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

Xavier Muracciole 1 Wassim El-Amine 2 Emeline Tabouret 3, 4 Mohamed Boucekine 5 Anne Barlier 2 Gregorio Petrirena 6 Tovo Harivony 2 Laetitia Solignac 2 Olivier Chinot 4, 3 Nicolas Macagno 3, 7 Dominique Figarella-Branger 3, 8 Laetitia Padovani 1
1 Département d'oncologie en radiothérapie [CHU de la Timone]
2 APHM - Assistance Publique - Hôpitaux de Marseille
3 INP - Institut de neurophysiopathologie
4 Neuro-Oncologie [Hôpital de la Timone - APHM]
5 CEReSS - Centre d'études et de recherche sur les services de santé et la qualité de vie
6 Service de Neurologie [CHU Pitié-Salpêtrière]
7 Service de Neuropathologie [AP-HM Hôpital de la Timone]
8 TIMONE - Hôpital de la Timone [CHU - APHM]
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.
Keywords : glioblastoma neural niches dose survival impact stem neural niches radiotherapy MGMT
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CNRS | UNIV-AMU | INP | INP-GLIOME | SORBONNE-UNIVERSITE | SU-TI | SU-MEDECINE

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Xavier Muracciole, Wassim El-Amine, Emeline Tabouret, Mohamed Boucekine, Anne Barlier, et al.. Negative Survival Impact of High Radiation Doses to Neural Stem Cells Niches in an IDH-Wild-Type Glioblastoma Population. Frontiers in Oncology, Frontiers, 2018, 8, pp.426. ⟨10.3389/fonc.2018.00426⟩. ⟨hal-02110558⟩

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