Optimization of the temporal pattern of radiation: an IMRT based study.

Purpose: To investigate how the temporal pattern of dose applied during a single-intensity modulated radiation therapy (IMRT) fraction can be arranged to maximize or minimize cell kill.

Methods And Materials: Using the linear-quadratic repair-time model and a simplified IMRT delivery pattern model, the surviving fraction of cells for a single fraction was calculated for all permutations of the dose delivery pattern for an array of clinically based IMRT cases. Maximization of cell kill was achieved by concentrating the highest doses in the middle of a fraction, while minimization was achieved by spreading the highest doses between the beginning and end. The percent difference between maximum and minimum cell kill (%Diff(min/max)) and the difference between maximum and minimum total doses normalized to 2 Gy/fx (deltaNTD(2 Gy)) was calculated for varying fraction durations (T), alpha/beta ratios, and doses/fx.

Results: %Diff(min/max) and deltaNTD(2 Gy) both increased with increasing T and with decreasing alpha/beta. The largest increases occurred with dose/fx. With alpha/beta = 3 Gy and 30 min/fx, %Diff(min/max) ranged from 2.7-5.3% for 2 Gy/fx to 48.6-74.1% for 10 Gy/fx, whereas deltaNTD(2 Gy) ranged from 1.2 Gy-2.4 Gy for 30 fractions of 2 Gy/fx to 2.3-4.8 Gy for 2 fractions of 10.84 Gy/fx. Using alpha/beta = 1.5 Gy, an analysis of prostate hypofractionation schemes yielded differences in clinical outcome based on the pattern of applied dose ranging from 3.2%-6.1% of the treated population.

Conclusions: Rearrangement of the temporal pattern of dose for a single IMRT fraction could be used to optimize cell kill and to directly, though modestly, affect treatment outcome.