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