Predicting Changes in Circulating Immune Cells During Thoracic Radiation in Patients With Lung Cancer

Abstract

To exam the changes in circulating immune cells during radiation therapy (RT) and study whether radiation dose to organ at risk of immune system is associated with such changes in patients with lung cancer.Study population included stage I-IV lung cancer patients treated with RT to the thorax from March 2015 to December 2019 Patients with complete blood counts with differentials at baseline and weekly or bi-weekly during the course of RT were eligible. Circulating immune cells, including rapidly circulating ones in the heart, lung and blood vessels, and slowly circulating ones in the lymphatic system and blood reservoirs (a portion of veins/capillaries), were considered as a surrogate for organ at risk of immune system. The effective dose to the immune cells (EDIC) was modeled with assumptions that in each fraction, radiation dose was uniformly delivered to all cells for rapidly circulating ones, and only to those in the irradiated volume for slowly circulating ones. EDIC was thus calculated as a function of the number of RT fractions and doses to the lung, heart, and the whole body integral dose. "Immune cells" of our interest including lymphocyte, neutrophil, monocyte and platelet were assessed quantitatively and graded according to CTCAE4.03 for cytopenia. Associations between EDIC and changes of blood immune cells were assessed using linear regression model.A total of 110 consecutive patients were eligible. Median age was 62 years old (range 33-83 years old). Eighty percent were male. The percentage of patients with adenocarcinoma was 35.5%, squamous cell carcinoma 27.3%, small cell lung cancer 27.3% and others 10%. The distribution was 3.6%, 2.7%, 62.7% and 30.9% for stage I, II, III and IV, respectively. The median RT dose was 50 Gy (range 20-66 Gy). Compared t-test showed that total counts of lymphocyte, neutrophil, monocyte and platelet decreased significantly during radiation (All P < 0.001). The rates of grade 3-4 lymphopenia, neutropenia and thrombocytopenia were 61.8% (68/110), 17.3% (19/110) and 10.9% (12/110), respectively. The EDIC ranged from 0.87-6.12 Gy and was significantly and linearly correlated with the reduction in percentage of lymphocyte during RT (R = 0.322, P = 0.001). EDIC had no significant association with the reduction in neutrophil (R = 0.075, P = 0.437), monocyte (R = 0.003, P = 0.975) and platelet (R = 0.181, P = 0.059). Binary logistic regression revealed that EDIC was independently correlated with grade 3-4 lymphopenia (odds ratio 2.237, 95% confidence interval 1.132-4.423, P = 0.021) during RT after adjusting counts of lymphocyte at baseline (P < 0.001), use of concurrent chemotherapy (P < 0.001) and total prescription RT dose (P = 0.827).Circulating immune cells reduced significantly during RT and lymphocytes seemed to be most sensitive cell type. EDIC can predict the reduction of lymphocyte and predict severe lymphopenia during RT in patients with lung cancer.