2625
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collagen deposition, and macrophage activation at 10 weeks post-RT. The use of amifostine as a radioprotectant may be useful in the prophylaxis of radiation induced esophageal injury. Author Disclosure: B. Thrasher, None; M. Brizel, None; Z. Vujaskovic, None; D. Brizel, Medimmune Inc., B. Research Grant. 2625 A Bench-Top “Micro” Image Guided Radiation Therapy (IGRT) System for Laboratory Animals J. W. Wong 1 , E. A. Armour 1 , E. Tryggestad 1 , H. Deng 1 , C. Kennedy 1 , E. Ford 1 , T. McNutt 1 , I. Iordachita 2 , P. Kazanzides 2 , T. L. DeWeese 1 1 Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD, 2 Computer Science Engineering Research Center, Johns Hopkins University, Baltimore, MD Purpose/Objective(s): To construct a bench-top IGRT system that complements advanced small animal imaging systems for conducting discovery and translational research using radiation alone or in conjunction with bio-molecular imaging and therapeutic agents. Materials/Methods: The IGRT system employs a single constant voltage 225 kVp x-ray source. An 80 kVp beam from a 0.4 mm focal spot is used for imaging; a 225 kVp beam from a 3 mm focal spot is used for irradiation. A gantry provides limited 90° rotation of the x-ray source from the AP to the LAT direction with an isocenter of 35 cm. Computer controlled translation and rotation stages are used to position the animal. On-board cone-beam CT (CBCT) imaging ensures accurate repeat irradiation and co-registration with other imaging studies. A novel approach of CBCT acquisition is devised where only the animal is rotated with the x-ray source and detector stationary at the LAT position. A mirror-CCD fluoroscopic system is used for projection image acquisition. Conformal irradiation capability accommodates field dimensions from 60 to 1 mm. Beams are collimated with brass blocks or with a novel graphite x-ray focusing lens. Volumetric CT-based treatment planning for small animals is used to design beam arrangements that conform dose distributions to a tumor or normal tissue target. Near water equivalent radiochromic EBT films are used for dosimetry measurements. Pencil beam dose calculations are employed for the smallest (1 mm) beam; while Monte Carlo methods are employed for the larger conformal beams. Dose calculations and treatment planning are performed on a research Pinnacle system. Feasibility imaging and irradiation experiments are conducted with euthanized rodents. Results: CBCT images with 0.5 mm voxel resolution and adequate quality for guidance were reconstructed using the novel animal rotation setup. Each CBCT session imparts 20 cGy at mid-plane, and is considered acceptable for limited repeat imaging. The collimated beams are diverging. At 35 cm SAD, the dose output in water at 5 mm depth is 300 cGy/min for square fields with sides ranging from 60 to 3 mm. The profile of the smallest collimated beam of 1 mm diameter is “peaky” with a full width at half max (FWHM) of 1.5 mm over first 20 mm depth. Using a descriptor of the average dose within a 1.5 mm diameter area, the dose at 5 and 20 mm depths were 160 and 100 cGy/min respectively. The focusing lens produces an x-ray pencil beam of 40 – 80 keV photons from 32.5 to 35.5 cm downstream from the source. It also has a FWHM of 1.5 mm which is maintained over its 4 cm focal length. The 1.5 cm area dose rate at 5 and 20 mm depths were 175 and 75 cGy/min respectively. Although dosimetrically similar, the 1 mm collimated beam is considerably simpler to deploy than the focused beam. Monte Carlo dose calculations for the 225 kVp beams were performed for treatment planning. Calculations of relative dosimetry agreed with measurements to about 10%. Conclusions: We have demonstrated the full imaging, planning and delivery capabilities of our IGRT system. The compact bench-top design readily allows set up inside an animal barrier along with other research imaging systems. The use of a flat panel detector for imaging and deployment as a self-shielded cabinet system will further enhance its utility. Focal irradiation with live laboratory mice is on-going and is the subject of a separate ASTRO abstract submission. Supported in part by NCI R01–108449. Author Disclosure: J.W. Wong, None; E.A. Armour, None; E. Tryggestad, None; H. Deng, None; C. Kennedy, None; E. Ford, None; T. McNutt, None; I. Iordachita, None; P. Kazanzides, None; T.L. DeWeese, None. 2626 c-MET Inhibition Radiosensitizes Melanoma by Inhibiting Double Strand DNA Repair J. Welsh, D. Mahadevan, G. Dougherty, B. Stea University of Arizona Health Sciences Ctr., Tucson, AZ Purpose/Objective(s): Melanoma has proven relatively resistant to current cytotoxic therapies, while multiple mechanisms undoubtedly contribute to this process, the ability to effectively repair sublethal damage appears to be of particular importance. Signal transduction via the receptor tyrosine kinase c-Met has been shown, to confer protection from cytotoxic response triggered by DNA damage. Thus inhibiting c-Met may radiosensitize resistant tumor types such as melanoma. The small Histologic analysis 10 weeks post-RT Treatment Group Submucosal Collagen Tunica Muscularis Damage Inflammatory Response (Mean Counts per Field) Control 0.38 0.24 0.27 0.10 24.37 2.14 Amifostine Only 0.52 0.16 0.23 0.07 32.46 1.77 RT Placebo 1.71 0.18 1.26 0.13 68.60 5.75 RT Amifostine 1.10 0.14 0.60 0.10 41.83 2.53 S557 Proceedings of the 48th Annual ASTRO Meeting
Transcript of 2625
collagen deposition, and macrophage activation at 10 weeks post-RT. The use of amifostine as a radioprotectant may be usefulin the prophylaxis of radiation induced esophageal injury.
