Is Visible Aminolevulinic Acid-Induced Fluorescence an Independent Biomarker for Prognosis in Histologically Confirmed (World Health Organization 2016) Low-Grade Gliomas?

Abstract

This is the first report investigating the role of ALA-induced fluorescence in histologically confirmed LGG. Fluorescence appeared to be a marker for inherent malignant transformation and OS, independently of known prognostic markers. Fluorescence in LGG might be taken into account when deciding on adjuvant therapies.

Spectral complexity of 5-ALA induced PpIX fluorescence in guided surgery: a clinical study towards the discrimination of healthy tissue and margin boundaries in high and low grade gliomas

“…The contribution of State 634 is constant in healthy tissues and in LGG, and increases of only 37% in low density margin of HGG. This is consistent with the actual sensitivity issues of the 5-ALA induced PpIX fluorescence surgical microscopy in HGG and LGG [21][22][23]. However, the contribution of State 620 is 80% higher in LGG and 95% higher in low density margins of HGG than in healthy tissues.…”

“…Then, a decrease in fluorescence intensity might not only reveal a decrease in PpIX concentration but also a change of PpIX aggregate, in favor of State 620 [37]. Our results suggest that the decrease of PpIX fluorescence intensity in low-density tumor cells regions [21][22][23] attributed mainly to low PpIX concentrations could also be linked to a different aggregation of PpIX in these regions, due to a microenvironment favoring the PpIX State 620. The similarities in the PpIX fluorescence behaviors in LGG and HGG low density margins could be explained by biological processes rather close from each other: presence of infiltrative but not joined tumor cells without blood brain barrier breakage around.…”

“…The contribution of state 634 is 10 to 100 times higher in high-density tumor cells regions as compared to healthy or low density tumor cells regions. This should be related to the actual sensitivity issues of the 5-ALA induced PpIX fluorescence surgical microscopy in the low density margin of HGG [21,22] and in LGG [23]. Surgical microscopy fluorescence intensity was also assessed in this study.…”

“…It is also investigated for intracranial stereotactic biopsies [19,20]. However, its sensitivity is still limited when applied to low density infiltrative parts of HGG [21,22] or to LGG [23]. Some studies also emphasize that the link between the subjective fluorescence intensity scale chosen by the surgeon and the pathological status of tissues is still to be clarified [24,25].…”

In order for the light to shine so brightly, the darkness must be present—why do cancers fluoresce with 5-aminolaevulinic acid?

“…83 Only a small proportion of low-grade diffuse gliomas exhibited 5-ALA-induced fluorescence, although visible fluorescence was suggested to be associated with a worse prognosis. 87 Vague, diffuse fluorescence or lack of fluorescence in brain tumours may be due to infiltrative tumour invading healthy tissue 88 and the inability of 5-ALA to cross an intact blood-brain barrier. 89 Strategies aimed at improving detection include combining 5-ALA PDT with sensitive quantitative fluorescent measurement, 90 sophisticated fluorescence imaging tools such as a scanning fibre endoscope 91 and improving light penetration.…”