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.
Highlights
The immunological side effects of radiation therapy (RT) for tumor treatment are complex and include both stimulatory and inhibitory activity [1, 2]
Alterations of mean cell counts and percentages of total lymphocytes belonging to specific lymphocyte subsets following stereotactic body RT (SBRT)
Univariate analyses revealed that higher Pre-SBRT total peripheral lymphocyte count (TLC) level, higher mean lung dose, longer treatment duration, and longer total beam-on time (TBT) were significantly associated with a lower Post-SBRT TLC level
Summary
The immunological side effects of radiation therapy (RT) for tumor treatment are complex and include both stimulatory and inhibitory activity [1, 2]. The enhancement of anti-tumor immunity by RT is best exemplified by the observation that RT could promote the death of tumor immunogenicity through the generation of an analogous in situ cancer vaccine [1, 3] This positive impact is often counteracted by RT-induced lymphopenia (RIL) [4]. Previous work has shown that RIL would further compromise the therapeutic efficacy of immune checkpoint inhibitors through the loss of effector cells, which identify and destroy tumor cells [11, 12] This further emphasized the importance of preserving and maintaining circulating lymphocytes in the setting of the new therapeutic strategy of combining radiotherapy (RT) and immunotherapy in cancer patients. 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
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