Radiation-Induced Lymphopenia Predicts Poorer Prognosis in Patients With Breast Cancer: A Post Hoc Analysis of a Randomized Controlled Trial of Postmastectomy Hypofractionated Radiation Therapy

Purpose: The aim of this study was to determine whether radiation-induced lymphopenia affects the survival of patients with breast cancer. Methods and Materials: Post hoc analysis was conducted on data from 598 patients with breast cancer from a randomized controlled trial comparing postmastectomy hypofractionated radiation therapy (HFRT; 43.5 Gy in 15 fractions over 3 weeks) with conventional fractionated radiation therapy (CFRT; 50 Gy in 25 fractions over 5 weeks). Mean peripheral lymphocyte count (PLC) at different time points in the 2 groups was compared by the t test. Disease-free survival and overall survival were analyzed by the Kaplan-Meier method and compared between groups by the log-rank test. Results: Baseline PLC (pre-PLC) was comparable between HFRT and CFRT patients (1.60 +/- 0.57 x 10(9)/L vs 1.56 +/- 0.52 x 10(9)/L; P = .33). In both groups, the PLC declined steadily during the course of radiation therapy but started to recover at 1 month after radiation therapy. Incidence of lymphopenia was significantly lower in HFRT patients (45.4% vs 55.7%; P = .01). Nadir-PLC was significantly higher in HFRT patients (1.08 +/- 0.37 x 10(9)/L vs 0.97 +/- 0.31x 10(9)/L; P < .001), as was the nadir-PLC/pre-PLC ratio (0.72 +/- 0.28 vs 0.67 +/- 0.28; P = .02). Median follow-up was 57.6 months (interquartile range, 38.5-81.4). The 5-year disease-free survival was significantly lower in patients with a nadir-PLC/pre-PLC ratio <0.8 than in those with a ratio >= 0.8 (71.8% vs 82.6%; P = .01); however, overall survival was comparable between the groups (85.8% vs 90.6%; P = .24). Conclusions: The risk of radiation-induced lymphopenia in patients with breast cancer is lower with HFRT than with CFRT. A low nadir-PLC/pre-PLC ratio may predict poor prognosis. (C) 2020 Elsevier Inc. All rights reserved.