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Introduction to Radiobiological aspects of Hadron therapy
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Introduction to Radiobiological aspects of Hadron therapy Wilma K. Weyrather GSI Biophysik, Planckstr. 1, 64291 Darmstadt, Germany, Tel.: +49 (0) 6159/71-2585, -2 607, Fax: +49 (0) 6159/712106, email: W. Kraft-Weyrather(~,.qsi .d_ee The increase of the relative biological effectiveness (RBE) with increasing penetration depth is the greatest advantage of heavier ions compared to protons in respect of their use in radiotherapy is. Consequently, the radiobiological research for therapy will focus on ions where the RBE is large but concentrated to the end of the range that will be located in the target volume. In the entrance channel, the RBE should be low and close to the values for sparsely ionising radiation. This will potentiate the benefit from the inverse depth-dose distributions and yields a hig h therapeutic gain, especially for tumors radioresistant to x-ray irradiation. Extensive radiobiological research has shown that carbon beams fulfil in an optimal way these conditions for the treatment of deep seated tumors. The variation of RBE is due to an increase in the ionisation density in each particle track, leading to clusters of DNA damage. This is expressed in a different pattern of the measured and calculated DNA fragments of high LET radiation compared to low LET. In addition the distribution of chromosomal damage as well as the cell cycle progression differs between the two types of radiation and the radiation response depends less on cell-environmental conditions like hypoxia or the cell cycle phase. While our understanding of the acute radiation effects, i. e. cell inactivation by protons and carbon ions on tumor and normal tissue has made significant progress there is still a lack of data for potential late effects in the normal tissue. An important source of information for these effects is the careful analysis of the late reactions found in patients that have been treated with particles many years ago. These studies should be complemented by an intense radiobiological research on the cellular level. The induction of fibrosis in normal tissue is a prominent example for a late effect that can be also studied in in-vitro experiments using primary cells. In these experiments the regulatory mechanism by the activation and induction of cytokines can be studied. This will contribute to a deeper understanding of the radiation response in general. The induction of secondary tumors in man and animals is a stochastic event and occurs many years after exposure. Therefore neoplastic transformation in tissue culture cells has to be studied for a risk estimation of the different irradiation modalities. The risk estimation for particle exposure is also of great importance for radiation protection especially for manned space flights exposed to the galactic cosmic rays. There, heavy particles with high energies can penetrate the space craft and contribute significantly to the total radiation environment. Because extensive shielding is nearly impossible the search for radioprotective agents is still an interesting field for further investigations. Because it is not feasible to measure the consequences of exposure to all particles and all biological endpoints, theoretical predictions are necessary. The existing models use different mathematical strategies and different physical and biological parameters. Therefore, they need to be tailored to the problem under study and may vary in their applicability. They range from ab-initio models, based on detailed simulation of track structures and DNA molecules, which can be used e. g. to predict strand break induction, to more empirical models like the Local Effect Model which is already used for heavy ion therapy treatment planning. The validation of these models for application in a clinical environment, as well as the general biological characterization of treatment fields requires the development of biological dosimetry. In the following articles, many of these aspects are discussed and some of the problems still unsolved are outlined.
Introduction to Radiobiological aspects of Hadron therapy Wilma K. Weyrather GSI Biophysik, Planckstr. 1, 64291 Darmstadt, Germany, Tel.: +49 (0) 6159/71-2585, -2 607, Fax: +49 (0) 6159/712106, email: W. Kraft-Weyrather(~,.qsi .d_ee The increase of the relative biological effectiveness (RBE) with increasing penetration depth is the greatest advantage of heavier ions compared to protons in respect of their use in radiotherapy is. Consequently, the radiobiological research for therapy will focus on ions where the RBE is large but concentrated to the end of the range that will be located in the target volume. In the entrance channel, the RBE should be low and close to the values for sparsely ionising radiation. This will potentiate the benefit from the inverse depth-dose distributions and yields a hig h therapeutic gain, especially for tumors radioresistant to x-ray irradiation. Extensive radiobiological research has shown that carbon beams fulfil in an optimal way these conditions for the treatment of deep seated tumors. The variation of RBE is due to an increase in the ionisation density in each particle track, leading to clusters of DNA damage. This is expressed in a different pattern of the measured and calculated DNA fragments of high LET radiation compared to low LET. In addition the distribution of chromosomal damage as well as the cell cycle progression differs between the two types of radiation and the radiation response depends less on cell-environmental conditions like hypoxia or the cell cycle phase. While our understanding of the acute radiation effects, i. e. cell inactivation by protons and carbon ions on tumor and normal tissue has made significant progress there is still a lack of data for potential late effects in the normal tissue. An important source of information for these effects is the careful analysis of the late reactions found in patients that have been treated with particles many years ago. These studies should be complemented by an intense radiobiological research on the cellular level. The induction of fibrosis in normal tissue is a prominent example for a late effect that can be also studied in in-vitro experiments using primary cells. In these experiments the regulatory mechanism by the activation and induction of cytokines can be studied. This will contribute to a deeper understanding of the radiation response in general. The induction of secondary tumors in man and animals is a stochastic event and occurs many years after exposure. Therefore neoplastic transformation in tissue culture cells has to be studied for a risk estimation of the different irradiation modalities. The risk estimation for particle exposure is also of great importance for radiation protection especially for manned space flights exposed to the galactic cosmic rays. There, heavy particles with high energies can penetrate the space craft and contribute significantly to the total radiation environment. Because extensive shielding is nearly impossible the search for radioprotective agents is still an interesting field for further investigations. Because it is not feasible to measure the consequences of exposure to all particles and all biological endpoints, theoretical predictions are necessary. The existing models use different mathematical strategies and different physical and biological parameters. Therefore, they need to be tailored to the problem under study and may vary in their applicability. They range from ab-initio models, based on detailed simulation of track structures and DNA molecules, which can be used e. g. to predict strand break induction, to more empirical models like the Local Effect Model which is already used for heavy ion therapy treatment planning. The validation of these models for application in a clinical environment, as well as the general biological characterization of treatment fields requires the development of biological dosimetry. In the following articles, many of these aspects are discussed and some of the problems still unsolved are outlined.