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

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.