Intensity modulated radiation therapy versus three dimensional conformal radiation therapy for treatment of high grade glioma: a radiobiological modeling study.

Treatment of glioblastoma results in a median survival of 12 months. Radiation dose escalation trials for high grade gliomas have resulted in modest improvements in survival in selected patients with small peripheral tumors at the expense of normal brain toxicity. Neurotoxicity includes radiation necrosis but it is increasingly recognized that long-term survivors may develop neuro-cognitive deficits. Tumor control probability (TCP) and normal tissue complication probability (NTCP) are radiobiological models used to predict treatment outcomes. This study assesses the impact of radiation dose escalation from 59.6 Gy to 90 Gy on TCP and NTCP in ten patients planned with Three Dimensional Conformal Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT). No difference in TCP was observed between 3DCRT and IMRT at doses of 59.4 Gy and 90 Gy. However, dose escalation to 90 Gy resulted in about 25% relative TCP increase. Compared to 3DCRT, dose escalation with IMRT significantly reduced NTCP by 70% (10.75% v. 3.75%, respectively). As a result, highly conformal techniques are recommended to obviate radiation exposure of normal brain especially when radiation dose escalation is used. Further understanding of the molecular mechanisms underlying neurotoxicity will allow the development of more precise radiobiological predictive models and of approaches to prevent or treat radiation-induced brain damage.