Page 214 - 2014 Printable Abstract Book
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using collagen matrix, physioxia (2% O2) and well defined chondrosarcoma cell lines or primary
chondrocytes from healthy donors, we developed a pertinent in vitro 3D model for radiobiology studies.
With this engineered cartilage and the corresponding 2D cells as an internal control, we study the impact
of ionizing radiations on cell fate. We use a physical dose of 2 Gy and radiations at different LETs (Linear
Energy Transfer): X-rays (0.2 keV/µm) as radiation exposure control and heavy ions (30-40 keV/µm or 80-
90 keV/µm) to mimic energy distribution in healthy cartilage and the tumor during hadrontherapy with
carbon ions. As expected, results show that, 2D cells are more resistant to X-rays than carbon ions
(clonogenic assay, RBE from 2 to 3.5). Furthermore, both 2D primary chondrocytes and chondrosarcoma
cell line are more resistant to 30-40 keV/µm irradiations than 80-90 keV/µm irradiations for the same
physical dose. However, 3D models cell survivals (necrosis and viability) do not show such differences.
Thus, it may explain some discrepancies between canonical radiobiology studies and clinical data. We are
currently analyzing samples from 2D and 3D systems to investigate protein expression kinetics implicated
in cell damage responses at different LETs.
(PS3-43) Pulmonary vascular pruning in response to radiation. Matthew Wilhelm; Dustin Begosh-Mayne;
Walter O'Dell, PhD; Dept. of Radiation Oncology, Gainesville, FL
Background: The lungs are highly sensitive to radiation. Following irradiation, acute endothelial
cell damage and inflammatory responses are associated with increased production of IL-6 and TNFα and
lead to blockage of the lumen of small arterioles. We believe that the long-term vascular response to
radiation is similar to that seen with chronic pulmonary arterial hypertension (PAH) where permanent
occlusion leads to resorption (pruning) of microvessels and an unfavorable cycle of increased vascular
resistance, leading to increased arterial pressure, escalating damage to the vascular endothelium, and
progressive pruning. Accurate quantification of the vascular tree structure may enhance our ability to
understand the biological and biomechanical underpinnings of tissue radiation response and the sequelae
of events that lead to progressive vascular degeneration and the late effects of irradiation.
Methods: Our team recently solved the technical challenges of extracting and characterizing vascular tree
structures in 3D from clinical X-ray computed tomography images of the chest. The image processing tools
were created in-house as a culmination of a decade of software development to investigate lung radiation
dose response and vascular changes with PAH. We have employed these tools to characterize acute and
chronic changes to pulmonary vascular structure in cancer patients receiving either whole-lung radiation
or high-dose stereotactic radiation therapy (SRT) to local targets in the lung.
Results: We observed a substantial decrease in the number of small (0.7 to 1.5 mm radius) vessels that
were apparent at 2-3 months after radiation exposure and were maximal at 7-9 months. The number of
small vessels then increased through 10-14 months after exposure and appeared to level off after 14
months, out to our longest follow-up of 17 months. Conclusions: These observations are consistent with
the expectation of radiation-induced vascular pruning with partial recovery. In patients receiving SRT, the
decrease in the number of small vessels occurs before the appearance of radiation-induced fibrosis.
Future work will investigate the relationship between vascular changes and radiation dose and the
association between early-stage pruning and the development of radiation-induced fibrosis at later time
points.
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chondrocytes from healthy donors, we developed a pertinent in vitro 3D model for radiobiology studies.
With this engineered cartilage and the corresponding 2D cells as an internal control, we study the impact
of ionizing radiations on cell fate. We use a physical dose of 2 Gy and radiations at different LETs (Linear
Energy Transfer): X-rays (0.2 keV/µm) as radiation exposure control and heavy ions (30-40 keV/µm or 80-
90 keV/µm) to mimic energy distribution in healthy cartilage and the tumor during hadrontherapy with
carbon ions. As expected, results show that, 2D cells are more resistant to X-rays than carbon ions
(clonogenic assay, RBE from 2 to 3.5). Furthermore, both 2D primary chondrocytes and chondrosarcoma
cell line are more resistant to 30-40 keV/µm irradiations than 80-90 keV/µm irradiations for the same
physical dose. However, 3D models cell survivals (necrosis and viability) do not show such differences.
Thus, it may explain some discrepancies between canonical radiobiology studies and clinical data. We are
currently analyzing samples from 2D and 3D systems to investigate protein expression kinetics implicated
in cell damage responses at different LETs.
(PS3-43) Pulmonary vascular pruning in response to radiation. Matthew Wilhelm; Dustin Begosh-Mayne;
Walter O'Dell, PhD; Dept. of Radiation Oncology, Gainesville, FL
Background: The lungs are highly sensitive to radiation. Following irradiation, acute endothelial
cell damage and inflammatory responses are associated with increased production of IL-6 and TNFα and
lead to blockage of the lumen of small arterioles. We believe that the long-term vascular response to
radiation is similar to that seen with chronic pulmonary arterial hypertension (PAH) where permanent
occlusion leads to resorption (pruning) of microvessels and an unfavorable cycle of increased vascular
resistance, leading to increased arterial pressure, escalating damage to the vascular endothelium, and
progressive pruning. Accurate quantification of the vascular tree structure may enhance our ability to
understand the biological and biomechanical underpinnings of tissue radiation response and the sequelae
of events that lead to progressive vascular degeneration and the late effects of irradiation.
Methods: Our team recently solved the technical challenges of extracting and characterizing vascular tree
structures in 3D from clinical X-ray computed tomography images of the chest. The image processing tools
were created in-house as a culmination of a decade of software development to investigate lung radiation
dose response and vascular changes with PAH. We have employed these tools to characterize acute and
chronic changes to pulmonary vascular structure in cancer patients receiving either whole-lung radiation
or high-dose stereotactic radiation therapy (SRT) to local targets in the lung.
Results: We observed a substantial decrease in the number of small (0.7 to 1.5 mm radius) vessels that
were apparent at 2-3 months after radiation exposure and were maximal at 7-9 months. The number of
small vessels then increased through 10-14 months after exposure and appeared to level off after 14
months, out to our longest follow-up of 17 months. Conclusions: These observations are consistent with
the expectation of radiation-induced vascular pruning with partial recovery. In patients receiving SRT, the
decrease in the number of small vessels occurs before the appearance of radiation-induced fibrosis.
Future work will investigate the relationship between vascular changes and radiation dose and the
association between early-stage pruning and the development of radiation-induced fibrosis at later time
points.
212 | P a g e
