The addition of figitumumab to erlotinib did not improve outcomes in patients with advanced, pretreated, nonadenocarcinoma NSCLC.
Figitumumab (CP-751,871) is a fully human IgG2 monoclonal antibody ...that inhibits the insulin-like growth factor 1 receptor. This multicenter, randomized, phase III study investigated the efficacy of figitumumab plus erlotinib compared with erlotinib alone in patients with pretreated, nonsmall-cell lung cancer (NSCLC).
Patients (stage IIIB/IV or recurrent disease with nonadenocarcinoma histology) who had previously received at least one platinum-based regimen were randomized to receive open-label figitumumab (20 mg/kg) plus erlotinib 150 mg/day or erlotinib alone every 3 weeks. The primary end point was overall survival (OS).
Of 583 patients randomized, 579 received treatment. The study was closed early by an independent data safety monitoring committee due to results crossing the prespecified futility boundary. At the final analysis, median OS was 5.7 months for figitumumab plus erlotinib and 6.2 months for erlotinib alone hazard ratio (HR) 1.09; 95% confidence interval (CI) 0.91–1.31;P = 0.35. Median progression-free survival was 2.1 months for figitumumab plus erlotinib and 2.6 months for erlotinib alone (HR 1.08; 95% CI 0.90–1.29;P = 0.43). Treatment-related nonfatal serious adverse events occurred in 18% and 5% of patients in the figitumumab arm or erlotinib alone arm, respectively. There were nine treatment-related deaths (three related to both drugs, four related to erlotinib alone and two related to figitumumab).
The addition of figitumumab to erlotinib did not improve OS in patients with advanced, pretreated, nonadenocarcinoma NSCLC. Clinical development of figitumumab has been discontinued.
NCT00673049.
Introduction
Curiosity toward the effects of psychedelic drugs on neural activation has increased due to their potential therapeutic benefits, particularly serotonergic psychedelics that act as ...5-HT2A receptor agonists such as LSD, psilocybin, and MDMA. However, the pattern of their effects on neural activity in various brain regions in both clinical and healthy populations is still not well understood, and primary studies addressing this issue have sometimes generated inconsistent results.
Objectives
The present meta-analysis aims to advance our understanding of the most widely used serotonergic psychedelics – LSD, psilocybin, and MDMA – by examining their effects on the functional activation throughout the whole brain among both clinical and healthy participants.
Methods
We conducted this meta-analysis by applying multilevel kernel density analysis (MKDA) with ensemble thresholding to quantitatively combine existing functional magnetic resonance imaging (fMRI) studies that examined whole-brain functional activation of clinical or healthy participants who were administered a serotonergic psychedelic.
Results
Serotonergic psychedelics, including LSD, psilocybin, and MDMA, exhibited significant effects (α=0.05) on neural activation in several regions throughout the cerebral cortex and basal ganglia, including effects that may be common across and unique within each drug.
Conclusions
These observed effects of serotonergic psychedelics on neural activity advance our understanding of the functional neuroanatomy associated with their administration and may inform future studies of both their adverse and therapeutic effects, including emerging clinical applications for the treatment of several psychiatric disorders.
Disclosure of Interest
None Declared
•Non-small cell lung cancer (NSCLC) patients with single organ metastases (SOM) tends to have better overall survival than those with multiple organ metastases (MOM).•NSCLC patients with SOM exhibit ...distinct metastasis patterns and molecular profiles compared to those with MOM.•NSCLC SOM treatments vary by metastatic site. Studies would be beneficial to identify tailored treatment plans to optimize outcomes for this group.•Future studies should include SOM as a distinct category for NSCLC cases in survival analysis and consider it as a stratification factor in clinical trials.
There is a paucity of information about the characteristics, treatment patterns, and outcomes of non-small cell lung cancer (NSCLC) patients with single organ metastasis (SOM).
This retrospective cohort study includes all patients with a diagnosis of stage IV NSCLC diagnosed from 2014 to 2016 and treated at Princess Margaret Cancer Centre. We compared baseline characteristics and patterns of metastatic sites between patients with SOM versus multiple (M)OM. Additionally, we identified treatment modalities and outcomes for patients with SOM. Cox multivariable models (MVA) were utilized to evaluate differences in overall survival (OS) between the SOM and MOM cohorts.
