The NXDC-MEN-301 Study on 5-ALA for Meningiomas Surgery for the Assessing the Benefit of Intra-Operative Fluorescence Imaging

Introduction: 5-aminolevulinic acid (5-ALA; GleolanTM, NXDC.) is approved for fluorescence-guided resections of malignant gliomas. Meningiomas are also known to fluorescence, which may be a useful surgical adjunct. We here present the results of a multicenter, prospective, blinded study to determine safety and benefit of fluorescence-guided resections of meningiomas.

Methods: Patients with suspected meningioma received GleolanTM 20mg/kg 2–4h prior to surgery using microscopes adapted for fluorescence detection. Surgeons were asked whether they observed residual fluorescing tumor under blue light after tumor was no longer perceived under white light. In addition, when faced with uncertain ( “indeterminate”) tissue, this study recorded how often surgeons made a correct surgical decision based on fluorescence and correlative histology. Primary endpoint was the percentage of patients in whom one of these two benefits were observed in an intent-to-image collective (i.e. any patient having received Gliolan and operated). We predefined 30% as threshold for success. Other endpoints included the diagnostic accuracy of fluorescence compared to white light versus correlative histology. For bias reduction, pertinent data were derived from surgical videos reviewed by independent reviewers blinded to surgeons’ assessments of tissue type and fluorescence status. Eleven centres from the US and Europe participated in this study.

Results: A total of 108 patients (newly diagnosed/recurrent meningiomas, all grades) were operated on. We noted no safety issues related to 5-ALA fluorescence-guided resections. The primary endpoint was met with the percentage of patients with either 1) an indeterminate tissue that fluoresced during surgery, consistent with histology or 2) an unexpected tissue that fluoresced at the end of surgery, consistent with histology was 60.2% (95% CI 50.8-68.9, p < 0.0001) and above our predefined 30% threshold for success. The analysis of secondary endpoints is pending and will be presented.

Conclusion : Our results from a prospective, blinded study on the use of 5-ALA for fluorescence-guided resection in meningiomas demonstrate a clear benefit in 6 out of 10 patients, based on better tissue discrimination and decision making during resection or the detection of residual tumor.