In LUX-Lung 7, the irreversible ErbB family blocker, afatinib, significantly improved progression-free survival (PFS), time-to-treatment failure (TTF) and objective response rate (ORR) versus ...gefitinib in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Here, we present primary analysis of mature overall survival (OS) data.
LUX-Lung 7 assessed afatinib 40 mg/day versus gefitinib 250 mg/day in treatment-naïve patients with stage IIIb/IV NSCLC and a common EGFR mutation (exon 19 deletion/L858R). Primary OS analysis was planned after ∼213 OS events and ≥32-month follow-up. OS was analysed by a Cox proportional hazards model, stratified by EGFR mutation type and baseline brain metastases.
Two-hundred and twenty-six OS events had occurred at the data cut-off (8 April 2016). After a median follow-up of 42.6 months, median OS (afatinib versus gefitinib) was 27.9 versus 24.5 months hazard ratio (HR) = 0.86, 95% confidence interval (CI) 0.66‒1.12, P = 0.2580. Prespecified subgroup analyses showed similar OS trends (afatinib versus gefitinib) in patients with exon 19 deletion (30.7 versus 26.4 months; HR, 0.83, 95% CI 0.58‒1.17, P = 0.2841) and L858R (25.0 versus 21.2 months; HR 0.91, 95% CI 0.62‒1.36, P = 0.6585) mutations. Most patients (afatinib, 72.6%; gefitinib, 76.8%) had at least one subsequent systemic anti-cancer treatment following discontinuation of afatinib/gefitinib; 20 (13.7%) and 23 (15.2%) patients received a third-generation EGFR tyrosine kinase inhibitor. Updated PFS (independent review), TTF and ORR data were significantly improved with afatinib.
In LUX-Lung 7, there was no significant difference in OS with afatinib versus gefitinib. Updated PFS (independent review), TTF and ORR data were significantly improved with afatinib.
NCT01466660.
Gefitinib was demonstrated to be synergistic with cisplatin and radiotherapy (RT) in in vitro studies. Biomarkers predictive of response to gefitinib in squamous cell head and neck cancer is still ...lacking.
Thirty-one patients with locally advanced and easily accessible primary tumor sites for biopsies were recruited. Gefitinib was started 3 weeks before the start of cisplatin/concurrent radiotherapy (CTRT) and continued during the CTRT phase and thereafter for 4 months as consolidation phase. Two baselines and a repeat tumor sample were taken after 2 weeks of gefitinib alone to study its impact on tumor gene expression. Epidermal growth factor receptor (EGFR) protein expression, FISH and mutational status, and matrix metallopeptidase 11 (MMP11) protein expression were correlated with response and survival outcome.
The overall response rate to gefitinib alone was 9.7%. The survival outcome is as follows: median disease free 1.3 years, median survival time 2.4 years, 3-year disease free 42.9%, and 3-year overall survival 48.4%. EGFR FISH, protein expression, and mutational status did not predict for response nor survival outcome of patients. Although MMP11 overexpression did not predict for response, it predicted significantly for a poorer survival outcome.
Gefitinib can be combined safely with cisplatin/RT. More studies are needed to uncover predictive biomarkers of benefit to gefitinib.
Background
We aimed to compare outcomes and cost effectiveness of extra-corporeal anastomosis (ECA) versus intra-corporeal anastomosis (ICA) for laparoscopic right hemicolectomy using the National ...Surgical Quality Improvement Programme data.
Methods
Patients who underwent elective laparoscopic right hemicolectomy for colon cancer from January 2018 to December 2022 were identified. Non-cancer diagnoses, emergency procedures or synchronous resection of other organs were excluded. Surgical characteristics, peri-operative outcomes, long-term survival and hospitalisation costs were compared. Incremental cost-effectiveness ratio (ICER) was used to evaluate cost-effectiveness.
Results
A total of 223 patients (175 ECA, 48 ICA) were included in the analysis. Both cohorts exhibited comparable baseline patient, comorbidity, and tumour characteristics. Distribution of pathological TMN stage, tumour largest dimension, total lymph node harvest and resection margin lengths were statistically similar. ICA was associated with a longer median operative duration compared with ECA (255 min vs. 220 min,
P
< 0.001). There was a quicker time to gastrointestinal recovery, with a shorter median hospital stay in the ICA group (4.0 versus 5.0 days,
P
= 0.001). Overall complication rates were comparable. ICA was associated with a higher surgical procedure cost (£6301.57 versus £4998.52,
P
< 0.001), but lower costs for ward accommodation (£1679.05 versus £2420.15,
P
= 0.001) and treatment (£3774.55 versus £4895.14,
P
= 0.009), with a 4.5% reduced overall cost compared with ECA. The ICER of −£3323.58 showed ICA to be more cost effective than ECA, across a range of willingness-to-pay thresholds.
