5-Aminolevulinic acid for recurrent malignant gliomas: A systematic review

Objectives: Nowadays, several techniques have been developed in order to guide neurosurgeons during intended maximal safe resection of high-grade gliomas (HGG). Fluorescence-guided microsurgery using 5-aminolevulinic acid (5-ALA) is one of these. A large amount of studies have been performed evaluating benefits in newly diagnosed HGG. However, little is known about the safety, accuracy and efficacy in recurrent HGG. The primary objective of this thesis is to examine the value of 5-ALA in patients with recurrent HGG concerning diagnostic accuracy, extent of resection (EOR), safety and survival compared to white-light resection. As a secondary objective, we compared these results with current literature concerning 5-ALA in newly diagnosed HGG. Patients and methods: We performed a systematic review and included eighteen articles obtained from MEDLINE, EMBASE, Web of Science and TRIP database. Search terms include "glioma" and "aminolevulinic acid". Additional studies were identified through checking the reference lists. This study is in conformity with the PRISMA and BMJ guidelines. Results: 5-ALA shows similar results regarding diagnostic accuracy in recurrent HGG compared to newly diagnosed HGG, although specificity and negative predictive value seem lower. It shows complementary value in identifying tumor boundaries compared to MRI-neuronavigation. Diagnostic accuracy is not influenced by previous chemo- or radiotherapy. New neurological deficits proved to be similar and were in general mainly temporary. However, adverse events overall were more common. Therefore, indications for repeat surgery should be followed strictly. 5-ALA might increase overall survival in recurrent gliomas, but has no clear impact on progression-free survival. Conclusion: 5-ALA should be regarded as a useful and safe intraoperative tool in recurrent glioma surgery.