![]() ![]() Optimization corresponding to BED normal of 150 Gy was also obtained to evaluate the possibility in further recurrence delay with dose escalation. The efficacy of a super hyperfractionated approach with a prolonged treatment duration of one year was therefore tested, with both fixed regular and optimized variable time intervals between dose fractions corresponding to total number of fractions equivalent to weekly, bi-weekly, and monthly deliveries (n = 53, 27, 13). Optimization was performed for conventional treatment time frames equivalent to currently and historically utilized fractionation schemes, in which limited improvement in recurrence time delay was observed. The recurrence time, defined as the time point at which the total tumor cell number regrows to 2.8×10 9 cells, was used to evaluate optimization outcome. With specified total number of dose fractions and treatment duration, the optimization was performed using a paired simulated annealing algorithm with fractional doses delivered to the CSC and DCC compartments and time intervals between fractions as variables. A non-convex optimization problem with the objective of minimizing the total cancer cell number while maintaining the normal tissue biological effective dose (BED normal) at 100 Gy, equivalent to the conventional 2 Gy × 30 dosing scheme was formulated. ![]()
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