Conclusion
ICA in laparoscopic right hemicolectomy is associated with quicker post-operative recovery and may be more cost effective compared with ECA, despite increased operative costs.
BACKGROUND AND PURPOSE Shogaols are reported to possess anti‐inflammatory and anticancer activities. However, the antimetastatic potential of shogaols remains unexplored. This study was performed to ...assess the effects of shogaols against breast cancer cell invasion and to investigate the underlying mechanisms.
EXPERIMENTAL APPROACH The anti‐invasive effect of a series of shogaols was initially evaluated on MDA‐MB‐231 breast cancer cells using the matrigel invasion assay. The suppressive effects of 6‐shogaol on phorbol 12‐myristate 13‐acetate (PMA)‐induced matrix metalloproteinase‐9 (MMP‐9) gelatinolytic activity and nuclear factor‐κB (NF‐κB) activation were further determined.
KEY RESULTS Shogaols (6‐, 8‐ and 10‐shogaol) inhibited PMA‐stimulated MDA‐MB‐231 cell invasion with an accompanying decrease in MMP‐9 secretion. 6‐Shogaol was identified to display the greatest anti‐invasive effect in association with a dose‐dependent reduction in MMP‐9 gene activation, protein expression and secretion. The NF‐κB transcriptional activity was decreased by 6‐shogaol; an effect mediated by inhibition of IκB phosphorylation and degradation that subsequently led to suppression of NF‐κB p65 phosphorylation and nuclear translocation. In addition, 6‐shogaol was found to inhibit JNK activation with no resulting reduction in activator protein‐1 transcriptional activity. By using specific inhibitors, it was demonstrated that ERK and NF‐κB signalling, but not JNK and p38 signalling, were involved in PMA‐stimulated MMP‐9 activation.
CONCLUSIONS AND IMPLICATIONS 6‐Shogaol is a potent inhibitor of MDA‐MB‐231 cell invasion, and the molecular mechanism involves at least in part the down‐regulation of MMP‐9 transcription by targeting the NF‐κB activation cascade. This class of naturally occurring small molecules thus have potential for clinical use as antimetastatic treatments.
The conductivity of graphene samples with various levels of disorder is investigated for a set of specimens with mobility in the range of 1-20x10(3) cm2/V sec. Comparing the experimental data with ...the theoretical transport calculations based on charged impurity scattering, we estimate that the impurity concentration in the samples varies from 2-15x10(11) cm(-2). In the low carrier density limit, the conductivity exhibits values in the range of 2-12e2/h, which can be related to the residual density induced by the inhomogeneous charge distribution in the samples. The shape of the conductivity curves indicates that high mobility samples contain some short-range disorder whereas low mobility samples are dominated by long-range scatterers.
Abstract Objectives To compare standard breast MRI to dedicated axillary ultrasound (with or without tissue sampling) for differentiating between no, limited and advanced axillary nodal disease in ...breast cancer patients. Methods All patients who underwent breast MRI and dedicated axillary ultrasound between 2009-2014 were eligible. Exclusion criteria were recurrent disease, neoadjuvant systemic therapy and not receiving completion axillary lymph node dissection after positive sentinel lymph node biopsy (SLNB). Two radiologists independently reassessed all MRI exams. Axillary ultrasound findings were retrospectively collected. Probability of advanced axillary nodal disease (pN2-3) given clinically node negative (cN0) or limited (cN1) findings was calculated, with corresponding negative predictive value (NPV) to exclude pN2-3 and positive predictive value (PPV) to identify axillary nodal disease. Histopathology served as gold standard. Results A total of 377 cases resulted in 81.4% no, 14.4% limited and 4.2% advanced axillary nodal disease at final histopathology. Probability of pN2-3 given cN0 for breast MRI and axillary ultrasound was 0.7-0.9% versus 1.5% and probability of pN2-3 given cN1 was 11.6-15.4% versus 29.0%. When cN1 on breast MRI was observed, PPV to identify positive axillary nodal disease was 50.7% and 59.0%. Conclusions Evaluation of axillary nodal status on standard breast MRI is comparable to dedicated axillary ultrasound in breast cancer patients. In patients who underwent preoperative standard breast MRI, axillary ultrasound is only required in case of suspicious nodal findings on MRI.
