Extent of resection in patients with glioblastoma: limiting factors, perception of resectability, and effect on survival

Orringer, Daniel A.; Lau, Darryl; Khatri, Sameer; Zamora-Berridi, Grettel J.; Zhang, Kathy; Wu, Chris Y.; Chaudhary, Neeraj; Sagher, Oren

doi:10.3171/2012.8.jns12234

Cited by 257 publications

(154 citation statements)

References 26 publications

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“…Although prior studies suggest that postoperative tumor volume, as well as extent of resection, have prognostic significance in newly diagnosed glioblastomas, 13,14 the importance of tumor volume in patients with recurrent tumor receiving anti-angiogenic therapy is unclear. In patients with recurrent tumor receiving bevacizumab, results from a phase 2 clinical trial have shown that 4-week posttreatment response based on 2-dimensional criteria correlates with PFS.…”

Section: Introductionmentioning

confidence: 99%

Recurrent glioblastoma: Volumetric assessment and stratification of patient survival with early posttreatment magnetic resonance imaging in patients treated with bevacizumab

Huang

Rahman

Hamdan

et al. 2013

Cancer

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BACKGROUND: Despite a high radiographic response rate in patients with recurrent glioblastoma following bevacizumab therapy, survival benefit has been relatively modest. We assess whether tumor volume measurements based on baseline and early posttreatment MRI can stratify patients in terms of progression-free survival (PFS) and overall survival (OS). METHODS: Baseline (24 1/-4 days) and posttreatment (30 1/-6 days) MRI exams of 91 patients with recurrent glioblastoma treated with bevacizumab were retrospectively evaluated for volume of enhancing tumor as well as volume of the T2/FLAIR hyperintensity. Overall survival (OS) and progression-free survival (PFS) were assessed using volume parameters in a Cox regression model adjusted for significant clinical parameters. RESULTS: In univariable analysis, residual tumor volume, percentage change in tumor volume, steroid change from baseline to posttreatment scan, and number of recurrences were associated with both OS and PFS. With dichotomization by sample median of 52% change of enhancing volume can stratify OS (52 weeks vs. 31 weeks, P 5.013) and PFS (21 weeks vs. 12 weeks, P 5.009). Residual enhancing volume, dichotomized by sample median of 7.8 cm 3 , can also stratify for OS (64 weeks vs. 28 weeks, P <.001) and PFS (21 weeks vs. 12 weeks, P 5.036). CONCLUSIONS: Volumetric percentage change and absolute early posttreatment volume of enhancing tumor can stratify survival for patients with recurrent glioblastoma receiving bevacizumab therapy. Cancer 2013;119:3479-88.

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Section: Introductionmentioning

confidence: 99%

Recurrent glioblastoma: Volumetric assessment and stratification of patient survival with early posttreatment magnetic resonance imaging in patients treated with bevacizumab

Huang

Rahman

Hamdan

et al. 2013

Cancer

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“…Studies have shown that gross-total resection (GTR) of contrast-enhancing tumor is achieved in only about 20%-30% of patients, and in patients deemed to have tumors amendable to GTR, and radiographic complete resection is achieved in only approximately 24% of patients. 1,3,16,24,33,35 These modest outcomes are likely due to difficulty in determining the distinction between tumor and brain parenchyma. 1 Several technological advances have been explored to aid in improving the ability to obtain greater EOR during glioma surgery: intraoperative MRI, 15 neuronavigation, 36 ultrasound, 13 and newer technologies such as Raman scattered microscopy.…”

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confidence: 99%

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

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127

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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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“…Fluorescence guidance in resection of malignant glioma has been shown to improve extent of resection and 6-month progression-free survival in a prospective, multi-institutional clinical and preliminary experience in the United States has confirmed the high correlation of this fluorescence with imaging and histologic features [99]. Of course that the outcome of surgical treatment in patients with GBM is highly influenced by tumor topography [97], extension [10] and the actual extent of the surgical resection [78]. Moreover, the extent of surgical resection is an independent prognostic factor-an analysis of 28 studies found a mean duration of survival advantage of total over subtotal resection for glioblastoma (14 vs. 11 month) [48].…”

Section: State Of the Art In The Treatment Of Gbmmentioning

confidence: 99%

Current perspectives concerning the multimodal therapy in Glioblastoma

Grigore¹,

Brehar²,

Gorgan³

2015

Romanian Neurosurgery

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GBM (Glioblastoma) is the most common, malignant type of primary brain tumor. It has a dismal prognosis, with an average life expectancy of less than 15 months. A better understanding of the tumor biology of GBM has been achieved in the past decade and set up new directions in the multimodal therapy by targeting the molecular paths involved in tumor initiation and progression. Invasion is a hallmark of GBM, and targeting the complex invasive mechanism of the tumor is mandatory in order to achieve a satisfactory result in GBM therapy. The goal of this review is to describe the tumor biology and key features of GBM and to provide an up-to-date overview of the current identified molecular alterations involved both in tumorigenesis and tumor progression.

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Extent of resection in patients with glioblastoma: limiting factors, perception of resectability, and effect on survival

Cited by 257 publications

References 26 publications

Recurrent glioblastoma: Volumetric assessment and stratification of patient survival with early posttreatment magnetic resonance imaging in patients treated with bevacizumab

Recurrent glioblastoma: Volumetric assessment and stratification of patient survival with early posttreatment magnetic resonance imaging in patients treated with bevacizumab

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

Current perspectives concerning the multimodal therapy in Glioblastoma

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