5-ALA fluorescence–guided surgery in pediatric brain tumors—a systematic review

Schwake, Michael; Schipmann, Stephanie; Köchling, Michaela; Brentrup, Angela; Stummer, Walter

doi:10.1007/s00701-019-03898-1

Cited by 50 publications

(41 citation statements)

References 85 publications

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“…Despite the good in vitro evidence of MB cells to accumulate PPIX [21, 29-32], the clinical reports of MB fluorescence are conflicting and ambiguous [33][34][35]. Our result of a strong fluorescence rate of 44% is similar to the existing literature [2,[33][34][35].…”

Section: Discussionsupporting

confidence: 80%

The Use of 5-Aminolevulinic Acid to Assist Gross Total Resection of Paediatric Posterior Fossa Tumours

Labuschagne

2020

Pediatr Neurosurg

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Background: 5-aminolevulinic acid (5-ALA) use is well established in the resection of adult high-grade gliomas. There is growing interest in its usefulness in the paediatric population. The potential benefit of 5-ALA-guided resection motivated our unit to offer the established adult protocol as off-label use. Objective: to determine if 5-ALA guided resection was routinely useful and offered increased gross total resection (GTR) results. Methods: Nineteen patients harbouring a posterior fossa tumour suggestive of either an ependymoma or medulloblastoma (MB) underwent surgery between January 2018 and October 2019. The mean age was 5 years (range 2–12 years). A dose of 20 mg/kg of 5-ALA (Gliolan®) was given 4 h preoperatively. Intraoperatively, the tumours were viewed under violet-blue light and the presence of fluorescence was recorded. Fluorescence status was compared with histopathological classification and grade, Ki-67 index, GTR rate, and a subjective determination of “usefulness” was determined. Results: The case series included ependymoma grade II (n = 6), ependymoma grade III (n = 4), and MB grade IV (n = 9). For the combined cohort, the strong fluorescence rate was 68% (n = 13), the heterogenous fluorescence rate was 26% (n = 5), and the completely negative fluorescence rate was 5% (n = 1). The strong fluorescence rate of 90% found in the combined ependymoma group compared to the 45% strong fluorescence rate in the MB group was statistically significant (p = 0.05). Within the MB group the Ki-67 index was found to be significantly higher in the strongly fluorescent group as opposed to the patchy or non-fluorescent group (77.5 vs. 40%, p = 0.016). Fluorescence was determined to be useful in 63% of all cases. There was no significant relationship between fluorescence and GTR. The relationship between perceived usefulness and resection was not statistically significant. No adverse drug reactions were recorded. Conclusion: This case series adds to the growing body of evidence demonstrating the safety of 5-ALA in the paediatric population. 5-ALA guided resection was found to be useful in the majority of cases but this did not correlate with GTR status. Ependymomas reliably fluoresce in 90% of cases, and 5-ALA-guided resection should be considered when a preoperative diagnosis of ependymoma is suspected.

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Section: Discussionsupporting

confidence: 80%

The Use of 5-Aminolevulinic Acid to Assist Gross Total Resection of Paediatric Posterior Fossa Tumours

Labuschagne

2020

Pediatr Neurosurg

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“…Fluorescence-guided surgery (FGS) is a novel intra-operative imaging technique that empowers surgeons to visualize tumor tissue in real time using exogenous fluorescent agents. Most of the FDA-approved FGS probes are targeted against generic tumor markers 8 , with fluorescent 5-aminolevulinic acid (5-ALA) widely used for FGS on pediatric brain tumors 9 . However, recently, there has been a shift in this field towards the development of targeted probes that specifically bind surface markers on cancerous cells for molecular imaging 10 .…”

Section: Introductionmentioning

confidence: 99%

Anti-GD2-IRDye800CW as a targeted probe for fluorescence-guided surgery in neuroblastoma

