Objectives
To compare the efficacy of natalizumab or fingolimod in a nationwide observational cohort using prospectively collected data.
Materials and methods
We included all patients starting ...treatment with natalizumab or fingolimod documented in the Austrian MS Treatment Registry (AMSTR) from 2011 and staying on therapy for at least 24 months. We used propensity scores for several matching methods and as a covariate in multivariate models to correct for the bias of this non‐randomized registry study.
Results
The study cohort includes 588 patients with RRMS. Ten patients did not produce a propensity score in the common support region, thus leaving 578 cases for final analyses, 332 in the fingolimod and 246 in the natalizumab group. Mean annualized relapse rates (ARR) during the 24 months observation period were 0.19 under fingolimod and 0.12 under natalizumab treatment (P = .005). No statistical significant differences were found analysing the log‐transformed ARR, probability for experiencing a relapse, EDSS progression and EDSS regression. The hazard ratio for switching treatment from fingolimod comparing with natalizumab was 0.36 (95% CI: 0.247‐0.523), P < .001.
Conclusions
The generalized linear model (GLM) for relapse count as Poisson distributed dependent variable and propensity score as covariate showed a statistically significant reduction for the mean relapse count in the natalizumab group compared with fingolimod. This effect was smaller in the analyses of log‐transformed ARR with propensity score matching, loosing statistical significance although showing the same direction for the effect. We assume that the GLM was the more sensitive model analysing this question.
This study explored whether autoregulatory shifts in cerebral blood volume induce susceptibility changes large enough to be depicted by quantitative susceptibility mapping. Eight healthy subjects ...underwent fast quantitative susceptibility mapping at 3T while lying down to slowly decrease mean arterial pressure. A linear relationship between mean arterial pressure and susceptibility was observed in cortical and subcortical structures, likely representing vessels involved in autoregulation. The slope of this relationship is assumed to indicate the extent of cerebral vascular compliance.
Background
We report the final results of the randomized phase 2 FIGHT trial that evaluated bemarituzumab, a humanized monoclonal antibody selective for fibroblast growth factor receptor 2b (FGFR2b), ...plus mFOLFOX6 in patients with FGFR2b-positive (2 + /3 + membranous staining by immunohistochemistry), HER-2–negative gastric or gastroesophageal junction cancer (GC).
Methods
Patients received bemarituzumab (15 mg/kg) or placebo once every 2 weeks with an additional bemarituzumab (7.5 mg/kg) or placebo dose on cycle 1 day 8. All patients received mFOLFOX6. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, and safety. Efficacy was evaluated after a minimum follow-up of 24 months.
Results
In the bemarituzumab-mFOLFOX6 (N = 77) and placebo-mFOLFOX6 (N = 78) arms, respectively, 59.7% and 66.7% of patients were FGFR2b-positive in ≥ 10% of tumor cells. The median PFS (95% confidence interval CI) was 9.5 months (7.3–13.7) with bemarituzumab-mFOLFOX6 and 7.4 months (5.7–8.4) with placebo-mFOLFOX6 (hazard ratio HR, 0.72; 95% CI 0.49–1.08); median OS (95% CI) was 19.2 (13.6–24.2) and 13.5 (9.3–15.9) months, respectively (HR 0.77; 95% CI 0.52–1.14). Observed efficacy in FGFR2b-positive GC in ≥ 10% of tumor cells was: PFS: HR 0.43 (95% CI 0.26–0.73); OS: HR 0.52 (95% CI 0.31–0.85). No new safety findings were reported.
Conclusions
In FGFR2b-positive advanced GC, the combination of bemarituzumab-mFOLFOX6 led to numerically longer median PFS and OS compared with mFOLFOX6 alone. Efficacy was more pronounced with FGFR2b overexpression in ≥ 10% of tumor cells. Confirmatory phase 3 trials are ongoing (NCT05052801, NCT05111626).
Clinical trial registration
NCT03694522.
Epidermal growth factor receptor (EGFR) is overexpressed in a significant proportion of esophageal and gastric carcinomas. Although previous studies have examined tyrosine kinase inhibitors of EGFR, ...there remains limited data regarding the role of EGFR-directed monoclonal antibody therapy in these malignancies. We carried out a multi-institutional phase II study of cetuximab, a monoclonal antibody against EGFR, in patients with unresectable or metastatic esophageal or gastric adenocarcinoma.
Thirty-five patients with previously treated metastatic esophageal or gastric adenocarcinoma were treated with weekly cetuximab, at an initial dose of 400 mg/m2 followed by weekly infusions at 250 mg/m2. Patients were followed for toxicity, treatment response, and survival.
