Page 208 - 2014 Printable Abstract Book
P. 208
(PS3-31) In vivo effects of lattice radiation therapy on local and distant lung cancer: Potential role of
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1
2
immunomodulation. Seema Gupta ; Saravana Kanagavelu ; Xiaodong Wu ; Sakhi Philip ; James W.
2
2
4
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Hodge ; Mariluz D. Couto ; Kristina D. Chung ; and Mansoor M. Ahmed , Biophysics Research Institute of
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2
America, North Miami Beach, FL ; University of Miami, Miami, FL ; National Cancer Institute, National
3
Institutes of Health, Bethesda, MD ; and National Cancer Institute, National Institutes of Health, Rockville,
MD
4
Radiation is a potent inducer of cytokines and hence has the ability to modulate both adaptive as
well as innate immune responses in a host that elicits cell death upon tumor, stromal and angiogenic
compartments of tumor microenvironment. Here, we test a novel approach of high dose radiation delivery
using three dimensional volume based lattice radiation therapy (LRT) in eliciting both local and
metastatic/distant tumor control through modulation of tumor immune micro-environment. LRT is a
dosimetrically superior 3-dimensional technique for delivery of spatially fractionated radiation, delivering
high radiation dose islands within the tumor, but allowing for maximal normal tissue sparing. To study
such effects of LRT, contra-lateral tumors were implanted in both hind legs of C57BL/6 mice using Lewis
lung carcinoma 1 (LLC1) cells. Mice were divided into five groups: untreated, two 10% of tumor volume
vertices, one 20% vertex, one 50% vertex and 100% open field IR. Tumors implanted in the left leg were
irradiated with a single dose of 20Gy while the tumors in the right leg were left unirradiated. Tumor
growth and regression as well as immune responses in the form of secretion of various cytokines were
determined following radiation treatment. Single fraction, high-dose LRT significantly reduced irradiated
left tumor (local) and unirradiated tumor (distant) growth irrespective of tumor volume irradiated. Mice
treated with two 10% volume vertices elicited a robust anti-tumor immune modulation response both in
the irradiated left tumor and unirradiated right tumor. LRT also induced secretion of cytokines involved
in cell-mediated immune response and increased CD3 infiltration in tumor. Further, serum obtained from
any of the LRT treated mice caused growth inhibition of endothelial cells when compared to serum
obtained from either untreated or open field IR groups. These results suggest that LRT is an effective
treatment modality that leads to both local and metastatic tumor control with evidence that these effects
are most likely mediated by strong cell-mediated immune responses.
(PS3-32) Carbon ions decrease the heterogeneity in tumor radiation response: RBE comparison in three
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prostate tumors differing in progression. Christin Glowa, PhD ; Peter Peschke, PhD ; Stephan Brons,
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PhD ; Peter E. Huber, PhD, MD ; Jürgen Debus, PhD, MD ; and Christian P. Karger, PhD
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German Cancer Research Center, Heidelberg, Germany ; University Hospital of Heidelberg, Heidelberg,
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2
Germany ; and Heidelberg Ion Beam Therapy Center (HIT), Heidelberg, Germany
Background: Morphological and physiological heterogeneity, displayed by many solid tumors
12
poses challenges for the development of successful therapies. Carbon ions ( C-ions) show an increased
relative biological effectiveness (RBE) relative to photons. To compare the impact of differentiation on the
12
RBE, dose-response curves for photons and C-ions were determined for three different rat prostate
adenocarcinomas. Methods: Fresh tumor fragments from three sublines (AT1, HI and H) of the Dunning
prostate tumor R3327 were transplanted s.c. into the distal right thigh of male Copenhagen rats. Tumors
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1
1
2
immunomodulation. Seema Gupta ; Saravana Kanagavelu ; Xiaodong Wu ; Sakhi Philip ; James W.
2
2
4
3
Hodge ; Mariluz D. Couto ; Kristina D. Chung ; and Mansoor M. Ahmed , Biophysics Research Institute of
1
2
America, North Miami Beach, FL ; University of Miami, Miami, FL ; National Cancer Institute, National
3
Institutes of Health, Bethesda, MD ; and National Cancer Institute, National Institutes of Health, Rockville,
MD
4
Radiation is a potent inducer of cytokines and hence has the ability to modulate both adaptive as
well as innate immune responses in a host that elicits cell death upon tumor, stromal and angiogenic
compartments of tumor microenvironment. Here, we test a novel approach of high dose radiation delivery
using three dimensional volume based lattice radiation therapy (LRT) in eliciting both local and
metastatic/distant tumor control through modulation of tumor immune micro-environment. LRT is a
dosimetrically superior 3-dimensional technique for delivery of spatially fractionated radiation, delivering
high radiation dose islands within the tumor, but allowing for maximal normal tissue sparing. To study
such effects of LRT, contra-lateral tumors were implanted in both hind legs of C57BL/6 mice using Lewis
lung carcinoma 1 (LLC1) cells. Mice were divided into five groups: untreated, two 10% of tumor volume
vertices, one 20% vertex, one 50% vertex and 100% open field IR. Tumors implanted in the left leg were
irradiated with a single dose of 20Gy while the tumors in the right leg were left unirradiated. Tumor
growth and regression as well as immune responses in the form of secretion of various cytokines were
determined following radiation treatment. Single fraction, high-dose LRT significantly reduced irradiated
left tumor (local) and unirradiated tumor (distant) growth irrespective of tumor volume irradiated. Mice
treated with two 10% volume vertices elicited a robust anti-tumor immune modulation response both in
the irradiated left tumor and unirradiated right tumor. LRT also induced secretion of cytokines involved
in cell-mediated immune response and increased CD3 infiltration in tumor. Further, serum obtained from
any of the LRT treated mice caused growth inhibition of endothelial cells when compared to serum
obtained from either untreated or open field IR groups. These results suggest that LRT is an effective
treatment modality that leads to both local and metastatic tumor control with evidence that these effects
are most likely mediated by strong cell-mediated immune responses.
(PS3-32) Carbon ions decrease the heterogeneity in tumor radiation response: RBE comparison in three
1
1;2
prostate tumors differing in progression. Christin Glowa, PhD ; Peter Peschke, PhD ; Stephan Brons,
1
1
2
3
PhD ; Peter E. Huber, PhD, MD ; Jürgen Debus, PhD, MD ; and Christian P. Karger, PhD
1
German Cancer Research Center, Heidelberg, Germany ; University Hospital of Heidelberg, Heidelberg,
3
2
Germany ; and Heidelberg Ion Beam Therapy Center (HIT), Heidelberg, Germany
Background: Morphological and physiological heterogeneity, displayed by many solid tumors
12
poses challenges for the development of successful therapies. Carbon ions ( C-ions) show an increased
relative biological effectiveness (RBE) relative to photons. To compare the impact of differentiation on the
12
RBE, dose-response curves for photons and C-ions were determined for three different rat prostate
adenocarcinomas. Methods: Fresh tumor fragments from three sublines (AT1, HI and H) of the Dunning
prostate tumor R3327 were transplanted s.c. into the distal right thigh of male Copenhagen rats. Tumors
206 | P a g e
