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Neutron Production with Carbon Therapy Beams
Proceedings of the 50th Annual ASTRO Meeting Materials/Methods: Three tumors of human origin, an ependymoblastoma (EB) with wild-type p53, a primitive neuroectodermal tumor (PNET) with wild-type p53, and a glioblastoma (GB) with mutant-type p53, were transplanted to nude mice subcutaneously, and the mice were irradiated with carbon ion beams (290MeV/u, 6cm spread-out Bragg peak) or 200kV X-rays. Tumors were excised 4, 6, or 24 hours after 2 Gy irradiation. A part of each tumor was fixed in formalin and embedded in paraffin for microscopic study. Hematoxylin and eosin staining and TUNEL assay was performed to evaluate microscopic morphological changes and apoptosis. The other part of each tumor was stored in RNA stabilization solution, and total RMA was extracted for cDNA microarray analysis. GeneChip Human Genome U133 Plus 2.0 array (Affymetrix) was utilized to evaluate gene expression profiles following carbon ion beam or X-ray irradiation. Furthermore, hierarchical clustering of the gene expression, gene ontology analysis, and pathway analysis was also performed. Results: Apoptosis increased 4 and 6 hours after irradiation, and then they decreased. The incidences in EB 6 hours after 2 Gy irradiation were 25.2/high power field area (HPF) by carbon ion and 23.5/HPF by X-rays. Those values were 18.0/HPF by carbon ion and 15.0 /HPF by X-rays in PNET, 1.0/HPF by carbon ion and 0.5/HPF by X-rays in GB. The tumors with wild-type p53 showed significant changes in gene expression following irradiation. EB exhibited the most significant changes after carbon ion irradiation. Pathway analysis of up-regulated and down-regulated genes demonstrated that apoptosis, p53 signaling pathway, and cell cycle are involved significantly (p = 0.000). There was little difference between the gene expression profiles induced by carbon ion beams and those by X-rays, but the extent of up- or down-regulation was more evident after carbon ion irradiation than after X-rays. In contrast, GB with mutant-type p53 showed much less change in gene expression after irradiation. Conclusions: The present study demonstrated that most gene expression profiles induced by high LET carbon ion beams are similar to those induced by X-rays in radiosensitive tumors with wild-type p53. Apoptosis, cell cycle, p53 signaling pathways are suggested to be involved. In contrast, limited changes in gene expression were shown in a radioresistant tumor with mutant-type p53 following 2 Gy of carbon ion or X-ray irradiation. Author Disclosure: M. Hasegawa, None; I. Asakawa, None; T. Tamamoto, None; C. Kajitani, None; H. Okada, None; E. Katayama, None; S. Ishiuchi, None; T. Ohno, None; T. Nakano, None; T. Murakami, None.
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Neutron Production with Carbon Therapy Beams
Y. M. Charara1,2, C. Ramsey1, L. Townsend2 1
Thompson Cancer Survival Center, Knoxville, TN, 2University of Tennessee, Knoxville, TN
Purpose/Objective(s): There is currently a great deal of excitement in the radiotherapy community about the potential of charged particles. In proton therapy, secondary neutron production is an area of active research by a multitude of investigators. For carbon ion therapy, there are a limited number of studies on secondary particle production and their biological implications. The purpose of this study was to investigate the production of secondary particles (protons, neutron, and spallation products) for carbon ion beams using the state-of-the-art Monte Carlo code HETC-HEDS. Materials/Methods: HETC-HEDS simulates particle cascades using Monte Carlo to compute the trajectories of the primary particles and all the secondary particles produced in nuclear collisions. Protons, neutrons, p+, p-, m+, m-, light ions, and heavy ions are arbitrarily distributed in angle, energy, and space. Each particle in the cascade is followed until it disappears by escaping from the boundaries of the system, undergoes a nuclear collision or absorption, and comes to rest due to energy losses from ionization and excitation of atomic electrons in the target medium. In the study, an A-150 Tissue Equivalent Plastic cylinder was simulated with a 30 cm radius and a thickness that was greater than the Bragg peak depth. Energies between 290 - 400 MeV/nucleon were used at a 10 MeV/nucleon increment. The fluence, energy distribution, and spatial distributions of neutrons, protons, and heavy particles were analyzed. Results: The secondary particle production increased at a linear rate with increasing carbon energy. Approximately 3.2 neutrons were produced in the phantom for each incident carbon ion for the 290 MeV/nucleon beam, while the 400 MeV/nucleon primary beam produced 5.3 neutrons per incident carbon ion. On average, the neutron production rate increased at a rate of 20% per 10 MeV/nucleon. Secondary protons were created at a rate between 2.62-2.87 particles per carbon ion, while spallation products were created at a rate between 0.20-0.24 particles per carbon ion. The average energies of the neutrons ranged between 488840 MeV, the proton energies ranged from 360-467 MeV, and the spallation products ranged from 95-154 MeV/nucleon. The spatial distribution of the neutrons in the phantom was uniform, while the distribution of protons and heavy particles had a maximum of 8 cm radially. Conclusions: There are a large number of secondary particles produced with carbon ion beams. These particles are produced in the patient and deposit a significant amount of their energy locally. Because the Relative Biological Effectiveness for these highenergy secondary particles is not well known, further investigation is needed to determine the risk associated with carbon ion therapy. Author Disclosure: Y.M. Charara, None; C. Ramsey, None; L. Townsend, None.
