Hypothesis about Celluar Structure of Tumor Tissues and Probability of Her Curing Depending on Plan of RT

Abstract

Purpose: In 1988 Withers H.R., Taylor J.M., Maciejewski B., proposed a hypothesis about the cellular structure of normal body tissues, according to which their radioresistance is determined by the presence of functional cellular units (FСU) in them. But, unfortunately, in their work there was no substantiation of this hypothesis.
 In our work, we substantiate the hypothesis that tumor tissue contains structured tissue-like formations (TLF) from malignant cells that determine its radioresistance. The success of radiation therapy is determined both by the destruction of TLF and the death of their fragments and free clonogenic cells formed as a result of the breakdown of TLF.
 Material and methods: To substantiate the hypothesis, mathematical models were created that made it possible to describe the results of radiation exposure to squamous cell carcinoma of the larynx (CL) and breast cancer (BC) after surgical removal of the BC tumor and total irradiation of breast to destroy cells that could migrate from tumor. For segregation of the parameters values that characterize the radiosensitivity of the tumor and for plotting a dose-response curve, a special method was developed for Reconstruction the Radiobiological Tumor Parameters (RRTP), based on the Poisson mathematical model and other mathematical models used in radiation therapy planning.
 Results: Dependencies of radiobiological parameters on the dose were plotted using the RRTP method:
 1. Dependence of the number of tumor units N on the dose, which include TLF, TLF fragments and independent tumor cells formed as a result of TLF decay after irradiation.
 2. Dependence of the radiobiological parameter t (D,d) Gy–1 on the total dose and dose per fraction.
 3. Dependence of the radiobiological parameter g (D,d) Gy on total dose and dose per fraction.
 In this paper, it is shown that for CL the number of tumor units N and the parameter t (D,d) are increasing functions of the dose D. This confirms the hypothesis that CL consists of TLF, which, after irradiation, decompose into TLF fragments and independent tumor cells. For breast cancer, it was found, as expected, that the number of tumor units N is a decreasing function of the dose D, i.e., that there are no TLF formations in breast cancer.
 Conclusion: The hypothesis that the CL tumor contains TPO formations from malignant cells, which increase its radioresistance was confirmed. At a dose close to the therapeutic dose, the number of tumor units becomes close to the number of all tumor cells.