Hanin Leonid, Zaider Marco
Department of Mathematics, Idaho State University, Pocatello, ID 83209-8085, USA.
Phys Med Biol. 2014 Jul 21;59(14):3829-42. doi: 10.1088/0031-9155/59/14/3829. Epub 2014 Jun 23.
The probability of a cure in radiation therapy (RT)-viewed as the probability of eventual extinction of all cancer cells-is unobservable, and the only way to compute it is through modeling the dynamics of cancer cell population during and post-treatment. The conundrum at the heart of biophysical models aimed at such prospective calculations is the absence of information on the initial size of the subpopulation of clonogenic cancer cells (also called stem-like cancer cells), that largely determines the outcome of RT, both in an individual and population settings. Other relevant parameters (e.g. potential doubling time, cell loss factor and survival probability as a function of dose) are, at least in principle, amenable to empirical determination. In this article we demonstrate that, for heavy-ion RT, microdosimetric considerations (justifiably ignored in conventional RT) combined with an expression for the clone extinction probability obtained from a mechanistic model of radiation cell survival lead to useful upper bounds on the size of the pre-treatment population of clonogenic cancer cells as well as upper and lower bounds on the cure probability. The main practical impact of these limiting values is the ability to make predictions about the probability of a cure for a given population of patients treated to newer, still unexplored treatment modalities from the empirically determined probability of a cure for the same or similar population resulting from conventional low linear energy transfer (typically photon/electron) RT. We also propose that the current trend to deliver a lower total dose in a smaller number of fractions with larger-than-conventional doses per fraction has physical limits that must be understood before embarking on a particular treatment schedule.
放射治疗（RT）中的治愈概率——被视为所有癌细胞最终灭绝的概率——是无法观测的，计算它的唯一方法是对治疗期间和治疗后癌细胞群体的动态进行建模。旨在进行这种前瞻性计算的生物物理模型的核心难题是缺乏关于克隆源性癌细胞（也称为干细胞样癌细胞）亚群初始大小的信息，这在很大程度上决定了RT在个体和群体环境中的结果。其他相关参数（例如潜在倍增时间、细胞损失因子和作为剂量函数的存活概率）至少在原则上可以通过经验确定。在本文中，我们证明，对于重离子放疗，微剂量学考虑（在传统放疗中被合理忽略）与从放射细胞存活的机制模型中获得的克隆灭绝概率表达式相结合，可得出克隆源性癌细胞治疗前群体大小的有用上限以及治愈概率的上限和下限。这些极限值的主要实际影响是能够根据传统低线性能量传递（通常是光子/电子）放疗对相同或相似群体的经验性治愈概率，预测接受更新的、仍未探索的治疗方式的给定患者群体的治愈概率。我们还提出，目前在较少分次中给予较低总剂量且每次分次剂量大于传统剂量的趋势存在物理极限，在开始特定治疗方案之前必须了解这些极限。
