Background/Aims: Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC. Methods: Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy. Results: With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (Pinteraction=0.023 for PFS, Pinteraction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC. Conclusions Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.

Objective: Central nervous system involvement in coronavirus disease 2019 (COVID-19) has been increasingly reported. We performed a systematic review and meta-analysis to evaluate the incidence of radiologically demonstrated neurologic complications and detailed neuroimaging findings associated with COVID-19. Materials and Methods: A systematic literature search of MEDLINE/PubMed and EMBASE databases was performed up to September 17, 2020, and studies evaluating neuroimaging findings of COVID-19 using brain CT or MRI were included. Several cohort-based outcomes, including the proportion of patients with abnormal neuroimaging findings related to COVID-19 were evaluated. The proportion of patients showing specific neuroimaging findings was also assessed. Subgroup analyses were also conducted focusing on critically ill COVID-19 patients and results from studies that used MRI as the only imaging modality. Results: A total of 1394 COVID-19 patients who underwent neuroimaging from 17 studies were included; among them, 3.4% of the patients demonstrated COVID-19-related neuroimaging findings. Olfactory bulb abnormalities were the most commonly observed (23.1%). The predominant cerebral neuroimaging finding was white matter abnormality (17.6%), followed by acute/subacute ischemic infarction (16.0%), and encephalopathy (13.0%). Significantly more critically ill patients had COVID-19-related neuroimaging findings than other patients (9.1% vs. 1.6%; p = 0.029). The type of imaging modality used did not significantly affect the proportion of COVID-19-related neuroimaging findings. Conclusion Abnormal neuroimaging findings were occasionally observed in COVID-19 patients. Olfactory bulb abnormalities were the most commonly observed finding. Critically ill patients showed abnormal neuroimaging findings more frequently than the other patient groups. White matter abnormalities, ischemic infarctions, and encephalopathies were the common cerebral neuroimaging findings.

OBJECTIVE: We aimed to determine the optimized image-based surrogate endpoints (IBSEs) in targeted therapies for glioblastoma through a systematic review and meta-analysis of phase III randomized controlled trials (RCTs).MATERIALS AND METHODS: A systematic search of OVID-MEDLINE and EMBASE for phase III RCTs on glioblastoma was performed in December 2017. Data on overall survival (OS) and IBSEs, including progression-free survival (PFS), 6-month PFS (6moPFS), 12-month PFS (12moPFS), median PFS, and objective response rate (ORR) were extracted. Weighted linear regression analysis for the hazard ratio for OS and the hazard ratios or odds ratios for IBSEs was performed. The associations between IBSEs and OS were evaluated. Subgroup analyses according to disease stage (newly diagnosed glioblastoma versus recurrent glioblastoma), types of test treatment, and types of response assessment criteria were performed.RESULTS: Twenty-three phase III RCTs published between 2000 and 2017, including 8387 patients, met the inclusion criteria. OS showed strong correlations with PFS (standardized β coefficient [R] = 0.719), 6moPFS (R = 0.647), and 12moPFS (R = 0.638). OS showed no correlations with median PFS and ORR. In subgroup analysis according to types of therapies, PFS showed the highest correlations with OS in targeted therapies for cell cycle pathways (R = 0.913) and growth factor receptors and their downstream pathways (R = 0.962). 12moPFS showed the highest correlation with OS in antiangiogenic therapy (R = 0.821). The response assessment in neuro-oncology criteria provided higher correlation coefficients between OS and IBSEs than the Macdonald criteria.CONCLUSION: Overall, PFS is an optimized IBSE in targeted therapies for glioblastoma; however, 12moPFS is optimal in antiangiogenic therapy.

Adult ; Aneurysm ; Arteries ; Carotid Artery, Internal ; Embolization, Therapeutic ; Female ; Follow-Up Studies ; Humans ; Magnetic Resonance Angiography ; Parents ; Prospective Studies ; Recurrence ; Retinal Artery ; Retreatment ; Stents ; Stroke, Lacunar ; Thromboembolism

OBJECTIVE: To identify potential imaging biomarkers of Alzheimer's disease by combining brain cortical thickness (CThk) and functional connectivity and to validate this model's diagnostic accuracy in a validation set. MATERIALS AND METHODS: Data from 98 subjects was retrospectively reviewed, including a study set (n = 63) and a validation set from the Alzheimer's Disease Neuroimaging Initiative (n = 35). From each subject, data for CThk and functional connectivity of the default mode network was extracted from structural T1-weighted and resting-state functional magnetic resonance imaging. Cortical regions with significant differences between patients and healthy controls in the correlation of CThk and functional connectivity were identified in the study set. The diagnostic accuracy of functional connectivity measures combined with CThk in the identified regions was evaluated against that in the medial temporal lobes using the validation set and application of a support vector machine. RESULTS: Group-wise differences in the correlation of CThk and default mode network functional connectivity were identified in the superior temporal (p < 0.001) and supramarginal gyrus (p = 0.007) of the left cerebral hemisphere. Default mode network functional connectivity combined with the CThk of those two regions were more accurate than that combined with the CThk of both medial temporal lobes (91.7% vs. 75%). CONCLUSION: Combining functional information with CThk of the superior temporal and supramarginal gyri in the left cerebral hemisphere improves diagnostic accuracy, making it a potential imaging biomarker for Alzheimer's disease.
Alzheimer Disease* ; Biomarkers ; Brain ; Cerebrum ; Humans ; Magnetic Resonance Imaging ; Neuroimaging* ; Parietal Lobe ; Retrospective Studies ; Support Vector Machine ; Temporal Lobe

