Prognosis and Risk Factors of Radiation-Induced Lymphopenia in Early-Stage Lung Cancer Treated With Stereotactic Body Radiation Therapy

Abstract

Background: To investigate the role of stereotactic body RT (SBRT) in decreased total peripheral lymphocyte count (TLC) in patients with early-stage lung cancer and to explore possible risk factors for RT-induced lymphopenia. Materials and Methods:We analyzed the TLCs and lymphocyte subsets of 76 patients in our prospective clinical database who received SBRT for early-stage lung cancer treatment. Relationships between clinical factors or dosimetric parameters and TLC were evaluated using Spearman's correlation analysis and Chi-square tests for continuous and categorical variables, respectively. Multivariate linear regression analysis was used to control for confounding factors. Kaplan-Meier analysis with a log-rank test and a multivariate Cox regression model were used for survival analysis.Results: Most patients (64/76, 84.2%) experienced decreased absolute lymphocyte counts following SBRT, as well as shifts in lymphocyte subset distributions. Spearman's correlation coefficients between post-SBRT TLC and the percentage of the lung and heart receiving 5 to 50 Gy (in 5 Gy increments) shown that most lung DVH parameters [V(10)-V(50)] were significantly negatively correlated with post-SBRT TLC, while only heart V(5), V(20), V(25), V(30), and V(45) were significant. Univariate analyses revealed that a lower Pre-SBRT TLC level, higher mean lung dose, longer treatment duration, and longer TBT were significantly associated with a lower Post-SBRT TLC level (all P < 0.05).Stepwise multivariate linear regression, which incorporated all of the significantly clinical variables and SBRT-related parameters in univariate analysis, revealed that lower pre -SBRT TLC (P < 0.001), higher heart V5 (P = 0.002), and longer total beam-on time (TBT) (P = 0.001) were the independent risk factors for decrease in post-SBRT TLC. Patients with lower post-SBRT TLC and longer TBT exhibited significantly inferior progression-free survival (PFS) (P < 0.001 and P = 0.013) and overall survival (P = 0.006 and P = 0.043).Conclusions: G2 and more severe lymphopenia after SBRT might be an independent prognostic factor for poorer outcome in early-stage lung cancer. Lowering heart V5 and TBT when designing SBRT plans may spare circulating lymphocytes and have the potential to further improve survival outcomes.

Stereotactic body radiation therapy mitigates radiation induced lymphopenia in early stage non-small cell lung cancer

“…Our results suggest that SBRT may not induce clinically meaningful RIL despite the associated risk of a large volume of healthy lung receiving low-dose spillage. Our results differ from those recently published by Zhao et al, where RIL was associated with both lower PFS and OS in patients treated with SBRT for early stage NSCLC [ 17 ]. One major explanatory difference lies in the timing of lymphocyte collection, with Zhao’s analysis focusing on lymphocyte counts collected within a week of SBRT completion and this analysis focusing on a period of up to 6 months post-treatment.…”

Potential Determinants for Radiation-Induced Lymphopenia in Patients With Breast Cancer Using Interpretable Machine Learning Approach

“…For the contribution of irradiation volume at heart, our findings are consistent with our previous study in lung cancer patients, i.e. higher heart V5 (the heart volume in 5Gy) was significant with decrease in post-radiation lymphocyte counts (31). The results of these studies were all consistent with our findings.…”

“…Considering the impact of irradiation dose on lymphopenia, the contribution of integral dose of the total body also has been presented in our previous work of EDIC formula containing integral dose of the total body resulted lymphopenia in 488 esophageal cancer patients ( 29 ); V5 of ipsilateral lung/bilateral lungs have been previously reported to impact lymphopenia in non-small cell lung cancer patients ( 30 ). Similar findings have been reported in patients with early-stage lung cancer, V10 to V50 were significantly negatively correlated with the decrease of absolute lymphocyte counts following radiation ( 31 ). In patients with pancreatic cancer, V10, V15, and V20 were significantly higher in patients with severe lymphopenia ( 32 ), and the same findings in patients with esophageal squamous cell carcinoma ( 33 ).…”

Safety and efficacy of a nonmyeloablative pretransplant conditioning regimen using total lymphoid irradiation with volumetric modulated arc therapy in healthy dogs: A pilot study

“…An experimental canine study demonstrated that the number of lymphocytes in the peripheral blood decreases after TBI or TLI procedures (Storb et al., 1999). In a previous clinical study, a subset analysis of peripheral blood lymphocytes in human patients after radiation therapy was performed, and the authors reported that the levels of B‐ and T‐helper lymphocytes significantly decreased compared with those of other lymphocytes (Zhao et al., 2020). The human and veterinary clinical studies described a reduction in the levels of peripheral blood lymphocytes with localized radiotherapy (Belka et al., 1999; Kent et al., 2020).…”