Abstract
Background: High-grade glioma (HGG) is associated with a dismal prognosis despite significant advances in adjuvant therapies, including chemotherapy, immunotherapy, and radiotherapy. Extent of resection continues to be the most important independent prognosticator of survival. This underlines the significance of increasing gross total resection (GTR) rates by using adjunctive intraoperative modalities to maximize resection with minimal neurological morbidity. 5-aminolevulinic acid (5-ALA) is the only US Food and Drug Administration–approved intraoperative optical agent used for fluorescence-guided surgical resection of gliomas. Despite several studies on the impact of intra-operative 5-ALA use on the extent of HGG resection, a clear picture of how such usage affects patient survival is still unavailable.Methods: A systematic review was conducted of all relevant studies assessing the GTR rate and survival outcomes [overall survival (OS) and progression-free survival (PFS)] in HGG. A meta-analysis of eligible studies was performed to assess the influence of 5-ALA-guided resection on improving GTR, OS, and PFS. GTR was defined as >95% resection.Results: Of 23 eligible studies, 19 reporting GTR rates were included in the meta-analysis. The pooled cohort had 998 patients with HGG, including 796 with newly diagnosed cases. The pooled GTR rate among patients with 5-ALA–guided resection was 76.8% (95% confidence interval, 69.1–82.9%). A comparative subgroup analysis of 5-ALA–guided vs. conventional surgery (controlling for within-study covariates) showed a 26% higher GTR rate in the 5-ALA subgroup (odds ratio, 3.8; P < 0.001). There were 11 studies eligible for survival outcome analysis, 4 of which reported PFS. The pooled mean difference in OS and PFS was 3 and 1 months, respectively, favoring 5-ALA vs. control (P < 0.001).Conclusions: This meta-analysis shows a significant increase in GTR rate with 5-ALA–guided surgical resection, with a higher weighted GTR rate (~76%) than the pivotal phase III study (~65%). Pooled analysis showed a small yet significant increase in survival measures associated with the use of 5-ALA. Despite the statistically significant results, the low level of evidence and heterogeneity across these studies make it difficult to conclusively report an independent association between 5-ALA use and survival outcomes in HGG. Additional randomized control studies are required to delineate the role of 5-ALA in survival outcomes in HGG.
Highlights
High-grade gliomas (HGGs), including World Health Organization (WHO) grade III and grade IV gliomas, are the most common subtype of primary adult malignant cerebral neoplasms with a poor prognosis
Twenty-three studies were included in the final meta-analysis of the pooled gross total resection (GTR) and survival outcomes analysis
Of the 23 studies included in the analyses, 19 reported a GTR or Complete resection of enhancing tumor (CRET) rate [5, 25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42]
Summary
High-grade gliomas (HGGs), including World Health Organization (WHO) grade III and grade IV gliomas, are the most common subtype of primary adult malignant cerebral neoplasms with a poor prognosis. Complete resection of enhancing tumor (CRET) or gross total resection (GTR) have been demonstrated to be independent prognosticators of increased progression-free survival (PFS) and overall survival (OS) [1]. High-grade glioma (HGG) is associated with a dismal prognosis despite significant advances in adjuvant therapies, including chemotherapy, immunotherapy, and radiotherapy. Extent of resection continues to be the most important independent prognosticator of survival. This underlines the significance of increasing gross total resection (GTR) rates by using adjunctive intraoperative modalities to maximize resection with minimal neurological morbidity. Despite several studies on the impact of intra-operative 5ALA use on the extent of HGG resection, a clear picture of how such usage affects patient survival is still unavailable
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
