Incorporating the Local Biological Effect of Dose Per Fraction in IMRT Inverse Optimization

In intensity modulated radiation therapy (IMRT), the dose in each voxel of the organs at risk (OAR) can be strongly reduced compared to conformal radiation therapy (RT). Due to the sensitivity of late side-effects to fraction size, a smaller dose per fraction in the normal tissues represent an increased tolerance to RT. This expected reduction in biological effect may then be used as an additional degree of freedom during IMRT optimization. In this study, the comparison between plans optimized with and without a voxel-based fractionation correction was made. Four patients diagnosed with a head and neck (HN), a breast, a lung or a prostate tumor were used as test cases. Voxel-based fractionation corrections were incorporated into the optimization algorithm by converting the dose in each normal tissue voxel to EQD2 (equivalent dose delivered at 2 Gy per fraction). The maximum gain in the probability of tumor control (PB), due to the incorporation of the correction for fractionation in each voxel, was 1.3% with a 0.1% increase in the probability of complications (PI) for the HN tumor case. However, in plan optimization and evaluation, when tolerance doses were compared with the respective planned EQD2 (calculated from the 3-dimensional dose distribution), PB increased by 19.3% in the HN, 12.5% in the lung, 6.2% in the breast and 2.7% in the prostate tumor case, respectively. The corresponding increases in PI were 2.3%, 6.2%, 1.0% and 0.7%, respectively. Incorporating voxel-based fractionation corrections in plan optimization is important to be able to show the clinical quality of a given plan against established tolerance constraints. To properly compare different plans, their dose distributions should be converted to a common fractionation scheme (e.g. 2 Gy per fraction) for which the doses have been associated with clinical outcomes.