Doublet BRAF/MEK inhibition versus single-agent BRAF inhibition in the management of BRAF-mutant advanced melanoma, biological rationale and meta-analysis of published data

2015 ◽  
Vol 18 (8) ◽  
pp. 848-858 ◽  
Author(s):  
O. Abdel-Rahman ◽  
H. ElHalawani ◽  
H. Ahmed
Keyword(s):  
Meta Analysis ◽  
Single Agent ◽  
Advanced Melanoma ◽  
Published Data ◽  
Mek Inhibition ◽  
Braf Inhibition ◽  
Braf Mutant

scholarly journals Efficacy and safety of BRAF inhibition alone versus combined BRAF and MEK inhibition in melanoma: a meta-analysis of randomized controlled trials

Oncotarget ◽  
2017 ◽  
Vol 8 (19) ◽  
pp. 32258-32269 ◽  
Author(s):  
Mengdong Liu ◽  
Xuekang Yang ◽  
Jiaqi Liu ◽  
Bin Zhao ◽  
Weixia Cai ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Mek Inhibition ◽  
Randomized Controlled ◽  
Braf Inhibition

Biochemotherapy versus chemotherapy for metastatic malignant melanoma: A meta-analysis of the randomised trials

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8544-8544 ◽  
Author(s):  
N. J. Ives ◽  
R. L. Stowe ◽  
P. Lorigan ◽  
K. Wheatley
Keyword(s):  
Meta Analysis ◽  
Single Agent ◽  
Objective Response ◽  
Interleukin 2 ◽  
Standard Of Care ◽  
Response Rates ◽  
Complete Response ◽  
Metastatic Malignant Melanoma ◽  
Published Data ◽  
The Individual

8544 Background: Metastatic melanoma is associated with a poor survival rate. High response rates have been reported for both chemotherapy and biochemotherapy. To assess whether adding interferon-a (IFN) ± interleukin-2 (IL-2) to chemotherapy is advantageous, a published data meta-analysis of trials of biochemotherapy versus chemotherapy has been performed. Methods: Standard published data meta-analysis methods were used to assess response rates (partial, complete and objective (i.e. partial+complete)) and overall survival (OS), with odds ratios (OR) and 95% confidence intervals (CI) calculated. The only subgroup analysis performed was by type of immunotherapy, with trials divided according to the type of immunotherapy given in the biochemotherapy arm - IFN or IFN+IL-2. Results: Data were available from 18 trials (11 trials of chemotherapy ± IFN and 7 of trials chemotherapy ± IFN+IL-2). Nearly 2500 patients were included in the analysis, with 555 responses and 2,039 deaths observed. There was a clear benefit for biochemotherapy for partial response (OR=0.67, CI=0.54–0.83, p=0.0002), complete response (0.50, 0.35–0.73, p=0.0003) and objective response (0.60, 0.49–0.73, p<0.00001). For objective response, these benefits were significant for both the IFN (0.60, 0.46–0.79, p=0.0002) and IFN+IL2 (0.60, 0.45–0.78, p=0.00002) subgroups. In contrast, there was no benefit on OS (0.99, 0.91–1.08, p=0.9), and there was also evidence of heterogeneity of treatment effect between the individual trials (p=0.006). Conclusions: This meta-analysis shows that biochemotherapy clearly improves response rates, but this does not appear to translate into a survival benefit. Single agent chemotherapy is considered the standard of care for the majority of patients receiving treatment for advanced melanoma outside a clinical trial, and the result of this meta-analysis shows no reason to change this. No significant financial relationships to disclose.

