The volume of low-dose thoracic irradiation influences systemic inflammation-immunity status after chemoradiation in esophageal cancer

Abstract

Background: Definitive chemoradiation is an essential treatment for non-operative thoracic esophageal cancer. However, it may trigger radiation-induced lymphopenia, impacting survival outcomes. The neutrophil-lymphocyte ratio (NLR) is an indicator of inflammatory status and survival outcomes. Here, we determined the association of clinical and dosimetric parameters with changes in hematological variables. Methods: We recruited 93 thoracic esophageal squamous-cell cancer patients who have completed definitive concurrent chemoradiotherapy (CCRT) between 2010 and 2015. Clinical, dosimetric, and hematological data, including absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and NLR, were analyzed at baseline and during CCRT. Cox regression model and Kaplan-Meier analyses were used to analyze different survival outcomes. Associations between clinical, hematological, and dosimetric variables were determined using Spearman's rank or Pearson correlation coefficients, and a multivariable logistic regression was used to verify identified correlations. Results: Patients (mean age =58.6 y) were predominantly males (94%), 27% of which were stage II (n=25) and 73% were stage III (n=68), with a median overall survival (OS) of 13 months [95% confidence interval (CI): 10.304-15.696]. Baseline NLR (NLR-b) and highest NLR during CCRT (NLR-h) was significantly correlated with OS, progression-free survival (PFS), disease-specific survival (DSS), and freedom from distant metastasis (FFDM). Dichotomized NLR-b, >3.68 or ≤3.68, was also correlated with survival. Primary esophageal tumor length (Spearman's r=0.324, P=0.011) and baseline body weight (Spearman's r=-0.251, P=0.019) were significantly correlated with NLR-b >3.68. In multivariable logistic regression, primary esophageal tumor length (OR =1.345, P=0.021) was associated with a higher NLR-b. Lung V5 (Pearson r=0.254, P=0.014) and V10 (Pearson r=0.317, P=0.002) were significantly correlated with NLR-h. Lung V5 (Pearson r=0.299, P=0.005) and heart V10 (Pearson r=0.273, P=0.011) were significantly correlated with the decrease in ALC during CCRT.Conclusions: Status of inflammation is correlated with survival outcomes and tumor size, and low-dose thoracic irradiation affects inflammation-immunity dynamics. A novel approach that decreases unnecessary exposures to radiation may further improve survival outcomes in esophageal cancer treated with CCRT.

Cardiac Dose Predicts the Response to Concurrent Chemoradiotherapy in Esophageal Squamous Cell Carcinoma

“…It is difficult to explain the whole picture of the pro- or anti-tumorigenic host response to cancer therapies with a simple NLR-h level [ 45 ]; however, it may still reflect dynamic immune alterations during treatment and predict further prognosis. RT has been correlated with negative effects on immunity in non-small cell lung cancer [ 46 ], and we found that the volume of low-dose thoracic irradiation affects systemic inflammation-immunity status, as the absolute lymphocyte count is the most correlated with decreasing blood cell count [ 47 ]. It has been proposed that radiation-induced lymphopenia impacts complete pathological response rates, and that the cardiac dose is a leading dosimetric factor associated with severe lymphopenia [ 17 ].…”