2685 - Interplay of Monocytes and Lymphocytes during Radiation for Glioblastoma Impacts Patient Survival
Presenter(s)
S. Workman1, A. Li2, Y. Tarui3, I. C. Liu1, L. K. Greenlund4, L. Sloan5, K. J. Redmond1, and L. R. Kleinberg1; 1Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 2Department of Psychology, Johns Hopkins University, Baltimore, MD, 3Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 4Riverside Community Hospital, Riverside, CA, 5University of Minnesota: Department of Radiation Oncology, Minneapolis, MN
Purpose/Objective(s): Lymphopenia occurring in some patients during or after treatment has been associated with a poor prognosis for patients with glioblastoma (GBM). Myeloid-derived suppressor cells (MDSCs), a myeloid subtype, are associated with poor outcome and may increase in the peripheral blood of some patients contributing to lymphopenia. A subset of MDSCs are known to be monocytic. Now, we aim to evaluate the interplay between peripheral monocytes and lymphocytes and how their relationship impacts survival in patients with GBM.
Materials/Methods: We retrospectively reviewed patients with GBM treated with conventionally fractionated radiotherapy (RT) with or without concurrent temozolomide from 2010 to 2020 at our institution and affiliated hospitals. Patients without peripheral lymphocyte or monocyte count at baseline (+/- 7 days of radiation start date) and post-RT (1 to 2 weeks after radiation completion) were excluded from the study. We collected clinical characteristics, pathology features, dosimetry, and baseline and post-RT lymphocyte and monocyte counts. Our main endpoint was overall survival (OS), defined as time from completion of RT. Paired t-test was used for comparisons between baseline and post-RT lymphocyte and monocyte values. Association between key clinical characteristics with survival was assessed with Cox proportional hazard ratio (HR) models.
Results: 248 patients are included in our analysis. The median age at start of RT was 61 years (range: 21 – 85). Of the 219 patients with MGMT methylation status available, 84 patients (38%) had MGMT methylated promoters. From baseline to post-RT, absolute lymphocytes and monocytes decreased by an average fold of 0.63 (95% CI: 0.57 – 0.69) and 0.83 (95% CI: 0.78 – 0.89), but when evaluating changes in percentages of total white blood cells, there was a significant decrease in lymphocytes (20.3% to 16.7%) while increase in monocytes (7.8% to 9.2%). There was also a significant increase in the monocyte-to-lymphocyte ratio (MLR) from 0.51 to 0.74. Median OS was 1.14 years (95% CI: 0.98 – 1.25). A post-RT MLR > 0.5 was associated with worse OS (51% vs 59% at 1 year, p = 0.016 on log-rank test). On univariate HR, age = 65 years and MLR > 0.5 were significantly associated with a worse prognosis, post-RT lymphocyte < 900 cells/µL was trending towards significance (p=0.0893).
Conclusion: Thus far in our analyzed cohort of patients with treated GBM, there was an increase in MLR from baseline to completion of radiation, potentially a biomarker for relative preservation of MDSC. Post-RT MLR greater than 0.5 was associated with worse overall survival. These data suggest than an increase in MLR from baseline to completion of RT may be an important biomarker for survival in GBM patients treated with radiation. Our preliminary findings warrant further investigation.