Fig 1.
Radial distribution of vascular fraction and tumor cell density in the investigated virtual tumors prior to irradiation.
Left axis: homogeneous (o) and inhomogeneous (.) tumor cell density distributions, ρ. Right axis: homogeneous (*) and inhomogeneous (□) vascular fraction distributions, vf. Each tumor consist of a combination of one vf and ρ profiles (see text for details).
Table 1.
Biological parameters used for the simulations.
Fig 2.
Time points of dose optimization within the investigated treatment schedules.
Vertical arrows indicate the days (represented with dots) when dose optimization was performed. The optimized distributions are applied in all the treatment fractions from the day of optimization until a new optimization is performed. Note: No irradiations were performed at weekend (dots in red) and after 3 weeks (FBF3W) or 4 weeks (all other schedules), fractions were delivered with uniform dose (u.d. = 2Gy). The response of each virtual tumor was simulated for a uniform dose distribution as well as for the five adaptive schemes (1F, 2F, 3F, FBF3W and FBF4W) optimizing the dose distribution either with OFsurv and OFstd.
Fig 3.
Tumor response to a uniform dose distribution.
(a) Number of surviving tumor cells with time for the 4 tumor types irradiated with a uniform dose distribution. The weekend treatment breaks lead to small plateaus in the cells survival curves, in which the number of tumor cells increases slightly due to proliferation. (b) TCP curves for the simulated tumors and experimental response of a 200 mm3 xenograft of the H&N FaDu line [67]. The D50conv values (in Gy) of the simulated TCP curves are 68.6 ± 1.4, 65.6 ± 2.1, 71.3 ± 2.0 and 66.0 ± 2.0, for T1, T2, T3 and T4 respectively.
Fig 4.
Radiation induced reoxygenation in the investigated virtual tumors.
Evolution of the vascular fraction (averaged in the 1 cm diameter tumor core) for the 4 tumors when irradiated with a uniform dose distribution.
Fig 5.
Treatment gains obtained for the studied tumors (T1-T4) using dose distributions optimized with either OFsurv (∘) or OFstd (*) under different adaptive schemes.
Fig 6.
Sthocastic and population radiosensitivity variability effects.
Response curves for tumor T1 when irradiated with the FBF4W scheme using OFsurv. Solid line, treatment response achieved when the treatment is optimized using the population-averaged radiosensitivity α; dashed line, TCP curve calculated using the same population-averaged radiosensitivity (the cell killing stochasticity produces the shallowing and displacement towards higher dose of the response curve); and dashed-dotted line, TCP curve calculated for a population with a normally distributed α radiosensitivity parameter (further shallowing and displacement).
Fig 7.
Impact of the adaptive scheme on treatment gain.
Treatment gains associated to the DPBN treatments under the adaptive schemes 3F, FBF3W and FBF4W. Tumors ordered on the x-axis by ascending reoxygenation capability.