High-dose and fractionation effects in stereotactic radiation therapy: Analysis of tumor control data from 2965 patients.

BACKGROUND AND PURPOSE Two aspects of stereotactic radiotherapy (SRT) require clarification: First, are tumoricidal mechanisms at high-doses/fraction the same as at lower doses? Second, is single high-dose SRT treatment advantageous for tumor control (TCP) vs. multi-fraction SRT? MATERIAL AND METHODS We analyzed published TCP data for lung tumors or brain metastases from 2965 SRT patients, covering a wide range of doses and fraction numbers. We used: (a) a linear-quadratic model (including heterogeneity), which assumes the same mechanisms at all doses, and (b) alternative models with terms describing distinct tumoricidal mechanisms at high doses. RESULTS Both for lung and brain data, the LQ model provided a significantly better fit over the entire range of treatment doses than did any of the models requiring extra terms at high doses. Analyzing the data as a function of fractionation (1 fraction vs. >1 fraction), there was no significant effect on TCP in the lung data, whereas for brain data multi-fraction SRT was associated with higher TCP than single-fraction treatment. CONCLUSION Our analysis suggests that distinct tumoricidal mechanisms do not determine tumor control at high doses/fraction. In addition, there is evidence suggesting that multi-fraction SRT is superior to single-dose SRT.