Four-Dimensional Computed Tomography: Clinical Impact for Patients with Primary Hyperparathyroidism.

BACKGROUND: In recent years, four-dimensional computed tomography (4DCT) has emerged as a new localization study for primary hyperparathyroidism (pHPT). OBJECTIVE: We aimed to assess the added value of 4DCT in our institution in the first 4 years of use. METHODS: A retrospective cohort study was conducted from February 2004 to June 2015. Since 2011, patients over 50 years of age without concordant sestamibi-SPECT (SeS) and ultrasound (US) findings underwent 4DCT. Imaging results, surgical findings, histopathology, and postoperative biochemistry were collected. RESULTS: A total of 536 parathyroid operations in 510 patients were performed during the study period. The overall cure rate was 99.2% after reoperation in some patients, and the overall sensitivity for SeS was 76.0%, and 74.8% for US. Since 2011, 100 patients without concordant SeS/US findings have undergone 4DCT, with a sensitivity of 72.9%. This is in comparison to the sensitivities for SeS (48.3%) and US (52.3%). 4DCT was more sensitive in patients with persistent/recurrent disease (60.0% compared with SeS 43.8% and US 36.4%) and patients with multigland disease (67.4% compared with SeS 40.9% and US 42.1%). Comparison between outcomes in the pre- versus post-CT era demonstrated no difference in the initial cure rate (95.4 vs. 95.9%, p = 0.85) or the rate of minimally invasive parathyroidectomies (74.5 vs. 79.9%, p = 0.22). CONCLUSION: Parathyroid 4DCT can aid surgical planning in cases without concordant SeS/US findings; however, the introduction of 4DCT as a second-line test did not change our overall cure rate or rate of minimally invasive parathyroidectomy. The role of 4DCT as the primary localization study for pHPT merits further investigation.

Dynamic CT for Parathyroid Adenoma Detection: How Does Radiation Dose Compare With Nuclear Medicine?

OBJECTIVE: Dynamic CT is increasingly used for preoperative localization of parathyroid adenomas, but concerns remain about the radiation effective dose of CT compared with that of 99mTc-sestamibi scintigraphy. The purpose of this study was to compare the radiation dose delivered by three-phase dynamic CT with that delivered by 99mTc-sestamibi SPECT/CT performed in accordance with our current protocols and to assess the possible reduction in effective dose achieved by decreasing the scan length (i.e., z-axis) of two phases of the dynamic CT protocol. MATERIALS AND METHODS: The effective dose of a 99mTc-sestamibi nuclear medicine parathyroid study performed with and without coregistration CT was calculated and compared with the effective dose of our current three-phase dynamic CT protocol as well as a proposed protocol involving CT with reduced scan length. RESULTS: The median effective dose for a 99mTc-sestamibi nuclear medicine study was 5.6 mSv. This increased to 12.4 mSv with the addition of coregistration CT, which is higher than the median effective dose of 9.3 mSv associated with the dynamic CT protocol. Reducing the scan length of two phases in the dynamic CT protocol could reduce the median effective dose to 6.1 mSv, which would be similar to that of the dose from the 99mTc-sestamibi study alone. CONCLUSION: Dynamic CT used for the detection of parathyroid adenoma can deliver a lower radiation dose than 99mTc-sestamibi SPECT/CT. It may be possible to reduce the dose further by decreasing the scan length of two of the phases, although whether this has an impact on accuracy of the localization needs further investigation.

The role of early magnetic resonance imaging in predicting survival on bevacizumab for recurrent glioblastoma: Results from a prospective clinical trial (CABARET).

