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Justin S. Smith, Anita Lal, Miranda Harmon-Smith, Andrew W. Bollen and Michael W. McDermott

Object

The clinical behavior of meningiomas is variable. Because multiple growth factor receptors have been identified in these tumors, the authors sought to assess the capacity of the expression patterns of a subset of these receptors to stratify meningioma cases.

Methods

Eighty-four meningiomas were analyzed, including 36 benign, 29 atypical, and 19 malignant lesions. Immunohistochemical staining was performed for epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR)–β, basic fibroblast growth factor receptor (BFGFR), and MIB-1. Survival analyses were performed using follow-up data obtained in patients with newly diagnosed tumors.

Immunoreactivity for EGFR was observed in 47% of benign, 48% of atypical, and 42% of malignant tumors. Staining for BFGFR was identified in 89% of benign, 97% of atypical, and 95% of malignant lesions. Immunostaining for PDGFR-β was evident in all the lesions assessed. Mean MIB-1 indices for benign, atypical, and malignant cases were 3.6 (range 0.5–15.3), 8.2 (range 1.5–23.1) and 18.3 (range 1.0–55.8), respectively. Overall mean follow-up duration was 9.0 years (range 5.1–18.8 years). Lack of EGFR immunoreactivity was identified as a strong predictor of shorter overall survival in patients with atypical meningioma (p = 0.003, log-rank test). This association was not evident in cases of benign or malignant meningiomas.

Conclusions

There is a significant association between EGFR immunoreactivity and prolonged survival in patients with atypical meningioma. Given the variable behavior of atypical meningiomas, EGFR assessment could improve existing strategies for patient stratification and treatment.

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Matthew B. Potts, Justin S. Smith, Annette M. Molinaro and Mitchel S. Berger

Object

Low-grade gliomas (LGGs) are rarely diagnosed as an incidental, asymptomatic finding, and it is not known how the early surgical management of these tumors might affect outcome. The purpose of this study was to compare the outcomes of patients with incidental and symptomatic LGGs and determine any prognostic factors associated with those outcomes.

Methods

All patients treated by the lead author for an LGG incidentally discovered between 1999 and 2010 were retrospectively reviewed. “Incidental” was defined as a finding on imaging that was obtained for a reason not attributable to the glioma, such as trauma or headache. Primary outcomes included overall survival, progression-free survival (PFS), and malignant PFS. Patients with incidental LGGs were compared with a previously reported cohort of patients with symptomatic gliomas.

Results

Thirty-five patients with incidental LGGs were identified. The most common reasons for head imaging were headache not associated with mass effect (31.4%) and trauma (20%). Patients with incidental lesions had significantly lower preoperative tumor volumes than those with symptomatic lesions (20.2 vs 53.9 cm3, p < 0.001), were less likely to have tumors in eloquent locations (14.3% vs 61.9%, p < 0.001), and had a higher prevalence of females (57.1% vs 36%, p = 0.02). In addition, patients with incidental lesions were also more likely to undergo gross-total resection (60% vs 31.5%, p = 0.001) and had improved overall survival on Kaplan-Meier analysis (p = 0.039, Mantel-Cox test). Progression and malignant progression rates did not differ between the 2 groups. Univariate analysis identified pre- and postoperative volumes as well as the use of motor or language mapping as significant prognostic factors for PFS.

Conclusions

In this retrospective cohort of surgically managed LGGs, incidentally discovered lesions were associated with improved patient survival as compared with symptomatic LGGs, with acceptable surgical risks.

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Justin S. Smith, Ian F. Parney, Kathleen R. Lamborn, Michael W. McDermott, Penny K. Sneed and Susan M. Chang

Object

This study was designed to assess the presentation, management, and outcome of cases involving patients who had a supratentorial glioma that subsequently progressed in the posterior fossa (PF).