Wellens

Deken

Sier

et al. 2020

Sci Rep

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Neuroblastoma resection represents a major challenge in pediatric surgery, because of the high risk of complications. Fluorescence-guided surgery (FGS) could lower this risk by facilitating discrimination of tumor from normal tissue and is gaining momentum in adult oncology. Here, we provide the first molecular-targeted fluorescent agent for FGS in pediatric oncology, by developing and preclinically evaluating a GD2-specific tracer consisting of the immunotherapeutic antibody dinutuximab-beta, recently approved for neuroblastoma treatment, conjugated to near-infrared (NIR) fluorescent dye IRDye800CW. We demonstrated specific binding of anti-GD2-IRDye800CW to human neuroblastoma cells in vitro and in vivo using xenograft mouse models. Furthermore, we defined an optimal dose of 1 nmol, an imaging time window of 4 days after administration and show that neoadjuvant treatment with anti-GD2 immunotherapy does not interfere with fluorescence imaging. Importantly, as we observed universal, yet heterogeneous expression of GD2 on neuroblastoma tissue of a wide range of patients, we implemented a xenograft model of patient-derived neuroblastoma organoids with differential GD2 expression and show that even low GD2 expressing tumors still provide an adequate real-time fluorescence signal. Hence, the imaging advancement presented in this study offers an opportunity for improving surgery and potentially survival of a broad group of children with neuroblastoma.

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“…However, under current standard microscopes, only 10–20% low grade gliomas showed visible fluorescence [173233]. The papers reported sporadically the positivity of fluorescence in some low grade gliomas, including ependymoma, oligodendroglioma, and pleomorphic xanthoastrocytoma [3435]. In our experience, pilocytic astrocytoma of WHO grade I showed high rate of positive fluorescence (5 out of 9 cases).…”

Section: Discussionmentioning

confidence: 64%

Experience Profiling of Fluorescence-Guided Surgery I: Gliomas

Kim

Park

2019

Brain Tumor Res Treat

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Background Numerous studies reported a usefulness of 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery (FGS) in high grade gliomas. However, fluorescence patterns and intensities are variable among gliomas. In this study, we report our extensive experience with FGS in various gliomas, focusing on epidemiological data of fluorescence patterns. Methods A total of 827 histologically proven glioma patients out of 900 brain tumor patients who had undergone FGS using 5-ALA during the period of 8.5 years between July 2010 and January 2019 were analyzed. Indications of FGS in glioma surgery are evidence for possible high-grade foci in putative gliomas in preoperative MRI. Results Among the 827 gliomas, the number of cases corresponding to 2016 World Health Organization (WHO) grade IV, III, II, and I are 528 (58.7%), 193 (21.4%), 87 (9.7%) and 19 (2.1%), respectively. In terms of fluorescence rate, grade IV gliomas showed positive fluorescence in 95.4% of cases including strong intensity in 85.6%. Grade III gliomas showed fluorescence in about half of cases (55.0%), but 45.0% of the cases showed no fluorescence at all. Anaplastic oligodendroglioma had a higher positive rate (63.9%) than anaplastic astrocytoma (46.2%). Both grade II and I gliomas still showed positive fluorescence in about one-fourth of cases (24.1% and 26.3% respectively). Among them ependymoma and pilocytic astrocytoma were fluorescence-prone tumors. Conclusion This epidemiological data of 5-ALA fluorescence in various grades of glioma provides a basic reference to the clinical application of FGS with 5-ALA in glioma surgery.

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5-ALA fluorescence–guided surgery in pediatric brain tumors—a systematic review

Cited by 50 publications

References 85 publications

The Use of 5-Aminolevulinic Acid to Assist Gross Total Resection of Paediatric Posterior Fossa Tumours

The Use of 5-Aminolevulinic Acid to Assist Gross Total Resection of Paediatric Posterior Fossa Tumours

Anti-GD2-IRDye800CW as a targeted probe for fluorescence-guided surgery in neuroblastoma

Experience Profiling of Fluorescence-Guided Surgery I: Gliomas

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