Gregory W M, Richards M A, Slevin M L, Souhami R L
Imperial Cancer Research Fund Clinical Oncology Unit, Guy's Hospital, London.
Cancer Res. 1991 Feb 15;51(4):1210-6.
A mathematical model is presented which seeks to determine, from examination of the response durations of a group of patients with malignant disease, the mean and distribution of the resistant tumor volume. The mean tumor-doubling time and distribution of doubling times are also estimated. The model assumes that in a group of patients there is a log-normal distribution both of resistant disease and of tumor-doubling times and implies that the shapes of certain parts of an actuarial response-duration curve are related to these two factors. The model has been applied to data from two reported acute leukemia trials: (a) a recent acute myelogenous leukemia trial was examined. Close fits were obtained for both the first and second remission-duration curves. The model results suggested that patients with long first remissions had less resistant disease and had tumors with slower growth rates following second line treatment; (b) an historical study of maintenance therapy for acute lymphoblastic leukemia was used to estimate the mean cell-kill (approximately 10(4) cells) achieved with single agent, 6-mercaptopurine. Application of the model may have clinical relevance, for example, in identifying groups of patients likely to benefit from further intensification of treatment.
本文提出了一个数学模型，该模型旨在通过检查一组恶性疾病患者的反应持续时间，来确定耐药肿瘤体积的均值和分布。同时，还对平均肿瘤倍增时间和倍增时间的分布进行了估计。该模型假设，在一组患者中，耐药疾病和肿瘤倍增时间均呈对数正态分布，并表明精算反应持续时间曲线某些部分的形状与这两个因素有关。该模型已应用于两项已报道的急性白血病试验的数据：（a）对最近的一项急性髓性白血病试验进行了检查。首次和第二次缓解持续时间曲线均得到了紧密拟合。模型结果表明，首次缓解期长的患者耐药疾病较少，二线治疗后肿瘤生长速度较慢；（b）一项关于急性淋巴细胞白血病维持治疗的历史研究被用于估计单药6-巯基嘌呤实现的平均细胞杀伤量（约10⁴个细胞）。该模型的应用可能具有临床相关性，例如，在识别可能从进一步强化治疗中获益的患者群体方面。