OBJECTIVE: To determine whether pre-operative perfusion skewness and kurtosis derived from normalized cerebral blood volume (nCBV) histograms are associated with progression-free survival (PFS) of patients after partial resection of newly diagnosed glioblastoma. MATERIALS AND METHODS: A total of 135 glioblastoma patients who had undergone partial resection of tumor (resection of < 50% of pre-operative tumor volume or surgical biopsy) confirmed with immediate postsurgical MRI and examined with both conventional MRI and dynamic susceptibility contrast (DSC) perfusion MRI before the surgery were retrospectively reviewed in this study. They had been followed up post-surgical chemoradiotherapy for tumor progression. Using histogram analyses of nCBV derived from pre-operative DSC perfusion MRI, patients were sub-classified into the following four groups: positive skewness and leptokurtosis (group 1); positive skewness and platykurtosis (group 2); negative skewness and leptokurtosis (group 3); negative skewness and platykurtosis (group 4). Kaplan-Meier analysis and multivariable Cox proportional hazards regression analysis were performed to determine whether clinical and imaging covariates were associated with PFS or overall survival (OS) of these patients. RESULTS: According to the Kaplan-Meier method, median PFS of group 1, 2, 3, and 4 was 62, 51, 39, and 41 weeks, respectively, with median OS of 82, 77, 77, and 72 weeks, respectively. In multivariable analyses with Cox proportional hazards regression, pre-operative skewness/kurtosis pattern (hazard ratio: 2.98 to 4.64; p < 0.001), Karnofsky performance scale score (hazard ratio: 1.04; p = 0.003), and post-operative tumor volume (hazard ratio: 1.04; p = 0.02) were independently associated with PFS but not with OS. CONCLUSION: Higher skewness and kurtosis of nCBV histogram before surgery were associated with longer PFS in patients with newly diagnosed glioblastoma after partial tumor resection.
Adult ; Aged ; Aged, 80 and over ; Brain Neoplasms/*mortality/pathology/*surgery ; Chemoradiotherapy ; Disease-Free Survival ; Female ; Glioblastoma/*mortality/pathology/*surgery ; Humans ; Image Interpretation, Computer-Assisted ; Image Processing, Computer-Assisted ; Kaplan-Meier Estimate ; Magnetic Resonance Imaging/methods ; Male ; Middle Aged ; Regression Analysis ; Retrospective Studies ; Statistical Distributions ; Tumor Burden ; Young Adult

OBJECTIVE: To validate the usefulness of a diffusional anisotropic capillary array phantom and to investigate the effects of diffusion tensor imaging (DTI) parameter changes on diffusion fractional anisotropy (FA) and apparent diffusion coefficient (ADC) using the phantom. MATERIALS AND METHODS: Diffusion tensor imaging of a capillary array phantom was performed with imaging parameter changes, including voxel size, number of sensitivity encoding (SENSE) factor, echo time (TE), number of signal acquisitions, b-value, and number of diffusion gradient directions (NDGD), one-at-a-time in a stepwise-incremental fashion. We repeated the entire series of DTI scans thrice. The coefficients of variation (CoV) were evaluated for FA and ADC, and the correlation between each MR imaging parameter and the corresponding FA and ADC was evaluated using Spearman's correlation analysis. RESULTS: The capillary array phantom CoVs of FA and ADC were 7.1% and 2.4%, respectively. There were significant correlations between FA and SENSE factor, TE, b-value, and NDGD, as well as significant correlations between ADC and SENSE factor, TE, and b-value. CONCLUSION: A capillary array phantom enables repeated measurements of FA and ADC. Both FA and ADC can vary when certain parameters are changed during diffusion experiments. We suggest that the capillary array phantom can be used for quality control in longitudinal or multicenter clinical studies.
Anisotropy ; Diffusion Magnetic Resonance Imaging/*instrumentation/*methods ; Diffusion Tensor Imaging/*instrumentation/*methods ; Humans ; *Phantoms, Imaging ; Research Design ; Signal-To-Noise Ratio

