5-ALA-induced fluorescence behavior of reactive tissue changes following glioblastoma treatment with radiation and chemotherapy

Kamp, Marcel A.; Felsberg, Jörg; Sadat, Hosai; Kuzibaev, Jamshid; Steiger, Hans‐Jakob; Rapp, Marion; Reifenberger, Guido; Dibué, Maxine; Sabel, Michael

doi:10.1007/s00701-014-2313-4

Cited by 59 publications

(32 citation statements)

References 22 publications

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“…35-37 False positive labeling in recurrent glioma patients is likely the result of PpIX fluorescence in areas of reactive astrocytes and macrophages, 37 coagulation necrosis and vascular hyalinization. 36 False positive PpIX fluorescence also may be related to how recently patients received radiation therapy. 36 …”

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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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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“…Administration of 5-aminolevulinic acid (5-ALA), 32,33 which is incorporated into the fluorescent protoporphyrin IX of tumor cells, facilitates compelling increases in short-term progression-free survival (PFS) and resection volumes, as well as decreases in the rate of subtotal tumor resection. 28 However, questions regarding the tumor specificity of 5-ALA metabolism 15 and the dye's phototoxicity risk, 12 high cost, and lack of Food and Drug Administration approval have limited its use in the United States. Fluorescein sodium, an easily administered, widely marketed, biosafe green-fluorescing dye, has been used as an adjunct for the resection of intracranial tumors since the 1940s, 20,21 as well as in numerous other medical applications.…”

mentioning

confidence: 99%

Aggressive resection at the infiltrative margins of glioblastoma facilitated by intraoperative fluorescein guidance

Neira

Ung

Sims

et al. 2017

Journal of Neurosurgery

127

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ABBREVIATIONS 5-ALA = 5-aminolevulinic acid; BBB = blood-brain barrier; CE = contrast enhancing; CUMC = Columbia University Medical Center; EOR = extent of resection; GBM = glioblastoma; GTR = gross-total resection; HGG = high-grade glioma; n-ANOVA = multiway ANOVA; NCE = non-contrast enhancing; OS = overall survival; PFS = progression-free survival; PPV = positive predictive value; ROI = region of interest; STR = subtotal resection; UD = undetermined; WHO = World Health Organization; Y560 = YELLOW 560. OBJECTIVE Extent of resection is an important prognostic factor in patients undergoing surgery for glioblastoma (GBM). Recent evidence suggests that intravenously administered fluorescein sodium associates with tumor tissue, facilitating safe maximal resection of GBM. In this study, the authors evaluate the safety and utility of intraoperative fluorescein guidance for the prediction of histopathological alteration both in the contrast-enhancing (CE) regions, where this relationship has been established, and into the non-CE (NCE), diffusely infiltrated margins. METHODS Thirty-two patients received fluorescein sodium (3 mg/kg) intravenously prior to resection. Fluorescence was intraoperatively visualized using a Zeiss Pentero surgical microscope equipped with a YELLOW 560 filter. Stereotactically localized biopsy specimens were acquired from CE and NCE regions based on preoperative MRI in conjunction with neuronavigation. The fluorescence intensity of these specimens was subjectively classified in real time with subsequent quantitative image analysis, histopathological evaluation of localized biopsy specimens, and radiological volumetric assessment of the extent of resection. RESULTS Bright fluorescence was observed in all GBMs and localized to the CE regions and portions of the NCE margins of the tumors, thus serving as a visual guide during resection. Gross-total resection (GTR) was achieved in 84% of the patients with an average resected volume of 95%, and this rate was higher among patients for whom GTR was the surgical goal (GTR achieved in 93.1% of patients, average resected volume of 99.7%). Intraoperative fluorescein staining correlated with histopathological alteration in both CE and NCE regions, with positive predictive values by subjective fluorescence evaluation greater than 96% in NCE regions. CONCLUSIONS Intraoperative administration of fluorescein provides an easily visualized marker for glioma pathology in both CE and NCE regions of GBM. These findings support the use of fluorescein as a microsurgical adjunct for guiding GBM resection to facilitate safe maximal removal. SUBMITTEDhttps://thejns.org/doi/abs/10.3171/2016.7.JNS16232

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“…As describe by Kamp and cols., we also found it useful identifying normal brain tissue or changes like gliosis, necrosis, vascular hyalization and scar formation in our patient with prior history of TMZ and radiotherapy [31] .…”

Section: Discussionmentioning

confidence: 60%

Fluorescence Guided Brain Tumor Surgery: Case Report

Manrique-Guzman

Castillo-Rueda

Wolfsberger

et al. 2015

International Journal of Neurology Research

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Glioblastoma in the most common malignant glioma in adults with 22,500 new cases diagnosed each year. Median survival is less than one year with high rates of neurological disabilities. The current treatment approach includes surgery, chemotherapy and radiotherapy. Tumor resection has prognostic value and maximizing tumor resection should be always attempted. Fluorescence guided surgery for brain tumors have improved tumor resection with specificity up to 98%. Limitations for this technology includes lack of modified surgical microscopes in neurosurgical centers worldwide. We present the first two cases done in Mexico with no surgical complications using fluorescent technique. This paper supports the safety and advantages of using fluorescence guided surgery for malignant gliomas.

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5-ALA-induced fluorescence behavior of reactive tissue changes following glioblastoma treatment with radiation and chemotherapy

Cited by 59 publications

References 22 publications

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

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

Aggressive resection at the infiltrative margins of glioblastoma facilitated by intraoperative fluorescein guidance

Fluorescence Guided Brain Tumor Surgery: Case Report

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