Of 893 pts analyzed, 457 (51 %) had SOM, while 436 (49 %) had MOM at initial diagnosis. Demographics were comparable between the two groups. Brain was the most common site of metastasis for SOM patients. When compared to the MOM group, the SOM group had lower percentages of liver and adrenal metastases. Amongst SOM patients, 54 % received single modality treatment, and 20 % did not receive any treatment for their SOM. In MVA, patients with liver (HR 2.4), bone (HR 1.8), and pleural (HR 1.7) metastasis as their SOM site had the worst outcomes, with median OS of 6.8 months, 12.1 months, and 13.0 months respectively. Patients with SOM had a significantly improved median OS compared to those with MOM (15.9 months vs. 10.6 months; HR 0.56, 95 % CI 0.47–0.66, p < 0.001).
In NSCLC patients who presented with SOM, survival correlated with the initial organ involved and was better overall compared to patients with MOM. SOM NSCLC may benefit from specific management strategies and SOM patients could be considered as a specific subgroup for survival analyses in observational and non-randomized interventional studies. In clinical trials, SOM can be considered as a stratification factor in the future.
A multi-institutional phase II trial was performed to assess a hypofractionated accelerated radiotherapy regimen for early stage non-small cell lung cancer (NSCLC) in an era when stereotactic body ...radiotherapy was not widely available.
Eighty patients with biopsy-proven, peripherally located, T1-3 N0 M0 NSCLC were enrolled. Eligible patients received 60 Gy in 15 fractions using a three-dimensional conformal technique without inhomogeneity correction. The gross tumour volume (GTV) was the primary tumor only, and the planning target volume (PTV) margin was 1.0 to 1.5cm. The primary endpoint was the 2-year primary tumor control rate. Toxicities were measured using the Common Terminology Criteria for Adverse Events version 3.0.
The median follow-up of patients was 49 months (range = 21-63 months). The median age of patients was 75.9 years. The actuarial rate of primary tumor control was 87.4% (95% confidence interval CI = 76.2% to 93.5%) at 2 years. Overall survival was 68.7% (95% CI = 57.2% to 77.6%) at 2 years. The actuarial rates of developing regional and distant relapse at 2 years were 8.8% (95% CI = 4.1% to 18.7%) and 21.6% (95% CI = 13.5% to 33.5%), respectively. Tumor size greater than 3cm was associated with an increased risk of developing distant relapse (hazard ratio = 3.11; 95% CI = 1.30 to 7.42; two-sided log-rank test P = .007). The most common grade 3+ toxicities were fatigue (6.3%), cough (7.5%), dyspnea (13.8%), and pneumonitis (10.0%)
Conformal radiotherapy to a dose of 60 Gy in 15 fractions resulted in favorable primary tumor control and overall survival rates in patients with T1-3 N0 M0 NSCLC. Severe toxicities were uncommon with this relatively simple treatment technique.
IntroductionFunctional magnetic resonance imaging (fMRI) has been used to identify the neural activity of both youth and adults diagnosed with major depressive disorder (MDD) in comparison to healthy ...age-matched controls. Previously reported abnormalities in depressed youth appear to mostly align with those found in depressed adults; however, some of the reported aberrant brain activity in youth has not been consistent with what is observed in adults, and to our knowledge there has not yet been a formal, quantitative comparison of these two groups. In addition, it is not known whether these observed differences between youth and adults with depression are attributable to developmental age or length-of-illness.ObjectivesThe aim of this study is to elucidate the similarities and differences in patterns of abnormal neural activity between adults and youth diagnosed with MDD and to then determine whether these observed differences are due to either developmental age or length-of-illness.MethodsWe used multilevel kernel density analysis (MKDA) with ensemble thresholding and triple subtraction to separately determine neural abnormalities throughout the whole brain in primary studies of depressed youth and depressed adults and then directly compare the observed abnormalities between each of those age groups. We then conducted further comparisons between multiple subgroups to control for age and length-of-illness and thereby determine the source of the observed differences between youth and adults with depression.ResultsAdults and youth diagnosed with MDD demonstrated reliable, differential patterns of abnormal activation in various brain regions throughout the cerebral cortex that are statistically significant (p < .05; FWE-corrected). In addition, several of these brain regions that exhibited differential patterns of neural activation between the two age groups can be reliably attributed to either developmental age or length-of-illness.ConclusionsThese findings indicate that there are common and disparate patterns of brain activity between youth and adults with MDD, several of which can be reliably attributed to developmental age or length-of-illness. These results expand our understanding of the neural basis of depression across development and course of illness and may be used to inform the development of new, age-specific clinical treatments as well as prevention strategies for this disorder.Disclosure of InterestNone Declared
