Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial.
ABSTRACT 5-Aminolevulinic acid is a non-fluorescent prodrug that leads to intracellular accumulation of fluorescent porphyrins in malignant gliomas-a finding that is under investigation for intraoperative identification and resection of these tumours. We aimed to assess the effect of fluorescence-guided resection with 5-aminolevulinic acid on surgical radicality, progression-free survival, overall survival, and morbidity.
322 patients aged 23-73 years with suspected malignant glioma amenable to complete resection of contrast-enhancing tumour were randomly assigned to 20 mg/kg bodyweight 5-aminolevulinic acid for fluorescence-guided resection (n=161) or to conventional microsurgery with white light (n=161). The primary endpoints were the number of patients without contrast-enhancing tumour on early MRI (ie, that obtained within 72 h after surgery) and 6-month progression-free survival as assessed by MRI. Secondary endpoints were volume of residual tumour on postoperative MRI, overall survival, neurological deficit, and toxic effects. We report the results of an interim analysis with 270 patients in the full-analysis population (139 assigned 5-aminolevulinic acid, 131 assigned white light), which excluded patients with ineligible histological and radiological findings as assessed by central reviewers who were masked as to treatment allocation; the interim analysis resulted in termination of the study as defined by the protocol. Primary and secondary endpoints were analysed by intention to treat in the full-analysis population. The study is registered at http://www.clinicaltrials.gov as NCT00241670.
Median follow-up was 35.4 months (95% CI 1.0-56.7). Contrast-enhancing tumour was resected completely in 90 (65%) of 139 patients assigned 5-aminolevulinic acid compared with 47 (36%) of 131 assigned white light (difference between groups 29% [95% CI 17-40], p<0.0001). Patients allocated 5-aminolevulinic acid had higher 6-month progression free survival than did those allocated white light (41.0% [32.8-49.2] vs 21.1% [14.0-28.2]; difference between groups 19.9% [9.1-30.7], p=0.0003, Z test). Groups did not differ in the frequency of severe adverse events or adverse events in any organ system class reported within 7 days after surgery.
Tumour fluorescence derived from 5-aminolevulinic acid enables more complete resections of contrast-enhancing tumour, leading to improved progression-free survival in patients with malignant glioma.
SourceAvailable from: Viive Howell[Show abstract] [Hide abstract]
ABSTRACT: Glioblastomas, (grade 4 astrocytomas), are aggressive primary brain tumors characterized by histopathological heterogeneity. High-resolution sequencing technologies have shown that these tumors also feature significant inter-tumoral molecular heterogeneity. Molecular subtyping of these tumors has revealed several predictive and prognostic biomarkers. However, intra-tumoral heterogeneity may undermine the use of single biopsy analysis for determining tumor genotype and has implications for potential targeted therapies. The clinical relevance and theories of tumoral molecular heterogeneity in glioblastoma are discussed.Frontiers in Oncology 03/2015; 5:55. DOI:10.3389/fonc.2015.00055
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ABSTRACT: In their article “Fluorescein sodium-guided resection of cerebral metastases—experience with the first 30 patients”, Schebesch and colleagues examine the use of fluorescein sodium dye in patients harboring brain metastases. In their retrospective patient series, 30 patients with different tumor entities were included. All patients underwent surgical resection of brain metastasis while using fluorescein sodium and a YELLOW 560 nm (ZEISS) filter. According to them, sufficient fluorescent staining was observed in 27 patients and complete tumor resection in 25 patients.Their findings are in accordance with a prior study conducted by Okuda and colleagues , though Okuda and colleagues used fluorescein sodium under white light without a particular microscope filter.While of course their retrospective study permits no conclusion that the use of fluorescein sodium will help to improve the neurosurgical treatment of patients with brain metastases in regard to the extent of resection and local ...Acta Neurochirurgica 04/2015; DOI:10.1007/s00701-015-2404-x · 1.79 Impact Factor
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ABSTRACT: Linear array intraoperative ultrasound (lioUS) is an emerging technology for intracranial use. We evaluated sensitivity and specificity of lioUS to detect residual tumor in patients harboring a glioblastoma. After near total resection in 20 patients, residual tumor detection using lioUS, conventional intraoperative ultrasound (cioUS), and gadopentetic-diethylenetriamine penta-acetic acid (Gd-DTPA)-enhanced intraoperative MRI (iMRI) were compared. Sensitivity and specificity were calculated based on 68 navigated biopsies. Receiver operator characteristic (ROC) curves and correlation with histopathological findings of each imaging modality were calculated. Additionally, results were evaluated in the subgroup of recurrent disease (23 biopsies in 8 patients). Sensitivity of lioUS (76 %) was significantly higher compared with iMRI (55 %) and cioUS (24 %). Specificity of lioUS (58 %) was significantly lower than in cioUS (96 %), while there was no significant difference to iMRI (74 %). All imaging modalities correlated significantly with histopathological findings. In the subgroup of recurrent disease, sensitivity and specificity decreased in all modalities. However, cioUS showed significant lower values than iMRI and lioUS. In ROC curves, lioUS showed a higher area und the curve (AUC) in comparison with iMRI and cioUS. We found similar results in the subgroup of recurrent disease. Tumor detection using a lioUS is significantly superior to cioUS. Overall test performance in lioUS is comparable with results of iMRI. While, the latter has a higher specificity and a significantly lower sensitivity in comparison with lioUS.Neurosurgical Review 04/2015; DOI:10.1007/s10143-015-0627-1 · 1.86 Impact Factor