Abstract Background The current standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC) was conventional–fractionation radiotherapy plus concurrent–adjuvant chemotherapy as ...recommended by the Intergroup-0099 Study. This combined analysis of the NPC-9901 and the NPC-9902 Trials aims to provide more comprehensive data to evaluate the efficacy of the Intergroup-0099 regimen and the contributing factors. Methods Eligible patients with stage III-IVB non-keratinizing NPC were randomly assigned to radiotherapy-alone (RTi group: 218 patients) or chemoradiotherapy (CRTi group: 223 patients) using cisplatin (100 mg/m2 ) for three cycles in concurrence with radiotherapy, followed by cisplatin (80 mg/m2 ) plus fluorouracil (1000 mg/m2 /day for 4 days) for three cycles. The median follow-up was 6.1 years. Findings Comparison by intention-to-treat showed that the CRTi group achieved significant improvement in overall failure-free rate (FFR), locoregional-FFR and cancer-specific survival ( p ⩽ 0.019); but the improvements for distant-FFR and overall survival (OS) were statistically insignificant ( p ⩾ 0.14). Further exploratory studies based on actual treatment showed that an additional improvement achieved was a significant gain in OS (CRTa versus RTa group: 72% versus 63% at 5-year, p = 0.037). Multivariate analyses showed that the dose of cisplatin during the concurrent phase had significant impact on locoregional-FFR and OS, while that of fluorouracil during the adjuvant phase was significant for distant-FFR. The 5-year locoregional-FFR for patients who received 0–1, 2 and 3 concurrent cycles were 79%, 88% and 88%, respectively; the corresponding distant-FFR by adjuvant cycles were 68%, 78% and 77%, respectively. Interpretation Our results support the current practice of adding concurrent cisplatin plus adjuvant cisplatin-fluorouracil to radiotherapy for treating patients with locoregionally advanced NPC. The concurrent phase is important for locoregional control and survival, cisplatin 200 mg/m2 in two concurrent cycles might be adequate. Additional chemotherapy using fluorouracil-containing combination contributed to improving distant control.
A new type of composite material involving the in situ immobilization of tin oxide nanoparticles (SnO2‐NPs) within a monolithic metal–organic framework (MOF), the zeolitic imidazolate framework ...(ZIF)‐8 is presented. SnO2@monoZIF‐8 exploits the mechanical properties, structural resilience, and high density of a monolithic MOF, while leveraging the photocatalytic action of the nanoparticles. The composite displays outstanding photocatalytic properties and represents a critical advance in the field of treating toxic effluents and is a vital validation for commercial application. Crucially, full retention of catalytic activity is observed after ten catalytic cycles.
A new type of composite material involving the in situ immobilization of photoactive tin oxide nanoparticles within a monolithic metal–organic framework, monoZIF‐8, is presented. SnO2@monoZIF‐8 displays outstanding photocatalytic properties with full retention of activity observed after ten catalytic cycles. This achievement represents a critical advance in the field of treating toxic effluents and is a vital validation for commercial applications.
In patients with acute ischemic stroke with large vessel occlusion, the role of intra-arterial adjunctive medications (IAMs), such as urokinase, tPA (tissue-type plasminogen activator), or ...glycoprotein IIb/IIIa inhibitors, during mechanical thrombectomy (MT) has not been clearly established. We aim to evaluate the efficacy and safety of concomitant or rescue IAM for acute ischemic stroke with large vessel occlusion patients undergoing MT.
We searched Medline, Embase, and Cochrane Stroke Group Trials Register databases from inception until March 13, 2020. We analyzed all studies with patients diagnosed with acute ischemic stroke with large vessel occlusion in the anterior or posterior circulation that provided data for the two treatment arms, (1) MT+IAM and (2) MT only, and also reported on at least one of the following efficacy outcomes, recanalization and 90-day modified Rankin Scale, or safety outcomes, symptomatic intracranial hemorrhage and 90-day mortality. Data were collated in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
Sixteen nonrandomized observational studies with a total of 4581 patients were analyzed. MT only was performed in 3233 (70.6%) patients, while 1348 (29.4%) patients were treated with both MT and IAM. As compared with patients treated with MT alone, patients treated with combination therapy (MT+IAM) had a higher likelihood of achieving good functional outcome (risk ratio, 1.13 95% CI, 1.03-1.24) and a lower risk of 90-day mortality (risk ratio, 0.82 95% CI, 0.72-0.94). There was no significant difference in successful recanalization (risk ratio, 1.02 95% CI, 0.99-1.06) and symptomatic intracranial hemorrhage between the two groups (risk ratio, 1.13 95% CI, 0.87-1.46).
In acute ischemic stroke with large vessel occlusion, the use of IAM together with MT may achieve better functional outcomes and lower mortality rates. Randomized controlled trials are warranted to establish the safety and efficacy of IAM as adjunctive treatment to MT.
PDF
