A Systematic Review and Meta-analysis of the Impact of Radiation-Related Lymphopenia on Outcomes in High-Grade Gliomas

Abstract

Supriya MallickIntroduction Malignant gliomas are the most common primary malignant brain tumors and are typically treated with maximal safe surgical resection followed by chemoradiation. One of the unintended effects of radiation is depletion of circulating lymphocyte pool, which has been correlated with inferior overall survival outcomes. Methods A comprehensive and systematic searches of the PubMed, Cochrane Central, and Embase databases were done to assess the studies that have reported radiation-related lymphopenia in high-grade gliomas. Hazard ratios (HRs), odds ratios (OR), and mean differences were represented with Forest plots comparing patients with severe lymphopenia and no severe lymphopenia. Review Manager Version 5.3 (The Nordic Cochrane Centre, Copenhagen, Denmark) was used for the analysis. Results Nineteen studies were included in the final systematic review and 12 studies were included in the meta-analysis. The odds of developing severe lymphopenia were 0.39 (95% CI:0.19, 0.81, I ² = 94%, p = 0.01). Patients with severe lymphopenia were at increased risk of death with a pooled HR = 2.19 (95% CI: 1.70, 2.83, I ² = 0%, p <0.00001) compared to patients with no severe lymphopenia. The mean difference in survival between patients with severe lymphopenia and no severe lymphopenia was -6.72 months (95% CI: -8.95, -4.49, I ² = 99%, p <0.00001), with a better mean survival in the no severe lymphopenia group. Conclusion Radiation-induced severe lymphopenia was associated with poor overall survival and increased risk of death. Photon therapy, larger planning target volume, higher brain dose, higher hypothalamus dose, and female gender were associated with increased risk of severe lymphopenia.

Keywords: high-grade gliomas; lymphopenia; radiation; systematic review.

Supriya Mallick

Fig. 1

PRISMA flow diagram depicting the search strategy in the systematic review literature search.

Fig. 2

( A ) Forest plot of odds ratio of developing severe lymphopenia. ( B ) Forest plot of pooled hazard ratios of overall survival between patients with severe lymphopenia and no severe lymphopenia. ( C ) Forest plot of mean difference between patients with severe lymphopenia and no severe lymphopenia. The Forest plot for HR and mean difference was plotted by generic inverse variance method; OR by Mantel-Haenszel method and p -value from the Z -test to examine whether the pooled estimate of effect is statistically significant. CI, confidence interval.