BACKGROUND: Bevacizumab has been associated with prolonged progression-free survival for patients with recurrent glioblastoma; however, not all derive a benefit. An early indicator of efficacy or futility may allow early discontinuation for nonresponders. This study prospectively assessed the role of early magnetic resonance imaging (eMRI) and its correlation with subsequent routine magnetic resonance imaging (MRI) results and survival. METHODS: Patients were part of a randomized phase 2 clinical trial (CABARET) comparing bevacizumab with bevacizumab plus carboplatin for recurrent glioblastoma. eMRI was conducted after 4 weeks in the trial (after 2 treatments with bevacizumab [10 mg/kg every 2 weeks]). The results were compared with the results of the subsequent 8-week MRI standard. RESULTS: For 119 of 122 patients, eMRI was available, and 111 had subsequent MRI for comparison. Thirty-six (30%) had an early radiological response, and 17 (14%) had progressive disease. The concordance between eMRI and 8-week MRI was moderate (κ = 0.56), with most providing the same result (n = 79 [71%]). There was strong evidence that progression-free survival and overall survival were predicted by the eMRI response (both P values < .001). The median survival was 8.6 months for an eMRI response, 6.6 months for stable disease, and 3.7 months for progressive disease; the hazard ratio (progressive disease vs stable disease) was 3.4 (95% confidence interval, 1.9-6.0). Landmark analyses showed that eMRI progression was a strong predictor of mortality independent of other potential baseline predictors. CONCLUSIONS: In this study, early progression on MRI appears to be a robust marker of a poor prognosis for patients on bevacizumab. Cancer 2017;123:3576-82. © 2017 American Cancer Society.

Concomitant extraspinal hyperostosis and osteoporosis in a patient with congenital ichthyosis.

Ichthyosiform dermatosis is a term referred to a group of disorders that have as their basis a disorder of keratinization (1). These conditions which are present at birth result in a generalized dry, scaly skin without any inflammation. There are several types of ichthyosis based on their clinical presentation and mode of inheritance. The most common types are: ichthyosis vulgaris, X-linked recessive ichthyosis, epidermolytic hyperkeratosis (bullous), lamellar ichthyosis and non-bullous ichthyosiform erythroderma. Lamellar ichthyosis, which is inherited in an autosomal recessive pattern, shows genetic heterogeneity with the most severe type being due to mutations in the transglutaminase-1 gene. This condition presents with skin changes at birth and cases are referred to as collodion babies. Initially, the stratum corneum is smooth and appears as though it is covered with cellophane. This layer is discarded a few days after birth, leaving a generalized inflamed and scaly appearance. The skin is tight at this stage and may cause ectropion, and difficulties in feeding and temperature regulation. Lamellar ichthyosis is characterized by plate-like scales that last for life and can significantly impact the patient's quality of life (2). We report here a case of multiple extraspinal hyperostoses concomitant with marked osteoporosis and vitamin D deficiency in a patient taking acitretin for 20 years due to severe congenital lamellar ichthyosis.

Semi-automated hippocampal segmentation in people with cognitive impairment using an age appropriate template for registration.

BACKGROUND: To evaluate a new semi-automated segmentation method for calculating hippocampal volumes and to compare results with standard software tools in a cohort of people with subjective memory complaints (SMC) and mild cognitive impairment (MCI). METHODS: Data from 58 participants, 39 with SMC (17 male, 22 female, mean age 72.6) and 19 with MCI (6 male, 13 female, mean age 74.3), were analyzed. For each participant, T1-weighted images were acquired using an MPRAGE sequence on a 3 Tesla MRI system. Hippocampal volumes (left, right, and total) were calculated with a new, age appropriate registration template, based on older people and using the advanced software tool ANTs (Advanced Normalization Tools). The results were compared with manual tracing (seen as the reference standard) and two widely accepted automated software tools (FSL, FreeSurfer). RESULTS: The hippocampal volumes, calculated by using the age appropriate registration template were significantly (P < 0.05) more accurate (mean volume accuracy more than 90%) than those obtained with FreeSurfer and FSL (both less than 70%). Dice coefficients for the hippocampal segmentations with the new template method (75.3%) were slightly, but significantly (P < 0.05) higher than those from FreeSurfer (72.4%). CONCLUSION: These results suggest that an age appropriate registration template might be a more accurate alternative to calculate hippocampal volumes when manual segmentation is not feasible.

