5-Aminolevulinic acid (5-ALA)-induced fluorescence in intracerebral metastases: a retrospective study

Kamp, Marcel A.; Grosser, Philipp; Felsberg, Jörg; Slotty, Philipp J.; Steiger, Hans‐Jakob; Reifenberger, Guido; Sabel, Michael

doi:10.1007/s00701-011-1200-5

Cited by 126 publications

(99 citation statements)

References 21 publications

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“…11,30 Interestingly, there was 1 biopsy among our study cohort that demonstrated ALA fluorescence in the presence of completely normal brain tissue. While additional samples are needed to support this finding, this may suggest that even in the absence of tumor, surrounding brain may take up ALA and fluoresce.…”

Section: Discussionmentioning

confidence: 86%

A prospective Phase II clinical trial of 5-aminolevulinic acid to assess the correlation of intraoperative fluorescence intensity and degree of histologic cellularity during resection of high-grade gliomas

Lau

Hervey-Jumper

Chang

et al. 2016

JNS

139

110

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OBJECT There is evidence that 5-aminolevulinic acid (ALA) facilitates greater extent of resection and improves 6-month progression-free survival in patients with high-grade gliomas. But there remains a paucity of studies that have examined whether the intensity of ALA fluorescence correlates with tumor cellularity. Therefore, a Phase II clinical trial was undertaken to examine the correlation of intensity of ALA fluorescence with the degree of tumor cellularity. METHODS A single-center, prospective, single-arm, open-label Phase II clinical trial of ALA fluorescence-guided resection of high-grade gliomas (Grade III and IV) was held over a 43-month period (August 2010 to February 2014). ALA was administered at a dose of 20 mg/kg body weight. Intraoperative biopsies from resection cavities were collected. The biopsies were graded on a 4-point scale (0 to 3) based on ALA fluorescence intensity by the surgeon and independently based on tumor cellularity by a neuropathologist. The primary outcome of interest was the correlation of ALA fluorescence intensity to tumor cellularity. The secondary outcome of interest was ALA adverse events. Sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and Spearman correlation coefficients were calculated. RESULTS A total of 211 biopsies from 59 patients were included. Mean age was 53.3 years and 59.5% were male. The majority of biopsies were glioblastoma (GBM) (79.7%). Slightly more than half (52.5%) of all tumors were recurrent. ALA intensity of 3 correlated with presence of tumor 97.4% (PPV) of the time. However, absence of ALA fluorescence (intensity 0) correlated with the absence of tumor only 37.7% (NPV) of the time. For all tumor types, GBM, Grade III gliomas, and recurrent tumors, ALA intensity 3 correlated strongly with cellularity Grade 3; Spearman correlation coefficients (r) were 0.65, 0.66, 0.65, and 0.62, respectively. The specificity and PPV of ALA intensity 3 correlating with cellularity Grade 3 ranged from 95% to 100% and 86% to 100%, respectively. In biopsies without tumor (cellularity Grade 0), 35.4% still demonstrated ALA fluorescence. Of those biopsies, 90.9% contained abnormal brain tissue, characterized by reactive astrocytes, scattered atypical cells, or inflammation, and 8.1% had normal brain. In nonfluorescent (ALA intensity 0) biopsies, 62.3% had tumor cells present. The ALA-associated complication rate among the study cohort was 3.4%. CONCLUSIONS The PPV of utilizing the most robust ALA fluorescence intensity (lava-like orange) as a predictor of tumor presence is high. However, the NPV of utilizing the absence of fluorescence as an indicator of no tumor is poor. ALA intensity is a strong predictor for degree of tumor cellularity for the most fluorescent areas but less so for lower ALA intensities. Even in the absence of tumor cells, reactive changes may lead to ALA fluorescence.

