Page 271 - 2014 Printable Abstract Book
P. 271
significant drop in hemoglobin saturation of about 30% after 10 Gy over the time scale of less than 30
minutes. 2. The averaged R2* within the tumor volume increased by 15% after irradiation, which is
consistent with the optical results. 3. Irradiation sharply reduced the mean fluorescent lifetime of NADH
in the same way as KCN, indicating a radiation induced alteration in metabolism towards glycolysis. The
simulations and experiments support dynamic metabolic changes and/or fast vasoconstrictive signals that
are occurring within 30 minutes of radiation and that change the oxygen concentrations, independent of
cell death or proliferation. This dynamic change is likely important for patient specific adaptive therapy,
especially for large doses per fraction such as applied in SBRT. For hypofractionated therapy, the local
instantaneous oxygen concentration is likely the most important variable to control. Measuring the
instantaneous response to large radiation doses would be an important step to future improvements in
outcome for these emerging therapy dose schedules.
(PS4-62) Modeling the hematopoietic effects of combined burn and radiation injury. Jacqueline M.
Wentz; Darren Oldson, PhD; and Daniela Stricklin, PhD, Applied Research Associates, Arlington, VA
Our group is developing mechanistic, physiologically based computational models to understand
the impact of radiation/burn combined injury and help predict casualties associated with catastrophic
scenarios. Radiation and burn alone have profound effects on the hematopoietic system, but little is
understood about the potential synergistic effects of these insults. Models of hematopoiesis that describe
key physiological responses associated with radiation and burn individually provide a means for
understanding and predicting potential hematopoietic effects after radiation and burn combined injury.
We have developed three mechanistic models that simulate granulopoiesis, lymphopoiesis, and
thrombopoiesis following radiation and burn combined injury. Given a specified radiation dose and burn
size, these models predict cell kinetics for each of these lines. Output from these models may help predict
both probability of mortality and time to mortality. Each model has been parameterized using individual
data from at least 16 case studies of radiation victims with doses ranging from 0.12 to 12.5 Gy.
Optimization of burn injury parameters was performed using mean values from at least three separate
burn-size groups. Other radiation and burn studies were reserved for model validation. The models
accurately predict key trends in blood cell counts observed following a radiation or burn insult. When
combining the two injuries in the model, we can predict how combined injury affects blood cell kinetics.
This capability could facilitate disaster preparedness planning.
(PS4-63) Defining how radiation delivery alters the tumor microenvironment: studies using a murine
1
1
2
1;2
model. Jonathan L. Kane ; Sarah A. Krueger ; George D. Wilson ; Gerard Madlambayan ; and Brian
1
2
Marples, Beaumont Health System, Royal Oak, MI and Oakland University, Rochester, MI
1
Previous work from our group has indicated that pulsed radiation therapy (PRT) preserves tumor
vasculature and reduces the development of radiation-induced hypoxia. To define the mechanism of this
phenomenon, we investigated the effects of PRT and continuously-delivered standard radiation therapy
(SRT) on hypoxia-induced angiogenic cytokine expression using a syngeneic murine tumor model. C57BL/6
6
female mice were transplanted subcutaneously with 2e Lewis lung carcinoma cells in the rear flank.
3
Tumors were allowed to grow to 100-200mm before irradiation with a 160 kVp Faxitron cabinet (HVL:
0.77 mm Cu) using a dose rate of 0.69 Gy/min. Treatment consisted of 2 Gy/day (either PRT or SRT) given
269 | P a g e
minutes. 2. The averaged R2* within the tumor volume increased by 15% after irradiation, which is
consistent with the optical results. 3. Irradiation sharply reduced the mean fluorescent lifetime of NADH
in the same way as KCN, indicating a radiation induced alteration in metabolism towards glycolysis. The
simulations and experiments support dynamic metabolic changes and/or fast vasoconstrictive signals that
are occurring within 30 minutes of radiation and that change the oxygen concentrations, independent of
cell death or proliferation. This dynamic change is likely important for patient specific adaptive therapy,
especially for large doses per fraction such as applied in SBRT. For hypofractionated therapy, the local
instantaneous oxygen concentration is likely the most important variable to control. Measuring the
instantaneous response to large radiation doses would be an important step to future improvements in
outcome for these emerging therapy dose schedules.
(PS4-62) Modeling the hematopoietic effects of combined burn and radiation injury. Jacqueline M.
Wentz; Darren Oldson, PhD; and Daniela Stricklin, PhD, Applied Research Associates, Arlington, VA
Our group is developing mechanistic, physiologically based computational models to understand
the impact of radiation/burn combined injury and help predict casualties associated with catastrophic
scenarios. Radiation and burn alone have profound effects on the hematopoietic system, but little is
understood about the potential synergistic effects of these insults. Models of hematopoiesis that describe
key physiological responses associated with radiation and burn individually provide a means for
understanding and predicting potential hematopoietic effects after radiation and burn combined injury.
We have developed three mechanistic models that simulate granulopoiesis, lymphopoiesis, and
thrombopoiesis following radiation and burn combined injury. Given a specified radiation dose and burn
size, these models predict cell kinetics for each of these lines. Output from these models may help predict
both probability of mortality and time to mortality. Each model has been parameterized using individual
data from at least 16 case studies of radiation victims with doses ranging from 0.12 to 12.5 Gy.
Optimization of burn injury parameters was performed using mean values from at least three separate
burn-size groups. Other radiation and burn studies were reserved for model validation. The models
accurately predict key trends in blood cell counts observed following a radiation or burn insult. When
combining the two injuries in the model, we can predict how combined injury affects blood cell kinetics.
This capability could facilitate disaster preparedness planning.
(PS4-63) Defining how radiation delivery alters the tumor microenvironment: studies using a murine
1
1
2
1;2
model. Jonathan L. Kane ; Sarah A. Krueger ; George D. Wilson ; Gerard Madlambayan ; and Brian
1
2
Marples, Beaumont Health System, Royal Oak, MI and Oakland University, Rochester, MI
1
Previous work from our group has indicated that pulsed radiation therapy (PRT) preserves tumor
vasculature and reduces the development of radiation-induced hypoxia. To define the mechanism of this
phenomenon, we investigated the effects of PRT and continuously-delivered standard radiation therapy
(SRT) on hypoxia-induced angiogenic cytokine expression using a syngeneic murine tumor model. C57BL/6
6
female mice were transplanted subcutaneously with 2e Lewis lung carcinoma cells in the rear flank.
3
Tumors were allowed to grow to 100-200mm before irradiation with a 160 kVp Faxitron cabinet (HVL:
0.77 mm Cu) using a dose rate of 0.69 Gy/min. Treatment consisted of 2 Gy/day (either PRT or SRT) given
269 | P a g e
