MODELING OF TIME-DOSE RESPONSE OF HUMAN TUMORS AND NORMAL TISSUES

在临床放射治疗中，分割的选择 参数：总时间、分次次数、分次剂量 分数的时间间隔仍然在很大程度上基于 经验。本项目开发了一种形式主义来描述 正常组织对照射方案随时间的反应 正常组织功能的(间接)反应术语 与干细胞对辐射损伤的反应有关 或者是过渡细胞。正常情况下，有一个稳定的状态为常规 取代正常运转的细胞的磨损。这 辐射对人体的致命伤害破坏了人体的平衡状态 敏感干细胞和过渡细胞。饱满的或可容忍的 功能的恢复取决于 干细胞数量，损伤随时间的分布，以及其他 组织运动特征。类似的考虑也适用于 对于肿瘤来说。目前的模型使用线性二次型 或者说，脆弱群体的即时生存的双成分模型 正常组织或克隆形成的肿瘤细胞。它需要选择以下选项 组织特征，如整体正常组织翻转 时间，急性干细胞倍增时间，亚致死损伤恢复 时间和容差级别的功能，以便计算机- 绘制出与临床实际相符的时间-剂量反应曲线 用常规疗法观察到的应答模式。为 肿瘤，需要类似的选择，以及一个标准 治愈率。然后，对成功的选择进行已知测试 替代方案。最终目标是开发可靠的 临床放射治疗的预测规则。

In clinical radiotherapy, the choice of the fractionation parameters: total time, number of fractions, dose per fraction, time-spacing of the fractions, is still largely based on experience. The present project develops a formalism to describe the normal tissue reactions to irradiation regimens over time in terms of the (indirect) reactions of the functions of normal tissue in relation to the reaction to radiation damage to the stem cells or transition cells. Normally there is a steady state of regular replacement of the normal attrition of functioning cells. This equilibrium condition is upset by radiation lethal damage to sensitive stem cells and transition cells. Full or tolerable recovery of functionality depends on the level of damage to the stem cell population, the distribution of damage over time, and on the tissue kinetic characteristics. Similar considerations apply to the tumor. The present model uses either the Linear-Quadratic or the Two-Component model for the immediate survival of vulnerable normal tissue or clonogenic tumor cells. It requires selection of tissue characteristics such as overall normal tissue turn-over time, acute stem cell doubling time, sublethal damage recovery time, and tolerance level functionality, in order to computer- generate time-dose response curves consistent with actual clinical response patterns, observed with conventional regimens. For tumors, similar selections are needed, as well as a criterion for cure rate. Successful selections are then tested with known alternative schemes. The ultimate aim is to develop reliable predictive rules for clinical radiation therapy.