Higher than 60 Gy Radiotherapy with Temozolomide Improved Survival in Glioblastoma

Article Outline

• Purpose/Objective(s)
• Materials/Methods
• Results
• Conclusions
• Copyright

Back to Article Outline

Purpose/Objective(s) 

It has been shown that local radiotherapy of 60 Gy with concurrent and adjuvant temozolomide prolong the survival of patients with glioblastoma. In this trial, we investigated the efficacy of higher dose radiotherapy with temozolomide for patients with glioblastoma.

Back to Article Outline

Materials/Methods 

From December 2001 to January 2007, a total of 41 patients with histologically proven glioblastoma treated with 3D-conformal radiotherapy of 64 Gy or higher plus concurrent and adjuvant temozolomide, were analyzed. The median age was 55 years (range, 28-69 years). Total radiation doses were 64-76 Gy (median 70 Gy, fraction size 2 Gy). Gross tumor volume (GTV) was defined as surgical margin or gadolinium enhanced lesion observed in the T1 sequence MRI series. Clinical target volume (CTV) was defined as 1.5 cm margin from GTV. Surrounding edema outside more than 1.5 cm from GTV was not included in order to reduce the risk of late radiation-associated complication. The irradiated dose to CTV was 44 or 46 Gy. Temozolomide was administered during radiotherapy (75 mg/m²/d from the first to the last day of radiotherapy or 150-200 mg/m²/d x 5 days, every 3 weeks for 2 cycles) and after radiotherapy (150-300 mg/m²/d x 5 days, every 3-4 weeks for 4-6 cycles). Recurrences within GTV were considered central; those within CTV and outside CTV were considered marginal and out-field, respectively.

Back to Article Outline

Results 

The majority of patients underwent a total or subtotal resection of their tumors (66%). With a median follow-up of 17 months, 25 patients (61%) died 3-39 months (median, 15.8 months) after operation. Ten (24%) patients were alive without disease, and 5 (15%) patients were alive with disease. Their median follow-up times were 24 months (range, 9-60 months) and 16 months (range, 12-36 months). The median progression-free and overall survival times were 14.7 ± 2.6 months and 22.4 months ± 3.6 (3-60). The 1-year and 2-year survival rates were 77% and 41%. The patterns of failure was central in 13 of 30 (44%), marginal in 7 of 30 (23%), out-field in 3 of 30 (10%), and CSF seeding in 7 of 30 (23%). Radiation necrosis observed in the MRI occurred in 18 patients (44%). Fourteen patients had Grade 1, 3 patients had Grade 2, 1 patient had Grade 3. No patient had Grade 4 radiation necrosis.

Back to Article Outline

Conclusions 

Dose escalation of radiotherapy was feasible in the setting of concurrent chemoradiotherapy and resulted in improved survival for glioblastoma. Our results deserve further well-designed investigation of radiation dose escalation study for glioblastoma.