5-aminolevulinic acid (5-ALA) fluorescence guided surgery of high-grade gliomas in eloquent areas assisted by functional mapping. Our experience and review of the literature

Puppa, Alessandro Della; Pellegrin, Serena De; d’Avella, Elena; Gioffrè, Giorgio; Rossetto, Marta; A, Gerardi; Lombardi, Giuseppe; Manara, Renzo; Munari, Marina; Saladini, Marina; Scienza, Renato

doi:10.1007/s00701-013-1660-x

Cited by 85 publications

(42 citation statements)

References 20 publications

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“…Sixty-four studies describe the clinical use of fluorescent agents [1, 3, 5, 6, 9, 11, 13–16, 22–26, 28–31, 33–35, 37, 38, 40–42, 44, 49, 52–54, 58, 64–66, 69, 71, 74, 75, 78, 80–82, 84–87, 89, 92, 94, 97–101, 105–107, 109, 110, 113, 115, 118]. Three ways of labeling tumor cells were identified in the literature: (1) passive, (2) metabolic, and (3) molecular labeling.…”

Section: Resultsmentioning

confidence: 99%

“…Forty-four clinical studies described the use of 5-ALA for glioma surgery [3, 5, 6, 13–16, 22, 24–26, 28, 30, 31, 33, 34, 37, 40–42, 44, 66, 69, 74, 75, 78, 81, 82, 84, 85, 87, 89, 94, 97–101, 105, 106, 109, 110, 113, 115], of which only six studies included LGGs [28, 33, 84, 109, 110, 113]. 5-ALA is the only fluorescent agent that has been tested in an RCT.…”

Section: Resultsmentioning

confidence: 99%

“…The study by Stummer et al showed a higher GTR rate for the 5-ALA group compared to the group that was operated without 5-ALA (65 vs. 35%) [99]. In observational studies, the rate of GTR after 5-ALA administration ranges from 25 to 94.3% for HGGs [3, 5, 6, 14, 16, 22, 24, 25, 30, 31, 34, 40, 42, 44, 69, 75, 82, 87, 89, 94, 98, 99, 105, 106, 113]. However, studies that included a control group all confirm a significantly higher GTR rate in the FGS group [14, 24, 82, 94, 99].…”

Section: Resultsmentioning

confidence: 99%

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Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results

et al. 2016

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BackgroundFluorescence-guided surgery (FGS) is a technique used to enhance visualization of tumor margins in order to increase the extent of tumor resection in glioma surgery. In this paper, we systematically review all clinically tested fluorescent agents for application in FGS for glioma and all preclinically tested agents with the potential for FGS for glioma.MethodsWe searched the PubMed and Embase databases for all potentially relevant studies through March 2016. We assessed fluorescent agents by the following outcomes: rate of gross total resection (GTR), overall and progression-free survival, sensitivity and specificity in discriminating tumor and healthy brain tissue, tumor-to-normal ratio of fluorescent signal, and incidence of adverse events.ResultsThe search strategy resulted in 2155 articles that were screened by titles and abstracts. After full-text screening, 105 articles fulfilled the inclusion criteria evaluating the following fluorescent agents: 5-aminolevulinic acid (5-ALA) (44 studies, including three randomized control trials), fluorescein (11), indocyanine green (five), hypericin (two), 5-aminofluorescein-human serum albumin (one), endogenous fluorophores (nine) and fluorescent agents in a pre-clinical testing phase (30). Three meta-analyses were also identified.Conclusions5-ALA is the only fluorescent agent that has been tested in a randomized controlled trial and results in an improvement of GTR and progression-free survival in high-grade gliomas. Observational cohort studies and case series suggest similar outcomes for FGS using fluorescein. Molecular targeting agents (e.g., fluorophore/nanoparticle labeled with anti-EGFR antibodies) are still in the pre-clinical phase, but offer promising results and may be valuable future alternatives.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results

et al. 2016

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“…Several studies have examined use of a multimodal approach in glioma surgery. 64-69 Good operative results have been reported with iMRI or 5-ALA-guided surgery integrated with functional mapping techniques. This allows both for delineation of tumor tissue and identification of functional pathways in a single operation.…”

