Article
Double dose of 5-ALA and its effect on PPIX expression in low-grade glioma
Doppelte Dosis von 5-ALA und deren Auswirkung auf die PPIX-Expression in niedriggradigen Gliomen
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Authors
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Eric Suero Molina
- Universitätsklinikum Münster, Klinik für Neurochirurgie, Münster, Deutschland
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Sadahiro Kaneko
- Universitätsklinikum Münster, Klinik für Neurochirurgie, Münster, Deutschland; HokkaidoĀ University Graduate School of Medicine, Department of Neurosurgery, Sapporo, Japan
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David Black
- Carl Zeiss Meditec AG, Oberkochen, Deutschland; University of British Columbia, Vancouver, Kanada
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Walter Stummer
- Universitätsklinikum Münster, Klinik für Neurochirurgie, Münster, Deutschland
| Published: | June 4, 2021 |
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Outline
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Objective: 5-ALA-induced fluorescence does not regularly delineate low-grade glioma (LGG) tumor margins. It is possible that an intact or minimally disrupted blood-brain barrier is the reason for these difficulties. However, the clinical value and efficacy of fluorescence-guidance are still under current investigation. In this study, we aimed to analyze the effects of increasing 5-ALA administration dose in LGG glioma surgery on inducing visible fluorescence.
Methods: Patients undergoing surgery for lesions suspicious of malignant glioma, which were later diagnosed as LGG, were included in this study. 5-ALA (Gliolan®) was administered at a dose of 20 mg/kg b.w. four hours prior to induction of anesthesia. Several patients received a higher dose of 40 mg/kg b.w. at the same time point prior to surgery. Fluorescence was evaluated during surgery and by hyperspectral measurements in extracted biopsies. Estimated tumor Protoporphyrin-IX concentration (cPPIX) was assessed by evaluating fluorescence phantoms with known cPPIX.
Results: A total of 23 patients were enrolled in this study. Thirteen (n=13) patients received 20 mg/kg b.w., as a single dose, whereas 10 patients received 40 mg/kg b.w. as a double dose of 5-ALA. In the single-dose group, 30.8% (n=4) of patients harbored visible fluorescence, whereas in the double-dose group this occurred in 60% of cases (n=6). This demonstrates an increase of 95%. In both groups, the majority of evaluated pixels was found to be in concentrations below 2µg/ml. Below this threshold, mean cPPIX was 0.26 µg/ml in the single-dose and 0.35 µg/ml in the double-dose group, indicating an increase of 35%.
Conclusion: It appears that a double dose of 5-ALA on average doubles fluorescence in LGG. This might suggest a linear relationship between dosage and fluorescence, however, it does not seem to affect tumors that would otherwise have had an extremely high cPPIX. It appears to increase the frequency of “medium to high” concentrations in the 0.5-12µg/ml range. However, due to the small sample size of this cohort, further studies are still required to analyze optimal dosage for patients harboring this type of tumors.
