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. 2023 Apr;165(4):1075-1085.
doi: 10.1007/s00701-023-05544-3. Epub 2023 Mar 15.

Long-term survival in patients with IDH-wildtype glioblastoma: clinical and molecular characteristics

Georges Chehade  1   2 , Tévi Morel Lawson  1 , Julie Lelotte  3   4 , Lina Daoud  3 , Dario Di Perri  5 , Nicolas Whenham  6 , Thierry Duprez  7 , Nicolas Tajeddine  8 , Fadel Tissir  2   9 , Christian Raftopoulos  10
Affiliations

Long-term survival in patients with IDH-wildtype glioblastoma: clinical and molecular characteristics

Georges Chehade et al. Acta Neurochir (Wien). 2023 Apr.

Abstract

Backg round: Glioblastoma is an aggressive tumor that has a dismal prognosis even with multimodal treatment. However, some patients survive longer than expected. The objective of this study was to revisit patients diagnosed with glioblastoma according to the 2021 WHO classification and analyze clinical and molecular characteristics associated with long-term survival (LTS).

Methods: We retrospectively analyzed 120 IDH-wildtype glioblastomas operated on at our institution between 2013 and 2018. We divided them into LTS patients, surviving more than 3 years, and non-LTS patients, and then compared their features. Additionally, we performed DNA methylation-based brain tumor classification in LTS patients.

Results: Sixteen patients were long-term survivors. Age < 70 years, MGMT promoter methylation, extent of resection ≥ 95%, and administration of radiochemotherapy were associated with LTS (P = 0.005, P < 0.001, P = 0.048, and P = 0.008, respectively). In addition, when these factors were combined, the probability of LTS was 74% (95% CI: 62--84). The methylome analysis confirmed the diagnosis of glioblastoma in the majority of the tested LTS patients. Regarding subtypes, 29% of cases were mesenchymal (MES), 43% were RTK1, and 29% were RTK2. Interestingly, RTK1 and RTK2 cases tended to have longer overall survival than MES cases (P = 0.057). Moreover, the only tested LTS patient with an unmethylated MGMT promoter had an "adult-type diffuse high-grade glioma, IDH-wildtype, subtype E" rather than a glioblastoma. This tumor was characterized by multinucleated giant cells and a somatic mutation in POLE.

Conclusions: We suggest that glioblastoma patients with a combination of favorable prognostic factors can achieve LTS in 74% of cases. In addition, methylome analysis is important to ascertain the type of glioma in LTS patients, especially when the MGMT promoter is unmethylated.

Keywords: Adult-type diffuse high-grade glioma, IDH-wildtype, subtype E; DNA methylation-based brain tumor classification; Extent of resection; Glioblastoma; Long-term survival; o(6)-methylguanine-DNA methyltransferase.

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References

    1. Adeberg S, Bostel T, Konig L, Welzel T, Debus J, Combs SE (2014) A comparison of long-term survivors and short-term survivors with glioblastoma, subventricular zone involvement: a predictive factor for survival? Radiat Oncol 9:95. https://doi.org/10.1186/1748-717X-9-95 - DOI - PubMed - PMC
    1. Amelot A, De Cremoux P, Quillien V, Polivka M, Adle-Biassette H, Lehmann-Che J, Francoise L, Carpentier AF, George B, Mandonnet E, Froelich S (2015) IDH-mutation is a weak predictor of long-term survival in glioblastoma patients. PLoS One 10:e0130596. https://doi.org/10.1371/journal.pone.0130596 - DOI - PubMed - PMC
    1. Armocida D, Pesce A, Di Giammarco F, Frati A, Santoro A, Salvati M (2019) Long term survival in patients suffering from glio-blastoma multiforme: a single-center observational cohort study. Diagnostics (Basel) 9. https://doi.org/10.3390/diagnostics9040209
    1. Bady P, Sciuscio D, Diserens AC, Bloch J, van den Bent MJ, Marosi C, Dietrich PY, Weller M, Mariani L, Heppner FL, McDonald DR, Lacombe D, Stupp R, Delorenzi M, Hegi ME (2012) MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifies two distinct CpG regions associated with gene silencing and outcome, yielding a prediction model for comparisons across datasets, tumor grades, and CIMP-status. Acta Neuropathol 124:547–560. https://doi.org/10.1007/s00401-012-1016-2 - DOI - PubMed - PMC
    1. Beiko J, Suki D, Hess KR, Fox BD, Cheung V, Cabral M, Shonka N, Gilbert MR, Sawaya R, Prabhu SS, Weinberg J, Lang FF, Aldape KD, Sulman EP, Rao G, McCutcheon IE, Cahill DP (2014) IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection. Neuro Oncol 16:81–91. https://doi.org/10.1093/neuonc/not159 - DOI - PubMed

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