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 (ΔNTD_{2 Gy}) was calculated for varying fraction durations (T), α/β ratios, and doses/fx. Results: %Diff_min/max and ΔNTD_{2 Gy} both increased with increasing T and with decreasing α/β. The largest increases occurred with dose/fx. With α/β = 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 ΔNTD_{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 α/β = 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.