Treatment with cetuximab was well tolerated; no patients were taken off study due to drug-related adverse events. One (3%) partial treatment response was noted. Two (6%) patients had stable disease after 2 months of treatment. Median progression-free survival and overall survival were 1.6 and 3.1 months, respectively.
Although well tolerated, cetuximab administered as a single agent had minimal clinical activity in patients with metastatic esophageal and gastric adenocarcinoma. Ongoing studies of EGFR inhibitors in combination with other agents may define a role for these agents in the treatment of esophageal and gastric cancer.
Abnormal high cerebral iron deposition may be implicated in chronic neurologic disorders, including multiple sclerosis (MS). R2* relaxometry has been recently validated in a postmortem study to ...indicate brain iron accumulation in a quantitative manner. We used this technique to assess brain iron levels in different stages of MS and healthy controls (HC) and determined their relation with demographic, clinical, neuropsychological, and other imaging variables.
We studied 113 consecutive patients (35 clinically isolated syndrome CIS, 78 MS) and 35 HC with 3 T MRI and clinical and neuropsychological examination. Iron deposition in subcortical gray matter structures was assessed by automated, regional calculation of R2* rates.
Basal ganglia (BG) R2* levels were significantly increased in MS compared to CIS (p < 0.001) and HC (p < 0.005). They were correlated with age (r = 0.5, p < 0.001), disease duration (r = 0.5, p < 0.001), Expanded Disability Status Scale (r = 0.3, p < 0.005), and the z values of mental processing speed (r = -0.3, p < 0.01). Stepwise linear regression analysis revealed gray matter atrophy as the strongest independent predictor of BG R2* levels (p < 0.001), followed by age (p < 0.001) and T2 lesion load (p < 0.005).
BG iron accumulation in MS occurs with advancing disease and is related to the extent of morphologic brain damage, which argues for iron deposition as an epiphenomenon. The absence of increased iron levels in patients with CIS indicates that iron accumulation does not precede the development of MS.
Summary Background Previous phase 2 studies have shown antitumour activity with gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary-tract cancers (BTCs). In this phase 2 study, we ...assessed the efficacy and safety of combined bevacizumab with GEMOX (GEMOX-B) in patients with advanced BTCs, and investigated how changes in 18-fluorodeoxyglucose (18 FFDG)-PET correlate with clinical outcome. Methods Patients with advanced measurable BTCs were given the following treatment on days 1 and 15 of a 28-day cycle: bevacizumab 10 mg/kg, followed by gemcitabine 1000 mg/m2 (10 mg/m2 per min) and oxaliplatin 85 mg/m2 (2-h infusion). 18 FFDG-PET scans were obtained at baseline and after completion of the second cycle. The primary endpoint was progression-free survival (PFS). Efficacy and safety analyses were by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00361231. Findings 35 patients were enrolled and evaluable for efficacy and toxicity. Median PFS was 7·0 months (95% CI 5·3–10·3), and PFS at 6 months was 63% (47–79), which was below the targeted rate of 70%. Grade 3–4 toxic effects included neutropenia (n=7), raised alanine aminotransferase concentrations (n=5), peripheral neuropathy (n=5), and hypertension (n=5). 18 FFDG-PET scans showed a significant decrease in maximum standardised uptake value (SUVmax ) after two cycles of treatment (5·72 SD 2·01 at baseline; 3·73 SD 1·88 after two cycles; p<0·0001). These changes were more pronounced in patients with partial response or stable disease than those with progressive disease (24 patients, −2·80 SD 1·95 vs five patients, 1·41 SD 3·13; p=0·009). Change in SUVmax was a significant predictor of PFS (HR 1·35, 1·14–1·60, p=0·0006) and overall survival (1·25, 1·05–1·50, p=0·01). Interpretation GEMOX-B showed antitumour activity with tolerable safety in patients with advanced BTCs. Decreases in SUVmax on 18 FFDG-PET scans after treatment were associated with disease control and increases in PFS and overall survival. Funding Genentech Oncology and Sanofi-Aventis.