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Section: Discussionmentioning

confidence: 86%

A prospective Phase II clinical trial of 5-aminolevulinic acid to assess the correlation of intraoperative fluorescence intensity and degree of histologic cellularity during resection of high-grade gliomas

Lau

Hervey-Jumper

Chang

et al. 2016

JNS

139

110

View full text Add to dashboard Cite

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“…At the same time, no statistically significant effect on the overall survival rate was identified. Nevertheless, this technology has attracted an increased attention of neurosurgeons resulting in more reports on FN, as well as the application of this method for other central nervous system tumors [4,[7][8][9][10][11][12][13][14][15][16] including intracranial meningiomas [16][17][18][19][20]. However, the assessment of FN's sensitivity and specificity was not demonstrated clearly and in particular, no comparison was made between the data obtained from visible fluorescence, and the data obtained from laser biospectroscopy in meningiomas of different World Health Organization (WHO) grades.…”

Section: Introductionmentioning

confidence: 99%

Laser biospectroscopy and 5-ALA fluorescence navigation as a helpful tool in the meningioma resection

et al. 2016

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5-aminolevulinic acid (5-ALA) is a natural precursor of protoporphyrin IX (PP IX), which possesses fluorescent properties and is more intensively accumulated in tumor cells than in normal tissue. Therefore, the use of 5-ALA in the surgical treatment of intracranial tumors, particularly gliomas, has gained popularity in the last years, whereas its use in other intracranial pathological entities including meningiomas has been reported occasionally. This study describes a series of 28 patients with intracranial meningiomas, who were administered 5-ALA for a better visualization of tumor boundaries. Twelve patients underwent also laser spectroscopic analysis in order to confirm the visual impression of tumor tissue visualization. Bone infiltration was readily demonstrated. In one case, the tumor recurrence could have been prevented by removal of a tumor remnant, which would possibly have been better recognized if spectroscopic analysis had been used. Fluorescent navigation (FN) is a useful method for maximizing the radicality of meningioma surgery, particularly if the tumor infiltrates the bone, the skull base, and/or the surrounding structures

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“…5-ALA induced fluorescence is not seen in malignant gliomas only. Visualization and photodynamic therapy with 5-ALA of bladder, lung or gastrointestinal tumors has been established and for other cerebral intradural pathologies such as meningiomas, metastasis and medulloblastomas it has been recently explored [5,7,12,14,15,18,30].…”

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confidence: 99%

The impact of fluorescence guidance on spinal intradural tumour surgery

Eicker

Floeth²,

Kamp

et al. 2013

Eur Spine J

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Purpose 5-Aminolevulinic acid (5-ALA)-based fluorescence-guided surgery was shown to be beneficial for cerebral malignant gliomas. Extension of this technique for resection of meningiomas and cerebral metastasis has been recently evaluated. Aim of the present study is to evaluate the impact of fluorescence-guided surgery in spinal tumor surgery. Methods Twenty-six patients with intradural spinal tumors were included in the study. 5-ALA was administered orally prior to the induction of anesthesia. Intraoperative, 440 nm fluorescence was applied after exploration of the tumor and, if positive, periodically during and at the end of resection to detect tumor-infiltrated sites. Results Tumors of WHO grade III and IV were found in five patients. In detail intra-or perimedullary metastasis of malignant cerebral gliomas was found including glioblastoma WHO grade IV (n = 2), anaplastic astrocytoma WHO grade III (n = 1), anaplastic oligoastrocytoma WHO grade III (n = 1). In addition, one patient suffered from a spinal drop metastasis of a cerebellar medulloblastoma WHO grade IV. Tumors of WHO grade I were diagnosed in 18 patients: Eight cases of meningioma (two recurrences), six cases of neurinoma, one neurofibroma, two ependymoma and one plexus papilloma. At least, benign pathologies were histologically proven in three patients. All four spinal metastasis of malignant glioma (100 %), seven of eight meningiomas (87.5 %) and one of two ependymoma (50 %) were found to be ALA-positive. Conclusion The present study demonstrates that spinal intramedullary gliomas and the majority of spinal intradural meningiomas are 5-ALA positive. As a surgical consequence, especially in intramedullary gliomas, the use of 5-ALA fluorescence seems to be beneficial.

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5-Aminolevulinic acid (5-ALA)-induced fluorescence in intracerebral metastases: a retrospective study

Cited by 126 publications

References 21 publications

A prospective Phase II clinical trial of 5-aminolevulinic acid to assess the correlation of intraoperative fluorescence intensity and degree of histologic cellularity during resection of high-grade gliomas

A prospective Phase II clinical trial of 5-aminolevulinic acid to assess the correlation of intraoperative fluorescence intensity and degree of histologic cellularity during resection of high-grade gliomas

Laser biospectroscopy and 5-ALA fluorescence navigation as a helpful tool in the meningioma resection

The impact of fluorescence guidance on spinal intradural tumour surgery

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