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Purpose <p>High-grade glioma, IDH- and H3-wildtype in young adults is a rare and poorly known entity. We compared newly diagnosed cases in young adults (18–39 years) to those in adult patients (&gt; 39 years).</p> Methods <p>We performed an observational, retrospective, single-centre cohort study at a tertiary neurosurgical oncology centre between January 2006 and December 2023.</p> Results <p>We included 1.139 adult patients with a newly diagnosed high-grade glioma, IDH- and H3-wildtype. Young adults: (1) represent a small proportion of patients with high-grade glioma (<i>n</i> = 33, 2.9%); (2) have a high rate of unclassified cases based on epigenetics (<i>n</i> = 5, 15.2%); (3) have a longer progression-free survival (<i>p</i> = 0.003) and overall survival (<i>p</i> = 0.001) and; (4) do not have higher surgically-related adverse event rates (<i>p</i> = 0.198). Concerning young adults, surgical resection was associated with improved progression-free and overall survival (<i>p</i> &lt; 0.001 and <i>p</i> &lt; 0.001, respectively). The DNA-methylation class significantly impacts the overall survival (<i>p</i> = 0.028), however, the <i>MGMT</i> methylation status is not significantly associated with either progression-free or overall survival (<i>p</i> = 0.320 and <i>p</i> = 0.639, respectively).</p> Conclusion <p>High-grade glioma, IDH- and H3-wildtype is a rare histo-molecular subtype in young adults with a better prognosis than older adults. In young adults, DNA-methylation subtypes are different from their adult counterpart and had a significant impact on survival unlike <i>MGMT</i> status. Given the rarity in young adults, a dedicated management in specialized neurosurgical oncology centres is preferred. Further molecular and epigenetic analyses are required to understand the differences in prognosis compared to adult patients.</p>

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High-grade glioma, IDH- and H3-wildtype in young adults: a rare condition with a distinct epigenetic landscape

  • 期刊论文

  • 发表日期：

    2025年10月16日

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  • Alexandre Roux,
  • Arnault Tauziede-Espariat,
  • Giorgia Antonia Simboli,
  • Angela Elia,
  • Alessandro Moiraghi,
  • Benoit Hudelist,
  • Gonzague Defrance,
  • Alexandre Gehanno,
  • Edouard Dezamis,
  • Thomas Blauwblomme,
  • Volodia Dangouloff-Ros,
  • Nathalie Boddaert,
  • Christelle Dufour,
  • Jacques Grill,
  • Jun Muto,
  • Alice Metais,
  • Raphael Saffroy,
  • Pascale Varlet,
  • Fabrice Chretien,
  • Catherine Oppenheim,
  • Marc Zanello,
  • Johan Pallud

摘要

Purpose

High-grade glioma, IDH- and H3-wildtype in young adults is a rare and poorly known entity. We compared newly diagnosed cases in young adults (18–39 years) to those in adult patients (> 39 years).

Methods

We performed an observational, retrospective, single-centre cohort study at a tertiary neurosurgical oncology centre between January 2006 and December 2023.

Results

We included 1.139 adult patients with a newly diagnosed high-grade glioma, IDH- and H3-wildtype. Young adults: (1) represent a small proportion of patients with high-grade glioma (n = 33, 2.9%); (2) have a high rate of unclassified cases based on epigenetics (n = 5, 15.2%); (3) have a longer progression-free survival (p = 0.003) and overall survival (p = 0.001) and; (4) do not have higher surgically-related adverse event rates (p = 0.198). Concerning young adults, surgical resection was associated with improved progression-free and overall survival (p < 0.001 and p < 0.001, respectively). The DNA-methylation class significantly impacts the overall survival (p = 0.028), however, the MGMT methylation status is not significantly associated with either progression-free or overall survival (p = 0.320 and p = 0.639, respectively).

Conclusion

High-grade glioma, IDH- and H3-wildtype is a rare histo-molecular subtype in young adults with a better prognosis than older adults. In young adults, DNA-methylation subtypes are different from their adult counterpart and had a significant impact on survival unlike MGMT status. Given the rarity in young adults, a dedicated management in specialized neurosurgical oncology centres is preferred. Further molecular and epigenetic analyses are required to understand the differences in prognosis compared to adult patients.