Page 209 - 2014 Printable Abstract Book
P. 209
12
were treated once with increasing single doses of either C-ions or 6 MeV photons. Primary endpoint was
local tumor control within 300 days. In case of H-tumors, absence of BrdU-positivity on the histological
level was used as secondary endpoint. RBEs were calculated based on TCD50-values (dose to achieve 50%
12
12
tumor control probability) of photons and C-ions. Results: Local tumor control was achieved with C-
12
ions and photons in all three sublines showing a higher effectiveness of C-ions. The RBE for local tumor
control increased from 1.62 ± 0.11 (H) to 2.08 ± 0.13 (HI) to 2.30 ± 0.08 (AT1). Using histological tumor
control, the RBE for the H-tumor increased to 1.80 ± 0.13. Variation of TCD50-values between tumor
12
12
sublines was significantly smaller after C-ions than after photon irradiation. Conclusions: RBE of C-ions
in tumors was highest for the radioresistant anaplastic AT1-tumor and smallest for the well-differentiated
H-tumor, which indicates a clear correlation between decreasing differentiation status and increasing RBE.
12 C-ions may therefore be beneficial especially in undifferentiated tumors, which are highly resistant
against photon irradiation. Changes of RBE with tumor differentiation were predominantly caused by
12
changes in the photon response. This supports the assumption that the response to C- irradiation is less
dependent on tumor heterogeneity than that for photons. Thus heterogeneities within patient
populations or the existence of radioresistant sub-populations within single tumors may be expected to
have less impact on the radiation response. The underlying differential mechanisms are currently analyzed
in ongoing structural and functional longitudinal experiments.
(PS3-34) Circulating tumor DNA in mice after various radiation dose schedules. Mei Zhang, MD; Yansong
Guo, PhD; Steven B. Zhang, DVM, PhD; Shanmin Yang, MD; Zhenhuan Zhang, MD, PhD; Steven G. Swarts,
PhD; Lurong Zhang, MD, PhD; and Paul Okunieff, MD,UF Shands Cancer Center, Gainesville, FL
Purpose: To examine whether tumor response can be measured using circulating DNA. Human
tumor circulating DNA after hypofractionated and hyperfractionated irradiation was measured in a
murine allograph model with human DNA probes. Methods/Materials: Nude mice were inoculated with
PC-3 cancer cells in the right hind leg. 15 days after grafting, mice were treated as follows: 1.No tumor
groups: 2 fractions of 15 Gy or 15 fractions of 2 Gy to the right hind leg. 2. High-dose hypofractionated
group: 2 weekly 15 Gy fractions to the tumor. 3. Low-dose hyperfactionated group: 15 daily 2 Gy fractions
to the tumor. 4. Sham radiation control: Mice with tumors were sham irradiated for a time equal to that
of the irradiated mice. To determine a baseline DNA level, we collected plasma on day 0 before tumor
implantation. To monitor the tumor response, plasma was collected daily from days 15-35 and 9 hr after
fractional irradiation. Previous studies show that 9 hr is when peak DNA release occurs. Body weights
were recorded. Tumor size was determined from twice weekly vernier caliper measurements. Tumor DNA
concentration was determined by QuantiDNA. The DNA concentration and tumor volume for each mouse
were plotted. To determine the relationship between tumor DNA release and radiation dose, DNA
concentrations were also plotted against the dose. Results: 1.In the high-dose hypofractionated group,
st
tumor volume reached its peak at approximately 18 days after implantation (3 days after the 1 15 Gy
fraction) and then decreased dramatically. In both hyperfractionated groups, the tumor volume peaked
approximately 22 days after irradiation and then decreased. In the sham radiation control, the tumor
volume increased through day 38. 2. In the hypofractionated group, DNA release was substantial and
brisk; however, in the low-dose hyperfractionated group, DNA was gradually sustained when the dose
accumulated to 10-12 Gy. Minimal murine DNA was seen in the blood at any time. 3. In the sham radiation
group, no tumor DNA was detected until day 30. As the tumor grew, DNA release increased. Conclusions:
Tumor growth and treatment response can increase circulating DNA. Radiation response represents a
207 | P a g e
were treated once with increasing single doses of either C-ions or 6 MeV photons. Primary endpoint was
local tumor control within 300 days. In case of H-tumors, absence of BrdU-positivity on the histological
level was used as secondary endpoint. RBEs were calculated based on TCD50-values (dose to achieve 50%
12
12
tumor control probability) of photons and C-ions. Results: Local tumor control was achieved with C-
12
ions and photons in all three sublines showing a higher effectiveness of C-ions. The RBE for local tumor
control increased from 1.62 ± 0.11 (H) to 2.08 ± 0.13 (HI) to 2.30 ± 0.08 (AT1). Using histological tumor
control, the RBE for the H-tumor increased to 1.80 ± 0.13. Variation of TCD50-values between tumor
12
12
sublines was significantly smaller after C-ions than after photon irradiation. Conclusions: RBE of C-ions
in tumors was highest for the radioresistant anaplastic AT1-tumor and smallest for the well-differentiated
H-tumor, which indicates a clear correlation between decreasing differentiation status and increasing RBE.
