PNNL-13501 - Pacific Northwest National Laboratory

To illustrate the potential impact of detailed, threedimensional
tumor response modeling, we used our
modeling tools to examine ways that the temporal and
spatial delivery of radiation to a tumor can be modulated
to improve treatment outcome (Stewart and Traub in
press). Figure 1 shows an illustration of a idealized
cylindrical tumor that has been subdivided into 3,133
rectangular tissue regions. Figure 2 shows the results of
two simulated radiation treatments. The first treatment
design (Figure 2, left panel) shows tumor-cell survival
after a conventional radiation treatment that delivers a
uniform dose of radiation to all parts of the tumor. The
right panel in Figure 2 shows the expected outcome of a
radiation treatment that has been optimized to
preferentially kill the radioresistant tumor cells located in
region 4 (refer to Figure 1). Calculations (Stewart and
Traub in press) suggest that biologically motivated
treatment optimization could potentially improve some
treatment designs by factors on the order of 5 to 20% (isoeffect
dose).
1
4
3
2
Figure 1. Cylindrical tumor model with heterogeneous
biophysical properties (Stewart and Traub in press). The
properties of the tumor cells in the four tumor regions give
the same apparent “intrinsic radiosensitivity,” as
determined by a single acute dose of radiation. However, the
cell density and damage repair characteristics used in the
model are slightly different. For visualization purposes, the
tumor is shown with a section cutout. Tissue region 4 is a
particularly radioresistant portion of the tumor.
Summary and Conclusions
We have successfully demonstrated that detailed
molecular and cellular dose-response models can be
integrated into three-dimensional tissue simulations.
Although calculations to date have focused on high-dose
exposure conditions such as those found in radiation
therapy, the basic framework of our model is equally
applicable to low-dose exposure conditions. In fiscal year
2000, we plan to conduct several experiments to collect
the data needed to further refine and test the damage
repair model so that it is more useful for low-dose
exposure studies and also for combined exposure to
radiation and benzene, an organic solvent commonly
found at many DOE sites.
References
Deschavanne PJ, B Fertil, N Chavaudra, and EP Malaise.
1990. The relationship between radiosensitivity and
repair of potentially lethal damage in human tumor cell
lines with implications for radioresponsiveness.” Radiat.
Res. 122(1): 29-37.
Stewart RD, and RJ Traub. “Radiobiological Modeling in
Voxel Constructs.” In Proceedings of the MC2000. An
International Conference on Advanced Monte Carlo for
Radiation Physics, Particle Transport Simulation and
Applications. October 23-26, 2000 Lisbon, Portugal (in
press).
Publications and Presentations
Marler RT and RD Stewart. “A Quasi-Newton code
package to find the minimum value of a function.”
software package completed and benchmarked. User
manual in progress.
Marler RT and RD Stewart. “GACM: A genetic
algorithm code model to locate the global minimum of a
multidimensional function.” Initial version of software
completed. Code testing and user manual in progress.
Stewart RD. 1999. “On the complexity of the DNA
damages created by endogenous processes.” Radiat. Res.
152(1), 101-105.
Stewart RD, JK Shultis, and BA Montelone. 2000. A
kinetic biological effects model for quiescent cells.
PNNL-13258, Pacific Northwest National Laboratory,
Richland, Washington.
Stewart RD and RJ Traub R.J. “Temporal optimization
of radiotherapy treatment fractions.” In Proceedings of
the ANS (RPS 2000). Radiation Protection for our
National Priorities, Medicine, the Environment, and the
Legacy, Spokane, Washington, September 17-21, 2000
(in press).
Human Health and Safety 295