Radiation Induced Lymphopenia and Overall Survival in Patients with Limited Stage Small Cell Lung Cancer Receiving Definitive Chemoradiation

Abstract

Purpose/Objective(s): It has been strongly suggested that radiation-induced lymphopenia is a significant negative prognostic factor in non-small cell lung cancer, but there are fewer data in small cell lung cancer (SCLC). Here, we hypothesized that the baseline lymphocyte and/or lymphocyte nadir during chemoradiotherapy for SCLC is associated with survival. Materials/Methods: This is a retrospective study from a single Institution. Patients with limited stage SCLC treated from 2013 to 2017 were included. Additional eligibility included treatment with definitive thoracic radiation therapy (with or without concurrent chemotherapy) and the availability of complete-blood-count data from baseline and at least two time points during radiotherapy. The primary endpoint was Overall Survival, analyzed using the Kaplan-Meier method and Cox proportional hazard model. All tests were 2-sided and p-value less than 0.05 was considered to be significant. Results: A total of 623 patients were included: 424 male,199 female. Median age 59 years (range18-86 years). Median follow-up was 36.4 months (range: 33.1-39.7 months). Univariate analysis demonstrated that age, gender, clinical stage, concurrent chemotherapy (versus sequential), the use of prophylactic cranial irradiation (PCI), and the baseline lymphocyte were significantly associated with OS. Baseline lymphocyte (HR = 0.74, p = 0.005) and lymphocyte nadir during the course of radiation therapy (HR = 0.39, p = 0.002) were significant factors for OS under univariate analysis. On multivariate Cox regression models, after adjusting for gender (female Vs. male: HR = 1.2, p=0.0081), age(HR = 1.021, p＜0.0001), smoking history(HR = 1.313, p＜0.0001), clinical stage (Stage I-II Vs. stage III HR = 1.667, p＜0.0001), cycles of chemotherapy (HR = 1.14, p＜0.0001), RT timing ( HR = 0.890, p＜0.0001) and the receipt of PCI (HR = 0.44, p＜0.0001), the baseline lymphocyte count (HR = 0.88, p=0.003), and lymphocyte nadir (HR = 0.45 p＜0.0001) remained significant in predicting OS. Conclusion: Baseline lymphocyte and Lymphocyte nadir were significantly associated with survival in LS-SCLC patients treated with definitive chemoradiation therapy. This suggests that future research may focus on strategy to minimize lymphocyte reduction to improve survival.