Radiation Induced Lymphopenia in NSCLC Patients Was Associated with Age, Lung V5, Smoking, and AA Genotype of XRCC1 rs25487 Assayed in Peripheral Lymphocytes

Abstract

Lymphopenia is a type of severe radiation toxicity that may negatively impact the outcome of immunotherapy. We investigated whether single nucleotide polymorphisms (SNPs) of DNA repair gene XRCC1 in peripheral lymphocytes are connected with radiation induced lymphopenia (RIL). We genotyped XRCC1 rs25487 in 181 patients with non-small cell lung cancer (NSCLC) who received definitive radiotherapy (RT). Eligible patients were older than 18 years of age, had a Karnofsky performance score >70, stage IIb to IIIb disease. The median total radiation dose was 74 Gy (range, 60.0 to 78.0 Gy) given at 1.8 to 2.4 Gy/fraction. Results were assessed by Cox regression models for risk of ALC < 0.3*109/L during RT, which was median value and showed significant association with OS. Univariate and multivariate analyses were performed to identify independent risk factors. Univariate analyses showed older age, larger GTV volume, higher lung V5 and mean lung dose were associated with lymphocytes nadir < 0.3*109 /L with a statistically significant difference. XRCC1 rs25487 AA genotype was found to be associated with higher incidence of ALC < 0.3*109/L during RT relative to AG/GG genotypes (AA vs. AG/GG HR=1.626, 1.085-2.439, p=0.019). Multivariate analyses showed age>65y (HR=1.030, 1.008-1.053, p=0.008), smoking > 40 (pack*year) (HR=1.007, 1.002-1.012, p=0.005), lung V5 > 48% (HR=1.044, 1.028-1.060, p<0.001), and AA genotype (HR=1.879, 1.236-2.858, p=0.003) were independent risk factors associated with higher incidence of ALC < 0.3*109/L during RT. Based on these independent risk factors, we categorized patients into 3 groups with significant risk of developing RIL (Table 1). Old age, rs25487 AA genotype in XRCC1 gene in the peripheral blood, smoking, and lung V5 were independent risk factors associated with higher risk of RIL. This information is used to develop a predictive model for severe RIL which could be used to identify high risk patient clinically.Abstract 3238; Table 1Risk comparisons of ALC < 0.3*109 /L during RT among risk groups. Note: From V5 > 48 %, XRCC1 rs25487 AA genotype, age> 65y, smoking (pack*year)>40, each risk factor scores 1. Group 1 scores 0, group 2 scores 1-2, and group 3 scores 3-4Risk groupsHR95% CIpGroup 2 vs. Group 13.8511.270-12.2820.023Group 3 vs. Group 18.7472.680-28.545<0.001Group 3 vs. Group 22.2641.501-3.415<0.001 Open table in a new tab