Section: Resultsmentioning

confidence: 99%

Advances in the Surgical Management of Low-Grade Glioma

Hollon

Hervey-Jumper

Sagher

et al. 2015

Seminars in Radiation Oncology

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Over the past two decades, extent of resection has emerged as a significant prognostic factor in patients with low-grade gliomas. Greater extent of resection has been shown to improve overall survival, progression-free survival, and time to malignant transformation. The operative goal in the majority of low-grade glioma cases is to maximize extent of resection while avoiding post-operative neurologic deficits. Several advanced surgical techniques have been developed in an attempt to better achieve maximal safe resection. Intraoperative magnetic resonance imaging, fluorescence-guided surgery, intraoperative functional pathway mapping, and neuro-navigation are some of the most commonly utilized techniques with multiple studies to support their efficacy in glioma surgery. By utilizing these techniques either alone or in combination, patients harboring low-grade gliomas have a better prognosis with less surgical morbidity following tumor resection.

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“…Indeed, even if boundaries of surgery have recently moved forward thanks to the intraoperative assistance of neurophysiologic monitoring and more in general by new technologies [4,9,15], only few data are available on the real impact of surgery on this specific subgroup of patients and on criteria of patient selection. In particular, the consequence of surgery on the functional status (Karnofsky Performance Status, KPS) of these patients has not been investigated so far.…”

Section: Introductionmentioning

confidence: 99%

Surgery on motor area metastasis

et al. 2015

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The role of surgery on central area metastasis remains unclear, and outcome data are still controversial. The aim of our study is to analyze the predictive value of clinical and surgical data on motor and functional outcome of patients, taking into account new emerging data on boundary irregularity of brain metastasis. We retrospectively analyzed 47 consecutive patients who underwent surgery assisted by neurophysiologic monitoring for a solitary metastasis in central area between 2010 and 2013. Inclusion criteria were as follows: good functional status (Karnofsky Performance Status (KPS) ≥70), controlled systemic disease, and absence of extra-cranial dissemination. At 1-month follow up, motor and functional outcomes were compared with preoperative clinical status, response to corticosteroids, extent of tumor resection, boundary irregularity, and size of tumor. Gross total resection was achieved in 93.6% of cases. In preoperative symptomatic patients, motor outcome (according to Medical Research Council grading scale) improved in 55.5% and worsened in 16.7%, while functional outcome (according to KPS score) improved in 50% and worsened in 14.2% of cases. No worsening occurred in preoperative asymptomatic patients. Motor outcome resulted to be not correlated with preoperative deficits, tumor volume, or preoperative response to corticosteroid treatment. Remarkably, motor outcome and extent of surgical resection appeared strongly correlated with tumor boundary irregularity (p < 0.05). Surgery with neurophysiologic monitoring on motor area metastasis can improve functional and motor condition in selected patients. Tumor volume does not represent a limit in surgery. The high correlation between clinical outcome, resection rate, and tumor boundary irregularity strengthens a new belief on the infiltrative growing pattern of brain metastasis. Motor function was evaluated according to Medical Research Council grading scale (Ott et al. 2014) while functional status was assessed according to KPS score.

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5-aminolevulinic acid (5-ALA) fluorescence guided surgery of high-grade gliomas in eloquent areas assisted by functional mapping. Our experience and review of the literature

Abstract: 5-ALA surgery assisted by functional mapping makes high HGG resection in eloquent areas feasible , through a reasonable rate of late morbidity. This emerges even more remarkably for selected patients.

Cited by 85 publications

References 20 publications

Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results

Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results

Advances in the Surgical Management of Low-Grade Glioma

Surgery on motor area metastasis

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