Author Disclosure: B. Thrasher, None; M. Brizel, None; Z. Vujaskovic, None; D. Brizel, Medimmune Inc., B. Research Grant.
2625 A Bench-Top “Micro” Image Guided Radiation Therapy (�IGRT) System for Laboratory Animals
J. W. Wong1, E. A. Armour1, E. Tryggestad1, H. Deng1, C. Kennedy1, E. Ford1, T. McNutt1, I. Iordachita2,P. Kazanzides2, T. L. DeWeese1
1Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD,2Computer Science Engineering Research Center, Johns Hopkins University, Baltimore, MD
Purpose/Objective(s): To construct a bench-top �IGRT system that complements advanced small animal imaging systems forconducting discovery and translational research using radiation alone or in conjunction with bio-molecular imaging andtherapeutic agents.
Materials/Methods: The �IGRT system employs a single constant voltage 225 kVp x-ray source. An 80 kVp beam from a 0.4mm focal spot is used for imaging; a 225 kVp beam from a 3 mm focal spot is used for irradiation. A gantry provides limited90° rotation of the x-ray source from the AP to the LAT direction with an isocenter of 35 cm. Computer controlled translationand rotation stages are used to position the animal. On-board cone-beam CT (CBCT) imaging ensures accurate repeat irradiationand co-registration with other imaging studies. A novel approach of CBCT acquisition is devised where only the animal isrotated with the x-ray source and detector stationary at the LAT position. A mirror-CCD fluoroscopic system is used forprojection image acquisition. Conformal irradiation capability accommodates field dimensions from 60 to 1 mm. Beams arecollimated with brass blocks or with a novel graphite x-ray focusing lens. Volumetric CT-based treatment planning for smallanimals is used to design beam arrangements that conform dose distributions to a tumor or normal tissue target. Near waterequivalent radiochromic EBT films are used for dosimetry measurements. Pencil beam dose calculations are employed for thesmallest (�1 mm) beam; while Monte Carlo methods are employed for the larger conformal beams. Dose calculations andtreatment planning are performed on a research Pinnacle system. Feasibility imaging and irradiation experiments are conductedwith euthanized rodents.
Results: CBCT images with 0.5 mm voxel resolution and adequate quality for guidance were reconstructed using the novelanimal rotation setup. Each CBCT session imparts 20 cGy at mid-plane, and is considered acceptable for limited repeat imaging.The collimated beams are diverging. At 35 cm SAD, the dose output in water at 5 mm depth is �300 cGy/min for square fieldswith sides ranging from 60 to 3 mm. The profile of the smallest collimated beam of 1 mm diameter is “peaky” with a full widthat half max (FWHM) of 1.5 mm over first 20 mm depth. Using a descriptor of the average dose within a 1.5 mm diameter area,the dose at 5 and 20 mm depths were 160 and 100 cGy/min respectively. The focusing lens produces an x-ray pencil beam of40–80 keV photons from 32.5 to 35.5 cm downstream from the source. It also has a FWHM of 1.5 mm which is maintainedover its 4 cm focal length. The 1.5 cm area dose rate at 5 and 20 mm depths were 175 and 75 cGy/min respectively. Althoughdosimetrically similar, the 1 mm collimated beam is considerably simpler to deploy than the focused beam. Monte Carlo dosecalculations for the 225 kVp beams were performed for treatment planning. Calculations of relative dosimetry agreed withmeasurements to about 10%.
Conclusions: We have demonstrated the full imaging, planning and delivery capabilities of our �IGRT system. The compactbench-top design readily allows set up inside an animal barrier along with other research imaging systems. The use of a flatpanel detector for imaging and deployment as a self-shielded cabinet system will further enhance its utility. Focal irradiationwith live laboratory mice is on-going and is the subject of a separate ASTRO abstract submission.
Supported in part by NCI R01–108449.
Author Disclosure: J.W. Wong, None; E.A. Armour, None; E. Tryggestad, None; H. Deng, None; C. Kennedy, None; E. Ford,None; T. McNutt, None; I. Iordachita, None; P. Kazanzides, None; T.L. DeWeese, None.
2626 c-MET Inhibition Radiosensitizes Melanoma by Inhibiting Double Strand DNA Repair
J. Welsh, D. Mahadevan, G. Dougherty, B. Stea
University of Arizona Health Sciences Ctr., Tucson, AZ
Purpose/Objective(s): Melanoma has proven relatively resistant to current cytotoxic therapies, while multiple mechanismsundoubtedly contribute to this process, the ability to effectively repair sublethal damage appears to be of particular importance.Signal transduction via the receptor tyrosine kinase c-Met has been shown, to confer protection from cytotoxic responsetriggered by DNA damage. Thus inhibiting c-Met may radiosensitize resistant tumor types such as melanoma. The small
Histologic analysis 10 weeks post-RT
Treatment GroupSubmucosal
CollagenTunica Muscularis
DamageInflammatory Response(Mean Counts per Field)
Control 0.38 � 0.24 0.27 � 0.10 24.37 � 2.14Amifostine Only 0.52 � 0.16 0.23 � 0.07 32.46 � 1.77RT � Placebo 1.71 � 0.18 1.26 � 0.13 68.60 � 5.75RT � Amifostine 1.10 � 0.14 0.60 � 0.10 41.83 � 2.53
S557Proceedings of the 48th Annual ASTRO Meeting
