Protective effect on normal brain tissue during a combinational therapy of 2-deoxy-d-glucose and hypofractionated irradiation in malignant gliomas

PURPOSE: To investigate the effect of 2-deoxy–D-glucose (2-DG), an inhibitor of glucose transport and glycolysis, on glioblastoma and the normal brain tissue during combined treatment with hypofractionated radiotherapy. MATERIALS AND METHODS: Twenty patients with malignant gliomas (18 Glioblastoma Multiformae, 2 Anasplastic Astrocytoma grade III) following surgery were treated weekly (once) with 2-DG, (250 mg/kg body weight), followed by 5 Gy of radiation to the tumor bed per fraction for 7 weeks. Clinical evaluation, complete hemogram, and random blood sugar levels were carried out in each cycle. Follow-up computed tomography (CT)/magnetic resonance imaging (MRI) was done to evaluate radiation-induced changes. Kernofsky Performance scale (KPS) was recorded preoperatively; postoperatively, and post-therapy till the last follow-up. RESULTS: Twenty patients were recruited for this trail; 19 of them completed the treatment and 1 discontinued. The survival period ranged between 6 and 36 months after the treatment, with a median survival of 14 months. CT and MRI revealed significant tumor necrosis. Histological evidence from the tissue during reexploration confirms the hypothesis of protective effect of 2-DG on normal brain. KPS was above 80% in majority of the patients, 6 months after the surgery. CONCLUSION: Radiotherapy coupled with 2-DG enhances tumor necrosis selectively and significantly while the normal brain gets relatively protected. This has been reflected in our study both clinically by preservation of quality-of-life and pathologically by retaining the integrity of normal brain architecture.