Sigurdsson H, Baldetorp B, Borg A, Dalberg M, Fernö M, Killander D, Olsson H, Ranstam J
Department of Oncology, University Hospital, Lund, Sweden.
Br J Cancer. 1990 Nov;62(5):786-90. doi: 10.1038/bjc.1990.380.
The use of continuous prognostic variables is clinically impractical, and arbitrarily chosen cut-off points can result in a loss of prognostic information. Here we report findings from a study of primary breast cancer, showing how the prognostic value of the fraction of cells in the S-phase of the cell cycle (SPF), as measured by flow cytometry, can be affected by the SPF cut-off level(s) adopted. It was possible to evaluate the SPF in 566 (94%) of 603 consecutive cases where fresh frozen specimens were available in a tumour bank at our department. Clinically, all patients were without distant spread at the time of diagnosis, and the median duration of follow-up was 4 years. Using different survival end-points and chi 2 values for each cut-off level, two optimal cut-off points, at the 7% and 12% levels, were consistently obtained for the SPF. Furthermore, both disease-free survival and the relative risk of recurrence exhibited a non-linear relationship with SPF values; the curves implied that the prognosis was better among patients with SPF values about 2-5% than in patients with lower SPF values (parabolic shape), though the relationship with higher SPF values approached linearity. The non-linearity of the curves is incompatible with the general use of the median SPF as a prognostic cut-off value. An alternative procedure might be to use two cut-off levels, one to distinguish patients with the lowest SPF values (i.e. within the parabolic survival curve) from those with higher values (i.e. with a survival curve approaching linearity), the other to distinguish between patients with intermediate SPF values and those with high values (i.e. within the almost linear part of the survival curve). The 7% and 12% obtained here would be suitable for this purpose. We conclude that prognostic information can be gained by dividing the SPF into three prognostic categories (less than 7.0%, 7.0-11.9% and greater than or equal to 12%), instead of using the median SPF level.
连续预后变量的应用在临床上不切实际，任意选择的截断点可能导致预后信息的丢失。在此，我们报告一项原发性乳腺癌研究的结果，展示了通过流式细胞术测量的细胞周期S期细胞分数（SPF）的预后价值如何受到所采用的SPF截断水平的影响。在我们科室肿瘤库中有新鲜冷冻标本的603例连续病例中，有566例（94%）能够评估SPF。临床上，所有患者在诊断时均无远处转移，随访的中位时间为4年。针对每个截断水平，使用不同的生存终点和卡方值，一致获得了SPF的两个最佳截断点，分别为7%和12%水平。此外，无病生存期和复发的相对风险与SPF值均呈现非线性关系；曲线表明，SPF值约为2 - 5%的患者预后优于SPF值较低的患者（呈抛物线形状），尽管与较高SPF值的关系接近线性。曲线的非线性与将SPF中位数普遍用作预后截断值不相符。一种替代方法可能是使用两个截断水平，一个用于区分SPF值最低的患者（即在抛物线生存曲线内）和较高值的患者（即生存曲线接近线性），另一个用于区分SPF值中等的患者和高值患者（即在生存曲线几乎呈线性的部分内）。此处获得的7%和12%适用于此目的。我们得出结论，通过将SPF分为三个预后类别（小于7.0%、7.0 - 11.9%和大于或等于12%），而不是使用SPF中位数水平，可以获得预后信息。
