LAUSR

Abstract Systemic inflammatory indices are correlated with poor prognosis in cancer patients. The presence of lymphocytes in and around the tumor tissue is a predictor in rectal cancer. We aimed to explore the mechanism underlying the changes in circulating lymphocyte during neoadjuvant therapy and the way in which the count correlates with tumor response. Around 307 patients from FOWARC trial and 64 patients from FORTUNE trial were included in the training and validation group. Circulating lymphocyte count was recorded before neoadjuvant therapy and before rectal surgery. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off value of the reduction of lymphocytes. A logistic regression model was obtained in multivariate analysis. The blood absolute number of lymphocyte before and after therapy had no correlation with tumor response. However, total lymphocyte count (TLC) reduction was significantly higher in good response group (39.81% vs 33.31% P = .032) in the FOWARC cohort. The optimal cut-off value for TLC was 24.96%. Age, tumor length, and TLC reduction (P = .005, OR = 2.009, 95%CI 1.240–3.254) were significant factors for tumor regression in multivariate analysis. In the FORTUNE cohort, TLC reduction was the only significant factor for tumor regression in both univariate (P = .032, OR = 3.434, 95%CI 1.111–10.614) and multivariate analysis (P = .046, OR = 3.361, 95%CI 1.024–11.035). Circulating lymphocyte count decreases during neoadjuvant therapy for locally advanced rectal cancer, and it is associated with better tumor regression. It may be involved in the immune response provoked by radiotherapy and chemotherapy.