unbiased and automated identification of a circulating tumour cell definition that associates with overall survival无偏和自动循环肿瘤细胞的识别与总体存活率定义相关联.pdfVIP

Unbiased and Automated Identification of a Circulating Tumour Cell Definition That Associates with Overall Survival 1 1 2 2 2 Sjoerd T. Ligthart , Frank A. W. Coumans , Gerhardt Attard , Amy Mulick Cassidy , Johann S. de Bono , Leon W. M. M. Terstappen1* 1 Medical Cell BioPhysics group, MIRA Institute, University of Twente, Enschede, The Netherlands, 2 The Royal Marsden National Health Service Foundation Trust, Sutton, Surrey, United Kingdom Abstract Circulating tumour cells (CTC) in patients with metastatic carcinomas are associated with poor survival and can be used to guide therapy. Classification of CTC however remains subjective, as they are morphologically heterogeneous. We acquired digital images, using the CellSearchTM system, from blood of 185 castration resistant prostate cancer (CRPC) patients and 68 healthy subjects to define CTC by computer algorithms. Patient survival data was used as the training parameter for the computer to define CTC. The computer-generated CTC definition was validated on a separate CRPC dataset comprising 100 patients. The optimal definition of the computer defined CTC (aCTC) was stricter as compared to the manual CellSearch CTC (mCTC) definition and as a consequence aCTC were less frequent. The computer-generated CTC definition resulted in hazard ratios (HRs) of 2.8 for baseline and 3.9 for follow-up samples, which is comparable to the mCTC definition (baseline HR 2.9, follow-up HR 4.5). Validation resulted in HRs at baseline/follow-up of 3.9/5.4 for computer and 4.8/5.8 for manual definitions. In conclusion, we have defined and validated CTC by clinical outcome using a perfectly reproducing automated algorithm. Citation: Ligthart ST, Coumans FAW, Attard G, Mulick Cassidy A, de