Shortened Radiation Time Promotes Recovery From Radiation-induced Lymphopenia in Early-Stage Non-small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy

Abstract

Background: To evaluate the potential impact of radiation time on radiation-induced lymphopenia (RIL) and subsequently recovery after stereotactic body radiation therapy (SBRT) and to examine the associations between radiation time and with patient outcomes in early-stage non-small cell lung cancer (NSCLC). Methods: Clinical and laboratory records of subjects consisted of 115 patients who had received SBRT for early-stage NSCLC. Clinical and laboratory records were retrospective reviewed to assess the changes in total lymphocyte counts (TLCs) following SBRT. Associations of TLCs kinetics with the clinical and treatment features, and outcomes were analyzed. Results: Most patients (100/115, 86.96%) experienced significantly decreased median TLCs following SBRT (1700 vs 1100 cells/µL; P < .001), and 52 patients (45.21%) met the criteria for lymphopenia. Six months after SBRT, 44 patients (38.26%) had recovered. A negative correlation between TLCs reduction and radiation time was observed (r = -0.381, P < .001). According to the receiver-operating characteristic curve analysis, the optimal cut-off value for radiation time to was 3950 s to predict lymphocyte count recovery (LR) following RIL was 3950 s (P < .001). Multivariate analyses demonstrated that radiation time was significantly associated with LR (odds ratio [OR], 0.113; 95% confidence interval [CI], 0.029-0.432; P = .001) but not TLCs reduction (P = .575). LR within 6 months after SBRT was associated with improved progression-free survival in patients without non-lymphopenia (P = .034), but had little effect in patients with lymphopenia (P = .405). Conclusion: A longer radiation time was associated with a lower rate of LR within 6 months after SBRT in patients with early-stage NSCLC. Given the association of severe and persistent RIL with survival in NSCLC, further study of the effect of radiation time on immune status is warranted.

Keywords: lymphocyte count recovery; non-small cell lung cancer; prognosis; radiation-induced lymphopenia; radiotherapy.

Figure 1.

(A) Distribution of TLCs from baseline levels before SBRT to 6 months after SBRT in patients with early stage NSCLC. Note: Not all patients had TLCs data available at each time point. (B) Correlation between ATLCs and radiation time. (C) ROC curve analysis of radiation time for LR.

Figure 2.

(A and B) Distribution of TLCs at each time stratified by survival (PFS > 2 years vs PFS < 2 years and OS > 2 years vs OS < 2 years). ***P < .001, **P < .01, and *P < .05. (C) PFS curves are shown for G0 lymphopenia patients with LR within 6 months after SBRT (red), G0 lymphopenia patients with no LR (green), G1-3 lymphopenia patients with LR (blue), and G1-3 lymphopenia patients with no LR (light blue). (D) OS curves for the groups of patients described for (C).