OS03.4.A Irradiation of the subventricular and subgranular zone and overall survival in high-grade glioma patients

BACKGROUND Previous research has shown that neural stem cells (NSCs) in the subventricular zone (SVZ) may support the growth of glioma by recruiting new cells to the tumor. NSCs are located in the SVZ as well as in the subgranular zone (SGZ) of the hippocampus, the two neurogenic niches of the brain. This might indicate that irradiation of the SVZ and SGZ, and thereby damaging NSCs, reduces tumor growth and improves overall survival (OS). However, irradiation may also inhibit the repair capacity of healthy brain tissue by these neurogenic niches. Therefore, we investigated the effects of SVZ and SGZ irradiation dose on OS, in a cohort of high-grade glioma patients. MATERIAL AND METHODS We have retrospectively selected 221 patients (2014–2020) with WHO grade III and IV gliomas that underwent radiotherapy. Next to clinical baseline characteristics, T1 weighted MRI- and CT-images were collected. The SVZ and SGZ regions on the individual T1 images were delineated via non-linear registration of brain atlases. SVZ labels were created in 0.5mm isotropic MNI T1 and T2 templates, while SGZ atlas labels were available via the Hippocampus and Subfields CoBrA atlas. Next, the mean dose from the acquired SVZ and SGZ labels were extracted. The relationship between SVZ doses, SGZ doses and OS were examined using the Cox proportional hazards model and the Kaplan-Meier method (using the Log Rank test for significance). RESULTS For the mean dose in the SVZ, the hazard ratio (HR) was 1.024 per Gy (P = 0.002, [95% confidence interval, 1.009–1.040]) and the mean SGZ dose had a HR of 1.021 per Gy (P< 0.001, [95% confidence interval, 1.012–1.031]). These results were then corrected for the following covariates: sex, age, total intracranial volume and extent of surgery. This resulted in a HR of 1.031 per Gy (P = 0,001, [95% confidence interval, 1.014–1.050]) for the mean SVZ dose, and a HR of 1.025 per Gy (P< 0.001, [95% confidence interval, 1.015–1.036]) for the mean SGZ dose. Patients whose SVZ received greater than the median SVZ dose (= 31.3 Gy) showed a significant decrease in OS compared to patients who received less than the median dose (10.7 months vs 13.5 months median OS, P = 0.001). Patients whose SGZ received greater than the median SGZ dose (= 31.9) showed a significant decrease in OS compared to patients who received less than the median dose (10.7 months vs 15.1 months median OS, P< 0.001). CONCLUSION Here, we present a large cohort of high-grade glioma patients, in which we show a statistically significant decrease in overall survival with increasing radiation dose on the SGZ and SVZ. This correlation suggests that both neurogenic niches might need to be spared during radiotherapy treatment to improve overall survival even in high-grade glioma patients. Modern radiotherapy planning and delivery options are available to implement this.