Lymphopenia in Esophageal Squamous Cell Carcinoma: Relationship to Malnutrition, Various Disease Parameters, and Response to Concurrent Chemoradiotherapy

BACKGROUND. Lymphopenia occurs commonly in esophageal squamous cell carcinoma (ESCC) and may influence treatment outcomes. We aimed to examine its association with treatment response and tumor progression in patients with locally advanced ESCC treated with concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS. A total of 286 patients with stage II–IVa ESCC treated with CCRT between 2015 and 2017 were analyzed. Total lymphocyte counts were assessed at baseline, weekly, and 4 weeks after CCRT. Pretreatment lymphopenia was defined as total lymphocyte count <1,000 cells per mm(3) at diagnosis, and treatment‐related lymphopenia was defined as total lymphocyte count <200 cells per mm(3) with 6 weeks after starting CCRT. Univariate and multivariate logistic regression methods were used to analyze factors associated treatment‐related lymphopenia and treatment response. RESULTS. Lymphopenia was observed in 44 patients (15.4%) at initial diagnosis. Pretreatment lymphopenia was significantly associated with greater tumor length, worse T status, body mass index ≤18.5 kg/m(2), and weight loss ≥3 kg in the previous 3 months. Six weeks after starting CCRT, 89 patients (31%) developed treatment‐related lymphopenia. Tumor progression and cancer‐related death were more frequently observed in treatment‐related lymphopenia group than those without (76.4% vs. 52.8% and 58.4% vs. 39.6%). A complete response (CR) was achieved in 62 patients (21.7%). In multivariate analysis, treatment‐related lymphopenia was significantly associated with lack of clinical CR, and older age, lower tumor location, greater tumor length, and larger planning target volume were independent predictors of treatment‐related lymphopenia. CONCLUSION. Treatment‐related lymphopenia during CCRT is an independent predictor for poor treatment response in ESCC. IMPLICATIONS FOR PRACTICE. A total of 286 patients with locally advanced esophageal squamous cell carcinoma were treated with concurrent chemoradiotherapy (CCRT), and treatment‐related lymphopenia occurred in 31% of patients within 6 weeks from the start of CCRT. Treatment‐related lymphopenia was significantly associated with lack of treatment response, and older age, lower tumor location, greater tumor length, and larger planning target volume were independent predictors of treatment‐related lymphopenia. Lymphocyte count is an inexpensive biomarker that may be easily used by clinicians to identify patients who are most likely to benefit from CCRT.