Use of fluorescence to guide resection or biopsy of primary brain tumors and brain metastases

Abstract

<jats:sec> <jats:title>Object</jats:title> <jats:p>The accurate discrimination between tumor and normal tissue is crucial for determining how much to resect and therefore for the clinical outcome of patients with brain tumors. In recent years, guidance with 5-aminolevulinic acid (5-ALA)–induced intraoperative fluorescence has proven to be a useful surgical adjunct for gross-total resection of high-grade gliomas. The clinical utility of 5-ALA in resection of brain tumors other than glioblastomas has not yet been established. The authors assessed the frequency of positive 5-ALA fluorescence in a cohort of patients with primary brain tumors and metastases.</jats:p></jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>The authors conducted a single-center retrospective analysis of 531 patients with intracranial tumors treated by 5-ALA–guided resection or biopsy. They analyzed patient characteristics, preoperative and postoperative liver function test results, intraoperative tumor fluorescence, and histological data. They also screened discharge summaries for clinical adverse effects resulting from the administration of 5-ALA. Intraoperative qualitative 5-ALA fluorescence (none, mild, moderate, and strong) was documented by the surgeon and dichotomized into negative and positive fluorescence.</jats:p></jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>A total of 458 cases qualified for final analysis. The highest percentage of 5-ALA–positive fluorescence in open resection was found in glioblastomas (96%, n = 99/103). Among other tumors, 5-ALA–positive fluorescence was detected in 88% (n = 21/32) of anaplastic gliomas (WHO Grade III), 40% (n = 8/19) of low-grade gliomas (WHO Grade II), no (n = 0/3) WHO Grade I gliomas, and 77% (n = 85/110) of meningiomas. Among metastases, the highest percentage of 5-ALA–positive fluorescence was detected in adenocarcinomas (48%, n = 13/27). Low rates or absence of positive fluorescence was found among pituitary adenomas (8%, n = 1/12) and schwannomas (0%, n = 0/7). Biopsies of high-grade primary brain tumors showed positive rates of fluorescence similar to those recorded for open resection. No clinical adverse effects associated with use of 5-ALA were observed. Only 1 patient had clinically silent transient elevation of liver enzymes.</jats:p></jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Study findings suggest that the administration of 5-ALA as a surgical adjunct for resection and biopsy of primary brain tumors and brain metastases is safe. In light of the high rate of positive fluorescence in high-grade gliomas other than glioblastomas, meningiomas, and a variety of metastatic cancers, 5-ALA seems to be a promising tool for enhancing intraoperative identification of neoplastic tissue and optimizing the extent of resection.</jats:p></jats:sec>

Chemically triggered release of 5-aminolevulinic acid from liposomes

“…2, 3 5-ALA is finding increasing clinical use as an adjunct in fluorescence-guided surgery, where it is especially effective for guiding resection of high grade glioma. 4 Low intensity, blue light illumination of the surgical field produces a two-color fluorescence image that helps surgeons delineate tumor margins. 5-ALA is also clinically important as a prodrug for photodynamic therapy (PDT) of several medical conditions.…”

“…After systemic treatment, the patient remains photosensitive until all of the 5-ALA is cleared from the body, which can take up two days. 4, 10 In principle, this clinical drawback could be ameliorated if the 5-ALA was delivered selectively to tumors. Recent research efforts have explored covalent modification 11, 12 or colloidal encapsulation 8, 13, 14 as new methods to enhance cellular uptake of 5-ALA after topical administration.…”

The Role of Fast Cell Cycle Analysis in Pediatric Brain Tumors

“…Nevertheless, administration of 5-ALA is required and not all tumors have noticeable fluorescence. In a recent study, 88% of high-grade gliomas, 40% of low-grade gliomas, 77% of meningiomas and 52% of metastatic tumors were positive [20]. In pediatric tumors, except malignant glioma, 5-ALA was found to be inconsistently useful in primitive neuroectodermal tumors, gangliogliomas, MB and pilocytic astrocytomas [19].…”

405 nm versus 633 nm for protoporphyrin IX excitation in fluorescence‐guided stereotactic biopsy of brain tumors

“…It leads to a significantly increased complete resection rate of these diffusely growing tumors and to a significantly enhanced progression-free survival rate after 6 months, translating into a progression-free survival prolongation of 1.5 months as compared to conventional white light resection. [23] The method has also been tested on excised tissue samples during stereotactic biopsy using surgical microscopes [21,[29][30][31]. In the latter case, the diagnostic yield of the fluorescent samples was always 100% (total n = 98).…”