MRI in transverse myelitis.

Transverse myelitis is an acute inflammatory disease of the spinal cord, characterized by rapid onset of bilateral neurological symptoms. Weakness, sensory disturbance, and autonomic dysfunction evolve over hours or days, most progressing to maximal clinical severity within 10 days of onset. At maximal clinical severity, half will have a paraparesis, and almost all patients have sensory disturbance and bladder dysfunction. Residual disability is divided equally between severe, moderate and minimal or none. The causes of transverse myelitis are diverse; etiologies implicated include demyelinating conditions, collagen vascular disease, and parainfectious causes, however, despite extensive diagnostic work-up many cases are considered idiopathic. Due to heterogeneity in pathogenesis, and the similarity of its clinical presentation with those of various noninflammatory myelopathies, transverse myelitis has frequently been viewed as a diagnostic dilemma. However, as targeted therapies to optimize patient outcome develop, timely identification of the underlying etiology is becoming increasingly important. In this review, we describe the imaging and clinical features of idiopathic and disease-associated transverse myelitis and its major differentials, with discussion of how MR imaging features assist in the identification of various sub-types of transverse myelitis. We will also discuss the potential for advanced MR techniques to contribute to diagnosis and prognostication.

Anatomic comparison of nasal versus lateral surgical access to the petrous apex.

To compare anatomic access to the petrous apex via the nasal and lateral approaches. Hundred consecutive fine-cut CT temporal bones at the Royal Melbourne Hospital from July 27, 2007 to October 30, 2010 were reviewed. Easy lateral access allowed use of a 4 mm burr past vital structures. Easy nasal access was defined as sphenoid pneumatization to/beyond the posterior sella and laterally beyond the maxillary/vidian nerves. Three patients with petrous apex pathology were also reviewed. Easy lateral and nasal access occurred in 74 (37%) and 79 (39.5%) sides, respectively. Easy nasal and lateral access were not strongly correlated (r = 0.10, P = 0.15). A well-pneumatized mastoid (62.5%) was strongly correlated with a large sphenoid (63%, P < 0.001). Pneumatization of the mastoid corresponds to sphenoid sinus size. However, surgical access to the petrous apex is more determined by proximity of vital structures. Easy surgical access via the nasal or lateral approaches was not strongly correlated. Petrous apex lesions requiring surgery should be considered for both approaches.

Protocol for a randomized controlled trial evaluating the effect of physical activity on delaying the progression of white matter changes on MRI in older adults with memory complaints and mild cognitive impairment: the AIBL Active trial.

BACKGROUND: Older adults free of dementia but with subjective memory complaints (SMC) or mild cognitive impairment (MCI) are considered at increased risk of cognitive decline. Vascular risk factors (VRF), including hypertension, heart disease, smoking, hypercholesterolemia and lack of physical activity (PA) have been identified as modifiable risk factors contributing to cognitive decline, and white matter hyperintensities (WMH) are associated with VRF, SMC and cognitive impairment. Findings from a growing number of clinical trials with older adults are providing strong evidence for the benefits of physical activity for maintaining cognitive function, but few studies are investigating these benefits in high-risk populations. The aim of AIBL Active is to determine whether a 24-month physical activity program can delay the progression of white matter changes on magnetic resonance imaging (MRI). METHODS/DESIGN: This single-blind randomized controlled trial (RCT) is offered to 156 participants, aged 60 and older, in the Melbourne arm of the Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging (AIBL). Participants must have SMC with or without MCI and at least one VRF. The PA intervention is a modification of the intervention previously trialed in older adults with SMC and MCI (Fitness for the Ageing Brain Study). It comprises 24 months of moderate, home-based PA (150 minutes per week) and a behavioral intervention package. The primary outcome measure will be change in WMH after 24 months on MRI. Cognition, quality of life, functional fitness, level of physical activity, plasma biomarkers for cerebrovascular disease and amyloid positron emission tomography (PET) imaging comprise secondary measures. DISCUSSION: Currently, there is no effective pharmacological treatment available to delay cognitive decline and dementia in older adults at risk. Should our findings show that physical activity can slow down the progression of WMH, this RCT would provide an important proof of concept. Since imbedded in AIBL this RCT will also be able to investigate the interaction between vascular and Alzheimer's disease pathologies. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ACTRN12611000612910.

