Lymphocyte nadir predicts tumor response and survival in locally advanced rectal cancer after neoadjuvant chemoradiotherapy: Immunologic relevance

Background and purpose: Neoadjuvant chemoradiation (nCRT) could reduce tumor infiltrating lymphocytes. We examined absolute lymphocyte count (ALC) nadir during nCRT, pathologic response and prognosis for locally advanced rectal cancer (LARC). Materials and methods: 102 patients with LARC (cT3-4N0, or node-positive) treated between 2010 and 2015 with nCRT followed by complete resection were analyzed. The ALC value was obtained prior to, weekly during the treatment, and one month after nCRT. Associations of ALC nadir with immune cells' infiltrations, pathologic response and survival were analyzed. Results: Twenty-four (23.5%) and 60 (58.9%) patients achieved pathologic complete response and partial response respectively. Response rate was higher in high ALC nadir group than low nadir group (89.7% vs. 67.6%, p = 0.006). Compared to low ALC nadir group, increased tumor infiltrates of CD4+ (4% vs. 17.5%, p < 0.001), CD8+ (8% vs. 30%, p < 0.001) T cells and CD68+ macrophages (6% vs. 25%, p < 0.001) were observed in high ALC nadir group. High ALC nadir [OR = 4.32 (95% CI, 1.22-15.26), p = 0.023] and well differentiation [OR = 10.53 (1.87-59.36), p = 0.008] were associated with pathologic response. Patients with high ALC nadir yielded better DFS [HR = 0.36 (0.16-0.81), p = 0.010] and OS [HR = 0.24 (0.08-0.69), p = 0.004]. Conclusions: Higher ALC nadir during nCRT is associated with a higher rate of pathologic response and better survival for LARC patients, suggesting that ALC may be a potential stratification strategy for LARC patients. (C) 2018 Elsevier B.V. All rights reserved.