Title：Severe lymphopenia as a prognostic factor in rectal cancer patients receiving adjuvant chemoradiotherapy: a retrospective study Running head: lymphopenia related with DFS in rectal cancer

Abstract Purposes: The relationship between total lymphocyte counts (TLCs) and survival is not well documented in rectal cancer. This study aimed to investigate the association between TLCs and disease-free survival (DFS) and identify factors associated with lymphopenia in locally advanced rectal cancer patients receiving chemoradiotherapy. Methods: Thirty-six patients with locally advanced rectal cancer were retrospectively analyzed. TLCs were evaluated before surgery (pre-S), before radiotherapy (pre-RT), and during concurrent chemoradiotherapy (CCRT). The relationship between TLCs and DFS was analyzed by univariate and multivariate analysis. Potential clinical factors associated with lymphopenia were also evaluated. Results: Median TLC declined significantly during radiotherapy. Severe lymphopenia during CCRT was significantly associated with poorer DFS on Kaplan-Meier analysis (p=0.01), univariate regression analysis (p=0.036), and multivariate regression analysis (p=0.038). Pre-S TLCs (p=0.009) and pre-RT TLCs (p=0.042) were significantly associated with severe lymphopenia on univariate regression analysis; however, only pre-S TLCs (p=0.026) were significantly associated with severe lymphopenia on multivariate regression analysis. Conclusions: Severe lymphopenia was a predictor of poorer DFS in patients with locally advanced rectal cancer receiving adjuvant chemoradiotherapy. Pre-S TLCs were predictors of severe lymphopenia. Further study is warranted to reduce the rate of severe lymphopenia.