The Volume of Low-Dose Thoracic Irradiation Influences Systemic Inflammation-Immunity Status After Chemoradiation in Esophageal Cancer

Abstract

Definitive chemoradiation is essential in non-operative thoracic esophageal cancer. Concerns have posed onto the possible radiation-induced lymphopenia and correlation with different survival outcomes. Neutrophil to lymphocyte ratio (NLR) is a simple way to surrogate the inflammation-immunity status and predict survival. We aim to evaluate the clinical variables and radiation dosimetric parameters associated with hematologic variables changes.Between 2010 and 2015, we identified 93 newly diagnosed thoracic esophageal squamous-cell cancer patients who had completed definitive concurrent chemoradiotherapy (CCRT). Patients' clinical, dosimetric, and hematological data, including absolute neutrophil count, absolute lymphocyte count, and NLR were analyzed at baseline and during CCRT. Cox regression model and Kaplan-Meier analyses were used to validate different survival outcomes. The possible relationships between clinical, hematologic, and dosimetric variables were tested using Spearman's rank or Pearson correlation coefficients, and a further multivariable logistic regression model was created to verify these significant variables.The participant group (mean age = 58.6 y) predominantly comprised males (94%) with 27% stage II (n = 25) and 73% stage III (n = 68). Median overall survival (OS) was 13 months (95% confidence interval: 10.304-15.696). We confirmed that baseline NLR (NLR-b) and highest NLR during CCRT (NLR-h) significantly predicted OS, progression-free survival, disease-specific survival, and freedom from distant metastasis. Dichotomized NLR-b with > 3.68 or ≤3.68 also predicted the survival outcomes. Primary esophageal tumor length (Spearman's correlation coefficient r = 0.324, P = 0.011) and baseline body weight (Spearman's r = -0.251, P = 0.019) were significantly correlated with baseline NLR > 3.68. In multivariable logistic regression, primary esophageal tumor length (OR = 1.345, P = 0.021) remained associated with a higher NLR-b. For NLR-h, lung V5 (Pearson r = 0.254, P = 0.014) and V10 (Pearson r = 0.317, P = 0.002) were significantly correlated. In the percentage of ALC nadir decreased during CCRT, lung V5 (Pearson r = 0.299, P = 0.005) and heart V10 (Pearson r = 0.273, P = 0.011) were significantly correlated.Inflammation predicts survival outcomes and is correlated with tumor size. Low-dose thoracic irradiation affects inflammation-immunity dynamics because lung V5 and V10 are related to NLR-h; lung V5 and heart V10 with extent of lymphocyte decrease. A novel approach to decrease these unnecessary exposures may further improve survival outcomes in esophageal cancer treated with CCRT.