| The objective of radiotherapy is to obtain the maximum tumor control probability (TCP) or lower tumor cell survival while minimizing the likelihood of significant normal tissue damage around the tumor. Now, the fractionated radiotherapy protocols have been used in clinics. And it's well known that, the TCP calculating model is a good method to estimate the effect of a certain irradiation protocol.Because of the different fractionation radiosensitivity and different recovery kinetics, the tissue response to the same total radiation dose may changed with the different irradiation parameters such as fraction size, fraction numbers and overall treatment time. So the optimum protocol is to optimize the irradiation parameters. For a given irradiation dose and time, there are two kinds of protocols which can be used, one is the protocol with constant fraction sizes(CFS), which has been widely used in clinics; The other is the protocol with variable fraction sizes(VFS), which has not been studied systematically.In our work, the effect of irradiation with VFS protocol was analyzed theoretically and experimentally. It was done in two steps: (1) A TCP model which including the effect of DNA single-strand damage repair, repopulation of clonogens, reoxygenation and redistribution will be derived and compared with the other TCP models. Then with a group of assumed characteristic parameter values for a tumor, the relationship between TCP and total treatment dose of two assumed special VFS protocols(The fraction size changed with the ratio k or differenceδ) were presented and compared with that of CFS protocol by calculation. (2) A concise experiment with SMMC7721 liver malignancy cells was done to analyze the effect of VFS protocols while the total absorbed dose, fraction numbers and treatment time keep constant. The cells were cultured and irradiated with the assumed different VFS protocols, then the cell survival probability(S) after different irradiation protocols were calculated with the absorbance result obtained from the MTT method to testify whether the calculation result is right..The comparison between the different TCP models shows that, the derived model in this paper is better than the others, and it can be used to estimate the effect of any fractionated irradiation protocols. The calculation result shows that:①All TCP-Dose relationship curves of irradiation with VFS protocols are better than that of CFS protocol, and the TCP-Dose relationship curves will become better when the absolute value of k-1orδincreases. And the TCD50 value(the dose needed to get the 50％TCP) is largest whenδ=0 or k=1(i. e. CFS protocol), and it turns to be smaller with the increasing absolute value of k-1orδ. Hence, for the given treatment time, radiation dose and fraction numbers, treatment with the VFS can get the better TCP-DOSE curve and lower TCD50 value than treatment with the CFS.②For the same variety range, treatment with the decreasing fraction sizes is slightly better than treatment with the increasing fraction sizes. And the TCD50 values of using decreasing fraction sizes protocol is slightly lower than that of using increasing fraction sizes protocol.③The TCD50 vs. k or TCD50 vs.δrelationship of using VFS over all treatment time is much sharper than that of using VFS in a week with a week cycle period, the reason is that the fraction sizes in the former protocol are more heterogeneous than that in the latter protocol.The experiment result showed that:①All the S values irradiated with VFS are lower than that irradiated with the CFS. And the significant differences are found between the S value irradiated with the CFS protocol and irradiated with the part of assumed VFS protocols.②As the VFS protocols were used, with the same variety range, irradiated with decreasing fraction sizes can get the lower S value than using increasing fraction sizes, and the significant difference were found between the S value after irradiated with the part of couple VFS protocols.In general, with the given fraction numbers, treatment time and radiation dose, treatment with VFS can get the better effect than treatment with CFS. As a result, perhaps the VFS protocol, especially the protocol with decreasing VFS can be used in fractionated radiotherapy to improve the tumor control. But how to choose the optimum one within the infinite VFS still need to be studied with a lot of experiments in vivo or in vitro, maybe when the parameter values of a tumor and the variation of these parameters in the process of radiotherapy is known accurately, it will be reality to design and use the optimum VFS in clinics exactly. And in our opinion, before it is really used in fractionated radiotherapy, the effect of this kind of protocols and how to design the optimum one to get the optimum TCP still need to be studied and qbe proved with a lot of experiments. |
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