Page 210 - 2014 Printable Abstract Book
P. 210
dramatic pulsatile increase, while tumor growth produces a stable increase. Plasma DNA is a potential
tool to monitor tumor response following irradiation.
(PS3-35) Characterizing ischemia-reperfusion in a human tumor xenograft after single-dose
radiosurgery. Stephen L. Brown; Madhava P. Aryal; Panda Swayamprava; Kelly-Ann Randall; Glauber
Cabral; Tavarekere N. Nagaraja; James R. Ewing; and Jae Ho Kim, Henry Ford Health System, Detroit, MI
Purpose: To characterize blood flow kinetics in a rat brain model of human glioblastoma after a
large single dose of radiation. Methods: Rats were implanted with U251 tumors intracerebrally and
irradiated to either 6 Gy or 20 Gy using a Novalis™ 6MV Linac. Blood flow was measured by MRI using spin
echo arterial spin labeling before radiation exposure and in the same rat either 2, 4, 8, 12 or 24 hours after
radiation exposure. Results: After 20 Gy, tumor blood flow decreased 76 ± 4 % within 2 hours and
remained below pre-irradiation blood flow values for 6 additional hours. Tumor blood flow returned and
eventually overshot pre-irradiation levels such that one day after the radiation exposure, blood flow was
elevated 40% above pre-irradiation values. Blood flow in normal brain irradiated to 20 Gy decreased only
minimally, about 23 ± 5 %, within the range of fluctuations normally observed in cerebral blood flow and
returned to pre-irradiation values, 24 hours after radiation. Unlike tumor blood flow changes after 20 Gy,
tumor blood flow after 6 Gy exposure was unchanged at 2 hours after radiation and at 24 hours after 6
Gy radiation, a small increase in blood flow, 30 ± 6 % above pre-irradiation values, was observed.
Discussion and Conclusion: Large acute blood flow decreases were observed in tumor hours after 20 Gy
irradiation exposure using non-invasive MRI techniques. The large decrease in blood flow was not
observed in tumor at 6 Gy or normal brain at 20 Gy. The changes are consistent with the kinetics of
ischemia-reperfusion (I-R) observed in brain after stroke and cardiac muscle after a heart attack, both of
which lead to I-R tissue injury. The results presented could explain the tumor response of some human
tumors that are particularly sensitive to SRS or SBRT. Grant sponsor: NIH-NCI; MRI Biomarkers of Response
in Cerebral Tumors; R01 CA135329 (JRE).
(PS3-36) Response of a poorly immunogenic breast tumor to the combination of local radiotherapy and
anti-PD-1 immunotherapy. Karsten A. Pilones, MD PhD; Joseph Aryankalayil; Ralph Vatner, MD PhD; Silvia
Formenti, MD; and Sandra Demaria, MD, New York University, New York, NY
Local suppression in the tumor is an important obstacle to immunotherapy. Radiotherapy (RT)
promotes anti-tumor immunity via multiple mechanisms. Pro-inflammatory signals induced in the tumor
in response to RT upregulate molecules that aid tumor recognition, facilitate interaction between tumors
and effector cells (Ruocco et al., J Clin Invest 2012) and induce tumor expression of Programmed Death
Ligand-1 (PDL-1) that hinders elimination by CD8 T cells. PDL-1 binds to PD-1 a checkpoint receptor
upregulated on T cells shortly after activation and expressed at high levels on exhausted T cells. Here we
tested the hypothesis that blocking PD-1 can improve response to RT. Methods: BALB/c mice were
inoculated with TSA breast cancer cells on day 0. When tumors became palpable (day 12) mice were
randomly assigned to one of 4 groups: control, RT, anti-PD-1 mAb and RT+anti-PD-1 mAb. RT was delivered
to the primary tumor in 8 Gy fractions on days 13, 14 and 15. PD-1 blocking mAb RMP1-14 was given on
day 15 and every 4 days thereafter and mice were followed for tumor growth. Some mice were euthanized
on day 20 to characterize tumor-infiltrating lymphocytes and development of tumor epitope (AH1)-
208 | P a g e
tool to monitor tumor response following irradiation.