Assessing signal intensity change on well-registered images: comparing subtraction, color-encoded subtraction, and parallel display formats.

PURPOSE: To assess the sensitivity, specificity, accuracy, and interobserver reliability of subtraction, color-encoded subtraction, and parallel display formats in assessing signal intensity (SI) differences between well-registered images. MATERIALS AND METHODS: Institutional ethics approval for the study and a waiver of individual patient consent were obtained. Five radiologists graded the severity of fatty liver by using a seven-point scale for four imaging sets created from 179 pairs of dual-echo in- and opposed-phase magnetic resonance images from 179 patients. The four sets contained images displayed in parallel, subtraction images, color-encoded subtraction images, and images from the three previous formats presented together. The order of the images and sets was randomized. Sensitivity and specificity were assessed with the McNemar test. Accuracy was assessed by using three-way analysis of variance, with Tukey post hoc methods used to assess differences between the four formats. Interobserver reliability was assessed by using the Fleiss κ value. RESULTS: Subtraction (P = .016 at a 5% SI difference threshold) and color-encoded subtraction (P = .031 at a 4% SI difference threshold) formats had higher sensitivity than did the parallel format. The accuracy of the subtraction format was superior to that of the parallel format (P < .0001). Interobserver reliability of the subtraction (κ = 0.53) and color-encoded subtraction (κ = 0.39) formats was superior to that of the parallel format (κ = 0.33) (P < .0001 and P = .0085, respectively). CONCLUSION: When images are well registered, subtraction and color-encoded subtraction techniques offer advantages over the traditional parallel presentation format for the assessment of SI differences.

MR imaging characteristics of protoplasmic astrocytomas.

INTRODUCTION: Protoplasmic astrocytomas are a poorly recognized and uncommon subtype of astrocytoma. While usually categorized with other low-grade gliomas, there is literature to suggest that protoplasmic astrocytomas have differences in biology compared to other gliomas in this group. This paper presents the MR imaging characteristics of a series of eight protoplasmic astrocytomas. METHODS: We retrospectively reviewed MR images and histopathology of eight consecutive cases of histologically proven protoplasmic astrocytomas. RESULTS: Patients ranged from 17 to 51 years of age with a 5:3 male to female ratio. The tumors were located in the frontal or temporal lobes and tended to be large, well defined, and had a very high signal on T2 (close to cerebrospinal fluid). Generally, a large proportion of the tumor showed substantial signal suppression on T2 fluid-attenuated inversion recovery (FLAIR). Six of the eight lesions also demonstrated a partial or complete rim of reduced apparent diffusion coefficient (ADC) around the T2 FLAIR suppressing portion. CONCLUSIONS: The possibility that a primary cerebral neoplasm represents a protoplasmic astrocytoma should be considered in a patient with a large frontal or temporal tumor that has a very high signal on T2 with a large proportion of the tumor showing substantial T2 FLAIR suppression. A further clue is a partial or complete rim of reduced ADC.

Effects of a physical activity intervention on brain atrophy in older adults at risk of dementia: a randomized controlled trial.

