Atct-21a Prospective Phase Ii Clinical Trial of 5-aminolevulinic Acid to Correlate Intraoperative Fluorescence Intensity With Histologic Cellularity
Year: 2015
Type: article
Study design: Clinical Trial
Abstract: There is evidence that 5-aminolevulinic acid (ALA) facilitates greater extent of resection and improves 6-month progression-free survival in patients with high grade gliomas. But there remains a paucity of studies that have examined whether the intensity of ALA fluorescence correlates with tumor cellularity. A phase II clinical trial was undertaken to correlate the intensity of 5-aminolevulinic acid (ALA) fluorescence with degree of tumor cellularity during resection of high grade gliomas. A single-center, single arm, phase II clinical trial of ALA fluorescence-guided resection of high grade gliomas was held from 2010 to 2014. Biopsies were graded on a 4 point scale (0-none to 3-highest) based on ALA fluorescence intensity by the neurosurgeon and independently based on tumor cellularity by a neuropathologist. Outcome of interest was the correlation of ALA fluorescence intensity to tumor cellularity and adverse events. A total of 211 biopsies from 59 patients were included: 79.7% glioblastoma. ALA intensity 3 correlated with tumor presence 97.4% of cases and ALA intensity 0 correlated with tumor absence only 37.7% of cases. For all tumor types, glioblastoma, high grade, and recurrent tumors, ALA fluorescence intensity 3 correlated strongly with cellularity grade 3; correlation coefficients were 0.65, 0.66, 0.65, and 0.62, respectively. Specificity and PPV of ALA intensity 3-cellularity grade 3 match ranged from 95% to 100% and 86% to 100%, respectively. In samples without tumor, 35.4% had ALA fluorescence. Of those, 90.9% contained reactive astrocytes and atypical cells; 8.1% were normal brain. In non-fluorescent samples, 62.3% had tumor cells present. ALA associated complication was 3.4%. ALA demonstrated high PPV and ALA intensity 3 correlated strongly with cellularity grade 3. However, ALA had low NPV for excluding tumor presence. In addition, even in the absence of tumor cells, reactive changes including inflammation may lead to ALA fluorescence.
Source: Neuro-Oncology
Institution: University of California, San Francisco
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2342029841