5-aminolevulinic acid Guided Resection Indications

5-aminolevulinic-acid (5-ALA) guided resection. In addition to stereotactic localization, as well as intraoperative brain mapping, techniques to enhance visual identification of tumor, intraoperatively may be used and include 5-aminolevulinic acid (5-ALA). 5-ALA is metabolized into fluorescent porphyrins, which accumulate in malignant glioma cells. This property permits the use of ultraviolet illumination during surgery as an adjunct to map out the tumor. This has been proven with RCT where the use of 5-ALA leads to more complete resection (65% vs. 36%, p < 0.0001), which translates into a higher 6-month progression-free survival (41% vs. 21.1%, p = 0.0003) but no effect on OS 1).

New indications are being considered especially in benign lesion biopsies with the assistance of 5-ALA. Using fluorescence as an aid in biopsies may improve procedure time, the number of samples, and the necessity of intraoperative pathology. Further studies should include this technology to encourage more beneficial uses 2).


It facilitates tumor identification; its use improves gross total resection rates and prolongs progression free survival in patients with high-grade gliomas 3). 4).

Meningeal sarcoma

First case published in the literature of meningeal sarcoma in a child in which intraoperative fluorescence with 5-ALA was used to achieve a complete resection 5).

Meningioma

Metabolic imaging tools such as 5-ALA fluorescence-guided resection and navigated FET-PET were helpful for the resection of complex-shaped, recurrent skull base meningioma. 5-ALA fluorescence was useful to dissect the adherent interface between tumor and brain. Furthermore, it helped to delineate tumor margins in the nasal cavity. FET-PET improved the assessment of bony and dural infiltration. We hypothesize that these imaging technologies may reduce recurrence rates through better visualization of tumor tissue that might be left unintentionally. This has to be verified in larger, prospective trials 6).

Tumor fluorescence can occur in benign meningiomas (WHO grade I) as well as in WHO grade II and WHO grade III meningiomas. Most of the reviewed studies report fluorescence of the main tumor mass with high sensitivity and specificity. However, different parts of the same tumor can present with a different fluorescent pattern (heterogenic fluorescence). Quantitative probe fluorescence can be superior, especially in meningiomas with difficult anatomical accessibility. However, only one study was able to consistently correlate resected tissue with histopathological results and nonspecific fluorescence of healthy brain tissue remains a confounder. The use of 5-ALA as a tool to guide resection of intracranial meningiomas remains experimental, especially in cases with tumor recurrence. The principle of intraoperative fluorescence as a real-time method to achieve complete resection is appealing, but the usefulness of 5-ALA is questionable. 5-ALA in intracranial meningioma surgery should only be used in a protocolled prospective and long-term study 7).


1)
Stummer W, Pichlmeier U, Meinel T, et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomized controlled multicentre phase III trial. Lancet Oncol. 2006; 7:392–401
2)
Duarte JFS, Jung GS, da Silva EB Jr, de Almeida Teixeira BC, Cavalcanti MS, Ramina R. 5-Aminolevulinic acid fluorescence in brain non-neoplastic lesions: a systematic review and case series. Neurosurg Rev. 2022 Aug 16. doi: 10.1007/s10143-022-01843-y. Epub ahead of print. PMID: 35972631.
3)
Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ; ALA-Glioma Study Group. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006 May;7(5):392-401. PubMed PMID: 16648043.
4)
Lakomkin N, Hadjipanayis CG. Fluorescence-guided surgery for high-grade gliomas. J Surg Oncol. 2018 Aug 19. doi: 10.1002/jso.25154. [Epub ahead of print] Review. PubMed PMID: 30125355.
5)
Bernal García LM, Cabezudo Artero JM, Royano Sánchez M, Marcelo Zamorano MB, López Macías M. Fluorescence-guided resection with 5-aminolevulinic acid of meningeal sarcoma in a child. Childs Nerv Syst. 2015 Apr 12. [Epub ahead of print] PubMed PMID: 25863951.
6)
Cornelius JF, Slotty PJ, Stoffels G, Galldiks N, Langen KJ, Steiger HJ. 5-Aminolevulinic Acid and (18)F-FET-PET as Metabolic Imaging Tools for Surgery of a Recurrent Skull Base Meningioma. J Neurol Surg B Skull Base. 2013 Aug;74(4):211-6. doi: 10.1055/s-0033-1342918. Epub 2013 Apr 1. PubMed PMID: 24436914.
7)
Motekallemi A, Jeltema HR, Metzemaekers JD, van Dam GM, Crane LM, Groen RJ. The current status of 5-ALA fluorescence-guided resection of intracranial meningiomas-a critical review. Neurosurg Rev. 2015 Mar 5. [Epub ahead of print] PubMed PMID: 25736455.
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