Negative Survival Impact of High Radiation Doses to Neural Stem Cells Niches in an IDH-Wild-Type Glioblastoma Population

高剂量辐射对IDH野生型胶质母细胞瘤细胞群中神经干细胞微环境的生存产生负面影响

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Abstract

Aims: Assess the impact of radiation doses to neural stem cell (NSC) niches in patients with IDH-wild-type glioblastoma. Materials and Methods: Fifty patients were included in the study. NSC niches [SubVentricular Zone (SVZ) and Sub Granular Zone (SGZ)] were contoured by fusing CT scans and pre-therapy MRI, Tumor location defined ipsilateral and contralateral SVZ and SGZ. Prognostic significance of clinical, biological and dosimetric parameters were examined. We generated a Recursive Partitioning Analysis (RPA) model with independent prognostic classes. Results: Median follow-up: 23.8 months. Event free and overall survival (OS): 10 and 19.1 months. Incomplete surgery, PTV (planning target volume), ipsilateral SVZ or NSC niche mean dose > 57.4 Gy, contralateral NSC niche mean dose > 35 Gy and bilateral NSC niche mean dose > 44 Gy were significantly correlated with reduced OS. Only EGFR amplification was an independent prognostic factor (p = 0.019) for OS. RPA generated independent risk groups: 1 (low risk): [ipsilateral NSC mean dose (INMD) < 58.01 Gy and methylated MGMT promoter], 2: (INMD < 58.01 Gy and unmethylated MGMT promoter and contralateral SVZ mean dose < 18.6 Gy; p = 0.43), 3: (INMD < 58.01 Gy and unmethylated MGMT promoter and contralateral SVZ mean dose > 18.6 Gy; p = 0.002) and 4: (very high risk) (INMD > 58.01 Gy; p < 0.001). Conclusion: High radiation doses to ipsilateral NSC and contralateral SVZ could have a negative impact on overall survival in IDH-wild-type glioblastoma population.

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