Purpose/Objective: To investigate the effects of radiation dose-escalation on treatment outcome, complications, and other prognostic variables in glioblastoma patients who were treated with 3D-conformal radiotherapy (3D-CRT). Materials/Methods: From Jan 1997 to July 2002, a total of 75 patients with histologically proven diagnosis of glioblastoma, 60 or higher Karnofsky Peformance Score (KPS), and 50 Gy or higher radiation to tumor bed, were analyzed. All patients were divided into two arms; Arm 1, high-dose group, enrolled prospectively, and Arm 2, low-dose group, as a retrospective control. Arm 1 patients received 63~70 Gy (Median 66 Gy, fraction size 1.8~2 Gy) with 3D-conformal radiotherapy, and Arm 2 patients received 59.4 Gy or less (Median 59.4 Gy, fraction size 1.8 Gy) with 2D-conventional radiotherapy. Gross Tumor Volume (GTV) was defined by surgical margin and the residual gross tumor on a contrast enhanced MRI. Surrounding edema was not included in GTV in Arm 1, high dose group, to reduce the risk of late radiation associated complication, in contrast with Arm 2, low-dose group, whose GTV included it (Table 1). Postoperative MRI was routinely performed within 72 hours after surgery. Overall survival and progression free survival times were calculated from the date of surgery with Kaplan-Meier method. The significance of the prognostic variables was identified with Log Rank Test and Cox Regression Hazard model. The time to progression was measured with serial neurologic examinations and MRI or CT scans after RT completion. Acute and late toxicity was evaluated using Radiation Therapy Oncology Group neurotoxicity scores. Results: During the relatively short follow up period of 14 months, the median overall survival and progression free survival time was 15±1.65 and 11±0.95 months, respectively. There was a significantly longer survival time in Arm 1 patients who were treated with high-doses with respect to Arm 2 patients who were treated with low-doses (p=0.028, Fig. 1). For Arm 1 patients, the median survival and progression free survival time were 21±5.03 and 12±1.59 months while for Arm 2 patients it was 14±0.94 and 9±1.75 months, respectively. Especially in terms of the 2-year survival rate, the high-dose group showed much better survival time than the low-dose group ; 44.7% versus 19.2%. In univariate analyses, age, performance status, location of tumor, extent of surgery, tumor volume, and radiation dose group were significant factors for survival. Multivariate analyses confirmed that the impact on survival of radiation dose was independent of age, performance status, extent of surgery, and target volume. For the follow-up period, complications related directly with radiation like radionecrosis, has not been identified. Conclusions: Using 3D-conformal radiotherapy, which is able to reduce radiation dose to normal tissues compared to 2D-conventional treatment, we could deliver up to 70 Gy of radiation to GTV without significant toxicity. As an approach to intensify local treatment, radiation dose escalation through 3D-CRT can be expected to increase overall and progression free survival time in patients with glioblastoma.
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