Abstract 4532: Peripheral blood lymphocyte subsets can predict the pathological response of rectal cancer patients to chemoradiation

Abstract

Abstract Purpose Neoadjuvant chemoradiotherapy (CRT) is used to downstage locally advanced rectal cancer (RC), prior to surgery. Although CRT is the standard treatment for RC, markers to predict the treatment response have not been fully established. Although some biomarkers, such as the absolute number of lymphocytes subsets and the proportion of CD57(+) T cells have been shown to be associated with prognosis in advanced cancer patients, only few studies report on the predictive factors of response to therapy. Recently, the neutrophil to lymphocyte (N/L) ratio has been reported as a promising marker with ability to predict the effectiveness of CRT in advanced rectal cancer. Thus, in the present study, we aimed to identify other potential predictive factors of tumor response to CRT in RC patients. Patients and Methods From April, 2010 to August, 2011, 15 patients with histologically-proven locally advanced adenocarcinoma, receiving preoperative CRT and total mesorectal excision, were enrolled. They received a radiation dose of 50-50.4 Gy with a concomitant 5-fluorouracil-based chemotherapy. Analysis of tumor response was based on the lowering of T stage. The association of the response to treatment and the predictive factors was analyzed. Peripheral venous blood samples were obtained before neoadjuvant CRT, after 2 and 4 weeks of the start of neoajuvant CRT, and before surgery. Peripheral blood lymphocytes were stained by the antibody combination of CD3/CD8 or CD4/CD8/CD19/CD56, and analyzed by flow-cytometry. Results Among the 15 patients, 13 had received total mesorectal excision at 6∼8 weeks after the end of CRT. Two patients showed a clinical complete remission (cCR) after CRT, and thus were followed without surgery. Those patients with response grade 2 or 3, and those with cCR, were considered good response (6 cases), and those with response grade 1a or 1b were considered poor response (9 cases), according to the histological response grade defined in the Japanese Classification of Colorectal Carcinoma. The absolute number of CD3(+) and CD4(+) T cells was significantly higher in the good response than the poor response group (P<0.01). Both markers showed a significant correlation with tumor response to CRT. Also, the N/L ratio could effectively predict response to CRT, with higher values obtained in the poor response group (P=0.01). Other markers, such as the percentage of NK cell and the CD4+/CD8+ ratio, did not correlate with response to CRT in our study. Conclusion In this study, the absolute number of CD3(+) and CD4(+) T cells in peripheral blood obtained prior to initiation of treatment, as well as the N/L ratio, were associated with tumor downstaging. Despite the small number of patients and the possible biologic variations of the lymphocyte subsets, this finding highlights the potential prognostic value of the baseline lymphocyte count in patients with RC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4532. doi:1538-7445.AM2012-4532