Methods

The authors performed a retrospective chart review of adult patients treated between 1997 and 2005 for supratentorial gliomas that progressed in the PF. The 29 patients with PF progression in this study were relatively young (median age of 34 years at original presentation). Twenty of these patients presented with symptoms. The symptoms were typically nonspecific to this population, at times leading to delays in diagnosis. Overall, these symptoms resolved in eight patients (40%) and progressed or remained unchanged in 12 (60%). Patients treated with more than 5000 cGy of radiation administered to the PF were more likely to have symptom resolution than those who received any other form of treatment, including reduced doses of radiation (p = 0.004). The patients treated with higher doses also survived significantly longer after PF progression (univariate analysis, p = 0.01, and after adjusting for tumor grade, p = 0.04).

Conclusions

Patients with PF progression of supratentorial infiltrative gliomas may benefit from treatment, and the authors recommend more than 5000 cGy of radiation to the PF if prior radiotherapy ports and doses allow.

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Justin S. Smith, Soonmee Cha, Mary Catherine Mayo, Michael W. McDermott, Andrew T. Parsa, Susan M. Chang, William P. Dillon and Mitchel S. Berger

Object

Diffusion-weighted magnetic resonance (MR) imaging is an invaluable tool in the diagnosis of acute stroke and other types of brain injury. Abnormalities in and around the resection cavity on diffusion-weighted imaging have been observed following surgery for infiltrating glioma. The purpose of this study was to investigate prospectively the incidence, time course, and ultimate outcome of these abnormalities.

Methods

Forty-four consecutive patients with newly diagnosed gliomas were prospectively observed using serial MR imaging including diffusion-weighted sequences. Clinical and surgical data were also collected. Immediately postoperatively neuroimaging identified 28 patients (64%) in whom areas of reduced diffusion appeared in or around the resection cavity (mean volume 8.2 ± 1.5 cm3). Complete resolution of this reduced diffusion was demonstrated within 90 days in 24 patients (86%). On subsequent neuroimages these areas demonstrated Gd enhancement as early as postoperative Day 15 and as late as Day 198 and ultimately took on the appearance of encephalomalacia in 26 (93%) of 28 cases. Postoperative reduced diffusion was not predicted by the clinical or surgical parameters that were assessed. No clinical deficits were attributable to the reduced diffusion.

Conclusions

An abnormality related to diffusion-weighted sequences on postoperative MR imaging can occur after resection of newly diagnosed gliomas. In this study the abnormality typically resolved and was replaced by contrast enhancement on follow-up imaging, ultimately demonstrating encephalomalacia on long-term follow up. Findings on neuroimaging during the period of enhancement could be confused with recurrent tumor and interpreted as early treatment failure. Based on the findings of this study the authors strongly suggest that the inclusion of diffusion-weighted sequences in postoperative MR imaging is essential, as is MR imaging immediately before radiation therapy to monitor disease progression. A new enhancement observed after glioma surgery should be interpreted in the context of the diffusion-weighted image obtained immediately postoperatively.

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Edward F. Chang, Justin S. Smith, Susan M. Chang, Kathleen R. Lamborn, Michael D. Prados, Nicholas Butowski, Nicholas M. Barbaro, Andrew T. Parsa, Mitchel S. Berger and Michael M. Mcdermott

Object

Hemispheric low-grade gliomas (LGGs) have an unpredictable progression and overall survival (OS) profile. As a result, the objective in the present study was to design a preoperative scoring system to prognosticate long-term outcomes in patients with LGGs.

Methods

The authors conducted a retrospective review with long-term follow-up of 281 adults harboring hemispheric LGGs (World Health Organization Grade II lesions). Clinical and radiographic data were collected and analyzed to identify preoperative predictors of OS, progression-free survival (PFS), and extent of resection (EOR). These variables were used to devise a prognostic scoring system.

