Annals of Oncology Advance Access published online on October 27, 2009
Annals of Oncology, doi:10.1093/annonc/mdp463
Circulating tumour cells early predict progression-free and overall survival in advanced colorectal cancer patients treated with chemotherapy and targeted agents
1 Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
2 Clinical Sciences, Veridex, LLC, Raritan, NJ, USA
3 Department of Gastroenterology, The Netherlands Cancer Institute, Amsterdam
4 Department of Internal Medicine, Catharina Hospital, Eindhoven
5 Department of Internal Medicine, Bernhoven Hospital, Oss
6 Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen
7 Department of Applied Physics, Twente University, Enschede, The Netherlands
* Correspondence to: Prof. C. J. A. Punt, Department of Medical Oncology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Tel: +31-24-3610353; Fax: +31-24-3540788; E-mail: C.Punt{at}onco.umcn.nl
Background: Early predictive markers for response are needed for advanced colorectal cancer (ACC) patients. We assessed the value of circulating tumour cells (CTC) in ACC patients treated with chemotherapy plus targeted agents (CAIRO2 phase III trial) and compared the results with computed tomography (CT) imaging.
Materials and methods: CTC were determined at baseline and at different time points during treatment. Patients were stratified into low (less than three CTC per 7.5 ml of blood) or high CTC (three or more CTC per 7.5 ml of blood).
Results: A total of 467 patients were assessable for CTC analysis. Among them, 129 patients (29%) with high baseline CTC had a significantly decreased progression-free survival [PFS; hazard ratio (HR) 1.5] and overall survival (OS; HR 2.2) compared with 322 patients with low baseline CTC. This difference remained statistically significant during treatment. The sensitivity and specificity of high CTC at baseline for the prediction of progressive disease on CT imaging were 16.7% and 70.1%, respectively, and of high CTC at 1–2 weeks after the start of treatment 20.0% and 95.1%, respectively. The combined analysis of CTC and CT imaging provided a more accurate outcome assessment than either modality alone.
Conclusions: The CTC count before and during treatment independently predicts PFS and OS in ACC patients treated with chemotherapy plus targeted agents and provides additional information to CT imaging.
circulating tumour cells, colorectal cancer, CT imaging, predictive marker, prognostic marker, targeted therapy
Received for publication May 13, 2009. Revision received July 30, 2009. Accepted for publication August 18, 2009.