereotactic radiosurgery, radiosensitizers, hyperthermia, interstitial brachytherapy, or intraoperative radiation therapy used in conjunction with EBRT to improve local control of the tumor. These patients are also candidates for studies that evaluate new drugs and biological response modifiers following radiation therapy.[13,14,15,16] Cooperative groups are evaluating new treatment options (RTOG-9803RTOG-0211RTOG-BR 0023RTOG BR-0013).