Lymphocyte Count Kinetics, Factors Associated with the End-of-Radiation-Therapy Lymphocyte Count, and Risk of Infection in Patients with Solid Malignant Tumors Treated with Curative-Intent Radiation Therapy

Abstract

Lymphopenia has been associated with poor outcomes in patients with cancer. We sought to describe the lymphocyte kinetics in patients who received radiation therapy; to identify factors associated with the end-of-radiation-therapy (EoRT) lymphocyte count; and to determine the association of radiation therapy-induced lymphopenia with subsequent infection. Patients with solid malignant tumors treated at the Department of Oncology at Rigshospitalet, University of Copenhagen, Denmark, were included if they had received their first external beam radiation therapy with curative intent from January 2005 to December 2016 and had pretreatment and EoRT lymphocyte counts measured. Factors associated with the EoRT lymphocyte count were identified using regression analyses. The risk of subsequent infection was estimated using Cox proportional hazards regression. We included 3920 patients. More patients had lymphopenia (<1000 cells/μL) at EoRT than at pretreatment (67.1% vs 14.9%; P < .001). Patients who received schemes with higher intensities (equivalent dose in 2-Gy fractions [EQD2] >65 Gy) in shorter time (<25 days) had a higher predicted EoRT lymphocyte count than patients who received schemes delivering EQD2 of 50 to 65 Gy in 25 to 45 days (1439 cells/μL, 95% confidence interval [1293-1585] vs 784 [754-814]). Radiation to multiple sites and concomitant chemotherapy use, particularly platinum compounds versus none, were associated with a lower EoRT lymphocyte count (698 [655-742] vs 852 [833-870]; and 612 [565-659] vs 937 [909-964], respectively). Patients with EoRT lymphopenia grade ≥3 (<500 cells/μL) had a higher risk of infection in the 3 months after radiation therapy (hazard ratio, 2.15 [95% confidence interval, 1.53-3.02]; P < .001), compared with patients with an EoRT lymphocyte count >1000 cells/μL. The lymphocyte count declined during radiation therapy. Short duration schemes (<25 days), despite high total radiation dose (EQD2 >65 Gy), were associated with a higher EoRT lymphocyte count, whereas radiation to multiple sites and concomitant chemotherapy were associated with a lower count. EoRT lymphopenia was associated with an increased risk of infection.