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. 2022 Feb 17:12:848036.
doi: 10.3389/fonc.2022.848036. eCollection 2022.

5-Aminolevulinic Acid False-Positive Rates in Newly Diagnosed and Recurrent Glioblastoma: Do Pseudoprogression and Radionecrosis Play a Role? A Meta-Analysis

Luca Ricciardi  1 , Carmelo Lucio Sturiale  2   3 , Alba Scerrati  4   5 , Vito Stifano  2   3 , Teresa Somma  6 , Tamara Ius  7 , Sokol Trungu  1   8 , Michele Acqui  1 , Antonino Raco  1 , Massimo Miscusi  1 , Giuseppe Maria Della Pepa  2   3
Affiliations

5-Aminolevulinic Acid False-Positive Rates in Newly Diagnosed and Recurrent Glioblastoma: Do Pseudoprogression and Radionecrosis Play a Role? A Meta-Analysis

Luca Ricciardi et al. Front Oncol. .

Abstract

Background: Several studies have confirmed the impact of 5-aminolevulinic acid (5-ALA) on the extent of resection in newly diagnosed glioblastoma (GBM). However, there are controversies on the 5-ALA fluorescence status in recurrent GBM surgery, with specific reference to pseudoprogression or radionecrosis; therefore, the safety and accuracy of surgical planning in 5-ALA-assisted procedures in the recurrent context are still unclear.

Materials and methods: This is a systematic review and meta-analysis of comparative studies on the use of 5-ALA in newly diagnosed and recurrent GBM, consistently conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Data on fluorescence status and correlation between fluorescence and histological findings were collected. We performed a meta-analysis of proportions to estimate the pooled rates of each outcome.

Results: Three online medical databases (PubMed, Scopus, Cochrane Library) were screened, 448 articles were evaluated, and 3 papers were finally included for data analysis. Fluorescence rate was not different between newly diagnosed and recurrent GBM [p = 0.45; odds ratio (OR): 1.23; 95% CI: 0.72-2.09; I2 = 0%], while the rate of 5-ALA fluorescence-positive areas not associated with histological findings of GBM cells was higher in recurrent GBM (p = 0.04; OR: 0.24; 95% CI: 0.06-0.91; I2 = 19%). Furthermore, there were no cases of radionecrosis in false-positive samples, while inflammation and signs of pseudoprogression were found in 81.4% of the cases.

Discussion and conclusions: Therefore, a robust awareness of 5-ALA potentialities and pitfalls in recurrent GBM surgery should be considered for a cognizant surgical strategy. Further clinical trials could confirm the results of the present meta-analysis.

Keywords: 5-ALA fluorescence; glioblastoma; high-grade glioma (HGG); pseudoprogression; radionecrosis; recurrent glioblastoma.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Search strategy.
Figure 2
Figure 2
5-Aminolevulinic acid (5-ALA) fluorescence rate in newly diagnosed and recurrent glioblastoma. The Foster Plot, from the meta-analyses of proportions to estimate the pooled rates of 5-ALA-positive fluorescence rate in newly diagnosed and recurrent glioblastoma. According to the Plot, there are no significative differences comparing the pooled rates from the two meta-analytic groups (p = 0.45).
Figure 3
Figure 3
5-Aminolevulinic acid (5-ALA) fluorescence-positive areas non-associated with histological finding of glioblastoma cells. The Foster Plot, from the meta-analyses of proportions to estimate the pooled rates of 5-ALA-positive fluorescence areas non-associated with histological finding of glioblastoma cells, defined in the paper as false-positive areas. According to the Plot, a significantly higher false-positive rate occurs in recurrent glioblastoma.
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