Evaluating clinical responses to BRAF inhibition in BRAF/TERT promoter mutated melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21551-e21551
Author(s):  
Colleen Ciccosanti ◽  
Alexander Hershey ◽  
Chunxia Chen ◽  
Dirk F. Moore ◽  
Ryan D. Stephenson ◽  
...  
Keyword(s):  
Mouse Models ◽  
Small Sample ◽  
Braf V600e ◽  
Braf Mutations ◽  
Mek Inhibition ◽  
Preclinical Data ◽  
Tert Promoter ◽  
Braf Inhibition ◽  
Significant Difference ◽  
Braf Mutant

e21551 Background: Combined BRAF/MEK inhibition results in improved progression free and overall survival in BRAF mutated melanoma, but significant response is not universally observed. TERT promoter activating mutations often co-occur with BRAF mutations and have been associated with aggressive features and poorer prognosis. The TERT promotor inhibits apoptosis via a mechanism dependent upon BRAF mutant MAPK activation. Preclinical data in mouse models suggests that BRAF/TERT genetic duet melanomas are associated with improved response to BRAF/MEK inhibition as compared with BRAF mutant/TERT-WT melanomas. Methods: We performed a single center retrospective analysis of adults with melanoma with confirmed BRAF mutations +/- TERT promoter mutations. Responses and progression free survival in response to BRAF/MEK inhibition was assessed. Differences in RR and PFS were compared using Kaplan-Meier and Log-Rank. Results: 52 cases of BRAF/TERT genetic duet and BRAF mutated/TERT-WT melanomas were assessed. A total of 24 patients received BRAF/MEK inhibitors over the course of treatment meeting criteria for study inclusion; 9 (37.5%) BRAF/TERT genetic duet and 15 (62.5%) BRAF mutated/TERT-WT. BRAF V600E was present in 19/24 (79.2%) and V600K in 5/24 (20.8%). In the genetic duets, TERT -146C > T was present in 4/9 (44.4%), -124C > T in 2/9 (22.2%), -139_-138CC > TT in 2/9 (22.2%), and a SNV in 1/9 (11.1%). Mean age at diagnosis was 56 ± 13.5 years and 62.5% were male. ECOG PFS was 0-1 in 15/24 (62.5%), 2-3 in 6/24 (25%), and unreported in 3/24 (12.5%). Mean LDH at start of therapy was 391 (range 81-1664). At initial diagnosis 20.8% were Stage I, 25% Stage II, 37.5% Stage III, and 16.7% Stage IV. Two or more sites of disease were present in 10/24 (41.7%) and 2/24 (8.3%) had CNS metastases. BRAF/MEK directed therapy was first line in 6/24 (25%) of patients, others received prior immunotherapy. No significant differences between groups were observed in baseline demographics, disease state at diagnosis, or treatment history. In BRAF/TERT genetic duet melanomas CR was observed in 1/9 (11.1%), PR in 7/9 (77.8%), and NR in 1/9 (11.1%). In BRAF mutated/TERT-WT CR was observed in 3/15 (20%), PR in 11/15 (73.3%), and NR in 1/15 (6.7%). BRAF/TERT genetic duets were observed to initially have somewhat better PFS on first exposure to BRAF/MEK directed therapy but the PFS curves crossed at about 5 months with no significant difference observed overall (p = 0.40). Conclusions: This study is the first to report on outcomes of BRAF/MEK directed therapy in BRAF/TERT genetic duet vs BRAF mutated/TERT-WT melanomas in humans. While preclinical data from mouse models observed an improved response to BRAF/MEK inhibition in genetic duet tumors, no significant difference was observed. Our study is limited by small sample size. A multicenter analysis may be of interest to better understand the effects of BRAF inhibition in patients with BRAF/TERT genetic duet melanoma.

scholarly journals Risk of venous thromboembolism in patients undergoing gastric cancer surgery: protocol for a systematic review and meta-analysis

BMJ Open ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. e033267
Author(s):  
Dengfeng Wang ◽  
Yang Yu ◽  
Pengxian Tao ◽  
Dan Wang ◽  
Yajing Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Systematic Review ◽  
Venous Thromboembolism ◽  
Evaluation Method ◽  
Clinical Decision Making ◽  
Meta Analysis ◽  
Cancer Surgery ◽  
Published Data ◽  
Gastric Cancer Surgery ◽  
Positive Prevention

