Abstract CT320: Longitudinal observational study to simultaneously evaluate multiple blood-based biomarkers to track the emergence of metastasis and drug resistance in colorectal cancer

Abstract

Abstract Background. Colorectal cancer (CRC) is the 3rd most common cancer globally. In cancer, the 2 most critical events that adversely affect outcomes are the emergence of metastasis and drug resistance. Blood-based markers permit the non-invasive serial monitoring of patients in order to study and track the emergence and evolution of metastasis and drug resistance. The multiple varied platforms utilize different components of blood (buffy coat, whole blood, plasma). We seek to establish a longitudinal observational study to simultaneously evaluate multiple blood-based biomarkers to track patient outcomes in colorectal cancer. Methods. In a planned 800 patient study, we prospectively recruit patients with all stages of CRC, focusing on patients with stage 3/4 CRC. At each patient's venipuncture performed during his/her routine clinical care, we serially collect additional blood specimens. All major components of the collected blood (buffy coat, red cells, whole blood and plasma) are stored. In patients undergoing primary tumor resection or metastasectomy, frozen tissue specimens are also prospectively collected and banked for subsequent biomarker analysis. A prospective electronic database of clinical information and patient outcomes is simultaneously maintained for the purpose of correlation with molecular assays. Results. To date, we have recruited 450 patients and obtained their serial blood samples. Blood is prospectively collected in an optimized manner to support the pre-analytical requirements of the different platforms. This includes whole blood for immediate assay performance (circulating tumor cells), buffy coat for immediate analysis or storage for pooled analysis (cell based assays, germline polymorphisms, white cell gene expression and assays on peripheral blood mononuclear cells), plasma for storage for pooled analysis (circulating cell free nucleic acids including DNA, miRNA, RNA and methylated DNA, novel proteomic tumor markers, cytokines). Optimization of pre-analytical processing, transport and storage parameters was carried out to enable studies across multiple platforms in this same cohort of patients to be performed in a prospective longitudinal manner. Conclusions. In this ongoing study, we have established a system for the simultaneous evaluation of multiple blood-based biomarkers operating on the various components of blood. Together with paired tissue specimens and a prospectively maintained electronic clinical database, comprehensive comparisons and correlative studies to monitor for metastasis and drug resistance and clinical outcomes in CRC across time can be carried out. Citation Format: Clarinda Chua, Rachel Ten, Thinzar Aung, Maricel Ang, Thein Htut Oo, Su Pin Choo, Matthew Ng, Iain Beehuat Tan. Longitudinal observational study to simultaneously evaluate multiple blood-based biomarkers to track the emergence of metastasis and drug resistance in colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT320. doi:10.1158/1538-7445.AM2014-CT320