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Mitchel S. Berger, Ilona V. Garner, and Michael W. McDermott

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James R. Bean

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Nader Sanai, Michael E. Sughrue, Gopal Shangari, Kenny Chung, Mitchel S. Berger, and Michael W. McDermott

Object

Although meningiomas are commonly found along the supratentorial convexity, the risk profile associated with this subset of lesions in the modern neurosurgical era is unknown.

Methods

The authors retrospectively reviewed the clinical course of patients with supratentorial convexity meningiomas treated during the past 10 years. All patients had undergone MR imaging within 72 hours after surgery and at least 1 year of clinical follow-up. Patients with multiple meningiomas, hemangiopericytomas, malignant meningiomas, or tumor-prone syndromes were excluded from analysis.

Results

Between 1997 and 2007, 141 consecutive patients (median age 48 years, range 18–95 years) underwent resection of a supratentorial convexity meningioma. The most common signs or symptoms at presentation were headache (48%), seizures (34%), and weakness (21%). The mean tumor volume was 146.3 cm3 (range 1–512 cm3). There were no intraoperative complications or deaths. Medical or neurosurgical morbidity was noted in the postoperative course of 14 patients, equating to a 10% overall complication rate. Postoperative surgical complications included hematoma requiring evacuation, CSF leakage, and operative site infection. Medical complications included pulmonary embolus and deep vein thrombosis requiring treatment. A Simpson Grade 0 or 1 resection was achieved in 122 patients (87%). One hundred six tumors (75%) were WHO Grade I, whereas 35 (25%) were WHO Grade II. The median clinical follow-up was 2.9 years (range 1–10 years), and the median radiographic follow-up was 3.7 years (range 1–10 years). Six patients (4%) had radiographic evidence of tumor recurrence, with 3 (2%) undergoing repeat resection.

Conclusions

With the conservative recommendations for surgery for asymptomatic meningiomas and the advent of radiosurgery during the past 10 years, microsurgically treated convexity meningiomas are now typically large in size. Nevertheless, the patient's clinical course following microsurgical removal of these lesions is expected to be uncomplicated. The authors' findings provide a defined risk profile associated with the resection of supratentorial convexity meningiomas in the modern neurosurgical era.

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Nader Sanai, Mei-Yin Polley, Michael W. McDermott, Andrew T. Parsa, and Mitchel S. Berger

Object

The value of extent of resection (EOR) in improving survival in patients with glioblastoma multiforme (GBM) remains controversial. Specifically, it is unclear what proportion of contrast-enhancing tumor must be resected for a survival advantage and how much survival improves beyond this threshold. The authors attempt to define these values for the patient with newly diagnosed GBM in the modern neurosurgical era.

Methods

The authors identified 500 consecutive newly diagnosed patients with supratentorial GBM treated at the University of California, San Francisco between 1997 and 2009. Clinical, radiographic, and outcome parameters were measured for each case, including MR imaging–based volumetric tumor analysis.

Results

The patients had a median age of 60 years and presented with a median Karnofsky Performance Scale (KPS) score of 80. The mean clinical follow-up period was 15.3 months, and no patient was unaccounted for. All patients underwent resection followed by chemotherapy and radiation therapy. The median postoperative tumor volume was 2.3 cm3, equating to a 96% EOR. The median overall survival was 12.2 months. Using Cox proportional hazards analysis, age, KPS score, and EOR were predictive of survival (p < 0.0001). A significant survival advantage was seen with as little as 78% EOR, and stepwise improvement in survival was evident even in the 95%–100% EOR range. A recursive partitioning analysis validated these findings and provided additional risk stratification parameters related to age, EOR, and tumor burden.

Conclusions

For patients with newly diagnosed GBMs, aggressive EOR equates to improvement in overall survival, even at the highest levels of resection. Interestingly, subtotal resections as low as 78% also correspond to a survival benefit.

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Dario J. Englot, Stephen T. Magill, Seunggu J. Han, Edward F. Chang, Mitchel S. Berger, and Michael W. McDermott

OBJECT

Meningioma is the most common benign intracranial tumor, and patients with supratentorial meningioma frequently suffer from seizures. The rates and predictors of seizures in patients with meningioma have been significantly under-studied, even in comparison with other brain tumor types. Improved strategies for the prediction, treatment, and prevention of seizures in patients with meningioma is an important goal, because tumor-related epilepsy significantly impacts patient quality of life.

