Radiation treatment planning with embedded dose escalation

Background: Heterogeneous target doses are a common by-product from attempts to improve normal tissue sparing in radiosurgery treatment planning. These regions of escalated dose within the target may increase tumor control probability (TCP). Purposely embedding hot spots within tumors during optimization may also increase the TCP. This study discusses and compares five optimization approaches that not only eliminate homogeneity constraints, but also maximize heterogeneity and internal dose escalation. Methods: Co-planar volumetric modulated arc therapy (VMAT) plans were produced for virtual spherical targets with 2-8 cm diameters, minimum target dose objectives of 25 Gy, and objectives to minimize normal tissue dose. Five other sets of plans were produced with additional target dose objectives: 1) minimum dose-volume histogram (DVH) objective on 10% of the target 2) minimum dose objective on a sub-structure within the target, and 3-5) minimum generalized equivalent uniform dose (gEUD) objectives assuming three different volume-effect parameters. Plans were normalized to provide equivalent maximum OAR dose and were compared in terms of target D0.1 cc, ratio of V12.5 Gy to PTV volume (R50%), monitor units per 5 Gy fraction (MU), and mean multi-leaf collimator (MLC) segment size. All planning approaches were also applied to a clinical patient dataset and compared. Results: Mean ± standard deviation metrics achievable using the baseline and experimental approaches 1-5) included D0.1 cc: 27.7 ± 0.8, 64.6 ± 10.5, 56.5 ± 10.3, 48.9 ± 5.7, 44.8 ± 5.0, and 37.4 ± 4.5 Gy. R50%: 4.64 ± 3.27, 5.15 ± 2.32, 4.83 ± 2.64, 4.42 ± 1.83, 4.45 ± 1.88, and 4.21 ± 1.75. MU: 795 ± 27, 1988 ± 222, 1766 ± 259, 1612 ± 112, 1524 ± 90, and 1362 ± 146. MLC segment size: 4.7 ± 1.6, 2.3 ± 0.7, 2.6 ± 0.8, 2.7 ± 0.7, 2.7 ± 0.8, and 2.8 ± 0.8 cm. Conclusions: The DVH-based approach provided the highest embedded doses for all target diameters and patient example with modest increases in R50%, achieved by decreasing MLC segment size while increasing MU. These results suggest that embedding doses > 220% of tumor margin dose is feasible, potentially improving TCP for solid tumors.