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.
Highlights
Glioblastomas are tumors which currently have a terrible prognosi Isocitrate Dehydrogenase (IDH)-wild-type glioblastoma (90%) is most often a primary or de novo tumor on the contrary to IDH-mutant glioblastoma (10%) which mostly corresponds to so called “secondary glioblastoma,” resulting from the progression of a low-grade glioma (according to the new 2016 World Health Organization (WHO) classification)(1)
High radiation doses to ipsilateral neural stem cells (NSC) and contralateral Sub Ventricular Zone (SVZ) could have a negative impact on overall survival in IDH-wild-type glioblastoma population
Our study reports a significant negative impact of higher doses of radiation received by normal stem cells on overall survival (OS) in a homogeneous subgroup of patients with IDH-wild-type glioblastoma, whilst taking into account MGMT promoter methylation status [3] and Epithelial Growth Factor Receptor (EGFR) amplification
Summary
Glioblastomas are tumors which currently have a terrible prognosi Isocitrate Dehydrogenase (IDH)-wild-type glioblastoma (90%) is most often a primary or de novo tumor on the contrary to IDH-mutant glioblastoma (10%) which mostly corresponds to so called “secondary glioblastoma,” resulting from the progression of a low-grade glioma (according to the new 2016 World Health Organization (WHO) classification)(1). In 1998, Eriksson et al reported the existence of neurogenesis from normal neural stem cells (NSC) in the adult human brain with a capacity to migrate, and to participate actively in brain tissue repair [4]. These can be found in two main zones or “neural niches” in the brain: the Sub Ventricular Zone (SVZ) located between the lateral ventricles and the striatal parenchyma, and the Sub Granular Zone (SGZ) confined to the hippocampal dentate gyrus. Different retrospective studies regarding this hypothesis have led to contradictory results on the prognostic impact of the total radiation dose to these neural niches [10,11,12]
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