Faculty Bibliography

PURPOSE: To retrospectively determine whether relative cerebral blood volume (CBV) measurements can be used to predict clinical outcome in patients with high-grade gliomas (HGGs) and low-grade gliomas (LGGs) and specifically whether patients who have gliomas with a high initial relative CBV have more rapid progression than those who have gliomas with a low relative CBV. MATERIALS AND METHODS: Approval for this retrospective HIPAA-compliant study was obtained from the Institutional Board of Research Associates, with waiver of informed consent. One hundred eighty-nine patients (122 male and 67 female patients; median age, 43 years; range, 4-80 years) were examined with dynamic susceptibility-weighted contrast material-enhanced perfusion magnetic resonance (MR) imaging and were followed up clinically with MR imaging (median follow-up, 334 days). Log-rank tests were used to evaluate the association between relative CBV and time to progression by using Kaplan-Meier curves. Binary logistic regression was used to determine whether age, sex, and relative CBV were associated with an adverse event (progressive disease or death). RESULTS: Values for the mean relative CBV for patients according to each clinical response were as follows: 1.41 +/- 0.13 (standard deviation) for complete response (n = 4), 2.36 +/- 1.78 for stable disease (n = 41), 4.84 +/- 3.32 for progressive disease (n = 130), and 3.82 +/- 1.93 for death (n = 14). Kaplan-Meier estimates of median time to progression in days indicated that patients with a relative CBV of less than 1.75 had a median time to progression of 3585 days, whereas patients with a relative CBV of more than 1.75 had a time to progression of 265 days. Age and relative CBV were also independent predictors for clinical outcome. CONCLUSION: Dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging can be used to predict median time to progression in patients with gliomas, independent of pathologic findings. Patients who have HGGs and LGGs with a high relative CBV (>1.75) have a significantly more rapid time to progression than do patients who have gliomas with a low relative CBV

INTRODUCTION: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), has shown promise in the treatment of patients with recurrent high-grade glioma. The purpose of this study is to test the feasibility of using bevacizumab with chemoradiation in the primary management of high-grade glioma. METHODS AND MATERIALS: Fifteen patients with high-grade glioma were treated with involved field radiation therapy to a dose of 59.4 Gy at 1.8 Gy/fraction with bevacizumab 10 mg/kg on Days 14 and 28 and temozolomide 75 mg/m(2). Subsequently, bevacizumab 10 mg/kg was continued every 2 weeks with temozolomide 150 mg/m(2) for 12 months. Changes in relative cerebral blood volume, perfusion-permeability index, and tumor volume measurement were measured to assess the therapeutic response. Immunohistochemistry for phosphorylated VEGF receptor 2 (pVEGFR2) was performed. RESULTS: Thirteen patients (86.6%) completed the planned bevacizumab and chemoradiation therapy. Four Grade III/IV nonhematologic toxicities were seen. Radiographic responses were noted in 13 of 14 assessable patients (92.8%). The pVEGFR2 staining was seen in 7 of 8 patients (87.5%) at the time of initial diagnosis. Six patients have experienced relapse, 3 at the primary site and 3 as diffuse disease. One patient showed loss of pVEGFR2 expression at relapse. One-year progression-free survival and overall survival rates were 59.3% and 86.7%, respectively. CONCLUSION: Use of antiangiogenic therapy with radiation and temozolomide in the primary management of high-grade glioma is feasible. Perfusion imaging with relative cerebral blood volume, perfusion-permeability index, and pVEGFR2 expression may be used as a potential predictor of therapeutic response. Toxicities and patterns of relapse need to be monitored closely

OBJECTIVE AND IMPORTANCE: In rare cases, posterior fossa meningiomas can involve the endolymphatic sac. Such involvement can result in endolymphatic hydrops and a constellation of symptoms suggestive of Meniere's disease. The diagnosis and management of patients with these tumors is discussed. CLINICAL PRESENTATION: Three patients, each of whom presented with symptoms consistent with Meniere's disease, were found to have posterior fossa meningiomas limited to the dura overlying the endolymphatic sac. INTERVENTION: All 3 patients were diagnosed by magnetic resonance imaging and underwent complete surgical resection. In all cases, the symptoms resolved after tumor removal. CONCLUSION: Clinicians should have a degree of suspicion of posterior fossa meningioma when patients present with symptoms suggestive of Meniere's disease. Failure to do so may result in delayed diagnosis or worse outcomes for an otherwise treatable tumor

