Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Downs Road, Sutton, Surrey, UK.
Clin Cancer Res. 2011 Aug 1;17(15):5188-96. doi: 10.1158/1078-0432.CCR-10-3019. Epub 2011 Apr 29.
High circulating tumor cell (CTC) counts are associated with poor prognosis in several cancers. Enrollment of patients on phase I oncology trials requires a careful assessment of the potential risks and benefits. Many patients enrolled on such trials using established eligibility criteria have a short life expectancy and are less likely to benefit from trial participation. We hypothesized that the incorporation of CTC counts might improve patient selection for phase I trials.
This retrospective analysis evaluated patients who had baseline CTCs enumerated prior to their starting on a phase I trial. CTCs were enumerated using the CellSearch System.
Between January 2006 and December 2009 a total of 128 patients enrolled in phase I trials had CTC counts evaluated. Higher CTC counts as a continuous variable independently correlated with risk of death in this patient population (P = 0.006). A multivariate point-based risk model was generated using CTCs as a dichotomous variable (≥3 or <3), and incorporated other established prognostic factors, including albumin <35 g/L, lactate dehydrogenase greater than upper limit of normal, and >2 metastatic sites. Comparison of receiver operating characteristic curves demonstrated that the addition of baseline CTC counts improved the performance of the prospectively validated Royal Marsden Hospital phase I prognostic score, which now identifies three risk groups (P < 0.0001): good prognosis [score 0-1, median overall survival (OS) 63.7 weeks], intermediate prognosis (score 2-3, median OS 37.3 weeks), and poor prognosis (score 4, median OS 13.4 weeks).
CTC enumeration improved the performance of a validated prognostic score to help select patients for phase I oncology trials.
高循环肿瘤细胞（CTC）计数与多种癌症的预后不良相关。在 I 期肿瘤学试验中招募患者需要仔细评估潜在的风险和获益。许多根据既定纳入标准入组此类试验的患者预期寿命较短，从试验参与中获益的可能性较小。我们假设纳入 CTC 计数可能会改善 I 期试验的患者选择。
本回顾性分析评估了在开始 I 期试验之前基线 CTC 计数的患者。使用 CellSearch 系统对 CTC 进行计数。
2006 年 1 月至 2009 年 12 月，共有 128 名患者入组 I 期试验，评估了 CTC 计数。在该患者人群中，CTC 计数作为连续变量与死亡风险独立相关（P=0.006）。使用 CTC 作为二分类变量（≥3 或 <3）生成了基于点的多变量风险模型，并纳入了其他已建立的预后因素，包括白蛋白<35g/L、乳酸脱氢酶高于正常值上限和>2 个转移部位。比较受试者工作特征曲线表明，基线 CTC 计数的加入改善了前瞻性验证的皇家马斯登医院 I 期预后评分的性能，该评分现在可识别三个风险组（P<0.0001）：预后良好[评分 0-1，中位总生存期（OS）63.7 周]、中等预后（评分 2-3，中位 OS 37.3 周）和预后不良（评分 4，中位 OS 13.4 周）。
CTC 计数提高了验证预后评分的性能，有助于选择患者参加 I 期肿瘤学试验。
