Lymphopenia and radiation dose to circulating lymphocyte with neoadjuvant chemoradiation in esophageal squamous cell carcinoma

Abstract Background We hypothesized that radiation-induced lymphopenia could be predicted by the effective dose to the circulating immune cells (EDIC) in advanced esophageal squamous cell carcinoma (ESCC) treated with trimodality therapy according to the Dutch CROSS trial regimen. To test this hypothesis, we examined the effect of EDIC on the degree of lymphocyte drop (lymphocyte nadir). Methods Patients with advanced non-metastatic ESCC treated in a single tertiary cancer centre from 2012–2018 were eligible for this study. All patients must have a radiotherapy plan available for EDIC computation and received neoadjuvant chemoradiation according to the Dutch CROSS trial regimen before radical esophagectomy. The EDIC was calculated as a function of integral doses to the lung, heart and total body with a verified mathematical model. The association between EDIC and lymphocyte nadir was studied, and the relationships of overall survival (OS) with lymphocyte nadir and EDIC were assessed using multivariable Cox regression model. Results This analysis included 92 eligible consecutive patients with 77 males and 15 females. The mean EDIC was 2.8 Gy (range 0.6–4.4). EDIC was significantly correlated with lymphocyte nadir (Spearman coefficient = -0.505; P 4 Gy). The 2–year OS rates were 66.7%, 42.7% and 16.7% for EDIC 4 Gy, respectively. Conclusions There was significant correlation between radiation dose to circulating immune cells and lymphocyte nadir which in turn impacted overall survival in patients with advanced non–metastatic ESCC treated by trimodality therapy.