A Data-Driven Approach to Predicting 5-Aminolevulinic Acid-Induced Fluorescence and World Health Organization Grade in Newly Diagnosed Diffuse Gliomas

• Published in: Neurosurgery Vol. 90; no. 6; p. 800
• Main Authors: Müther, Michael, Jaber, Mohammed, Johnson, Timothy D, Orringer, Daniel A, Stummer, Walter
• Format: Journal Article
• Language: English
• Published: United States 01.06.2022
• Subjects: Aminolevulinic Acid; Brain Neoplasms - diagnostic imaging; Brain Neoplasms - surgery; Glioma - diagnostic imaging; Glioma - surgery; Humans; Isocitrate Dehydrogenase - genetics; Mutation; World Health Organization
• ISSN: 1524-4040
• DOI: 10.1227/neu.0000000000001914

A growing body of evidence has revealed the potential utility of 5-aminolevulinic acid (5-ALA) as a surgical adjunct in selected lower-grade gliomas. However, a reliable means of identifying which lower-grade gliomas will fluoresce has not been established. To identify clinical and radiological factors predictive of intraoperative fluorescence in intermediate-grade gliomas. In addition, given that higher-grade gliomas are more likely to fluoresce than lower-grade gliomas, we also sought to develop a means of predicting glioma grade. We investigated a cohort of patients with grade II and grade III gliomas who received 5-ALA before resection at a single institution. Using a logistic regression-based model, we evaluated 14 clinical and molecular variables considered plausible determinants of fluorescence. We then distilled the most predictive features to develop a model for predicting both fluorescence and tumor grade. We also explored the relationship between intraoperative fluorescence and diagnostic molecular markers. One hundered seventy-nine subjects were eligible for inclusion. Our logistic regression classifier accurately predicted intraoperative fluorescence in our cohort with 91.9% accuracy and revealed enhancement as the singular variable in determining intraoperative fluorescence. There was a direct relationship between enhancement on MRI and the likelihood of observed fluorescence. Observed fluorescence correlated with MIB-1 index but not with isocitrate dehydrogenase (IDH) status, 1p19q codeletion, or methylguanine DNA methyltransferase promoter methylation. We demonstrate a strong correlation between enhancement on preoperative MRI and the likelihood of visible fluorescence during surgery in patients with intermediate-grade glioma. Our analysis provides a robust method for predicting 5-ALA-induced fluorescence in patients with grade II and grade III gliomas.