Prediction of Lymphopenia and Survival with Baseline Absolute Lymphocyte Count and Irradiated Dose to Immune Cells in Patients with Non-Small Cell Lung Cancer Treated with Concurrent Chemoradiotherapy

Abstract

This study aimed to investigate the effect of effective dose to immune cell (EDIC) combined with pre-radiotherapy (RT) absolute lymphocyte count (ALC) on treatment-related lymphopenia during RT and treatment outcome in patients with locally advanced non-small cell lung cancer (NSCLC). A subgroup analysis in patients who received consolidation immunotherapy was also conducted. Between August 2008 and December 2021, 517 patients with locally advanced NSCLC treated with definitive concurrent chemoradiotherapy (CRT) were retrospectively analyzed. All patients had serial complete-blood-count tests at pre-, and during-CRT. Severe lymphopenia was defined as ALC < 0.5x109cells/L during RT. EDIC was calculated according to mean doses of the lung, heart and the total body. The patients were grouped according to high and low EDIC and pre-RT ALC and was assessed for its correlation with radiation induced lymphopenia and survival outcomes. Of 517 eligible patients, most of the patients received weekly paclitaxel with carboplatin (90.3%) and 195 patients (37.7%) received consolidation immunotherapy following CRT. A median radiation dose of 63 Gy (IQR, 60-64.5) was delivered in 30 fractions. The optimal cutoff value of EDIC and pre-RT ALC for predicting severe lymphopenia were 2.89 Gy and 2.03x109cells/L, respectively. High risk group was defined as EDIC ≥ 2.89 Gy and pre-RT ALC < 2.03x109cells/L, low risk group as EDIC <2.89 Gy and pre-RT ALC ≥ 2.03x109cells/L, and intermediate group as EDIC ≥ 2.89 Gy and pre-RT ALC ≥ 2.03x109cells/L or EDIC < 2.89 Gy and pre-RT ALC < 2.03x109cells/L. The incidence of severe lymphopenia during RT in high, intermediate, and low risk group was 90.1%, 77.1%, and 52.3%, respectively (p<0.001). The risk groups were independent predictors for both progression-free survival (PFS) (p<0.001) and overall survival (OS) (p<0.001). The high-risk group had higher incidence of locoregional and distant recurrences (p<0.001). In the subset of patients who were treated with consolidation immunotherapy, the risk groups were predictive of severe lymphopenia (p = 0.001), PFS (p = 0.004), and OS (p = 0.012). This study demonstrated that the combination of EDIC and pre-RT ALC is a predictor for severe lymphopenia during RT, recurrence, and survival in patients with locally advanced NSCLC who received CRT. Moreover, the combination of EDIC and pre-RT ALC may serve as a potential biomarker for the benefit of maintenance immunotherapy.