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. 2021 Mar 9:12:644804.
doi: 10.3389/fneur.2021.644804. eCollection 2021.

Fluorescence-Guided High-Grade Glioma Surgery More Than Four Hours After 5-Aminolevulinic Acid Administration

Georgios A Maragkos  1 , Alexander J Schüpper  1 , Nikita Lakomkin  1 , Panagiotis Sideras  2 , Gabrielle Price  1 , Rebecca Baron  1 , Travis Hamilton  3 , Sameah Haider  3 , Ian Y Lee  3 , Constantinos G Hadjipanayis  1   4 , Adam M Robin  3
Affiliations

Fluorescence-Guided High-Grade Glioma Surgery More Than Four Hours After 5-Aminolevulinic Acid Administration

Georgios A Maragkos et al. Front Neurol. .

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.

Keywords: 5-ALA; brain tumors; fluorescence; glioblastomas; glioma; intraoperative imaging; neuro-oncology.

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Conflict of interest statement

CH is a consultant for NX Development Corporation (NXDC) and Synaptive Medical. NXDC, a privately held company, markets Gleolan (5-ALA, aminolevulinic acid hydrochloride). Gleolan is an optical imaging agent approved for the visualization of malignant tissue during glioma surgery. CH is a consultant for NXDC and receives royalty payments for the sale of Gleolan. CH receives financial compensation as a consultant and lecturer for Synaptive (manufacturer of the 3D Synaptive MODUS V device). He has also received speaker fees by Carl Zeiss and Leica. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Case demonstration of a 69-year-old male with glioblastoma multiforme, undergoing 5-ALA FGS. Time from 5-ALA administration to anesthesia induction was 7 h and 48 min, time to incision was 9 h and 4 min and time to closure was 12 h and 14 min. (A–D) Preoperative MRI with DTI. Axial (E) and sagittal (F) postoperative MRI scan, after 5-ALA FGS, demonstrating gross total resection of the lesion. 5-ALA, 5-aminolevulinic acid; FGS, fluorescence-assisted glioma surgery; MRI, magnetic resonance imaging; DTI, diffusion tensor imaging.
Figure 2
Figure 2
Intraoperative imaging for case demonstration patient. (A) Tumor bulk fluorescence after 5-ALA administration (asterisk). (B) Infiltrative margin fluorescence after 5-ALA administration (white arrows).
Figure 3
Figure 3
Kaplan-Meier curve for survival after surgical excision on the present cohort. The x axis represents time from surgical excision in days, with red vertical dashed lines at the 3-, 6-, 9-, 12-, and 15-month marks. The y axis represents the percentage of patients surviving at each time point. Drop points in the curve represent patient mortality and the short vertical lines represent subject concealment from further calculations due to end of follow-up, with patients either lost to follow-up or being operated on recently from the time of analysis.
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