Lack of physical activity is a risk factor for dementia, however, the utility of interventional physical activity programs as a protective measure against brain atrophy and cognitive decline is uncertain. Here we present the effect of a randomized controlled trial of a 24-month physical activity intervention on global and regional brain atrophy as characterized by longitudinal voxel-based morphometry with T1-weighted MRI images. The study sample consisted of 98 participants at risk of dementia, with mild cognitive impairment or subjective memory complaints, and having at least one vascular risk factor for dementia, randomized into an exercise group and a control group. Between 0 and 24 months, there was no significant difference detected between groups in the rate of change in global, or regional brain volumes.

Effect of a 24-month physical activity program on brain changes in older adults at risk of Alzheimer's disease: the AIBL active trial.

White matter hyperintensities (WMHs) are a risk factor for cognitive decline. Physical activity (PA) is associated with lower WMH. Whether long-term exposure to PA programs has beneficial effects on WMH progression in older adults with memory complaints and comorbid conditions has had limited exploration. This study explored whether a 24-month moderate-intensity PA intervention can delay the progression of WMH and hippocampus loss in older adults at risk for cognitive decline. Data acquired on magnetic resonance imaging were used to measure the progression of WMH and hippocampus loss. The results of this study showed no effect of intervention on either the primary outcome measure "WMH" or the secondary outcome measure "hippocampal volume." In addition, neither beta amyloid status nor the adherence to the intervention had any effect on the outcome. In this cohort of subjective memory complaints and mild cognitive impairment participants with vascular risk factors, there was no effect of long-term moderate-intensity PA on WMH or hippocampal loss.

Baseline White Matter Is Associated With Physical Fitness Change in Preclinical Alzheimer's Disease.

White matter (WM) microstructure is a sensitive marker to distinguish individuals at risk of Alzheimer's disease. The association of objective physical fitness (PF) measures and WM microstructure has not been explored and mixed results reported with physical activity (PA). Longitudinal studies of WM with PA and PF measures have had limited investigation. This study explored the relationship between objective PF measures over 24-months with "normal-appearing" WM microstructure. Data acquired on magnetic resonance imaging was used to measure "normal-appearing" WM microstructure at baseline and 24-months. Clinical variables such as cognitive and blood-based measures were collected longitudinally. Also, as part of the randomized controlled trial of a PA, extensive measures of PA and fitness were obtained over the 24 months. Bilateral corticospinal tracts (CST) and the corpus callosum showed a significant association between PF performance over 24-months and baseline WM microstructural measures. There was no significant longitudinal effect of the intervention or PF performance over 24-months. Baseline WM microstructural measures were significantly associated with PF performance over 24-months in this cohort of participants with vascular risk factors and at risk of Alzheimer's disease with distinctive patterns for each PF test.

A Randomized Controlled Trial of Adherence to a 24-Month Home-Based Physical Activity Program and the Health Benefits for Older Adults at Risk of Alzheimer's Disease: The AIBL Active-Study.

BACKGROUND: Previous studies have demonstrated that physical activity (PA) interventions can improve physical and cognitive outcomes in older adults, but most have been relatively short in duration (<1 year) with a few having specifically targeting individuals at risk of developing Alzheimer's disease. OBJECTIVE: To examine adherence and physical health outcomes in a 24-month home-based PA intervention in older adults at risk of Alzheimer's disease. METHODS: Participants 60 years and older with mild cognitive impairment (MCI) or subjective memory complaints (SMC) with at least 1 cerebrovascular risk factor recruited from The Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging (AIBL) were randomized to a PA or control group (n = 106). The control group continued with their usual lifestyle. The PA group received a 24-month home-based program with a target of 150 minutes/week of moderate PA and a behavioral intervention. Retention (participants remaining) and PA adherence (PA group only, percent PA completed to the PA prescribed) were determined at 6, 12, 18, and 24 months. Assessments at baseline, 6, 12, and 24 months included, PA; fitness; body composition and fat distribution. Key outcome measures were PA adherence and PA. RESULTS: The 24-month retention rate (97.2%) and the median PA adherence 91.67% (Q1-Q3, 81.96, 100.00) were excellent. In the long-term the intervention group achieved significantly better improvements in PA levels, leg strength, fat mass and fat distribution compared to the control. CONCLUSION: This study demonstrates that in this target group, long-term PA adherence is achievable and has physical health benefits.