Abstract
MRI and clinical features of myelin oligodendrocyte glycoprotein (MOG)-antibody disease may overlap with those of other inflammatory demyelinating conditions posing diagnostic challenges, ...especially in non-acute phases and when serologic testing for MOG antibodies is unavailable or shows uncertain results. We aimed to identify MRI and clinical markers that differentiate non-acute MOG-antibody disease from aquaporin 4 (AQP4)-antibody neuromyelitis optica spectrum disorder and relapsing remitting multiple sclerosis, guiding in the identification of patients with MOG-antibody disease in clinical practice. In this cross-sectional retrospective study, data from 16 MAGNIMS centres were included. Data collection and analyses were conducted from 2019 to 2021. Inclusion criteria were: diagnosis of MOG-antibody disease; AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis; brain and cord MRI at least 6 months from relapse; and Expanded Disability Status Scale (EDSS) score on the day of MRI. Brain white matter T2 lesions, T1-hypointense lesions, cortical and cord lesions were identified. Random forest models were constructed to classify patients as MOG-antibody disease/AQP4-neuromyelitis optica spectrum disorder/multiple sclerosis; a leave one out cross-validation procedure assessed the performance of the models. Based on the best discriminators between diseases, we proposed a guide to target investigations for MOG-antibody disease. One hundred and sixty-two patients with MOG-antibody disease 99 females, mean age: 41 (±14) years, median EDSS: 2 (0–7.5), 162 with AQP4-neuromyelitis optica spectrum disorder 132 females, mean age: 51 (±14) years, median EDSS: 3.5 (0–8), 189 with multiple sclerosis (132 females, mean age: 40 (±10) years, median EDSS: 2 (0–8) and 152 healthy controls (91 females) were studied. In young patients (<34 years), with low disability (EDSS < 3), the absence of Dawson’s fingers, temporal lobe lesions and longitudinally extensive lesions in the cervical cord pointed towards a diagnosis of MOG-antibody disease instead of the other two diseases (accuracy: 76%, sensitivity: 81%, specificity: 84%, P < 0.001). In these non-acute patients, the number of brain lesions < 6 predicted MOG-antibody disease versus multiple sclerosis (accuracy: 83%, sensitivity: 82%, specificity: 83%, P < 0.001). An EDSS < 3 and the absence of longitudinally extensive lesions in the cervical cord predicted MOG-antibody disease versus AQP4-neuromyelitis optica spectrum disorder (accuracy: 76%, sensitivity: 89%, specificity: 62%, P < 0.001). A workflow with sequential tests and supporting features is proposed to guide better identification of patients with MOG-antibody disease. Adult patients with non-acute MOG-antibody disease showed distinctive clinical and MRI features when compared to AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis. A careful inspection of the morphology of brain and cord lesions together with clinical information can guide further analyses towards the diagnosis of MOG-antibody disease in clinical practice.
In a multicentre MAGNIMS study, Cortese et al. show that brain and cord lesion characteristics on conventional MRI, together with clinical features, can help differentiate non-acute MOG-antibody disease from AQP4-NMOSD and multiple sclerosis, aiding identification of non-acute patients for MOG antibody testing.
Background
Recent studies have created awareness that facial features can be reconstructed from high-resolution MRI. Therefore, data sharing in neuroimaging requires special attention to protect ...participants’ privacy. Facial features removal (FFR) could alleviate these concerns. We assessed the impact of three FFR methods on subsequent automated image analysis to obtain clinically relevant outcome measurements in three clinical groups.
Methods
FFR was performed using QuickShear, FaceMasking, and Defacing. In 110 subjects of Alzheimer’s Disease Neuroimaging Initiative, normalized brain volumes (NBV) were measured by SIENAX. In 70 multiple sclerosis patients of the MAGNIMS Study Group, lesion volumes (WMLV) were measured by lesion prediction algorithm in lesion segmentation toolbox. In 84 glioblastoma patients of the PICTURE Study Group, tumor volumes (GBV) were measured by BraTumIA. Failed analyses on FFR-processed images were recorded. Only cases in which all image analyses completed successfully were analyzed. Differences between outcomes obtained from FFR-processed and full images were assessed, by quantifying the intra-class correlation coefficient (ICC) for absolute agreement and by testing for systematic differences using paired
t
tests.
Results
Automated analysis methods failed in 0–19% of cases in FFR-processed images versus 0–2% of cases in full images. ICC for absolute agreement ranged from 0.312 (GBV after FaceMasking) to 0.998 (WMLV after Defacing). FaceMasking yielded higher NBV (
p
= 0.003) and WMLV (
p
≤ 0.001). GBV was lower after QuickShear and Defacing (both
p
< 0.001).
Conclusions
All three outcome measures were affected differently by FFR, including failure of analysis methods and both “random” variation and systematic differences. Further study is warranted to ensure high-quality neuroimaging research while protecting participants’ privacy.
Key Points
•
Protecting participants’ privacy when sharing MRI data is important
.
•
Impact of three facial features removal methods on subsequent analysis was assessed in three clinical groups
.
•
Removing facial features degrades performance of image analysis methods
.
PDF