(PS3-35) Characterizing ischemia-reperfusion in a human tumor xenograft after single-dose
radiosurgery. Stephen L. Brown; Madhava P. Aryal; Panda Swayamprava; Kelly-Ann Randall; Glauber
Cabral; Tavarekere N. Nagaraja; James R. Ewing; and Jae Ho Kim, Henry Ford Health System, Detroit, MI
Purpose: To characterize blood flow kinetics in a rat brain model of human glioblastoma after a
large single dose of radiation. Methods: Rats were implanted with U251 tumors intracerebrally and
irradiated to either 6 Gy or 20 Gy using a Novalis™ 6MV Linac. Blood flow was measured by MRI using spin
echo arterial spin labeling before radiation exposure and in the same rat either 2, 4, 8, 12 or 24 hours after
radiation exposure. Results: After 20 Gy, tumor blood flow decreased 76 ± 4 % within 2 hours and
remained below pre-irradiation blood flow values for 6 additional hours. Tumor blood flow returned and
eventually overshot pre-irradiation levels such that one day after the radiation exposure, blood flow was
elevated 40% above pre-irradiation values. Blood flow in normal brain irradiated to 20 Gy decreased only
minimally, about 23 ± 5 %, within the range of fluctuations normally observed in cerebral blood flow and
returned to pre-irradiation values, 24 hours after radiation. Unlike tumor blood flow changes after 20 Gy,
tumor blood flow after 6 Gy exposure was unchanged at 2 hours after radiation and at 24 hours after 6
Gy radiation, a small increase in blood flow, 30 ± 6 % above pre-irradiation values, was observed.
Discussion and Conclusion: Large acute blood flow decreases were observed in tumor hours after 20 Gy
irradiation exposure using non-invasive MRI techniques. The large decrease in blood flow was not
observed in tumor at 6 Gy or normal brain at 20 Gy. The changes are consistent with the kinetics of
ischemia-reperfusion (I-R) observed in brain after stroke and cardiac muscle after a heart attack, both of
which lead to I-R tissue injury. The results presented could explain the tumor response of some human
tumors that are particularly sensitive to SRS or SBRT. Grant sponsor: NIH-NCI; MRI Biomarkers of Response
in Cerebral Tumors; R01 CA135329 (JRE).
(PS3-36) Response of a poorly immunogenic breast tumor to the combination of local radiotherapy and
anti-PD-1 immunotherapy. Karsten A. Pilones, MD PhD; Joseph Aryankalayil; Ralph Vatner, MD PhD; Silvia
Formenti, MD; and Sandra Demaria, MD, New York University, New York, NY
Local suppression in the tumor is an important obstacle to immunotherapy. Radiotherapy (RT)
promotes anti-tumor immunity via multiple mechanisms. Pro-inflammatory signals induced in the tumor
in response to RT upregulate molecules that aid tumor recognition, facilitate interaction between tumors
and effector cells (Ruocco et al., J Clin Invest 2012) and induce tumor expression of Programmed Death
Ligand-1 (PDL-1) that hinders elimination by CD8 T cells. PDL-1 binds to PD-1 a checkpoint receptor
upregulated on T cells shortly after activation and expressed at high levels on exhausted T cells. Here we
tested the hypothesis that blocking PD-1 can improve response to RT. Methods: BALB/c mice were
inoculated with TSA breast cancer cells on day 0. When tumors became palpable (day 12) mice were
randomly assigned to one of 4 groups: control, RT, anti-PD-1 mAb and RT+anti-PD-1 mAb. RT was delivered
to the primary tumor in 8 Gy fractions on days 13, 14 and 15. PD-1 blocking mAb RMP1-14 was given on
day 15 and every 4 days thereafter and mice were followed for tumor growth. Some mice were euthanized
on day 20 to characterize tumor-infiltrating lymphocytes and development of tumor epitope (AH1)-
208 | P a g e
