High-Grade Glioma/Glioblastoma Multiforme: Is There a Role for Photodynamic Therapy?

Presented by Harry T. Whelan, MD, Professor of Neurology, Bleser Endower Chair, Director of Hyperbaric Medicine, U.S. Navy Professional School Liaison, Officer Captain U.S. Navy, Medical College of Wisconsin, Milwaukee, Wisconsin.
Journal of the National Comprehensive Cancer Network: JNCCN (Impact Factor: 4.18). 10/2012; 10 Suppl 2:S31-4.
Source: PubMed


In the United States, the 5-year survival rate for patients of all ages with all types of brain tumors is approximately 20%, with the scale skewed toward even poorer survival in patients with gliomas. Although surgery and radiotherapy are primary treatment options, surgery is rarely curative and radiotherapy has had little impact on overall survival. Predominantly studied in adults with advanced high-grade gliomas, photodynamic therapy (PDT) represents a paradigmatic shift in the treatment of brain tumors. With no clear standard of care for brain tumors, PDT may emerge as a potential alternative, although challenges regarding its clinical use remain and studies confirming its promise are necessary.

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    ABSTRACT: Background and objectives: In high-grade meningiomas and a subgroup of clinically aggressive benign meningiomas tumor control is still insufficient. Recently 5-ALA fluorescence in meningiomas was reported. The impact of 5-ALA fluorescence-guided surgery (FGS) on surgical decision-making and extent of resection has not yet been systematically analyzed, especially not in high-grade meningiomas. The present study deals with three main questions regarding 5-ALA FGS in meningiomas: to assess the potential for discriminating different WHO grades intra-operatively, to analyze the influence on surgical strategy and to evaluate the impact on extent of resection. Methods: Data from 31 meningiomas operated with 5-ALA FGS were retrospectively analyzed. Intraoperative fluorescence was graded by the surgeon as "no", "low" or "high". Correlations between semi-quantitative fluorescence and histological features (WHO grade) were analyzed. The influence of 5-ALA fluorescence on surgical strategy and the impact of 5-ALA FGS on degree of resection (Simpson grade and post-operative imaging) were studied. In tumors showing infiltrative growth the extent of resection of fluorescence positive tissue was evaluated. Results: The population comprised 19 WHO grade I, 8 grade II and 4 grade III tumors (61% benign and 39% high-grade meningiomas). 94% of the tumors showed positive fluorescence. Different fluorescence intensities were observed: "no" in two, "high" in 12 and "low" in 17 tumors, respectively. A significant correlation between fluorescence intensity and WHO grade was found (ρ=0.557, p=0.001). 5-ALA improved the extent of resection in 3/16 (19%) of grade I and in 6/8 (75%) of grade II/III meningiomas. This improvement was not measurable by the Simpson grading as rated by the surgeon and controlled on post-operative imaging. Conclusions: In the present population a strong correlation between fluorescence intensity and WHO grade was observed. 5-ALA FGS improved the extent of resection in meningiomas. Especially in high-grade tumors additional information on brain and neurovascular infiltration was provided. The improved resection was not measurable by Simpson's grading necessitating an additional item, which rates residual fluorescence. Long-term studies are necessary to evaluate a possible impact of FGS on recurrence and overall survival.
    No preview · Article · Aug 2014 · Photodiagnosis and Photodynamic Therapy
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    ABSTRACT: Background: For glioma, temozolomide (TMZ) is a commonly used chemotherapy drug and photodynamic therapy (PDT) is an important adjuvant therapy. The aim of this study was to evaluate the effect of their combination for the treatment of glioma. Methods: A rat C6 glioma model using male Wistar rats (n=180) weighing 280-300 g was established. Glioma-bearing rats (n=100) were treated with mock, hematoporphyrin monomethyl ether (HMME), laser or PDT. The expression of P-glycoprotein (P-gp) in endothelial cells of the blood-tumor-barrier and in glioma tissues was detected using immunohistochemistry and western blot, respectively. Glioma-bearing rats (n=40) were treated with normal saline, TMZ (60 mg/m(2) for five consecutive days), PDT (630 nm for 10 min) or a combination of TMZ and PDT. TMZ concentration in glioma tissues was detected using liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) and cell death was observed using transmission microscopy. Concurrently, another batch of 40 glioma-bearing rats was subjected to the same treatment, and the survival of these rats was estimated using Kaplan-Meier analysis. Results: PDT significantly decreased the expression of P-gp in endothelial cells comprising the blood-tumor-barrier and in glioma tissues. The combination of TMZ with PDT significantly increased TMZ concentration in glioma tissues, enhanced glioma cell apoptosis and prolonged the median survival of glioma-bearing rats. Conclusion: The combination of PDT with TMZ shows synergistic effect in rat C6 glioma model, indicating its potential clinical use in glioma treatment.
    No preview · Article · Nov 2014 · Photodiagnosis and Photodynamic Therapy
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    No preview · Article · Jan 2016

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