Circulating endothelial cells as a biological marker for acute toxicity in rectal cancer patients receiving postoperative concurrent chemoradiation

B11

Concurrent chemoradiation (CCRT) is now a standard postoperative adjuvant treatment for high-risk rectal cancer patients. However, no surrogate marker for optimization of adjuvant CCRT is available. Circulating endothelial cells (CEC) and endothelial progenitor cells (EPC) were observed to correlate the tumor response after metronomic therapy. This study aimed to examine the feasibility of CEC and/or EPC as a marker for adjuvant CCRT toxicity in rectal cancer. Between November 2006 and April 2008, 11 rectal cancer patients treated with radical proctectomy were enrolled (ClinicalTrials.gov Identifier NCT00325871). Postoperative RT with concurrent UFT followed by metronomic UFT administration was applied as adjuvant treatment. Peripheral blood was sampled weekly before and during CCRT as well as monthly thereafter. The kinetics of CEC, apoptotic CEC and EPC was estimated by flow cytometry with proper parameters. CCRT toxicity was graded according to version 3.0 of the NCI-CTCAE. At various time points, 6 patients developed grade 3 diarrhea, 1 had grade 2 cystitis, 1 suffered from acute urinary tract infection and 1 experienced peritonitis. In all patients with acute CCRT toxicity, a burst of increase in the amounts of CEC was consistently noted at the time that severest toxicity developed. These changes recovered while symptoms/signs subsided. Neither the EPC nor the white blood cells (WBC) kinetics shows such evident correlation. The amounts of CEC and EPC had no significant correlation with WBC or absolute neutrophil counts. The follow-up CEC kinetics during adjuvant metronomic UFT administration show a recovery trend after completion of RT. Overall, the amounts of CEC declined during CCRT, except that increased while severe toxicity developed, and then resume during adjuvant metronomic therapy. In conclusion, the kinetics of CEC correlates with that of CCRT toxicity. To suggest CEC as a surrogate marker for optimization of CCRT, further validation by clinical investigations is warranted.