Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA.
Med Phys. 2011 Feb;38(2):574-83. doi: 10.1118/1.3521406.
Patients undergoing radiation therapy (and their physicians alike) are concerned with the probability of cure (long-term recurrence-free survival, meaning the absence of a detectable or symptomatic tumor). This is not what current practice categorizes as "tumor control (TC);" instead, TC is taken to mean the extinction of clonogenic tumor cells at the end of treatment, a sufficient but not necessary condition for cure. In this review, we argue that TC thus defined has significant deficiencies. Most importantly, (1) it is an unobservable event and (2) elimination of all malignant clonogenic cells is, in some cases, unnecessary. In effect, within the existing biomedical paradigm, centered on the evolution of clonogenic malignant cells, full information about the long-term treatment outcome is contained in the distribution Pm(T) of the number of malignant cells m that remain clonogenic at the end of treatment and the birth and death rates of surviving tumor cells after treatment. Accordingly, plausible definitions of tumor control are invariably traceable to Pm(T). Many primary cancers, such as breast and prostate cancer, are not lethal per se; they kill through metastases. Therefore, an object of tumor control in such cases should be the prevention of metastatic spread of the disease. Our claim, accordingly, is that improvements in radiation therapy outcomes require a twofold approach: (a) Establish a link between survival time, where the events of interest are local recurrence or distant (metastatic) failure (cancer-free survival) or death (cancer-specific survival), and the distribution Pm(T) and (b) link Pm(T) to treatment planning (modality, total dose, and schedule of radiation) and tumor-specific parameters (initial number of clonogens, birth and spontaneous death rates during the treatment period, and parameters of the dose-response function). The biomedical, mathematical, and practical aspects of implementing this program are discussed.
接受放射治疗的患者（以及他们的医生）关注的是治愈的可能性（长期无复发生存率，即不存在可检测或有症状的肿瘤）。这与当前实践中归类为“肿瘤控制（TC）”的内容不同；相反，TC 被认为是治疗结束时克隆性肿瘤细胞的灭绝，这是治愈的充分但非必要条件。在这篇综述中，我们认为这样定义的 TC 存在明显的缺陷。最重要的是，(1) 它是一个不可观察的事件，(2) 消除所有恶性克隆性细胞在某些情况下是不必要的。实际上，在现有的以克隆性恶性细胞演变为中心的生物医学范式中，关于长期治疗结果的全部信息都包含在治疗结束时剩余的克隆性恶性细胞数量 m 的分布 Pm(T) 以及治疗后存活肿瘤细胞的出生和死亡速率中。因此，肿瘤控制的合理定义总是可以追溯到 Pm(T)。许多原发性癌症，如乳腺癌和前列腺癌，本身并不致命；它们通过转移杀死。因此，在这种情况下，肿瘤控制的目标应该是防止疾病的转移扩散。因此，我们的主张是，改善放射治疗结果需要双管齐下：(a) 将生存时间（感兴趣的事件是局部复发或远处（转移）失败（无癌生存）或死亡（癌症特异性生存））与分布 Pm(T) 联系起来，(b) 将 Pm(T) 与治疗计划（治疗方式、总剂量和放射时间表）和肿瘤特异性参数（初始克隆数、治疗期间的出生和自发死亡速率以及剂量反应函数的参数）联系起来。讨论了实施该计划的生物医学、数学和实际方面。
