Correction to: 18F-Fluciclovine (18F-FACBC) PET imaging of recurrent brain tumors.

The article 18F-Fluciclovine (18F-FACBC) PET imaging of recurrent brain tumors written by Laure Michaud, B. J. Beattie, T. Akhurst, M. Dunphy, P. Zanzonico, R. Finn, A. Mauguen, H. Schöder, W. A. Weber, A. B. Lassman, R. Blasberg.

18F-Fluciclovine (18F-FACBC) PET imaging of recurrent brain tumors.

PURPOSE: The aim of our study was to investigate the efficacy of 18F-Fluciclovine brain PET imaging in recurrent gliomas, and to compare the utility of these images to that of contrast enhanced magnetic resonance imaging (MRI) and to [11C-methyl]-L-methionine (11C-Methionine) PET imaging. We also sought to gain insight into the factors affecting the uptake of 18F-FACBC in both tumors and normal brain, and specifically to evaluate how the uptake in these tissues varied over an extended period of time post injection. METHODS: Twenty-seven patients with recurrent or progressive primary brain tumor (based on clinical and MRI/CT data) were studied using dynamic 18F-Fluciclovine brain imaging for up to 4 h. Of these, 16 patients also had 11C-Methionine brain scans. Visual findings, semi-quantitative analyses and pharmacokinetic modeling of a subset of the 18F-Fluciclovine images was conducted. The information derived from these analyses were compared to data from 11C-Methionine and to contrast-enhanced MRI. RESULTS: 18F-Fluciclovine was positive for all 27 patients, whereas contrast MRI was indeterminate for three patients. Tumor 18F-Fluciclovine SUVmax ranged from 1.5 to 10.5 (average: 4.5 ± 2.3), while 11C-Methionine's tumor SUVmax ranged from 2.2 to 10.2 (average: 5.0 ± 2.2). Image contrast was higher with 18F-Fluciclovine compared to 11C-Methionine (p < 0.0001). This was due to 18F-Fluciclovine's lower background in normal brain tissue (0.5 ± 0.2 compared to 1.3 ± 0.4 for 11C-Methionine). 18F-Fluciclovine uptake in both normal brain and tumors was well described by a simple one-compartment (three-parameter: Vb,k1,k2) model. Normal brain was found to approach transient equilibrium with a half-time that varied greatly, ranging from 1.5 to 8.3 h (mean 2.7 ± 2.3 h), and achieving a consistent final distribution volume averaging 1.4 ± 0.2 ml/cc. Tumors equilibrated more rapidly (t1/2ranging from 4 to 148 min, average 57 ± 51 min), with an average distribution volume of 3.2 ± 1.1 ml/cc. A qualitative comparison showed that the rate of normal brain uptake of 11C-Methionine was much faster than that of 18F-Fluciclovine. CONCLUSION: Tumor uptake of 18F-Fluciclovine correlated well with the established brain tumor imaging agent 11C-Methionine but provided significantly higher image contrast. 18F-Fluciclovine may be particularly useful when the contrast MRI is non-diagnostic. Based on the data gathered, we were unable to determine whether Fluciclovine uptake was due solely to recurrent tumor or if inflammation or other processes also contributed.

Seizure prophylaxis and melanoma brain metastases.

Melanoma has a high propensity to metastasize to the brain. In patients with brain metastases (BM) survival is limited, neurologic morbidity is high, with seizure incidence reported up to 67%. Current guidelines recommend against antiepileptic drug prophylaxis (AED PPX) in patients without a history of seizure. We reviewed our experience with melanoma BM to determine the efficacy of AED PPX in the era of second generation AED and to delineate risk factors associated with development of seizures. We reviewed records of all patients treated at Memorial Sloan-Kettering Cancer Center with melanoma and BM between May 2006 and October 2008. Seizure risk was studied relative to BM characteristics at diagnosis and AED PPX. We identified 109 patients. Median age was 61 years (range 29-91); 56% had no neurologic symptoms at diagnosis. On neuroimaging, 94% (102/109) had cortical lesions, 60% (65/109) had more than one supratentorial lesion, 54% (59/109) had hemorrhage. Seizure led to diagnosis of BM in 13% (14/109); 20% (22/109) developed seizures later. On univariate analysis among patients without a seizure at diagnosis, AED-PPX was significantly associated with decreased risk of seizure (P = 0.03) with 3-month seizure rate of 0% compared to 17% without AED-PPX. Hemorrhage (P < 0.001) and multiple supratentorial metastases (P = 0.03) were associated with increased seizure risk. Melanoma patients with multiple supratentorial BM and hemorrhage may have an increased risk of seizure. AED PPX may be effective in selected patients, and should be addressed in a randomized controlled trial.

Semiautomated volumetric measurement on postcontrast MR imaging for analysis of recurrent and residual disease in glioblastoma multiforme.

BACKGROUND AND PURPOSE: A limitation in postoperative monitoring of patients with glioblastoma is the lack of objective measures to quantify residual and recurrent disease. Automated computer-assisted volumetric analysis of contrast-enhancing tissue represents a potential tool to aid the radiologist in following these patients. In this study, we hypothesize that computer-assisted volumetry will show increased precision and speed over conventional 1D and 2D techniques in assessing residual and/or recurrent tumor. MATERIALS AND METHODS: This retrospective study included patients with native glioblastomas with MR imaging performed at 24-48 hours following resection and 2-4 months postoperatively. 1D and 2D measurements were performed by 2 neuroradiologists with Certificates of Added Qualification. Volumetry was performed by using manual segmentation and computer-assisted volumetry, which combines region-based active contours and a level set approach. Tumor response was assessed by using established 1D, 2D, and volumetric standards. Manual and computer-assisted volumetry segmentation times were compared. Interobserver correlation was determined among 1D, 2D, and volumetric techniques. RESULTS: Twenty-nine patients were analyzed. Discrepancy in disease status between 1D and 2D compared with computer-assisted volumetry was 10.3% (3/29) and 17.2% (5/29), respectively. The mean time for segmentation between manual and computer-assisted volumetry techniques was 9.7 minutes and <1 minute, respectively (P < .01). Interobserver correlation was highest for volumetric measurements (0.995; 95% CI, 0.990-0.997) compared with 1D (0.826; 95% CI, 0.695-0.904) and 2D (0.905; 95% CI, 0.828-0.948) measurements. CONCLUSIONS: Computer-assisted volumetry provides a reproducible and faster volumetric assessment of enhancing tumor burden, which has implications for monitoring disease progression and quantification of tumor burden in treatment trials.

