Surgery guided by 5-aminolevulinic fluorescence in glioblastoma: volumetric analysis of extent of resection in single-center experience

Valle, Ricardo Díez; Solís, Sonia Tejada; Gastearena, Miguel Ángel Idoate; Eulate, Reyes García de; Echávarri, P.D. Domínguez; Aristu, Javier

doi:10.1007/s11060-010-0296-4

Cited by 185 publications

(119 citation statements)

References 27 publications

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“…of casesTumor grade of patientsControl groupGTR rate (%)TNRMedian survival (mo)PFS (mo)6-PFS (%)Stummer et al 2000 [98]5-ALACase series52GBMNo63–3––Stummer er al. 2006 [99]5-ALARCT322HGGYes65–15541Eljamel et al 2008 [26]5-ALARCT27GBMNo––129–Hefti et al 2008 [41]5-ALACase series74HGGNo–––––Nabavi et al 2009 [66]5-ALACase series36HGGNo–––––Feigl et al 2010 [31]5-ALACase series18HGGNo64–––83Ewelt et al 2011 [28]5-ALACase series17HGGNo–––––Ewelt et al 2011 [28]5-ALACase series13LGGNo–––––Floeth et al 2011 [33]5-ALACase series21HGGNo–––––Floeth et al 2011 [33]5-ALACase series17LGGNo–––––Diez Valle et al 2011 [25]5-ALACase series28GBMNo83–16…”

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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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%

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

et al. 2016

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“…First, PpIX displays limited fluorescence at tumor margins, 12 and does not identify all the infiltrative cells at invasive tumor margins. 7, 38, 39 Postoperative radiographic analysis has shown that on complete resection of tissue that fluoresces intraoperatively, postoperative/intraoperative MRI may continue to show abnormal areas of gadolinium enhancement consistent with tumor remnants. 40 A recent phase 2 clinical trial demonstrates that more than 60% of non-PpIX fluorescent biopsy tissue had tumor cells present, with a 37.7% negative predictive value.…”

Section: Non-targeted Fluorescent Imaging Agentsmentioning

confidence: 99%

Fluorescent-Guided Surgical Resection of Glioma with Targeted Molecular Imaging Agents: A Literature Review

et al. 2016

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The median life expectancy following a diagnosis of glioblastoma (GBM) is 15 months. While chemotherapeutics may someday cure GBM by killing the highly dispersive malignant cells, the most important contribution that clinicians can currently offer to improve survival is by maximizing the extent of resection and providing concurrent chemo-radiation, which has become standard. Strides have been made in this area with the advent and implementation of methods of improved intraoperative tumor visualization. One of these techniques, optical fluorescent imaging with targeted molecular imaging agents, allows the surgeon to view fluorescently labeled tumor tissue during surgery with the use of special microscopy – thereby highlighting where to resect, and indicating when tumor-free margins have been obtained. This advantage is especially important at the difficult to observe margins where tumor cells infiltrate normal tissue. Targeted fluorescent agents also may be valuable for identifying tumor versus non-tumor tissue. In this review, we briefly summarize non-targeted fluorescent tumor imaging agents before discussing several novel targeted fluorescent agents being developed for glioma imaging in the context of fluorescent guided surgery or live molecular navigation. Many of these agents are currently undergoing preclinical testing. As the agents become available, however, it is necessary to understand the strengths and weaknesses of each.

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“…15-19 Several methods are also being developed and tested to detect cases of low or variable tumor PpIX fluorescence signal, including intraoperative confocal microscopy 3,20-24 and intraoperative spectroscopy. 25-28 It is also unknown whether 5ALA detects clinically significant subsets of cancer cells such as cancer stem cells.…”

Section: Introductionmentioning

confidence: 99%

Fluorescent Cancer-Selective Alkylphosphocholine Analogs for Intraoperative Glioma Detection

et al. 2015

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Background 5-ALA induced tumor fluorescence aids brain tumor resections but is not approved for routine use in the United States. We developed and describe testing of two novel fluorescent, cancer-selective alkylphosphocholine analogs, CLR1501 (green) and CLR1502 (near-infrared), in a proof-of-principle study for fluorescence-guided glioma surgery. Objective To demonstrate CLR1501 and CLR1502 are cancer cell-selective fluorescence agents in glioblastoma models and compare tumor (T) to normal brain (N) fluorescence ratios with 5-ALA. Methods CLR1501, CLR1502, 5-ALA were administered to mice with MRI-verified orthotopic U251 GBM and GSC-derived xenografts. Harvested brains were imaged using confocal microscopy (CLR1501), IVIS Spectrum imaging system (CLR1501, CLR1502, and 5-ALA), or Fluobeam near-infrared fluorescence imaging system (CLR1502). Imaging and quantitative analysis of T:N fluorescence ratios were performed. Results Excitation/emission peaks are 500/517nm for CLR1501, and 760/778nm for CLR1502. The observed T:N ratio of CLR1502 (9.28±1.08) was significantly higher (p<0.01) than CLR1501 (3.51±0.44 on confocal imaging; 7.23±1.63 on IVIS imaging) and 5-ALA (4.81±0.92). Near-infrared Fluobeam CLR1502 imaging in a mouse xenograft model demonstrated high contrast tumor visualization compatible with surgical applications. Conclusion CLR1501 (green) and CLR1502 (near infrared) are novel tumor-selective fluorescent agents for discriminating tumor from normal brain. CLR1501 exhibits a tumor to brain fluorescence ratio similar to 5-ALA, whereas CLR1502 has a superior tumor to brain fluorescence ratio. This study demonstrates the potential use of CLR1501 and CLR1502 in fluorescence-guided tumor surgery.

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Surgery guided by 5-aminolevulinic fluorescence in glioblastoma: volumetric analysis of extent of resection in single-center experience

Cited by 185 publications

References 27 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

Fluorescent-Guided Surgical Resection of Glioma with Targeted Molecular Imaging Agents: A Literature Review

Fluorescent Cancer-Selective Alkylphosphocholine Analogs for Intraoperative Glioma Detection

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