3190
Effect of Heavy Ion 12-C Radiation on Primary Human Cell Cultures Studied by Whole Transcriptome Analysis
U. Wirkner, C. Rittmueller, S. Trinh, A. Abdollahi, P. Huber DKFZ/University Hospital Center, Radiation Oncology, Heidelberg, Germany Purpose/Objective(s): Early gene expression changes in human primary fibroblasts and endothelial cells were analyzed in order to elucidate initial molecular mechanisms in response to different doses of heavy ion (12-C) irradiation in normal human tissue. In parallel influence on clonogenic survival of both cell types was analyzed and correlated to the transcriptome analysis. Materials/Methods: Normal human dermal fibroblasts (NHDF) and human dermal micro-vascular endothelial cells (HDMEC) were irradiated with 0.5, 1, 2, and 4 Gy 12-C radiation, 110-144MeV/u, at GSI Darmstadt. For clonogenic survival assays, cells
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3189
Neutron Production with Carbon Therapy Beams
Y. M. Charara1,2, C. Ramsey1, L. Townsend2 1
Thompson Cancer Survival Center, Knoxville, TN, 2University of Tennessee, Knoxville, TN
Purpose/Objective(s): There is currently a great deal of excitement in the radiotherapy community about the potential of charged particles. In proton therapy, secondary neutron production is an area of active research by a multitude of investigators. For carbon ion therapy, there are a limited number of studies on secondary particle production and their biological implications. The purpose of this study was to investigate the production of secondary particles (protons, neutron, and spallation products) for carbon ion beams using the state-of-the-art Monte Carlo code HETC-HEDS. Materials/Methods: HETC-HEDS simulates particle cascades using Monte Carlo to compute the trajectories of the primary particles and all the secondary particles produced in nuclear collisions. Protons, neutrons, p+, p-, m+, m-, light ions, and heavy ions are arbitrarily distributed in angle, energy, and space. Each particle in the cascade is followed until it disappears by escaping from the boundaries of the system, undergoes a nuclear collision or absorption, and comes to rest due to energy losses from ionization and excitation of atomic electrons in the target medium. In the study, an A-150 Tissue Equivalent Plastic cylinder was simulated with a 30 cm radius and a thickness that was greater than the Bragg peak depth. Energies between 290 - 400 MeV/nucleon were used at a 10 MeV/nucleon increment. The fluence, energy distribution, and spatial distributions of neutrons, protons, and heavy particles were analyzed. Results: The secondary particle production increased at a linear rate with increasing carbon energy. Approximately 3.2 neutrons were produced in the phantom for each incident carbon ion for the 290 MeV/nucleon beam, while the 400 MeV/nucleon primary beam produced 5.3 neutrons per incident carbon ion. On average, the neutron production rate increased at a rate of 20% per 10 MeV/nucleon. Secondary protons were created at a rate between 2.62-2.87 particles per carbon ion, while spallation products were created at a rate between 0.20-0.24 particles per carbon ion. The average energies of the neutrons ranged between 488840 MeV, the proton energies ranged from 360-467 MeV, and the spallation products ranged from 95-154 MeV/nucleon. The spatial distribution of the neutrons in the phantom was uniform, while the distribution of protons and heavy particles had a maximum of 8 cm radially. Conclusions: There are a large number of secondary particles produced with carbon ion beams. These particles are produced in the patient and deposit a significant amount of their energy locally. Because the Relative Biological Effectiveness for these highenergy secondary particles is not well known, further investigation is needed to determine the risk associated with carbon ion therapy. Author Disclosure: Y.M. Charara, None; C. Ramsey, None; L. Townsend, None.
3190
Effect of Heavy Ion 12-C Radiation on Primary Human Cell Cultures Studied by Whole Transcriptome Analysis
U. Wirkner, C. Rittmueller, S. Trinh, A. Abdollahi, P. Huber DKFZ/University Hospital Center, Radiation Oncology, Heidelberg, Germany Purpose/Objective(s): Early gene expression changes in human primary fibroblasts and endothelial cells were analyzed in order to elucidate initial molecular mechanisms in response to different doses of heavy ion (12-C) irradiation in normal human tissue. In parallel influence on clonogenic survival of both cell types was analyzed and correlated to the transcriptome analysis. Materials/Methods: Normal human dermal fibroblasts (NHDF) and human dermal micro-vascular endothelial cells (HDMEC) were irradiated with 0.5, 1, 2, and 4 Gy 12-C radiation, 110-144MeV/u, at GSI Darmstadt. For clonogenic survival assays, cells
S703