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

authors

  • Muracciole Xavier
  • El-Amine Wassim
  • Tabouret Emeline
  • Boucekine Mohamed
  • Barlier Anne
  • Petrirena Gregorio
  • Harivony Tovo
  • Solignac Laetitia
  • Chinot Olivier
  • Macagno Nicolas
  • Figarella-Branger Dominique
  • Padovani Laetitia

keywords

  • Glioblastoma
  • Neural niches
  • Dose
  • Survival impact
  • Stem neural niches
  • Radiotherapy
  • MGMT

document type

ART

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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