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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, 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, Justin S. Smith, Mei-Yin Polley, Susan M. Chang, Nicholas M. Barbaro, Andrew T. Parsa, Michael W. McDermott, and Mitchel S. Berger

Object

Low-grade gliomas (LGGs) frequently infiltrate highly functional or “eloquent” brain areas. Given the lack of long-term survival data, the prognostic significance of eloquent brain tumor location and the role of functional mapping during resective surgery in presumed eloquent brain regions are unknown.

Methods

We performed a retrospective analysis of 281 cases involving adults who underwent resection of a supratentorial LGG at a brain tumor referral center. Preoperative MR images were evaluated blindly for involvement of eloquent brain areas, including the sensorimotor and language cortices, and specific subcortical structures. For high-risk tumors located in presumed eloquent brain areas, long-term survival estimates were evaluated for patients who underwent intraoperative functional mapping with electrocortical stimulation and for those who did not.

Results

One hundred and seventy-four patients (62%) had high-risk LGGs that were located in presumed eloquent areas. Adjusting for other known prognostic factors, patients with tumors in areas presumed to be eloquent had worse overall and progression-free survival (OS, hazard ratio [HR] 6.1, 95% CI 2.6–14.1; PFS, HR 1.9, 95% CI 1.2–2.9; Cox proportional hazards). Confirmation of tumor overlapping functional areas during intraoperative mapping was strongly associated with shorter survival (OS, HR 9.6, 95% CI 3.6–25.9). In contrast, when mapping revealed that tumor spared true eloquent areas, patients had significantly longer survival, nearly comparable to patients with tumors that clearly involved only noneloquent areas, as demonstrated by preoperative imaging (OS, HR 2.9, 95% CI 1.0–8.5).

Conclusions

Presumed eloquent location of LGGs is an important but modifiable risk factor predicting disease progression and death. Delineation of true functional and nonfunctional areas by intraoperative mapping in high-risk patients to maximize tumor resection can dramatically improve long-term survival.

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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