METHODS

The authors performed a systematic review of PubMed for manuscripts published between January 1980 and September 2014, examining rates of pre- and postoperative seizures in supratentorial meningioma, and evaluating potential predictors of seizures with separate meta-analyses.

RESULTS

The authors identified 39 observational case series for inclusion in the study, but no controlled trials. Preoperative seizures were observed in 29.2% of 4709 patients with supratentorial meningioma, and were significantly predicted by male sex (OR 1.74, 95% CI 1.30–2.34); an absence of headache (OR 1.77, 95% CI 1.04–3.25); peritumoral edema (OR 7.48, 95% CI 6.13–9.47); and non–skull base location (OR 1.77, 95% CI 1.04–3.25). After surgery, seizure freedom was achieved in 69.3% of 703 patients with preoperative epilepsy, and was more than twice as likely in those without peritumoral edema, although an insufficient number of studies were available for formal meta-analysis of this association. Of 1085 individuals without preoperative epilepsy who underwent resection, new postoperative seizures were seen in 12.3% of patients. No difference in the rate of new postoperative seizures was observed with or without perioperative prophylactic anticonvulsants.

CONCLUSIONS

Seizures are common in supratentorial meningioma, particularly in tumors associated with brain edema, and seizure freedom is a critical treatment goal. Favorable seizure control can be achieved with resection, but evidence does not support routine use of prophylactic anticonvulsants in patients without seizures. Limitations associated with systematic review and meta-analysis should be considered when interpreting these results.

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Michael E. Sughrue, Martin J. Rutkowski, Gopal Shangari, H. Quinn Chang, Andrew T. Parsa, Mitchel S. Berger, and Michael W. McDermott

Object

While the surgical and neurological risks of meningioma surgery have been reported, much less effort has been devoted to studying the rates of serious medical complications following such a procedure. The authors performed a review of 834 patients who underwent craniotomy for meningioma at their institution and analyzed the rate of major cardiac, pulmonary, renal, and hepatic complications.

Methods

The authors identified all patients between 1993 and 2007 who underwent craniotomy for meningioma. Clinical information was reconstructed using patient medical records, medication records, radiological data, and pathological specimens from both the author institution and outside medical facilities. Stepwise multivariate logistic regression analysis was performed to test the association between the dependent variable (rate of medical complications) and all covariates with a p < 0.2 on univariate testing.

Results

Fifty-seven patients (6.8%) experienced 61 serious medical complications following surgery for meningioma. Four patients died of medical complications. The most common complication was pneumonia, followed by renal dysfunction, arrhythmia, and deep venous thrombosis and/or pulmonary embolus. The development of a new or worsened neurological deficit (p < 0.00001), an age > 65 years (p < 0.03), hypertension (p < 0.02), and being on > 2 cardiac medications prior to surgery (p < 0.004) all demonstrated significantly increased rates of medical complications on univariate analysis. On multivariate analysis, only a new or worsened neurological deficit remained a significant risk factor for the occurrence of serious medical complications (p < 0.00001).

Conclusions

Overall, the authors found that the rate of clinically detected serious medical complications is relatively low in this population (6.8%), given the duration and complexity of the meningioma operations, and is strongly linked to the subsequent development of significant medical complications. This information may be useful to surgeons in discussing the morbidity of surgery during the informed consent process.

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Michael E. Sughrue, Martin J. Rutkowski, Gopal Shangari, Andrew T. Parsa, Mitchel S. Berger, and Michael W. McDermott

Object

The management of parasagittal and falcine meningiomas centers around the relationship between the tumor and the venous anatomy of the superior sagittal sinus (SSS) and the bridging veins. The present study aims to address surgical outcomes in a focused cohort of these patients for which there is not clinical equipoise between radiosurgery and transcranial resection.

Methods

The clinical outcomes of patients undergoing surgical removal of parasagittal and falcine meningiomas at the authors' institution over an 18-year period were analyzed. Analysis was limited to patients with large, symptomatic, or rapidly growing tumors, for whom radiosurgery was not a good option. Tumor control was assessed using Kaplan-Meier analysis, and specific attention was paid to the relationship between the tumor and the SSS, and its impact on tumor control and outcome.

