5-ALA Fluorescence Is a Powerful Prognostic Marker during Surgery of Low-Grade Gliomas (WHO Grade II)—Experience at Two Specialized Centers

Abstract

The prediction of the individual prognosis of low-grade glioma (LGG) patients is limited in routine clinical practice. Nowadays, 5-aminolevulinic acid (5-ALA) fluorescence is primarily applied for improved intraoperative visualization of high-grade gliomas. However, visible fluorescence is also observed in rare cases despite LGG histopathology and might be an indicator for aggressive tumor behavior. The aim of this study was thus to investigate the value of intraoperative 5-ALA fluorescence for prognosis in LGG patients. We performed a retrospective analysis of patients with newly diagnosed histopathologically confirmed LGG and preoperative 5-ALA administration at two independent specialized centers. In this cohort, we correlated the visible intraoperative fluorescence status with progression-free survival (PFS), malignant transformation-free survival (MTFS) and overall survival (OS). Altogether, visible fluorescence was detected in 7 (12%) of 59 included patients in focal intratumoral areas. At a mean follow-up time of 5.3 ± 2.9 years, patients with fluorescing LGG had significantly shorter PFS (2.3 ± 0.7 vs. 5.0 ± 0.4 years; p = 0.01), MTFS (3.9 ± 0.7 vs. 8.0 ± 0.6 years; p = 0.03), and OS (5.4 ± 1.0 vs. 10.3 ± 0.5 years; p = 0.01) than non-fluorescing tumors. Our data indicate that visible 5-ALA fluorescence during surgery of pure LGG might be an already intraoperatively available marker of unfavorable patient outcome and thus close imaging follow-up might be considered.

Evaluation of a Novel Three-Dimensional Robotic Digital Microscope (Aeos) in Neurosurgery

“…First, the visualization of tumor tissue and its discernment from healthy tissue is of utmost importance during neurooncological procedures. The introduction of 5-ALA-induced fluorescence has been a major scientific achievement in the intraoperative visualization of malignant tissue, which is independent of brain shift [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. In conventional microscopic surgery, tumor tissue “glows” after preoperatively administered 5-ALA and intraoperative switching from conventional white light to a blue light source, which is integrated into the microscope.…”

Reply to Stummer, W.; Thomas, C. Comment on “Hosmann et al. 5-ALA Fluorescence Is a Powerful Prognostic Marker during Surgery of Low-Grade Gliomas (WHO Grade II)—Experience at Two Specialized Centers. Cancers 2021, 13, 2540”

“…Interestingly, according to the Results section, including Table 2 of the original publication of Jaber et al [5], only 16 IDH wildtype gliomas were indicated. Nevertheless, a higher portion of IDH wildtype gliomas were analyzed in the study by Jaber et al [5] compared to our study [6]. Due to the low number of IDH wildtype gliomas in our cohort (n = 5), the statistical power of a multivariate survival analysis was thus too low.…”

“…We also thank the authors for the effort of summarizing and comparing the results of both studies [5,6]. Indeed, the number of isocitrate dehydrogenase (IDH) wildtype low-grade gliomas (LGG) was lower in our cohort (n = 5) compared to the study of Jaber et al [5].…”

“…We congratulate Jaber et al [5] on conducting the first systematical single center study in a large patient cohort and again pioneering work in this field investigating the prognostic value of 5-ALA in World Health Organization (WHO) grade II gliomas. As stated in our manuscript [6] and the comment, we performed "the first study [ . .…”

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

“… 21 Second, 5-ALA–induced fluorescence has proven to correlate with oncological prognosis in histologically verified low-grade gliomas. 5 , 22 Further confirmatory studies will need to show if these observations justify the expanding of FDA approval.…”