Acute severe lymphopenia by radiotherapy is associated with reduced overall survival in hepatocellular carcinoma

Purpose: Radiotherapy (RT) for peripheral organs can affect circulating lymphocytes and cause lymphopenia. We aimed to investigate RT-related lymphopenia in patients with hepatocellular carcinoma (HCC). Methods: Medical records of 920 patients who received RT for HCC during 2001–2016 were reviewed. Total lymphocyte count (TLC) were obtained and analyzed for clinical outcome. Acute severe lymphopenia (ASL) was defined as TLC <500/μL within the first 3 months of the start of RT. Results: The median TLCs before and 1 month after the start of RT were 1120 and 310/μl, respectively, and the TLCs did not recover to their initial level after 1 year. Overall, 87.4% of patients developed ASL. The median overall survival was 13.6 and 46.7 months for patients with and without ASL, respectively (p < 0.001). ASL was independently associated with poor overall survival with a hazard ratio (HR) of 1.40; 95% confidence interval (CI), 1.02–1.91 (p = 0.035). In the multivariate analysis, larger planning target volume (HR, 1.02; 95% CI, 1.01–1.03; p < 0.001) and lower baseline TLC (HR, 0.86; 95% CI, 0.82–0.91; p < 0.001) were significantly associated with an increased risk of ASL, while hypofractionation (stereotactic body RT: HR, 0.19; 95% CI, 0.07–0.49; p = 0.001) was significantly associated with a reduced risk of ASL. Conclusion: Acute severe lymphopenia after RT was associated with poor overall survival in patients with HCC. Stereotactic body RT may reduce the risk of ASL. Further attention to and research on the cause, prevention, and reversal of this phenomenon are needed.