205 Microglia-Mediated Survival Outcomes in Preoperative Radiation for Glioblastoma: Insights From a Preclinical Model

Abstract

INTRODUCTION: Glioblastoma (GBM) is the most common and devastating primary brain tumor in adults. The current standard of care includes maximal safe resection followed by concurrent radiation and temozolomide-based chemotherapy. However, preoperative radiotherapy is used in different cancer types and commonly used for brain metastasis to shrink tumors, but it has never been used in for primary GBM. METHODS: Thirty-nine immunocompromised adult athymic nude female rats were orthotopically engrafted with a GBM1A patient-derived glioma cell line and randomized to either receive radiotherapy prior to tumor resection (RTRE) or postoperative radiotherapy (RERT). The rats received 30 Gy hypofractionated stereotactic radiation in 5 fractions of 6 Gy. Kaplan-Meier curve was used to plot the survival. Hematoxylin-eosin staining, microglia/macrophages using IBA-1 and TMEM119 markers were used in resected and recurrent tumor tissues. Moreover, nuclei area was measured on all tumor samples. Student’s T-test and analysis of variance (ANOVA) were used for statistical analysis. RESULTS: Kaplan-Meier analysis showed a significant survival benefit in the RTRE group, with median survival of 18.28 weeks compared to 14.85 weeks for RERT (p < 0.001), which correlated with the time of recurrence. Simultaneously, an increase in the nuclei area was found in the resected tumor tissues from the RTRE group (p < 0.001) and RERT recurrent tumor tissues (p < 0.001). Interestingly, we found lower microglia/macrophage recruitment in RTRE in the recurrent tumors (p < 0.01) and throughout the tumor areas compared to the RERT group. CONCLUSIONS: Our study represents the first preclinical study demonstrating the feasibility and longer overall survival using RTRE instead of RERT in vivo. Moreover, RTRE shows an important effect in the macrophages/microglia recruitment and in the immune profile. This suggests strong superiority for new clinical radiation strategies.