Outcomes after combined use of intraoperative MRI and 5-aminolevulinic acid in high-grade glioma surgery

Schatlo, Bawarjan; Fandiño, Javier; Smoll, Nicolas R.; Wetzel, Oliver; Remonda, Luca; Marbacher, Serge; Perrig, Wolfgang Nicolas; Landolt, Hans; Fathi, Ali-Reza

doi:10.1093/neuonc/nov049

Cited by 59 publications

(44 citation statements)

References 22 publications

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“…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%

“…To increase the accuracy of LGGs, FGS was combined with intra-operative confocal microscopy [84] or an intraoperative probe for quantitative fluorescence measurement [109]. Other intraoperative techniques used to increase the extent of glioma resection are photodynamic therapy (PDT) [26], iMRI [14, 30, 34, 40, 78, 85], intra-operative CT [5], exoscope imaging [6, 75], fluorescence spectrometry [37, 100], confocal microscopy [84], and intraoperative mapping [22, 89]. …”

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%

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

et al. 2016

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“…The aim of FGS is to prolong progression free and overall survival safely, that is, not at the expense of functional deficits or compromised quality of life. This aim is achievable if most or all of the MRI‐contrast uptaking part of the GBM tissue can be removed , of course without extending surgery into functional brain. Several surgical guidance tools have therefore been developed as listed in Table .…”

Section: Fluorescence Guided Surgerymentioning

confidence: 99%

5‐ALA in the management of malignant glioma

Stepp¹,

2018

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Background: Patients suffering from malignant gliomas have a poor prognosis. For the surgical treatment of these tumors, 5-aminolevulinic acid (5-ALA) has become a new standard. Aims: This review intends to provide an overview over current status, significance, limitations, and future perspectives of 5-ALA based fluorescence guided surgery and photodynamic therapy for brain tumor patients. Materials and Methods: From peer reviewed publications on the many aspects connected with this topic, those with potential clinical relevance were selected and put in the context of our own experience. Results and Discussion: The high tumor selectivity of accumulation of fluorescent protoporphyrin IX (PpIX) after systemic administration of 5-ALA enables intra-operative fluorescence guidance, which is unimpaired by brainshift and does not require expensive equipment. The neurosurgical aim of complete resection of enhancing tumor can now more easily be achieved, which improves prognosis in these patients. Nevertheless, despite better surgery tumors will inevitably recur. In order to further prolong survival, the phototoxic properties of PpIX are presently being exploited in clinical trials of post-operative or interstitial photodynamic therapy (PDT). Conclusion: 5-ALA based fluorescence guidance and PDT offer an intriguing new option for the management of malignant gliomas. Lasers Surg. Med. 50:399-419, 2018.

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“…Both techniques were used in 23 cases of our series, increasing safety of 5-ALA-guided resection close to eloquent areas and improving GTR. We previously reported a series of iMRI aiming better tumor removal 15 , and the benefits of the combination of these tools (5-ALA, iMRI, neuronavigation) seems essential for overall survival and PFS improvement [16][17][18] . Transient neurological deficits seem justified by long-term benefits for the patients when applying these adjuvant techniques, especially 5-ALA 19 .…”

Section: Discussionmentioning

confidence: 99%

5-Aminolevulinic Acid–Protoporphyrin IX Fluorescence-Guided Surgery for CNS Tumors

Ramina¹,

Júnior²,

Neto³

et al. 2018

jbnc

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Introduction: In the last two decades the 5-aminolevulinic acid (5-ALA) has been utilized in primary brain lesions and metastases surgery to aid the identification of tumor limits and infiltration. Objectives: In this retrospective study, we demonstrate our experience with the first 41 cases Latin America of surgical resection of central nervous system (CNS) lesions with 5-ALA. Methods: In 41 consecutive patients, we recorded age, sex, histopathological diagnosis, intraoperative 5-ALA fluorescence tumor response, 5-ALA post-resection resection grade through magnetic resonance image (MRI) and other concomitantintra-operative techniques utilized (transoperative imaging, awake surgery, electrophysiological stimulation and monitoring). Results: Twenty seven high-grade gliomas and 4 non-glial lesions were 5-ALA fluorescence positive; 6 low-grade gliomas, 1 high-grade glioma and a hippocampal gliosis were 5-ALA fluorescence negative. In one case of a low-grade glioma, the patient developed a cardiac arrhythmia, probably not related to 5-ALA administration, but the surgery was suspended. Conclusions: 5-ALA fluorescence-guided surgery is a safe and easy technique to be used, increasing tumor total gross resection in glioma cases, proving to be an invaluable neurosurgical tool for intracranial tumor surgery. There was no serious side effect in this series. This dye should be utilized in all cases of high-grade gliomas.

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Outcomes after combined use of intraoperative MRI and 5-aminolevulinic acid in high-grade glioma surgery

Cited by 59 publications

References 22 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

5‐ALA in the management of malignant glioma

5-Aminolevulinic Acid–Protoporphyrin IX Fluorescence-Guided Surgery for CNS Tumors

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