P18.10.B CLINICAL AND NEUROPATHOLOGICAL MARKERS FOR DISTINGUISHING BETWEEN IDH-MUTANT ASTROCYTOMAS OF WHO GRADE 2 AND 3

• Published in: Neuro-oncology (Charlottesville, Va.) Va.), 2024-10, Vol.26 (Supplement_5), p.v97-v97
• Main Authors: Blobner, J, Harter, P N, Weller, J, Teske, N, Ruf, V, Schönecker, S, Forbrig, R, Albert, N L, von Baumgarten, L, Tonn, J, Thon, N, Karschnia, P
• Format: Article
• Language: English
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/noae144.326

Abstract BACKGROUND The neuropathological criteria of anaplasia to distinguish between IDH-mutant astrocytomas of WHO grade 2 and 3 are ill-defined by the WHO 2021 classification. Following the positive phase III trial results and the expected approval of Vorasidenib for astrocytomas grade 2, a salient point of the discussion remains which markers might be of prognostic relevance to distinguish between grade 2 and 3 tumors. MATERIAL AND METHODS We retrospectively searched our institutional database for patients meeting the diagnostic criteria for IDH-mutant astrocytomas according to the WHO 2021 classification. Clinical, neuropathological, and molecular data were collected; and outcome was compared using log-rank analysis. Prognostic markers identified on univariate analysis were forwarded into a multivariate model. RESULTS We identified 99 patients with IDH-mutant astrocytomas in which detailed neuropathological and clinical information were available for review, including 63 tumors (63.6%) which were assigned to WHO grade 2 and 36 tumors (36.4%) assigned to WHO grade 3. At a median follow-up of 7.5 years, median progression-free survival was 5.7 years for WHO grade 2 tumors and 4.4 years for WHO grade 3 tumors. Median overall survival for WHO grade 2 and WHO grade 3 tumors was not reached. On univariate analysis, higher WHO grade, an increased number of mitoses on histopathology, elevated Ki67 indices on immunohistochemistry, and the presence of contrast enhancement on pre-operative imaging were associated with less favourable outcome. However, only the presence of contrast enhancement retained its prognostic significance when forwarded into a multivariate model (p = 0.034 for overall survival, p = 0.012 for progression-free survival). The findings on the association between contrast enhancement and outcome were confirmed in treatment-based subgroups, including individuals treated with a watch-and-scan approach (n = 30), radiotherapy (n = 25), or chemotherapy (n = 33). Notably, neuropathological measurements of proliferation were generally higher in patients who underwent open resection compared to biopsy. CONCLUSION While our findings await confirmation in larger prospective cohorts, neuropathological criteria for anaplasia might need to be accompanied by clinical information including contrast enhancement to prognostically distinguish grade 2 from grade 3 tumors particularly in patients undergoing biopsy given the risk for undersampling. Centralized sl