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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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Michael E. Sughrue, Martin J. Rutkowski, Derick Aranda, Igor J. Barani, Michael W. McDermott, and Andrew T. Parsa

Object

Definitive data allowing clinicians to predict which meningioma patients will fail to respond to conservative management are lacking. To address this need, the authors systematically reviewed the published literature regarding the natural history of small, untreated meningiomas.

Methods

The authors performed a systematic review of the existing literature on untreated meningiomas that were followed with serial MR imaging. They summarize the published linear rates of tumor growth, and the risk factors for development of new or worsened symptoms during follow-up by using a stratified chi-square test.

Results

The search methods identified 22 published studies reporting on 675 patients with untreated meningiomas followed by serial MR imaging. Linear growth rates varied significantly: no growth was the most common rate, although reports of more aggressive tumors noted growth rates of up to a 93% linear increase in size per year. The authors found that few patients with initial tumor diameters < 2 cm went on to develop new or worsened symptoms over a median follow-up period of 4.6 years. Patients with initial tumor diameters of 2–2.5 cm demonstrated a marked difference in the rate of symptom progression if their tumors grew > 10% per year, compared with those tumors growing ≤ 10% per year (42% vs 0%; p < 0.001, chi-square test). Patients with tumors between > 2.5 and 3 cm in initial size went on to develop new or worsened symptoms 17% of the time.

Conclusions

This systematic review of the literature regarding the clinical behavior of untreated meningiomas suggests that most meningiomas ≤ 2.5 cm in diameter do not proceed to cause symptoms in the approximately 5-year period following their discovery. Those that do cause symptoms can usually be predicted with close radiographic follow-up. Based on these findings, the authors suggest the importance of observation in the early course of treatment for small asymptomatic meningiomas, especially those with an initial diameter < 2 cm.

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

Object

The study of patients with multiple neoplasms can yield valuable insight into the common pathogenesis of both diseases, as well as identify more subtle risk factors that might not be as readily apparent otherwise. The authors present an analysis of the prevalence of previously diagnosed extracranial malignancies at the time of meningioma diagnosis in 1228 patients evaluated at a single institution.

Methods

All patients who underwent evaluation and/or treatment for meningioma between 1991 and 2007 at the authors' institution were identified. The intake history and physical were assessed for any history of extracranial malignancy. Using the National Cancer Institute data, the authors calculated an expected cancer prevalence for their meningioma patient population, and compared this derived value to the observed rate of these cancers in this population.

Results

There were 1228 patients included in this study. A total of 50 patients (4.1%) with newly diagnosed meningioma had a history of an extracranial malignant tumor at the time of their initial meningioma diagnosis. In general, most malignancies did not differ in prevalence from their expected frequency in the population in the present study. Notable exceptions were acute leukemia (p < 0.0001), and papillary thyroid carcinoma, which had a prevalence 2.5 times that expected in this population (p < 0.05).

Conclusions

The data support a growing body of evidence suggesting an epidemiological link between papillary carcinoma of the thyroid and meningioma. Although the link between these tumors is not immediately apparent, it is possible that further exploration will yield interesting insight into the pathogenesis of both diseases.

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Meic H. Schmidt, Mitchel S. Berger, Kathleen R. Lamborn, Ken Aldape, Michael W. McDermott, Michael D. Prados, and Susan M. Chang

Object. Progression of infiltrative low-grade gliomas (LGGs) has been reported previously. The limitations of such studies include diverse histological grading systems, intervening therapy, and the lack of histological confirmation of malignant tumor progression. The aim of this study was to determine tumor progression in adult patients with an initial diagnosis of infiltrative LGG who subsequently underwent a repeated operation, but no other intervening therapy. The authors examined factors that may be associated with tumor progression.

Methods. The authors retrospectively reviewed a database of 300 patients with the initial diagnosis of LGG and who had been treated at their institution between 1990 and 2000. One hundred four of these patients had undergone a second surgery. Patients with infiltrative LGGs who had undergone two surgical procedures at least 3 months apart without intervening therapy were selected; the authors identified 40 patients who fit these criteria. Clinical, neuroimaging, and pathological data were centrally reviewed.

There were 29 men and 11 women in the study, whose median age was 35.5 years (range 23–48 years). At the time of the second surgery, 50% of patients had experienced tumor progression. Patients whose tumors had progressed had a longer median time to repeated operation (49 compared with 22.5 months). Patients who had undergone gross-total resection, as demonstrated on postoperative magnetic resonance images, had a median time to repeated operation of 49 compared with 25 and 24 months in patients who underwent subtotal resection and biopsy, respectively (p = 0.02). The extent of resection did not influence the likelihood of tumor progression (p > 0.3).