IntroductionVenous thromboembolism (VTE) is a serious life-threatening complication in patients with gastric cancer. Abnormal coagulation function and tumour-related treatment may contribute to the occurrence of VTE. Many guidelines considered that surgical treatment would put patients with cancer at high risk of VTE, so positive prevention is needed. However, there are no studies that have systematically reviewed the postoperative risk and distribution of VTE in patients with gastric cancer. We thus conduct this systematic review to determine the risk of VTE in patients with gastric cancer undergoing surgery and provide some evidence for clinical decision-making.Methods and analysisStudies reporting the incidence of VTE after gastric cancer surgery will be included. Primary studies of randomised controlled trials, cohort studies, population-based surveys and cross-sectional studies are eligible for this review and only studies published in Chinese and English will be included. We will search the Medline, Embase, Web of Science, CBM, CNKI and Wanfang data from their inception to November 2019. Two reviewers will independently select studies and extract data. The quality of each included study will be assessed with tools corresponding to their study design. Meta-analysis will be used to pool the incidence data from included studies. Heterogeneity of the estimates across studies will be assessed, if necessary, a subgroup analysis will be performed to explore the source of heterogeneity. The Grades of Recommendation, Assessment, Development and Evaluation method is applied to assess the level of evidence obtained from this systematic review.Ethics and disseminationThis proposed systematic review and meta-analysis is based on published data, and thus ethical approval is not required. The results of this review will be sought for publication.PROSPERO registration numberCRD42019144562

A systematic review and meta-analysis on endovascular treatment as an attractive alternative for acute superior mesenteric venous thrombosis

Vascular ◽  
2021 ◽  
pp. 170853812199127
Author(s):  
Lixin Wang ◽  
Enci Wang ◽  
Fei Liu ◽  
Wei Zhang ◽  
Xiaolong Shu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Treatment Group ◽  
Conservative Treatment ◽  
Venous Thrombosis ◽  
Endovascular Treatment ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Published Data ◽  
Mesenteric Venous Thrombosis ◽  
Surgery Group

Objective This systematic review and meta-analysis evaluated the published data on the efficacy and safety of therapies for superior mesenteric venous thrombosis (SMVT), aiming to provide a reference and set of recommendations for clinical treatment. Methods Relevant databases were searched for studies published from 2000 to June 2020 on SMVT treated with conservative treatment, surgical treatment, or endovascular approach. Different treatment types were grouped for analysis and comparison, and odds ratios with corresponding 95% confidence intervals were calculated. The outcomes were pooled using meta-analytic methods and presented by forest plots. Results Eighteen articles, including eight on SMVT patients treated with endovascular therapies, were enrolled. The treatment effectiveness was compared between different groups according to the change of symptoms, the occurrence of complications, and mortality as well. The conservative treatment group had better efficacy compared to the surgery group (89.0% vs. 78.6%, P <0.05), and the one-year survival rate was also higher (94.4% vs. 80.0%, P >0.05), but without statistical significance. As for endovascular treatment, the effectiveness was significantly higher than the surgery group (94.8% vs. 75.2%, P <0.05), and the conservative treatment group as well (93.3% vs. 86.3%, P >0.05), which still requires further research for the lack of statistical significance. Conclusions Present findings indicate that anticoagulation, as conservative treatment should be the preferred clinical option in the clinic for SMVT, due to its better curative effect compared to other treatment options, including lower mortality, fewer complications, and better prognosis. Moreover, endovascular treatment is a feasible and promising approach that is worth in-depth research, for it is less invasive than surgery and has relatively better effectiveness, thus can provide an alternative option for SMVT treatment and may be considered as a reliable method in clinical.

scholarly journals Therapeutic Use of Botulinum Neurotoxins in Dermatology: Systematic Review

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 120
Author(s):  
Emanuela Martina ◽  
Federico Diotallevi ◽  
Giulia Radi ◽  
Anna Campanati ◽  
Annamaria Offidani
Keyword(s):  
Systematic Review ◽  
Skin Diseases ◽  
Meta Analysis ◽  
Published Data ◽  
Efficacy And Safety ◽  
Botulinum Toxins ◽  
Epidermolysis Bullosa Simplex ◽  
Off Label ◽  
Facial Erythema ◽  
Notalgia Paresthetica

