K R Trott1. 1. Department of Radiation Biology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary & Westfield College, University of London, UK. krtrott@mds.qmw.ac.uk
Abstract
BACKGROUND: The radiobiological mechanisms which may be exploited in the design of new strategies of radiochemotherapy are discussed. METHODS: The identification of exploitable mechanisms of radiochemotherapy has to be based on the analysis of cellular and supracellular mechanisms of tumor cure, acute normal tissue injury and chronic normal tissue injury, respectively, as well as on experimentally documented mechanisms of cellular and supracellular interactions of chemotherapy and radiotherapy. RESULTS: Only the addition of independent cytotoxic effects of radiotherapy and of chemotherapy are a sound basis for predicting the therapeutic effects on tumor cure probability. In the pathogenesis of normal tissue damage, however, complex interactions of supracellular mechanisms play a decisive role which may increase the rate of chronic side effects even in the absence of cellular interactions. CONCLUSION: None of the presently used schedules of radiochemotherapy meets the scientific requirements outlined in the paper. For squamous cell carcinomas the most promising protocol would combine effective doses of chemotherapy and of radiotherapy without dose reduction and/or treatment prolongation simultaneously but without causing increased normal tissue injury.
BACKGROUND: The radiobiological mechanisms which may be exploited in the design of new strategies of radiochemotherapy are discussed. METHODS: The identification of exploitable mechanisms of radiochemotherapy has to be based on the analysis of cellular and supracellular mechanisms of tumor cure, acute normal tissue injury and chronic normal tissue injury, respectively, as well as on experimentally documented mechanisms of cellular and supracellular interactions of chemotherapy and radiotherapy. RESULTS: Only the addition of independent cytotoxic effects of radiotherapy and of chemotherapy are a sound basis for predicting the therapeutic effects on tumor cure probability. In the pathogenesis of normal tissue damage, however, complex interactions of supracellular mechanisms play a decisive role which may increase the rate of chronic side effects even in the absence of cellular interactions. CONCLUSION: None of the presently used schedules of radiochemotherapy meets the scientific requirements outlined in the paper. For squamous cell carcinomas the most promising protocol would combine effective doses of chemotherapy and of radiotherapy without dose reduction and/or treatment prolongation simultaneously but without causing increased normal tissue injury.