High-grade glioma: combined use of 5-aminolevulinic acid and intraoperative ultrasound for resection and a predictor algorithm for detection

OBJECTIVE The primary goal in neuro-oncology is the maximally safe resection of high-grade glioma (HGG). A more extensive resection improves both overall and disease-free survival, while a complication-free surgery enables better tolerance to adjuvant therapies such as chemotherapy and radiotherapy. Techniques such as 5-aminolevulinic acid (5-ALA) fluorescence and intraoperative ultrasound (ioUS) are valuable for safe resection and cost-effective. However, the benefits of combining these techniques remain undocumented. The aim of this study was to investigate outcomes when combining 5-ALA and ioUS. METHODS From January 2019 to January 2024, 72 patients (mean age 62.2 years, 62.5% male) underwent HGG resection at a single hospital. Tumor histology included glioblastoma (90.3%), grade IV astrocytoma (4.1%), grade III astrocytoma (2.8%), and grade III oligodendroglioma (2.8%). Tumor resection was performed under natural light, followed by using 5-ALA and ioUS to detect residual tumor. Biopsies from the surgical bed were analyzed for tumor presence and categorized based on 5-ALA and ioUS results. Results of 5-ALA and ioUS were classified into positive, weak/doubtful, or negative. Histological findings of the biopsies were categorized into solid tumor, infiltration, or no tumor. Sensitivity, specificity, and predictive values for both techniques, separately and combined, were calculated. A machine learning algorithm (HGGPredictor) was developed to predict tumor presence in biopsies. RESULTS The overall sensitivities of 5-ALA and ioUS were 84.9% and 76%, with specificities of 57.8% and 84.5%, respectively. The combination of both methods in a positive/positive scenario yielded the highest performance, achieving a sensitivity of 91% and specificity of 86%. The positive/doubtful combination followed, with sensitivity of 67.9% and specificity of 95.2%. Area under the curve analysis indicated superior performance when both techniques were combined, in comparison to each method used individually. Additionally, the HGGPredictor tool effectively estimated the quantity of tumor cells in surgical margins. CONCLUSIONS Combining 5-ALA and ioUS enhanced diagnostic accuracy for HGG resection, suggesting a new surgical standard. An intraoperative predictive algorithm could further automate decision-making.