WHO Grade Loses Its Prognostic Value in Molecularly Defined Diffuse Lower-Grade Gliomas

• Published in: Frontiers in oncology Vol. 11; p. 803975
• Main Authors: Carstam, Louise, Corell, Alba, Smits, Anja, Dénes, Anna, Barchéus, Hanna, Modin, Klara, Sjögren, Helene, Ferreyra Vega, Sandra, Bontell, Thomas Olsson, Carén, Helena, Jakola, Asgeir Store
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 10.01.2022
• Subjects: astrocytoma; Cancer and Oncology; Cancer och onkologi; CDKN2A/B deletion; extent of resection; IDH-mut; Kirurgi; lower-grade glioma; Neurologi; Neurology; oligodendroglioma; Oncology; prognostic factors; Surgery; WHO grade; IDH-mut; oligodendroglioma; astrocytoma; extent of resection; lower-grade glioma; prognostic factors; WHO grade; CDKN2A/B deletion
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2021.803975

While molecular insights to diffuse lower-grade glioma (dLGG) have improved the basis for prognostication, most established clinical prognostic factors come from the pre-molecular era. For instance, WHO grade as a predictor for survival in dLGG with ( ) mutation has recently been questioned. We studied the prognostic role of WHO grade in molecularly defined subgroups and evaluated earlier used prognostic factors in the current molecular setting. A total of 253 adults with morphological dLGG, consecutively included between 2007 and 2018, were assessed. mutations, codeletion of chromosomal arms 1p/19q, and deletions were analyzed. There was no survival benefit for patients with WHO grade 2 over grade 3 -mut dLGG after exclusion of tumors with known homozygous deletion (n=157) (log-rank p=0.97). This was true also after stratification for oncological postoperative treatment and when astrocytomas and oligodendrogliomas were analyzed separately. In mut astrocytomas, residual tumor volume after surgery was an independent prognostic factor for survival (HR 1.02; 95% CI 1.01-1.03; p=0.003), but not in oligodendrogliomas (HR 1.02; 95% CI 1.00-1.03; p=0.15). Preoperative tumor size was an independent predictor in both astrocytomas (HR 1.03; 95% CI 1.00-1.05; p=0.02) and oligodendrogliomas (HR 1.05; 95% CI 1.01-1.09; p=0.01). Age was not a significant prognostic factor in multivariable analyses (astrocytomas p=0.64, oligodendrogliomas p=0.08). Our findings suggest that WHO grade is not a robust prognostic factor in molecularly well-defined dLGG. Preoperative tumor size remained a prognostic factor in both -mut astrocytomas and oligodendrogliomas in our cohort, whereas residual tumor volume predicted prognosis in -mut astrocytomas only. The age cutoffs for determining high risk in patients with -mut dLGG from the pre-molecular era are not supported by our results.