Conclusions. Fifty percent of patients with initially diagnosed infiltrative LGGs had tumor progression at the time of a repeated operation. A gross-total resection was associated with an increased time to repeated surgery. There was no statistically significant effect of gross-total resection as a predictor of tumor progression.

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Editorial

Cavernous sinus meningiomas

Atul Goel and Manu Kothari

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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, Martin J. Rutkowski, Derick Aranda, Igor J. Barani, Michael W. McDermott, and Andrew T. Parsa

Object

Although there is a considerable volume of literature available on the treatment of patients with cavernous sinus meningiomas (CSMs), most of the data regarding tumor control and survival come from case studies or single-institution series. The authors performed a meta-analysis of reported tumor control and survival rates of patients described in the published literature, with an emphasis on specific prognostic factors.

Methods

The authors systematically analyzed the published literature and found more than 3000 patients treated for CSMs. Separate meta-analyses were performed to calculate pooled rates of recurrence and cranial neuropathy after 1) gross-total resection, 2) subtotal resection without adjuvant postoperative radiotherapy or radiosurgery, and 3) stereotactic radiosurgery (SRS) alone. Results were expressed as pooled proportions, and random-effects models were used to incorporate any heterogeneity present to generate a pooled proportion. Individual studies were weighted using the inverse variance method, and 95% CIs for each group were calculated from the pooled proportions.

Results

A total of 2065 nonduplicated patients treated for CSM met inclusion criteria for the analysis. Comparisons of the 95% CIs for recurrence of these 3 cohorts revealed that SRS-treated patients experienced improved rates of recurrence (3.2% [95% CI 1.9–4.5%]) compared with either gross-total resection (11.8% [95% CI 7.4–16.1%]) or subtotal resection alone (11.1% [95% CI 6.6–15.7%]) (p < 0.01). The authors found that the pooled mixed-effects rate of cranial neuropathy was markedly higher in patients undergoing resection (59.6% [95% CI 50.3–67.5%]) than for those undergoing SRS alone (25.7% [95% CI 11.5–38.9%]) (p < 0.05).

Conclusions

Radiosurgery provided improved rates of tumor control compared with surgery alone, regardless of the subjective extent of resection.

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Editorial

Malignant meningiomas

Roberto C. Heros

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Andrew T. Parsa, Scott Wachhorst, Kathleen R. Lamborn, Michael D. Prados, Michael W. McDermott, Mitchel S. Berger, and Susan M. Chang

Object. The clinical outcome and treatment of adult patients with disseminated intracranial glioblastoma multiforme (GBM) is unclear. The objective in the present study was to assess the prognostic significance of disseminated intracranial GBM in adults at presentation and at the time of tumor progression.

Methods. Clinical data from 1491 patients older than 17 years and harboring a GBM that had been diagnosed between 1988 and 1998 at the University of California at San Francisco neurooncology clinic were retrospectively reviewed. Dissemination of the GBM (126 patients) was determined based on Gd-enhanced magnetic resonance images. Classification of dissemination was as follows: Type I, single lesion with subependymal or subarachnoid spread; Type II, multifocal lesions without subependymal or subarachnoid spread; and Type III, multifocal lesions with subependymal or subarachnoid spread. Subgroups of patients were compared using Kaplan—Meier curves that depicted survival probability.

The median postprogression survival (PPS), defined according to neuroimaging demonstrated dissemination, was 37 weeks for Type I (23 patients), 25 weeks for Type II (50 patients), and 10 weeks for Type III spread (19 patients). Patients with dissemination at first tumor progression (52 patients) overall had a shorter PPS than those in a control group with local progression, after adjusting for age, Karnofsky Performance Scale score, and time from tumor diagnosis to its progression (311 patients). When analyzed according to tumor dissemination type, PPS was significantly shorter in patients with Type II (33 patients, p < 0.01) and Type III spread (11 patients, p < 0.01) but not in those with Type I spread (eight patients, p = 0.18).

Conclusions. Apparently, the presence of intracranial tumor dissemination on initial diagnosis does not in itself preclude aggressive treatment if a patient is otherwise well. A single focus of GBM that later demonstrates Type I dissemination on progression does not have a worse prognosis than a lesion that exhibits only local recurrence.