Orbital inflammatory disease.

OBJECTIVES: To familiarize rheumatologists and internists with the signs, symptoms, and management of orbital inflammatory disease (OID). METHODS: A comprehensive literature review related to OID was performed and reported from the perspectives of rheumatology, ophthalmology, and radiology. RESULTS: OID is a general term encompassing inflammatory diseases that affect some or all of the structures contained within the orbit external to the globe. Orbital involvement as a part of the initial symptom complex is not uncommon for systemic diseases such as Graves' disease, Wegener's granulomatosis, and sarcoidosis. The management of these and other causes of OID, such as idiopathic orbital inflammation (formerly known as "orbital pseudotumor"), orbital myositis, and Tolosa-Hunt syndrome frequently involves systemic immunosuppression. Before immunosuppression is considered, however, infectious and malignant causes of inflammation must be ruled out. DISCUSSION: Rheumatologists should be familiar with the differential diagnosis of OID and often need to assist colleagues in ophthalmology and internal medicine with the management of this group of diseases.

Qualitative comparison of 3-T and 1.5-T MRI in the evaluation of epilepsy.

OBJECTIVE: MRI at 3 T, which has a higher signal-to-noise ratio than 1.5-T MRI, is potentially more sensitive and specific at delineating epileptogenic lesions and may influence management of refractory epilepsy. The purposes of the current study were to compare image quality of 3-T MRI with that of 1.5-T MRI in the evaluation of epilepsy and, in cases of focal epilepsy, to compare the two field strengths in terms of lesion detection and characterization. MATERIALS AND METHODS: Retrospective review was performed on 50 sets of MR images of 25 patients who underwent both 3-T and 1.5-T brain imaging with a dedicated epilepsy protocol, including fast spin-echo T2-weighted, coronal FLAIR, coronal fast multiplanar inversion recovery, and 3D spoiled gradient-recalled echo pulse sequences. Parameters assessed were distortion and artifact, lesion conspicuity, gray-white matter differentiation, and motion. Each pulse sequence was graded on a 4-point scale. Reviewers performed qualitative assessments of the site of abnormality and the most likely diagnosis. RESULTS: MRI at 3 T outperformed MRI at 1.5 T in all four parameters and was statistically superior (p < 0.05) to 1.5-T MRI in all categories except motion. On 3-T MRI, lesions were detected in 65 of 74 cases compared with 55 of 74 cases at 1.5 T (p = 0.0364), and lesions were accurately characterized in 63 of 74 cases compared with 51 of 74 cases at 1.5 T (p = 0.0194). The odds ratios showed identification of a focal epileptogenic lesion with 3-T MRI 2.57 times as likely as identification with 1.5-T MRI and accurate characterization of lesions 2.66 times as likely as characterization with 1.5-T MRI. CONCLUSION: In evaluation of epilepsy, MRI at 3 T performed better than 1.5-T MRI in image quality, detection of structural lesions, and characterization of lesions. High-field-strength imaging should be considered for patients with intractable epilepsy and normal or equivocal findings on 1.5-T MRI.

Emotional reactivity following surgery to the prefrontal cortex.