PURPOSE: Diffusion-weighted MR images (DWI) obtained after endovascular treatment of cerebral aneurysms frequently show multiple high-signal intensity (HSI) dots. The purpose of this study was to see whether we could reduce their incidence after embolization of unruptured cerebral aneurysms by modification of our coiling technique, which involves the deliberate aspiration of the microcatheter lumen right after delivery of each detachable coil into the aneurysm sac. MATERIALS AND METHODS: From January 2011 to June 2011, all 71 patients with unruptured cerebral aneurysms were treated using various endovascular methods. During the earlier period, 37 patients were treated using our conventional embolization technique (conventional period). Then 34 patients were treated with a modified coiling technique (modified period). DWI was obtained on the following day. We compared the occurrence of any DWI HSI lesions and the presence of the symptomatic lesions during the two time periods. RESULTS: The incidence of the DWI HSI lesions differed significantly at 89.2% (33/37) during the conventional period and 26.5% (9/34) during the modified period (p < 0.0001). The incidence of symptomatic lesions differed between the two periods (29.7% during the conventional period vs. 2.9% during the modified period, p < 0.003). CONCLUSION: Aspiration of the inner content of the microcatheter right after detachable coil delivery was helpful for the reduction of the incidence of microembolisms after endovascular coil embolization for the treatment of unruptured cerebral aneurysms.
Aneurysm ; Embolization, Therapeutic ; Humans ; Incidence* ; Intracranial Aneurysm*

BACKGROUND AND PURPOSE: The diagnostic accuracy for unruptured intracranial aneurysms has increased, and incidental asymptomatic aneurysms have come to represent a substantial clinical burden because of their controversial natural history. However, their prevalence may be attributable to variations in evaluation methods and demographics. We therefore describe the prevalence and magnetic resonance angiography (MRA) findings of incidental intracranial saccular aneurysms over a 5-year period at a single large-volume center. METHODS: MRA images from 18,237 patients obtained between January 2001 and December 2005 were retrieved from the radiology report database. Patients diagnosed with incidental intracranial saccular aneurysms were identified and their MRA data were reviewed. Imaging and clinical follow-up data were evaluated. RESULTS: During the study period, 366 incidental intracranial saccular aneurysms were identified in 330 patients (prevalence, 1.8%; 95% confidence interval, 1.63%-2.01%; 115 men and 215 women; age range, 22-82 years; median age, 63 years). The prevalence was higher in women (215/8,112) than in men (115/10,125; P=0.02). The prevalence increased with age in women (P<0.01), but not in men (P=0.30). Aneurysm size ranged from 1.5 mm to 13 mm, with a median size of 4 mm. The most common location was the bifurcation of the middle cerebral artery (131/366; 35.8%). CONCLUSIONS: Our real world experience indicated a slightly lower overall prevalence of incidental intracranial saccular aneurysms than previously reported. The prevalence increased with age in women but not in men.
Aneurysm* ; Angiography* ; Demography ; Female ; Follow-Up Studies ; Head* ; Humans ; Intracranial Aneurysm ; Magnetic Resonance Angiography ; Male ; Middle Cerebral Artery ; Natural History ; Prevalence

BACKGROUND AND PURPOSE: The diagnostic accuracy for unruptured intracranial aneurysms has increased, and incidental asymptomatic aneurysms have come to represent a substantial clinical burden because of their controversial natural history. However, their prevalence may be attributable to variations in evaluation methods and demographics. We therefore describe the prevalence and magnetic resonance angiography (MRA) findings of incidental intracranial saccular aneurysms over a 5-year period at a single large-volume center. METHODS: MRA images from 18,237 patients obtained between January 2001 and December 2005 were retrieved from the radiology report database. Patients diagnosed with incidental intracranial saccular aneurysms were identified and their MRA data were reviewed. Imaging and clinical follow-up data were evaluated. RESULTS: During the study period, 366 incidental intracranial saccular aneurysms were identified in 330 patients (prevalence, 1.8%; 95% confidence interval, 1.63%-2.01%; 115 men and 215 women; age range, 22-82 years; median age, 63 years). The prevalence was higher in women (215/8,112) than in men (115/10,125; P=0.02). The prevalence increased with age in women (P<0.01), but not in men (P=0.30). Aneurysm size ranged from 1.5 mm to 13 mm, with a median size of 4 mm. The most common location was the bifurcation of the middle cerebral artery (131/366; 35.8%). CONCLUSIONS: Our real world experience indicated a slightly lower overall prevalence of incidental intracranial saccular aneurysms than previously reported. The prevalence increased with age in women but not in men.
Aneurysm* ; Angiography* ; Demography ; Female ; Follow-Up Studies ; Head* ; Humans ; Intracranial Aneurysm ; Magnetic Resonance Angiography ; Male ; Middle Cerebral Artery ; Natural History ; Prevalence