Results

The 5-year estimated survival probability was 0.86. Multivariate Cox proportional hazards modeling demonstrated that 4 factors were associated with lower OS: presumed eloquent location (hazard ratio [HR] 4.12, 95% confidence interval [CI] 1.71–10.42), Karnofsky Performance Scale score ≤ 80 (HR 3.53, 95% CI 1.56–8.00), patient age > 50 years (HR 1.96, 95% CI 1.47–3.77), and tumor diameter > 4 cm (HR 3.43, 95% CI 1.43–8.06). A scoring system calculated from the sum of these factors (range 0–4) demonstrated risk stratification across study groups, with the following 5-year cumulative survival estimates: Scores 0–1, OS = 0.97, PFS = 0.76; Score 2, OS = 0.81, PFS = 0.49; and Scores 3–4, OS = 0.56, PFS = 0.18 (p < 0.001 for both OS and PFS, log-rank test). This proposed scoring system demonstrated a high degree of interscorer reliability (kappa = 0.86). Four illustrative cases are described.

Conclusions

The authors propose a simple and reliable scoring system that can be used to preoperatively prognosticate the degree of lesion resectability, PFS, and OS in patients with LGGs. The application of a standardized scoring system for LGGs should improve clinical decision-making and allow physicians to reliably predict patient outcome at the time of the original imaging-based diagnosis.

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Edward F. Chang, Aaron Clark, Randy L. Jensen, Mark Bernstein, Abhijit Guha, Giorgio Carrabba, Debabrata Mukhopadhyay, Won Kim, Linda M. Liau, Susan M. Chang, Justin S. Smith, Mitchel S. Berger and Michael W. McDermott

Object

Medical and surgical management of low-grade gliomas (LGGs) is complicated by a highly variable clinical course. The authors recently developed a preoperative scoring system to prognosticate outcomes of progression and survival in a cohort of patients treated at a single institution (University of California, San Francisco [UCSF]). The objective of this study was to validate the scoring system in a large patient group drawn from multiple external institutions.

Methods

Clinical data from 3 outside institutions (University of Utah, Toronto Western Hospital, and University of California, Los Angeles) were collected for 256 patients (external validation set). Patients were assigned a prognostic score based upon the sum of points assigned to the presence of each of the 4 following factors: 1) location of tumor in presumed eloquent cortex, 2) Karnofsky Performance Scale (KPS) Score ≤ 80, 3) age > 50 years, and 4) maximum diameter > 4 cm. A chi-square analysis was used to analyze categorical differences between the institutions; Cox proportional hazard modeling was used to confirm that the individual factors were associated with shorter overall survival (OS) and progression-free survival (PFS); and Kaplan–Meier curves estimated OS and PFS for the score groups. Differences between score groups were analyzed by the log-rank test.

Results

The median OS duration was 120 months, and there was no significant difference in survival between the institutions. Cox proportional hazard modeling confirmed that the 4 components of the UCSF Low-Grade Glioma Scoring System were associated with lower OS in the external validation set; presumed eloquent location (hazard ratio [HR] 2.04, 95% CI 1.28–2.56), KPS score ≤ 80 (HR 5.88, 95% CI 2.44–13.7), age > 50 years (HR 1.82, 95% CI 1.02–3.23), and maximum tumor diameter > 4 cm (HR 2.63, 95% CI 1.58–4.35). The stratification of patients based on scores generated groups (0–4) with statistically different OS and PFS estimates (p < 0.0001, log-rank test). Lastly, the UCSF patient group (construction set) was combined with the external validation set (total of 537 patients) and analyzed for OS and PFS. For all patients, the 5-year survival probability was 0.79; the 5-year cumulative OS probabilities stratified by score group were: score of 0, 0.98; score of 1, 0.90; score of 2, 0.81; score of 3, 0.53; and score of 4, 0.46.

Conclusions

The UCSF scoring system accurately predicted OS and PFS in an external large, multiinstitutional population of patients with LGGs. The strengths of this system include ease of use and ability to be applied preoperatively, with the eventual goal of aiding in the design of individualized treatment plans for patients with LGG at diagnosis.

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Oral Presentations

2010 AANS Annual Meeting Philadelphia, Pennsylvania May 1–5, 2010