Massard Christophe, Borget Isabelle, Farace Françoise, Aspeslagh Sandrine, Le Deley Marie-Cécile, Le Tourneau Christophe, Bidard François-Clement, Pierga Jean-Yves, Dieras Veronique, Hofman Paul, Spano Jean-Philippe, Ferte Charles, Lacroix Ludovic, Soria Jean-Charles
Drug Development Department (DITEP), Department of Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, F-94805, France.
Faculty of Pharmacy, University Paris-Sud, Châtenay-Malabry, France; Department of Health Economics, Gustave Roussy Institute, Villejuif, France.
Eur J Cancer. 2017 Sep;83:185-193. doi: 10.1016/j.ejca.2017.05.016. Epub 2017 Jul 22.
Circulating tumour cell (CTC) counting could be a new biomarker for better evaluation of tumour response to molecules tested in phase I trials.
Consenting patients with advanced metastatic cancer referred to various phase I units were enrolled prospectively in this study. CTCs from 7.5 ml of whole blood drawn at baseline and after starting experimental therapy were counted using the CellSearch system, and tumour response was assessed using RECIST 1.1 criteria at baseline and 2 months after treatment initiation.
Between March 2010 and May 2013, a total of 326 patients were enrolled, among whom 214 were evaluable (49% male, median age = 56; main cancer types: lung [28], colon [53], ovarian [18], breast [28]). At baseline, we detected ≥1 CTC/7.5 ml in 113/214 patients (53%), and at day 30, we observed ≥1 CTC/7.5 ml in 103/214 patients (48%). Two months after treatment initiation, 11 (5%) of the 214 patients were classified as having a partial response, with no CTCs in 9 of them or a decrease in the CTC count after therapy. In contrast, among the 104 patients (49%) classified as having progressive disease, 38 patients had a higher CTC count. The remaining 99 patients (49%), 33 of whom (33%) had a lower CTC count, were classified as having stable disease. The sensitivity and specificity of CTC variation for predicting progressive disease were 41% (32-51%) and 80% (73-88%) respectively.
An early CTC change following therapy does not correlate with RECIST response in patients with advanced cancer enrolled in phase I trials.
循环肿瘤细胞（CTC）计数可能是一种新的生物标志物，用于更好地评估肿瘤对I期试验中所测试分子的反应。
前瞻性纳入了同意参与研究的晚期转移性癌症患者，这些患者被转诊至各个I期治疗单元。使用CellSearch系统对基线时以及开始实验性治疗后采集的7.5毫升全血中的CTC进行计数，并在基线和治疗开始后2个月使用RECIST 1.1标准评估肿瘤反应。
2010年3月至2013年5月期间，共纳入326例患者，其中214例可评估（男性占49%，中位年龄 = 56岁；主要癌症类型：肺癌[28例]、结肠癌[53例]、卵巢癌[18例]、乳腺癌[28例]）。基线时，113/214例患者（53%）检测到≥1个CTC/7.5毫升，第30天时，103/214例患者（48%）观察到≥1个CTC/7.5毫升。治疗开始后2个月，214例患者中有11例（5%）被分类为部分缓解，其中9例无CTC或治疗后CTC计数下降。相比之下，在104例（49%）被分类为疾病进展的患者中，38例患者的CTC计数更高。其余99例患者（49%），其中33例（33%）的CTC计数较低，被分类为疾病稳定。CTC变化预测疾病进展的敏感性和特异性分别为41%（32 - 51%）和80%（73 - 88%）。
在I期试验中纳入的晚期癌症患者中，治疗后早期CTC变化与RECIST反应不相关。
