Clinical utility of targeted next-generation sequencing assay in IDH-wildtype glioblastoma for therapy decision-making - Sorbonne Université Access content directly
Journal Articles Neuro-Oncology Year : 2022

Clinical utility of targeted next-generation sequencing assay in IDH-wildtype glioblastoma for therapy decision-making

Mary Jane Lim-Fat
  • Function : Author
Gilbert Youssef
  • Function : Author
J Bryan Iorgulescu
  • Function : Author
Sydney Whorral
  • Function : Author
Marie Allen
  • Function : Author
Rifaquat Rahman
Ugonma Chukwueke
  • Function : Author
J Ricardo Mcfaline-Figueroa
  • Function : Author
Lakshmi Nayak
  • Function : Author
Eudocia Lee
  • Function : Author
Tracy Batchelor
  • Function : Author
Omar Arnaout
Pier Paolo Peruzzi
  • Function : Author
E Antonio Chiocca
  • Function : Author
David Reardon
  • Function : Author
David Meredith
  • Function : Author
Sandro Santagata
Rameen Beroukhim
  • Function : Author
Wenya Linda Bi
  • Function : Author
Keith Ligon
  • Function : Author
Patrick Wen
  • Function : Author

Abstract

Background: Targeted gene NGS testing is available through many academic institutions and commercial entities and is increasingly incorporated in practice guidelines for glioblastoma (GBM). This single-center retrospective study aimed to evaluate the clinical utility of incorporating NGS results in the management of GBM patients at a clinical trials-focused academic center. Methods: We identified 1011 consecutive adult patients with pathologically confirmed GBM (IDHwt or IDHmut) who had somatic tumor sequencing (Oncopanel, ~500 cancer gene panel) at DFCI from 2013-2019. Clinical records of all IDHwt GBM patients were reviewed to capture clinical trial enrollment and off-label targeted therapy use based on NGS results. Results: Of the 557 IDHwt GBM patients with sequencing, 182 entered clinical trials at diagnosis (32.7%) and 213 (38.2%) entered after recurrence. Sequencing results for 130 patients (23.3%) were utilized for clinical trial enrollment for either targeted therapy indications (6.9 % upfront and 27.7% at recurrent clinical trials and 3.1% for off-label targeted therapy) or exploratory studies (55.4% upfront and 6.9% recurrent clinical trials). Median overall survival was 20.1 months with no survival difference seen between patients enrolled in clinical trials compared to those who were not, in a posthoc analysis. Conclusions: While NGS testing has become essential for improved molecular diagnostics, our study illustrates that targeted gene panels remain underutilized for selecting therapy in GBM-IDHwt. Targeted therapy and clinical trial design remain to be improved to help leverage the potential of NGS in clinical care.

Dates and versions

hal-04588696 , version 1 (27-05-2024)

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Cite

Mary Jane Lim-Fat, Gilbert Youssef, Mehdi Touat, J Bryan Iorgulescu, Sydney Whorral, et al.. Clinical utility of targeted next-generation sequencing assay in IDH-wildtype glioblastoma for therapy decision-making. Neuro-Oncology, 2022, 24 (7), pp.1140-1149. ⟨10.1093/neuonc/noab282⟩. ⟨hal-04588696⟩
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