IntroductionMajor depressive disorder (MDD) is a highly prevalent mental illness that often first occurs or persists into adulthood and is considered the leading cause of disability and disease ...burden worldwide. Unfortunately, individuals diagnosed with MDD who seek treatment often experience limited symptom relief and may not achieve long-term remission, which is due in part to our limited understanding of its underlying pathophysiology. Many studies that use task-based functional magnetic resonance imaging (fMRI) have found abnormal activation in brain regions in adults diagnosed with MDD, but those findings are often inconsistent; in addition, previous meta-analyses that quantitatively integrate this large body literature have found conflicting results.ObjectivesThis meta-analysis aims to advance our understanding of the neural basis of MDD in adults, as measured by fMRI activation studies, and address inconsistencies and discrepancies in the empirical literature.MethodsWe employed multilevel kernel density analysis (MKDA) with ensemble thresholding, a well-established method for voxel-wise, whole-brain meta-analyses, to conduct a quantitative comparison of all relevant primary fMRI activation studies of adult patients with MDD compared to age-matched healthy controls.ResultsWe found that adults with MDD exhibited a reliable pattern of statistically significant (p<0.05; FWE-corrected) hyperactivation and hypoactivation in several brain regions compared to age-matched healthy controls across a variety of experimental tasks.ConclusionsThis study supports previous findings that there is reliable neural basis of MDD that can be detected across heterogenous fMRI studies. These results can be used to inform development of promising treatments for MDD, including protocols for personalized interventions. They also provide the opportunity for additional studies to examine the specificity of these effects among various populations-of-interest, including youth vs. adults with depression as well as other related mood and anxiety disorders.Disclosure of InterestNone Declared
Introduction
Major depressive disorder (MDD) is a highly prevalent mental illness that frequently originates in early development and is pervasive during adolescence. Despite its high prevalence and ...early age of onset, our understanding of the potentially unique neural basis of MDD in this age group is still not well understood, and the existing primary literature on the topic includes many new and divergent results. This limited understanding of MDD in youth presents a critical need to further investigate its neural basis in youth and presents an opportunity to also improve clinical treatments that target its neural abnormalities.
Objectives
The present study aims to advance our understanding of the neural basis of MDD in youth by identifying abnormal functional activation in various brain regions compared with healthy controls.
Methods
We conducted a meta-analysis of functional magnetic resonance imaging (fMRI) studies of MDD by using a well-established method, multilevel kernel density analysis (MKDA) with ensemble thresholding, to quantitatively combine all existing whole-brain fMRI studies of MDD in youth compared with healthy controls. This method involves a voxel-wise, whole-brain approach, that compares neural activation of patients with MDD to age-matched healthy controls across variations of task-based conditions, which we subcategorize into affective processing, executive functioning, positive valence, negative valence, and symptom provocation tasks.
Results
Youth with MDD exhibited statistically significant (p<0.05; FWE-corrected) hyperactivation and hypoactivation in multiple brain regions compared with age-matched healthy controls. These results include significant effects that are stable across various tasks as well as some that appear to depend on task conditions.
Conclusions
This study strengthens our understanding of the neural basis of MDD in youth and may also be used to help identify possible similarities and differences between youth and adults with depression. It may also help inform the development of new treatment interventions and tools for predicting unique treatment responses in youth with depression.
Disclosure of Interest
None Declared
There are two major problems with ball and socket artificial joints; the migration of wear particles inducing an inflammatory response, causing toxicity, osteolysis and subsequent implant loosening; ...and the poor tribology between interstitial or synovial fluid and device׳s articulation surfaces. Experiments have been conducted to assess the potential of the promising bio-lubricant polyvinyl alcohol (PVA) at different concentrations with a range of materials (combinations of CoCr, UHMWPE and PEEK). Tests were conducted on a pin-on-disc tribometer and results were compared against Ringer׳s solution and bovine calf serum. The highest friction coefficient was for CoCr/CoCr for all lubricants. The lowest, and superlubricity was measured for UHMWPE/CoCr (a friction coefficient of 0.009) with 20g/100ml PVA (PVA-C).
•Friction coefficient has been tested for different biomaterial and bio-lubricants.•Range of materials (combinations of CoCr, UHMWPE and PEEK) have been used.•Polyvinyl alcohol (PVA) was compared with Ringer׳s solution and calf serum.•The PVA showed the lowest friction coefficient for all biomaterial combinations.•The lowest friction coefficient was measured for UHMWPE/CoCr with PVA C (20grs/100ml).
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