Botulinum toxin is a superfamily of neurotoxins produced by the bacterium Clostridium Botulinum with well-established efficacy and safety profile in focal idiopathic hyperhidrosis. Recently, botulinum toxins have also been used in many other skin diseases, in off label regimen. The objective of this manuscript is to review and analyze the main therapeutic applications of botulinum toxins in skin diseases. A systematic review of the published data was conducted, following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Botulinum toxins present several label and off-label indications of interest for dermatologists. The best-reported evidence concerns focal idiopathic hyperhidrosis, Raynaud phenomenon, suppurative hidradenitis, Hailey–Hailey disease, epidermolysis bullosa simplex Weber–Cockayne type, Darier’s disease, pachyonychia congenita, aquagenic keratoderma, alopecia, psoriasis, notalgia paresthetica, facial erythema and flushing, and oily skin. Further clinical trials are still needed to better understand the real efficacy and safety of these applications and to standardize injection and doses protocols for off label applications.

Reference intervals for venous blood gas measurement in adults

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Kirsty L. Ress ◽  
Gus Koerbin ◽  
Ling Li ◽  
Douglas Chesher ◽  
Phillip Bwititi ◽  
...  
Keyword(s):  
Partial Pressure ◽  
Meta Analysis ◽  
Venous Blood ◽  
Reference Interval ◽  
Reference Intervals ◽  
Published Data ◽  
Blood Gas ◽  
Arterial Blood Gas ◽  
Arterial Blood ◽  
Venous Blood Gas

AbstractObjectivesVenous blood gas (VBG) analysis is becoming a popular alternative to arterial blood gas (ABG) analysis due to reduced risk of complications at phlebotomy and ease of draw. In lack of published data, this study aimed to establish reference intervals (RI) for correct interpretation of VBG results.MethodsOne hundred and 51 adult volunteers (101 females, 50 males 18–70 y), were enrolled after completion of a health questionnaire. Venous blood was drawn into safePICO syringes and analysed on ABL827 blood gas analyser (Radiometer Pacific Pty. Ltd.). A non-parametric approach was used to directly establish the VBG RI which was compared to a calculated VBG RI based on a meta-analysis of differences between ABG and VBGResultsAfter exclusions, 134 results were used to derive VBG RI: pH 7.30–7.43, partial pressure of carbon dioxide (pCO2) 38–58 mmHg, partial pressure of oxygen (pO2) 19–65 mmHg, bicarbonate (HCO3−) 22–30 mmol/L, sodium 135–143 mmol/L, potassium 3.6–4.5 mmol/L, chloride 101–110 mmol/L, ionised calcium 1.14–1.29 mmol/L, lactate 0.4–2.2 mmol/L, base excess (BE) −1.9–4.5 mmol/L, saturated oxygen (sO2) 23–93%, carboxyhaemoglobin 0.4–1.4% and methaemoglobin 0.3–0.9%. The meta-analysis revealed differences between ABG and VBG for pH, HCO3−, pCO2 and pO2 of 0.032, −1.0 mmol/L, −4.2 and 39.9 mmHg, respectively. Using this data along with established ABG RI, calculated VBG RI of pH 7.32–7.42, HCO3− 23 – 27 mmol/L, pCO2 36–49 mmHg (Female), pCO2 39–52 mmHg (Male) and pO2 43–68 mmHg were formulated and compared to the VBG RI of this study.ConclusionsAn adult reference interval has been established to assist interpretation of VBG results.

Chemotherapy in focus: a meta-analysis confronts immunotherapy in the treatment of advanced melanoma

2021 ◽  
pp. 103304
Author(s):  
Vitoria Diana Mateus de Almeida Gonçalves ◽  
Marcelo Ferrari de Almeida Camargo Filho ◽  
Tânia Zaleski ◽  
Rogério Rodrigues Vilas Boas ◽  
Elaine Rossi Ribeiro ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Advanced Melanoma

scholarly journals A systematic review and network meta-analysis of immunotherapy and targeted therapy for advanced melanoma

2017 ◽  
Vol 6 (6) ◽  
pp. 1143-1153 ◽  
Author(s):  
Joao Paulo da Silveira Nogueira Lima ◽  
Mina Georgieva ◽  
Benjamin Haaland ◽  
Gilberto de Lima Lopes
Keyword(s):  
Systematic Review ◽  
Targeted Therapy ◽  
Meta Analysis ◽  
Advanced Melanoma
Sign in / Sign up

Export Citation Format

Share Document