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Background <p>The 2021 WHO classification of CNS tumors allows flexibility in the grading of IDH-mutant astrocytic gliomas, leading to some ambiguity. Following the approval of vorasidenib for WHO grade 2 astrocytomas and oligodendrogliomas based on the positive Phase III INDIGO trial, identifying prognostic criteria to differentiate between grade 2 and grade 3 tumors has become increasingly important.</p> Methods <p>We retrospectively searched our institutional database for patients meeting the diagnostic criteria for IDH-mutant astrocytomas (grade 2 and 3) according to the WHO 2021 classification. Clinical, radiological and molecular data were collected; outcome was compared using log-rank analysis and prognostic markers were subsequently forwarded in a multivariate model.</p> Results <p>We identified 91 patients with IDH-mutant astrocytomas with available neuropathological and clinical data, including 61 WHO grade 2 (67.0%) and 30 WHO grade 3 (33.0%) tumors. At a median follow-up of 89 months, median progression-free survival was 67 months for WHO grade 2 and 53 months for WHO grade 3 tumors. Median overall survival was 216 months for WHO grade 3 tumors, while it was not reached for WHO grade 2 tumors. Univariate analysis showed that higher WHO grade, increased mitotic count, elevated Ki67 indices and preoperative contrast enhancement were associated with poorer outcomes; however, only contrast enhancement retained prognostic significance on multivariate analysis (<i>p</i> = 0.03 for overall survival, <i>p</i> = 0.02 for progression-free survival).</p> Conclusion <p>While our findings await confirmation in larger prospective cohorts, neuropathological grading criteria might need to be accompanied by clinical information including contrast enhancement to prognostically distinguish grade 2 from grade 3 tumors.</p>

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Clinical and neuropathological criteria for distinguishing between IDH-mutant astrocytomas of WHO grade 2 and 3

  • 期刊论文

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  • 发表日期：

    2025年7月23日

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  • Jens Blobner,
  • Viktoria Ruf,
  • Jonathan Weller,
  • Nico Teske,
  • Robert Forbrig,
  • Niklas Thon,
  • Nathalie L. Albert,
  • Louisa von Baumgarten,
  • Stephan Schoenecker,
  • Joerg-Christian Tonn,
  • Florian Ringel,
  • Patrick N. Harter,
  • Philipp Karschnia

摘要

Background

The 2021 WHO classification of CNS tumors allows flexibility in the grading of IDH-mutant astrocytic gliomas, leading to some ambiguity. Following the approval of vorasidenib for WHO grade 2 astrocytomas and oligodendrogliomas based on the positive Phase III INDIGO trial, identifying prognostic criteria to differentiate between grade 2 and grade 3 tumors has become increasingly important.

Methods

We retrospectively searched our institutional database for patients meeting the diagnostic criteria for IDH-mutant astrocytomas (grade 2 and 3) according to the WHO 2021 classification. Clinical, radiological and molecular data were collected; outcome was compared using log-rank analysis and prognostic markers were subsequently forwarded in a multivariate model.

Results

We identified 91 patients with IDH-mutant astrocytomas with available neuropathological and clinical data, including 61 WHO grade 2 (67.0%) and 30 WHO grade 3 (33.0%) tumors. At a median follow-up of 89 months, median progression-free survival was 67 months for WHO grade 2 and 53 months for WHO grade 3 tumors. Median overall survival was 216 months for WHO grade 3 tumors, while it was not reached for WHO grade 2 tumors. Univariate analysis showed that higher WHO grade, increased mitotic count, elevated Ki67 indices and preoperative contrast enhancement were associated with poorer outcomes; however, only contrast enhancement retained prognostic significance on multivariate analysis (p = 0.03 for overall survival, p = 0.02 for progression-free survival).

Conclusion

While our findings await confirmation in larger prospective cohorts, neuropathological grading criteria might need to be accompanied by clinical information including contrast enhancement to prognostically distinguish grade 2 from grade 3 tumors.