5-ALA Fluorescence Is a Powerful Prognostic Marker during Surgery of Low-Grade Gliomas (WHO Grade II)—Experience at Two Specialized Centers
Open accessAbstract
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.
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Most high-grade gliomas show strong PpIX fluorescence, whereas low-grade gliomas typically do not exhibit PpIX fluorescence.
“Although most high-grade gliomas show strong PpIX fluorescence, low-grade gliomas typically do not exhibit PpIX fluorescence [50,51].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [51]
Results §3.2 reports no visible fluorescence in 52 of 59 low-grade gliomas (88%), supporting the claim that they typically do not fluoresce. The Introduction discusses fluorescence-guided surgery in high-grade gliomas, but does not establish that most show strong fluorescence. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPatients with low-grade gliomas that show PpIX fluorescence often have poor prognoses compared to patients whose tumors do not fluoresce.
“Nevertheless, patients with low-grade gliomas that do show PpIX fluorescence often have poor prognoses compared to patients whose tumors do not fluoresce, prompting the possible use of PpIX fluorescence as a prognostic marker for low-grade gliomas [51,52].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [51]
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- Authors
- Hosmann, A., Millesi, M., Wadiura, L. I., Kiesel, B., Mercea, P. A., Mischkulnig, M., Borkovec, M., Furtner, J., Roetzer, T., Wolfsberger, S., Phillips, J. J., Berghoff, A. S., Hervey-Jumper, S., Berger, M. S., & Widhalm, G.
- Affiliations
- Comprehensive Cancer Center Vienna (AT)
- Medical University of Vienna (AT)
- Comprehensive Cancer Center—Central Nervous System Tumours Unit (CCC-CNS), Medical University of Vienna, 1090 Vienna, Austria
- University of California, San Francisco (US)
- Department of Neurological Surgery, University of California, San Francisco (UCSF), CA 94143, USA
- Corresponding author
- Widhalm, Georg
- ORCID
- Venue
- Cancers
- Publisher
- MDPI AG
- Published
- 2021-05-21
- Volume
- 13
- Issue
- 11
- Pages
- 2540
- ISSN
- 2072-6694 (ISSN-L)
- PMC
- PMC8196836
- OpenAlex
- W3164402525
- Cited by
- 33
- References
- 41
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 8 · 2023: 4 · 2022: 9 · 2021: 5
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancers (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- University of California, San Francisco (P50CA097257)
- National Cancer Institute (P50CA097257)
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Keywords
- 5-aminolevulinic acid, intraoperative fluorescence, low-grade glioma, WHO grade II glioma, prognostic factors, malignant transformation, progression-free survival, overall survival, glioma surgery, tumor aggressiveness
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