Lymphopenia and Radiation Dose to Circulating Lymphocytes With Neoadjuvant Chemoradiation in Esophageal Squamous Cell Carcinoma

Abstract

Purpose 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 treated with trimodality therapy according to the Dutch ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial regimen. To test this hypothesis, we examined the effect of EDIC on the degree of lymphocyte drop (lymphocyte nadir). Methods and Materials Patients with advanced nonmetastatic esophageal squamous cell carcinoma treated in a single tertiary cancer center from 2012 to 2018 were eligible for this study. All patients had to have a radiation therapy 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 (77 men and 15 women). The mean EDIC was 2.8 Gy (range, 0.6-4.4). EDIC was significantly correlated with lymphocyte nadir (Spearman coefficient = –0.505; P < .01), and lymphocyte nadir was a significant independent factor for shorter OS (hazard ratio = 0.63; P < .001). Lymphocyte nadir was also the most significant factor in determining OS among other clinical parameters. Exploratory analysis showed significant OS differences between EDIC groups (<2, 2-4, and >4 Gy). The 2–year OS rates were 66.7%, 42.7%, and 16.7% for EDIC <2, 2 to 4, and >4 Gy, respectively. Conclusions There was a significant correlation between radiation dose to circulating immune cells and lymphocyte nadir, which in turn affected OS in patients with advanced nonmetastatic esophageal squamous cell carcinoma treated by trimodality therapy.

Risk factors for radiation induced lymphopenia in patients with breast cancer receiving adjuvant radiotherapy

“…Emerging evidence showing radiation-induced lymphopenia (RIL) or PLC-related parameters are associated with poor survival outcomes in several solid tumors (9)(10)(11)(12)(13)(14). Cho et al reported RIL was a potential predictor for ipsilateral breast tumor recurrence in 216 patients with early breast cancer treated with breast-conserving therapy (BCT) (15).…”

Neutrophil-to-Lymphocyte Ratio as a Factor Predicting Radiotherapy Induced Oral Mucositis in Head Neck Cancer Patients Treated with Radiotherapy

“…This is due to the fact that lymphocytes are responsible for the secretion of cytokines, which limit the proliferation and metastasis of tumour cells and a worse response to anti-cancer treatment. Lymphopenia is a negative prognostic factor in many cancers, including pancreatic cancer, non-small cell lung cancer (NSCLC), glioblastoma, and head and neck cancer [ 53 , 54 ]. Currently, there are a lack of effective methods to prevent the development of OM or to treat it.…”

Chronological Analysis of Acute Hematological Outcomes after Proton and Photon Beam Craniospinal Irradiation in Pediatric Brain Tumors

“…The significance of the radiation dose to circulating lymphocytes has been reported recently. The integral dose to large blood vessels, the heart, and lymphoid or non-lymphoid organs, including the lungs or liver, is associated with the reduction in the number of lymphocytes and the subsequent development of lymphopenia [24][25][26]. Furthermore, because lymphocytes are the effector of immune response against the tumor cells, lymphopenia is expected to be associated with poor outcomes, such as those reported in various types of malignancies [18,27,28].…”