Fluorescence-Guided Surgery Using 5-Aminolevulinic Acid/Protoporphyrin IX in Brain Metastases

The purpose of this systematic review was to provide a comprehensive overview of the available literature on 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence-guided surgery (FGS) for the resection of brain metastases (BMs).

A comprehensive search of the PubMed database for literature on 5-ALA use in BMs surgery was performed. For inclusion, BMs studies had to have data on the observed intraoperative fluorescence available. Additional data categories included the number of metastatic tumors, 5-ALA dosage and timing, the imaging system (eg, microscope) used, imaging wavelength(s), fluorescence grading ("simple" and "detailed"), fluorescence consistency (heterogeneous vs homogeneous), intracranial tumor location, metastatic primary tumor location, and extent of resection, among others.

Twenty-three articles published between 2007 and 2022 met the inclusion criteria. These studies comprised 1709 total patients; 870 metastatic samples were collected from 855 patients with 377 (43.3%) fluorescence-negative and 493 (56.7%) fluorescence-positive samples. The pooled overall prevalence of fluorescence-positive metastatic lesions was 66% (95% CI 55%-75%; I² = 85%, P < .01). The fluorescence grading was as follows: (a) simple fluorescence (n = 599): 295 (49.3%) fluorescence-negative and 304 (50.8%) fluorescence-positive samples and (b) detailed fluorescence (n = 271): 82 (30.3%) no fluorescence, 107 (39.5%) weak fluorescence, and 82 (30.3%) strong fluorescence. A total of 764 lesions had primary tumor site data available: 702 lesions had fluorescence data with 384 (54.7%) fluorescence-positive samples.

FGS using 5-ALA/PpIX in BMs demonstrates varying benefits as an adjunct for maximizing the extent of resection. Thus, preoperative knowledge of the primary tumors' origin may inform surgeons regarding the potential utility of 5-ALA/PpIX for FGS management of BMs.