Impact of different biologically-adapted radiotherapy strategies on tumor control evaluated with a tumor response model

Motivated by the capabilities of modern radiotherapy techniques and by the recent developments of functional imaging techniques, dose painting by numbers (DPBN) was proposed to treat tumors with heterogeneous biological characteristics. This work studies different DPBN optimization techniques for virtual head and neck tumors assessing tumor response in terms of cell survival and tumor control probability with a previously published tumor response model (TRM). Uniform doses of 2 Gy are redistributed according to the microscopic oxygen distribution and the density distribution of tumor cells in four virtual tumors with different biological characteristics. In addition, two different optimization objective functions are investigated, which: i) minimize tumor cell survival (OF(surv)) or; ii) maximize the homogeneity of the density of surviving tumor cells (OF(std)). Several adaptive schemes, ranging from single to daily dose optimization, are studied and the treatment response is compared to that of the uniform dose. The results show that the benefit of DPBN treatments depends on the tumor reoxygenation capability, which strongly differed among the set of virtual tumors investigated. The difference between daily (fraction by fraction) and three weekly optimizations (at the beginning of weeks 1, 3 and 4) was found to be small, and higher benefit was observed for the treatments optimized using OF(surv). This in silico study corroborates the hypothesis that DPBN may be beneficial for treatments of tumors which show reoxygenation during treatment, and that a few optimizations may be sufficient to achieve this therapeutic benefit.