Abstract
Background: Fluorescence-guided surgery (FGS) using 5-aminolevulic acid (5-ALA) is a widely used strategy for delineating tumor tissue from surrounding brain intraoperatively during high-grade glioma (HGG) resection. 5-ALA reaches peak plasma levels ~4 h after oral administration and is currently approved by the FDA for use 2–4 h prior to induction to anesthesia.Objective: To demonstrate that there is adequate intraoperative fluorescence in cases undergoing surgery more than 4 h after 5-ALA administration and compare survival and radiological recurrence to previous data.Methods: Retrospective analysis of HGG patients undergoing FGS more than 4 h after 5-ALA administration was performed at two institutions. Clinical, operative, and radiographic pre- and post-operative characteristics are presented.Results: Sixteen patients were identified, 6 of them female (37.5%), with mean (SD) age of 59.3 ± 11.5 years. Preoperative mean modified Rankin score (mRS) was 2 ± 1. All patients were dosed with 20 mg/kg 5-ALA the morning of surgery. Mean time to anesthesia induction was 425 ± 334 min. All cases had adequate intraoperative fluorescence. Eloquent cortex was involved in 12 cases (75%), and 13 cases (81.3%) had residual contrast enhancement on postoperative MRI. Mean progression-free survival was 5 ± 3 months. In the study period, 6 patients died (37.5%), mean mRS was 2.3 ± 1.3, Karnofsky score 71.9 ± 22.1, and NIHSS 3.9 ± 2.4.Conclusion: Here we demonstrate that 5-ALA-guided HGG resection can be performed safely more than 4 h after administration, with clinical results largely similar to previous reports. Relaxation of timing restrictions could improve procedure workflow in busy neurosurgical centers, without additional risk to patients.
Highlights
Maximal and safe resection has been established as the initial standard of care for the treatment of high-grade gliomas (HGG) [1,2,3,4,5]
The most commonly studied fluorophores are 5-aminolevulinic acid (5-ALA), fluorescein and indocyanine green (ICG) [11]. 5-ALA is the most widely studied agent for fluorescence-guided surgery (FGS) of HGG, and is currently the only agent (Gleolan R ) that is approved by the US Food and Drug Administration (FDA) for glioma surgery [9]
Administered as an oral solution, 5-ALA is metabolized in the heme biosynthesis pathway to protoporphyrin (PpIX), which accumulates intracellularly in tumor cells [12], absorbing light between 375 and 440 nm and emitting violetred fluorescence (640–710 nm) [13]. 5-ALA has been previously shown in multicenter studies to be safe and effective, with minimal associated side effects [9, 14]
Summary
Maximal and safe resection has been established as the initial standard of care for the treatment of high-grade gliomas (HGG) [1,2,3,4,5]. Due to the propensity of HGGs involving eloquent regions of the brain, maximal safe resection poses intraoperative challenges for tumor surgeons [8]. The use of fluorescence-guided surgery (FGS) provides surgeons with improved visualization of brain tumors and the infiltrative margin. 5-ALA is the most widely studied agent for FGS of HGG, and is currently the only agent (Gleolan R ) that is approved by the US Food and Drug Administration (FDA) for glioma surgery [9]. Fluorescence-guided surgery (FGS) using 5-aminolevulic acid (5-ALA) is a widely used strategy for delineating tumor tissue from surrounding brain intraoperatively during high-grade glioma (HGG) resection. 5-ALA reaches peak plasma levels ∼4 h after oral administration and is currently approved by the FDA for use 2–4 h prior to induction to anesthesia Fluorescence-guided surgery (FGS) using 5-aminolevulic acid (5-ALA) is a widely used strategy for delineating tumor tissue from surrounding brain intraoperatively during high-grade glioma (HGG) resection. 5-ALA reaches peak plasma levels ∼4 h after oral administration and is currently approved by the FDA for use 2–4 h prior to induction to anesthesia
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