Systematic investigation of the performance of different scheduling schemes.

<p><b>A</b> Comparison of total tumour size in response to altered scheduling of the standard dose of 2 Gy/24 h. While high-dose fractions have an advantage because of the quadratic term in the LQ radiation response, they are outperformed by some lower-dose schemes due to a better timing of the treatment to the tumour radiosensitivity development (compare e.g. 2 Gy/24 h and 2.5 Gy/30 h). <b>B</b> Overall performance of varied dose distribution measured as tumour burden for the time period from treatment begin at day 14 to day 44. <b>C–D</b> Timing of fractions in relation to the enhancement development for selected runs can explain the different schedule performance. <b>E–F</b> Repeated delivery of doses of 3 Gy with different delivery intervals until full sterilisation is achieved. The number of fractions required for sterilisation depends non-linearly on the inter-fraction time. This complex dependency is a result of the enhancement development within the tumour as discussed in the text and further illustrated in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003295#pcbi.1003295.s006" target="_blank">figure S6</a>.