We evaluate the effects of adjuvant treatment with the angiogenesis inhibitor Avastin (bevacizumab) on pathological tissue specimens of high-grade glioma. Tissue from five patients before and after treatment with Avastin was subjected to histological evaluation and compared to four control cases of glioma before and after similar treatment protocols not including bevacizumab. Clinical and radiographic data were reviewed. Histological analysis focused on microvessel density and vascular morphology, and expression patterns of vascular endothelial growth factor-A (VEGF-A) and the hematopoietic stem cell, mesenchymal, and cell motility markers CD34, smooth muscle actin, D2-40, and fascin. All patients with a decrease in microvessel density had a radiographic response, whereas no response was seen in the patients with increased microvessel density. Vascular morphology showed apparent 'normalization' after Avastin treatment in two cases, with thin-walled and evenly distributed vessels. VEGF-A expression in tumor cells was increased in two cases and decreased in three and did not correlate with treatment response. There was a trend toward a relative increase of CD34, smooth muscle actin, D2-40, and fascin immunostaining following treatment with Avastin. Specimens from four patients with recurrent malignant gliomas before and after adjuvant treatment (not including bevacizumab) had features dissimilar from our study cases. We conclude that a change in vascular morphology can be observed following antiangiogenic treatment. There seems to be no correlation between VEGF-A expression and clinical parameters. While the phenomena we describe may not be specific to Avastin, they demonstrate the potential of tissue-based analysis for the discovery of clinically relevant treatment response biomarkers

OBJECTIVE:To determine whether relative cerebral blood volume (rCBV) can predict patient outcome, specifically tumor progression, in low-grade gliomas (LGGs) and thus provide a second reference standard in the surgical and postsurgical management of LGGs. METHODS:Thirty-five patients with histologically diagnosed LGGs (21 low-grade astrocytomas and 14 low-grade oligodendrogliomas and low-grade mixed oligoastrocytomas) were studied with dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging. Wilcoxon tests were used to compare patients in different response categories (complete response, stable, progressive, death) with respect to baseline rCBV. Log-rank tests were used to evaluate the association of rCBV with survival and time to progression. Kaplan-Meier time-to-progression curves were generated. Tumor volumes and CBV measurements were obtained at the initial examination and again at follow-up to determine the association of rCBV with tumor volume progression. RESULTS:Wilcoxon tests showed patients manifesting an adverse event (either death or progression) had significantly higher rCBV (P = 0.003) than did patients without adverse events (complete response or stable disease). Log-rank tests showed that rCBV exhibited a significant negative association with disease-free survival (P = 0.0015), such that low rCBV values were associated with longer time to progression. Kaplan-Meier curves demonstrated that lesions with rCBV less than 1.75 (n = 16) had a median time to progression of 4620 +/- 433 days, and lesions with rCBV more than 1.75 (n = 19) had a median time to progression of 245 +/- 62 days (P < 0.005). Lesions with low baseline rCBV (< 1.75) demonstrated stable tumor volumes when followed up over time, and lesions with high baseline rCBV (> 1.75) demonstrated progressively increasing tumor volumes over time. CONCLUSION/CONCLUSIONS:Dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging may be used to identify LGGs that are either high-grade gliomas, misdiagnosed because of sampling error at pathological examination or that have undergone angiogenesis in the progression toward malignant transformation. This suggests that rCBV measurements may be used as a second reference standard to determine the surgical management/risk-benefit equation and postsurgical adjuvant therapy for LGGs.

OBJECTIVE: To determine treatment outcome after surgical resection for progressive brain metastases after gamma knife radiosurgery (GKR) and to explore the role of dynamic contrast agent-enhanced perfusion magnetic resonance imaging (MRI) and proton spectroscopic MRI studies (MRS/P) in predicting pathological findings. METHODS: Between 1997 and 2002, 32 patients underwent surgical resection for suspected progression of brain metastases from a cohort of 245 patients with brain metastases treated with GKR. Postradiosurgery MRI surveillance was performed at 6 and 12 weeks, and then every 12 weeks after GKR. In some cases, additional MRI scanning with spectroscopy or perfusion (MRS/P) was used to aid differentiation of radiation change from tumor progression. The decision to perform neurosurgical resection was based on MRI or clinical evidence of lesion progression among patients with a Karnofsky performance score of 60 or more and absent or stable systemic disease. RESULTS: Thirteen percent (32 out of 245) of patients and 6% (38 out of 611) of lesions required surgical resection after GKR. The median time from GKR to surgical resection was 8.6 months (range, 1.7-27.1 mo). The 6-, 12-, and 24-month actuarial survival from time of GKR was 97, 78, and 47% for the resected patients and 65, 40, and 19% for the nonresected patients (P < 0.0001). The two-year survival rate of patients requiring two resections after GKR was 100% compared with 39% for patients undergoing one resection (P = 0.02). The median survival of resected patients was 27.2 months (range, 7.0-72.5 mo) from the diagnosis of brain metastases, 19.9 months (range, 5.0-60.7 mo) from GKR, and 8.9 months (range, 0.2-53.1 mo) from surgical resection. Tumor was found in 90% of resected specimens and necrosis alone in 10%. MRS/P studies were performed in 15 resected patients. Overall, MRS/P predicted tumor in 11 lesions, confirmed pathologically in nine lesions, and necrosis alone was found in two. The MRS/P predicted necrosis alone in three, whereas pathology revealed viable tumor in two and necrosis in one lesion. CONCLUSION: Surgical intervention of progressive brain metastases after GKR in selected patients leads to a meaningful improvement in survival rates. Further studies are necessary to determine the role of MRS/P in the postradiosurgery surveillance of brain metastases