12 C-ions may therefore be beneficial especially in undifferentiated tumors, which are highly resistant
against photon irradiation. Changes of RBE with tumor differentiation were predominantly caused by
12
changes in the photon response. This supports the assumption that the response to C- irradiation is less
dependent on tumor heterogeneity than that for photons. Thus heterogeneities within patient
populations or the existence of radioresistant sub-populations within single tumors may be expected to
have less impact on the radiation response. The underlying differential mechanisms are currently analyzed
in ongoing structural and functional longitudinal experiments.
(PS3-34) Circulating tumor DNA in mice after various radiation dose schedules. Mei Zhang, MD; Yansong
Guo, PhD; Steven B. Zhang, DVM, PhD; Shanmin Yang, MD; Zhenhuan Zhang, MD, PhD; Steven G. Swarts,
PhD; Lurong Zhang, MD, PhD; and Paul Okunieff, MD,UF Shands Cancer Center, Gainesville, FL
Purpose: To examine whether tumor response can be measured using circulating DNA. Human
tumor circulating DNA after hypofractionated and hyperfractionated irradiation was measured in a
murine allograph model with human DNA probes. Methods/Materials: Nude mice were inoculated with
PC-3 cancer cells in the right hind leg. 15 days after grafting, mice were treated as follows: 1.No tumor
groups: 2 fractions of 15 Gy or 15 fractions of 2 Gy to the right hind leg. 2. High-dose hypofractionated
group: 2 weekly 15 Gy fractions to the tumor. 3. Low-dose hyperfactionated group: 15 daily 2 Gy fractions
to the tumor. 4. Sham radiation control: Mice with tumors were sham irradiated for a time equal to that
of the irradiated mice. To determine a baseline DNA level, we collected plasma on day 0 before tumor
implantation. To monitor the tumor response, plasma was collected daily from days 15-35 and 9 hr after
fractional irradiation. Previous studies show that 9 hr is when peak DNA release occurs. Body weights
were recorded. Tumor size was determined from twice weekly vernier caliper measurements. Tumor DNA
concentration was determined by QuantiDNA. The DNA concentration and tumor volume for each mouse
were plotted. To determine the relationship between tumor DNA release and radiation dose, DNA
concentrations were also plotted against the dose. Results: 1.In the high-dose hypofractionated group,
st
tumor volume reached its peak at approximately 18 days after implantation (3 days after the 1 15 Gy
fraction) and then decreased dramatically. In both hyperfractionated groups, the tumor volume peaked
approximately 22 days after irradiation and then decreased. In the sham radiation control, the tumor
volume increased through day 38. 2. In the hypofractionated group, DNA release was substantial and
brisk; however, in the low-dose hyperfractionated group, DNA was gradually sustained when the dose
accumulated to 10-12 Gy. Minimal murine DNA was seen in the blood at any time. 3. In the sham radiation
group, no tumor DNA was detected until day 30. As the tumor grew, DNA release increased. Conclusions:
Tumor growth and treatment response can increase circulating DNA. Radiation response represents a
207 | P a g e