We aimed to elicit emotion in patients with surgically circumscribed lesions of the prefrontal cortex (PFC) in order to elucidate the precise functional roles in emotion processing of the discrete subregions comprising the ventromedial PFC, including the medial PFC and orbitofrontal cortex (OFC). Three components of emotional reactivity were measured: subjective experience, behaviour, and physiological response. These included measures of self-reported emotion, observer-rated facial expression of emotion and measurements of heart rate and heart rate variability (HRV) during film viewing, and a measure of subjective emotional change since surgery. Patients with lesions to the ventromedial PFC demonstrated significant differences compared with controls in HRV during the film clips, suggesting a shift to greater dominance of sympathetic input. In contrast, patients with lesions restricted to the OFC showed significant differences in HRV suggesting reduced sympathetic input. They also showed less facial expression of emotion during positive film clips, and reported more subjective emotional change since surgery compared with controls. This human lesion study is important for refining theoretical models of emotion processing by the ventromedial PFC, which until now have primarily been based on anatomical connectivity, animal lesion, and human functional neuroimaging research. Such theories have implications for the treatment of a wide variety of emotional disorders.

Comparison between site and central radiological assessments for patients with recurrent glioblastoma on a clinical trial.

AIM: Assessment of magnetic resonance imaging (MRI) in glioblastoma can be challenging. For patients with recurrent glioblastoma managed on the CABARET trial, we compared disease status assessed at hospitals and subsequent blinded central expert radiological review. METHODS: MRI results and clinical status at specified time points were used for site and central assessment of disease status. Clinical status was determined by the site. Response Assessment in Neuro-Oncology (RANO) criteria were used for both assessments. Site and central assessments of progression-free survival (PFS) and response rates were compared. Inter-rater variability for central review progression dates was assessed. RESULTS: Central review resulted in shorter PFS in 45% of 89 evaluable patients (n = 40). Median PFS was 3.6 (central) versus 3.9 months (site) (hazard ratio 1.5, 95% confidence interval 1.3-1.8, P < 0.001). Responses were documented more frequently by sites (n = 16, 18%) than centrally (n = 11, 12%). Seven of 120 patients continued on trial without site-determined progression for more than 6 months beyond the central review determination of progression. Of scans reviewed by all three central reviewers, 33% were fully concordant for progression date. CONCLUSION: While the difference between site and central PFS dates was statistically significant, the 0.3-month median difference is small. The variability within central review is consistent with previous studies, highlighting the challenges in MRI interpretation in this context. A small proportion of patients benefited from treatment well beyond the centrally determined progression date, reinforcing that clinical status together with radiology results are important determinants of whether a therapy is effective for an individual.

Continuing or ceasing bevacizumab beyond progression in recurrent glioblastoma: an exploratory randomized phase II trial.

BACKGROUND: In patients with recurrent glioblastoma, the benefit of bevacizumab beyond progression remains uncertain. We prospectively evaluated continuing or ceasing bevacizumab in patients who progressed while on bevacizumab. METHODS: CABARET, a phase II study, initially randomized patients to bevacizumab with or without carboplatin (Part 1). At progression, eligible patients underwent a second randomization to continue or cease bevacizumab (Part 2). They could also receive additional chemotherapy regimens (carboplatin, temozolomide, or etoposide) or supportive care. RESULTS: Of 120 patients treated in Part 1, 48 (80% of the anticipated 60-patient sample size) continued to Part 2. Despite randomization, there were some imbalances in patient characteristics. The best response was stable disease in 7 (30%) patients who continued bevacizumab and 2 (8%) patients who stopped receiving bevacizumab. There were no radiological responses. Median progression-free survival was 1.8 vs 2.0 months (bevacizumab vs no bevacizumab; hazard ratio [HR], 1.08; 95% CI, .59-1.96; P = .81). Median overall survival was 3.4 vs 3.0 months (HR, .84; 95% CI, .47-1.50; P = .56 and HR .70; 95% CI .38-1.29; P = .25 after adjustment for baseline factors). Quality-of-life scores did not significantly differ between arms. While the maximum daily steroid dose was lower in the continuation arm, the difference was not statistically significant. CONCLUSIONS: Patients who continued bevacizumab beyond disease progression did not have clear survival improvements, although the study was not powered to detect other than very large differences. While these data provide the only randomized evidence related to continuing bevacizumab beyond progression in recurrent glioblastoma, the small sample size precludes definitive conclusions and suggests this remains an open question.