Isolated diffusion restriction precedes the development of enhancing tumor in a subset of patients with glioblastoma.

BACKGROUND AND PURPOSE: Most response criteria for patients with glioblastoma rely on increases in the contrast enhancing abnormality to determine tumor progression. Our aim was to determine retrospectively in patients with glioblastoma whether diffusion restriction can predict the development of new enhancing mass lesions. MATERIALS AND METHODS: We reviewed the brain MR imaging scans (including DWI and ADC maps) of 208 patients with glioblastoma. Patients with restricted diffusion in or adjacent to the tumor were identified, with further analysis only performed on those patients with low-ADC lesions without enhancement. These patients were followed to determine if new concordant enhancement developed at the site of the low-ADC lesion. A Wilcoxon signed rank test, competing risk analysis, and Kaplan-Meier curves were used to compare the mean drop in ADC values, assess enhancement-free survival, and determine overall survival, respectively. RESULTS: In 67 of the 208 patients (32.2%), visibly detectable restricted diffusion was seen during treatment. The study cohort was formed by the 27 patients with low-ADC lesions and no corresponding enhancement. Twenty-three (85.2%) patients developed gadolinium-enhancing tumor at the site of restricted diffusion a median of 3.0 months later (95% CI, 2.6-4.1 months). The mean decrease in ADC was 22.9% from baseline (P < .001). The 3-month enhancement-free survival probability was 0.481 (95% CI, 0.288-0.675). The 12-month overall survival probability was 0.521 (95% CI, 0.345-0.788). Restricted diffusion predicted enhancement regardless of antiangiogenic therapy with bevacizumab. CONCLUSIONS: In a subset of patients with glioblastoma, development of a new focus of restricted diffusion during treatment may precede the development of new enhancing tumor.

Patterns of relapse and prognosis after bevacizumab failure in recurrent glioblastoma.

BACKGROUND: Bevacizumab has recently been approved by the US Food and Drug Administration for recurrent glioblastoma (GBM). However, patterns of relapse, prognosis, and outcome of further therapy after bevacizumab failure have not been studied systematically. METHODS: We identified patients at Memorial Sloan-Kettering Cancer Center with recurrent GBM who discontinued bevacizumab because of progressive disease. RESULTS: There were 37 patients (26 men with a median age of 54 years). The most common therapies administered concurrently with bevacizumab were irinotecan (43%) and hypofractionated reirradiation (38%). The median overall survival (OS) after progressive disease on bevacizumab was 4.5 months; 34 patients died. At the time bevacizumab was discontinued for tumor progression, 17 patients (46%) had an increase in the size of enhancement at the initial site of disease (local recurrence), 6 (16%) had a new enhancing lesion outside of the initial site of disease (multifocal), and 13 (35%) had progression of predominantly nonenhancing tumor. Factors associated with shorter OS after discontinuing bevacizumab were lower performance status and nonenhancing pattern of recurrence. Additional salvage chemotherapy after bevacizumab failure was given to 19 patients. The median progression-free survival (PFS) among these 19 patients was 2 months, the median OS was 5.2 months, and the 6-month PFS rate was 0%. CONCLUSIONS: Contrast enhanced MRI does not adequately assess disease status during bevacizumab therapy for recurrent glioblastoma (GBM). A nonenhancing tumor pattern of progression is common after treatment with bevacizumab for GBM and is correlated with worse survival. Treatments after bevacizumab failure provide only transient tumor control.

Bevacizumab for recurrent ependymoma.

BACKGROUND: Ependymoma is a rare type of glioma, representing 5% of all CNS malignancies. Radiotherapy (RT) is commonly administered, but there is no standard chemotherapy. At recurrence, ependymoma is notoriously refractory to therapy and the prognosis is poor. In recurrent glioblastoma, encouraging responses with bevacizumab have been observed. METHODS: In this Institutional Review Board-approved study, we retrospectively analyzed the records of 8 adult patients treated for recurrent ependymoma and anaplastic ependymoma with bevacizumab containing chemotherapy regimens. We determined radiographic response (Macdonald criteria), median time to progression (TTP), and median overall survival (OS; Kaplan-Meier method). RESULTS: There were 4 men and 4 women with a median age of 40 years (range, 20-65). Prior treatment included surgery (n = 8), RT (8), temozolomide (5), and carboplatin (4). Bevacizumab (5-15 mg/kg every 2-3 weeks) was administered alone (2) or concurrently with cytotoxic chemotherapy including irinotecan (3), carboplatin (2), or temozolomide (1). Six patients achieved a partial response (75%) and 1 remained stable for over 8 months. Median TTP was 6.4 months (95% confidence interval 1.4-7.4) and median OS was 9.4 months (95% confidence interval 7.0-not reached), with a median follow-up of 5.2 months among 5 surviving patients (63%). CONCLUSIONS: The radiographic response rate to bevacizumab-containing regimens is high. A prospective study is warranted.