Results

The authors identified 135 patients with large, symptomatic, and/or growing parasagittal/falcine meningiomas who underwent resection at their institution between 1991 and 2007. The median length of follow-up was 7.6 years (range 1.7–18.6 years). The SSS was found to be invaded in 61 of 135 cases. In 6 cases the sinus was completely occluded. In 33 of the remaining 55 cases, the tumor invading the sinus was able to be removed with simple microsurgical techniques. There was no difference in rates of tumor control in patients who received subtotal resection for a WHO Grade I tumor, followed by close observation, compared with those undergoing gross-total resection, primarily because no cases were observed in which the tumor remnant in the SSS demonstrated interval growth on serial imaging studies. Of the patients in this series, 19% experienced at least one neurological, medical, or surgical complication.

Conclusions

Importantly, these data provide a more modern estimate of the expected outcomes that can be obtained with treatment of these tumors, in which a combination of image guidance, advanced microsurgical tools, and conformal radiation treatments is used.

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Michael E. Sughrue, Nader Sanai, Gopal Shangari, Andrew T. Parsa, Mitchel S. Berger, and Michael W. McDermott

Object

Despite an increased understanding of the biology of malignant meningioma tumor progression, there is a paucity of published clinical data on factors affecting outcomes following treatment for these lesions. The authors present the largest case series to date dealing with these tumors, providing analysis of 63 patients.

Methods

The authors identified all patients undergoing resection of WHO Grade III tumors at their institution over a 16-year period. They analyzed clinical data from these patients, and performed Kaplan-Meier and Cox regression analyses to determine the impact of different clinical characteristics and different treatment modalities on survival following initial and repeat surgery for these lesions.

Results

Sixty-three patients met inclusion criteria and were analyzed further. The median clinical follow-up time was 5 years (range 1–22 years). The 2-, 5-, and 10-year overall survival rates following initial operation were 82, 61, and 40%, respectively. Kaplan-Meier analysis demonstrated a marked survival benefit with repeat operation (53 vs 25 months, p = 0.02). Interestingly, patients treated with near-total resection experienced improved overall survival when compared with patients treated with gross-total resection at initial (p = 0.035) and repeat operations (p = 0.005). Twelve (19%) of 63 patients experienced significant neurological morbidity referable to the resection of their tumors.

Conclusions

Surgery is an effective treatment for WHO Grade III meningiomas at presentation and recurrence; however, aggressive attempts to achieve gross-total resection can be associated with significant neurological risk.

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Michael E. Sughrue, Ari J. Kane, Gopal Shangari, Martin J. Rutkowski, Michael W. McDermott, Mitchel S. Berger, and Andrew T. Parsa

Object

In 1957, Simpson published a seminal paper defining the risk factors for recurrence following surgical treatment of intracranial meningiomas. Given that Simpson's study was published more than 50 years ago, preceding image guidance technology and MR imaging, the authors reviewed their own experience with surgical treatment of Grade I meningiomas to determine if Simpson's grading scale is still relevant to modern neurosurgical practice.

Methods

From this cohort, the authors evaluated all patients undergoing craniotomy for resection of a histologically proven WHO Grade I meningioma as their initial therapy. Clinical information was retrospectively reconstructed using patient medical records and radiological data. Recurrence analysis was performed using the Kaplan-Meier method.

Results

The 5-year recurrence/progression-free survival for all patients receiving a Simpson Grade I, II, III, or IV resection was 95, 85, 88, and 81%, respectively (p = not significant, log-rank test). Kaplan-Meier analysis revealed no significant difference in recurrence-free survival between patients receiving a Simpson Grade I, II, III, or IV resection. Analysis limited to meningiomas arising from the skull base (excluding the cavernous sinus) similarly found no significant benefit to Simpson Grade I or II resection, and the survival curves were nearly superimposed.

Conclusions

In this study of a cohort of patients undergoing surgery for WHO Grade I meningiomas, the authors demonstrate that the benefit of more aggressive attempts to resect the tumor with dura and underlying bone was negligible compared with simply removing the entire tumor, or even leaving small amounts of tumor attached to critical structures. The authors believe that these data reflect an evolution in the nature of meningioma surgery over the past 2 decades, and bring into question the relevance of using Simpson's grading system as the sole predictor of recurrence.

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Darryl Lau, Shawn L. Hervey-Jumper, Susan Chang, Annette M. Molinaro, Michael W. McDermott, Joanna J. Phillips, and Mitchel S. Berger

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.