OBJECT: The goal of this study is to report the incidence and clinical evolution of neurological deficits in patients who underwent resection of gliomas confined to the parietal lobe. METHODS: Patient demographics, findings of serial neurological examinations, tumor location and neuroimaging characteristics, extent of resection, and surgical outcomes were tabulated by reviewing inpatient and office records, as well as all pre- and postoperative magnetic resonance (MR) images obtained in 28 consecutive patients who underwent resection of a glial neoplasm found on imaging studies to be confined to the parietal lobe. Neurological deficits were correlated with hemispheric dominance, location of the lesion within the superior or inferior parietal lobules, subcortical extension, and involvement of the postcentral gyrus. The tumors were located in the dominant hemisphere in 18 patients (64%); had a mean diameter of 39 mm (range 14-69 mm); were isolated to the superior parietal lobule in six patients (21%) and to the inferior parietal lobule in eight patients (29%); and involved both lobules in 14 patients (50%). Gross-total resection, documented by MR imaging, was achieved in 24 patients (86%). Postoperatively, nine patients (32%) experienced new neurological deficits, whereas seven (25%) had an improvement in their preoperative deficit. A correlation was noted between larger tumors and the presence of neurological deficits both before and after resection. Postoperatively higher-level (association) parietal deficits were noted only in patients with tumors involving both the superior and inferior parietal lobules in the dominant hemisphere. At the 3-month follow-up examination, five of nine new postoperative deficits had resolved. CONCLUSIONS: Neurological deterioration and improvement occur after resection of parietal lobe gliomas. Parietal lobe association deficits, specifically the components of Gerstmann syndrome, are mostly associated with large tumors that involve both the superior and inferior parietal lobules of the dominant hemisphere. New hemineglect or sensory extinction was not noted in any patient following resection of lesions located in the nondominant hemisphere. Nevertheless, primary parietal lobe deficits (for example, a visual field loss or cortical sensory syndrome) occurred in patients regardless of hemispheric dominance

The stereotaxic aspiration of cystic brain tumors is performed to provide cyst decompression and/or to facilitate surgical resection. The purpose of our study was to determine the diagnostic value of brain cyst fluid cytology, especially in clinically suspected recurrent tumors with no histological follow-up (HF), when a diagnosis is most needed. We reviewed the cytological diagnoses of 88 aspirates from 70 patients with cystic brain tumors between 1995 and 2001, of which 31 had a prior known malignancy including 18 primary brain tumors (PBTs) and 13 adenocarcinomas (ACAs). Sixty-nine of 88 aspirates were obtained intraoperatively. Nineteen of 88 aspirates were obtained from 10 patients with recurrent or persistent cystic brain tumors (8 patients with PBT and 2 patients with ACA), with available clinicoradiological correlation (magnetic resonance imaging/computed tomography [MRI/CT] scans) in 13 of them. The 88 aspirates were classified in three categories: 28 positive (32%), 15 atypical (17%), and 45 negative (51%). Eight of 28 positive cases (5 case of PBT, 2 cases of ACA, and 1 case of melanoma) were given a nonspecific diagnosis of malignant neoplasm (9% of all cases). Fifteen of 28 positive cases (6 cases of PBT, 8 cases of ACA, and 1 case of melanoma) were diagnosed correctly and confirmed by HF (17% of all cases). Four of 28 cases were ACA diagnosed solely by cytology (<4% of all cases). One neurocytoma (1/28) case was mistaken for an oligodendroglioma despite cell blocks (CBs) and immunophenotyping (IPT) (<1% of all cases). Eleven of 15 atypical cases were 8 cases of PBT, 2 cases of ACA, and 1 case of postoperative change (PC). Four of 15 atypical cases (from three patients with suspected PBT recurrence) could not be further characterized by CB/IPT and had no HF. Twenty-seven of 45 negative cases were falsely negative (23 cases of PBT, 3 cases of ACA, and 1 case of malignant neoplasm); 11/45 cases were PC, and 7/45 (from five patients with clinically suspected tumor recurrence) cases had no HF. Cytological evaluation of brain cyst fluid is not a reliable means of diagnosing cystic brain neoplasms (including recurrences) due to a high false negative rate and a low sensitivity. Most of the negative or atypical cases (68% of all cases) were recurrent PBT of glial origin that may not be prone to exfoliate. These cytological specimens consisted of lysed blood, obscuring inflammatory cells, and degenerated diagnostic cells if any, yielding inconclusive results.