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Frontiers in Oncology 2021The aim of this meta-analysis was to evaluate efficacy and toxicity of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in combination with...
First-Generation EGFR-TKI Plus Chemotherapy Versus EGFR-TKI Alone as First-Line Treatment in Advanced NSCLC With EGFR Activating Mutation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
OBJECTIVE
The aim of this meta-analysis was to evaluate efficacy and toxicity of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in combination with chemotherapy (CT) compared to EGFR-TKI monotherapy as first-line treatment in advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutation.
METHODS
A systematic literature search of randomized controlled trials using Cochrane Library, PubMed, Embase, and Web of Science, was performed up to Jan. 7th, 2020. Hazard ratios (HRs) with 95% confidence intervals (CI) were calculated as effect values for progress-free survival (PFS) and overall survival (OS). Risk ratio (RR) and Odds ratio (OR) were calculated as effect values for objective response rate (ORR) and toxicity, respectively.
RESULTS
A total of eight randomized trials involving 1,349 advanced NSCLC patients with sensitive EGFR mutation were included in the meta-analysis. All patients in both groups received first-generation TKI as first-line treatment. The pooled HR of PFS and OS was 0.56 (95% CI = 0.50-0.64; P <0.00001) and 0.70 (95% CI = 0.54-0.90; P = 0.005), respectively. Subgroup analysis showed significantly higher OS advantages in patients receiving doublet CT (P = 0.02) and concurrent therapy (P = 0.002). The ORR in the EGFR-TKI plus CT group was significantly higher than in the EGFR-TKI monotherapy group (RR = 1.18, 95% CI = 1.10-1.26). The combination regimen showed a higher incidence of chemotherapy-induced toxicities. Subgroup analysis indicated that doublet chemotherapy rather than single-agent chemotherapy significantly increased incidence of grade 3 or higher leukopenia, neutropenia and anemia.
CONCLUSIONS
Compared with EGFR-TKI monotherapy, the combination of first-generation EGFR-TKI and CT, especially when applying concurrent delivery of platinum-based doublet chemotherapeutic drugs, significantly improve ORR and prolong PFS and OS in first-line treatment for advanced EGFR-mutated NSCLC. Although increasing incidence of chemotherapy-induced toxicities occurs in the combination group, it is well tolerated and clinically manageable.
PubMed: 33928022
DOI: 10.3389/fonc.2021.598265 -
Critical Reviews in Oncology/hematology Apr 2024We conducted a systematic review and meta-analysis to evaluate outcomes after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in TP53-mutated... (Meta-Analysis)
Meta-Analysis Review
We conducted a systematic review and meta-analysis to evaluate outcomes after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in TP53-mutated myelodysplastic syndromes (MDS). A literature search was performed on PubMed, Cochrane, Embase, and Clinicaltrials.gov. After screening 626 articles, eight studies were included. Data were extracted following the PRISMA guidelines and analyzed using the meta-package by Schwarzer et al. We analyzed 540 patients. The pooled median 3 (1-5) year overall survival was 21% (95% CI 0.08-0.37, I2=91%, n=540). The pooled relapse rate was 58.9% (95% CI 0.38-0.77, I2=93%, n=487) at a median of 1.75 (1-3) years. The pooled 4-year progression- free survival was 34.8% (95% CI 0.15-0.57, I2=72%, n=105). Outcomes of Allo-HSCT for TP53-mutated MDS patients remain poor, with 21% OS at three years; however, Allo-HSCT confers a survival advantage as compared to non-transplant palliative therapies. Our findings suggest the need to explore novel therapeutic agents in prospective clinical trials.
Topics: Humans; Prospective Studies; Myelodysplastic Syndromes; Hematopoietic Stem Cell Transplantation; Progression-Free Survival; Transplantation Conditioning; Tumor Suppressor Protein p53
PubMed: 38423375
DOI: 10.1016/j.critrevonc.2024.104310 -
Translational Lung Cancer Research May 2021Although objective response rate and disease control rate are commonly used as primary endpoints of lung cancer trials, it remains unclear whether objective response... (Review)
Review
Disease control and objective responsive rates in randomized phase II trials evaluating non-first-line chemotherapy for non-small cell lung cancer: a systematic review of 74 trials.
Although objective response rate and disease control rate are commonly used as primary endpoints of lung cancer trials, it remains unclear whether objective response rate and disease control rate correctly reflect the overall survival in a non-small cell lung cancer phase II trial evaluating a non-first-line chemotherapy. Objective response rate might be easily affected by chance because the small number of patients in each trial achieved complete or partial response in the phase II non-first-line setting. This study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (UMIN000040412). Four databases were searched for eligible trials. A Spearman's rank correlation with hazard ratio of overall survival was calculated each for odds ratio of objective response rate, difference of objective response rate (%), odds ratio of disease control rate, and difference of disease control rate (%). Of 74 eligible trials, 73 reported objective response rate and 68 reported disease control rates. Nine (12%) trials included patients with driver mutation status. Thirteen (18%) and two (3%) RCTs specifically included adenocarcinoma/non-squamous and squamous subtype of non-small cell lung cancer, respectively. The Eastern Cooperative Oncology Group performance status 0-2 (N=41, 55%) and the performance status 0-1 (N=25, 34%) were frequently used performance status criteria. The median number of patients in the two arms was 116 (interquartile range, 82-159). The correlation between trial-level odds ratio of objective response rate and hazard ratio of overall survival was weak (r=-0.29, 95% CI: -0.49 to -0.05, P=0.014). An exploratory subgroup analysis suggested that fewer responders were associated with poorer correlation. Odds ratio of disease control survival (r=-0.53, 95% CI: -0.68 to -0.32, P<0.001) had moderate rank correlations with hazard ratio of overall survival. Instead of objective response rate, disease control rate should be used as the primary endpoint in a randomized phase II trial evaluating non-first-line chemotherapy for non-small cell lung cancer.
PubMed: 34164275
DOI: 10.21037/tlcr-20-1120 -
Frontiers in Surgery 2021The role of targeted therapy in the neoadjuvant field of stage IIIA epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) is...
Efficacy and Safety of Neoadjuvant Targeted Therapy vs. Neoadjuvant Chemotherapy for Stage IIIA EGFR-Mutant Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis.
The role of targeted therapy in the neoadjuvant field of stage IIIA epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) is still controversial. We sought to evaluate the efficacy and safety of neoadjuvant targeted therapy (NTT) with neoadjuvant chemotherapy (NCT) used as a benchmark comparator. A systematic search was conducted in four databases (Pubmed, Cochrane Library, Embase, CNKI) for eligible studies on NTT published before October 2020. The primary endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and grade 3/4 adverse events (AEs). Statistical analysis and bias assessment were performed by RevMan 5.3. A total of 319 patients, including 3 randomized controlled trials and 2 non-randomized controlled trials, were included in the meta-analysis. Perform the second subgroup analysis after excluding 2 non-randomized controlled trials. The meta-analysis reveals that, for EGFR mutation-positive stage IIIA NSCLC patients, compared with NCT, NTT can significantly increase ORR (relative risk [RR]:1.70, 95% confidence interval [CI]:1.35-2.15; subgroup-RR:1.56, 95% CI 1.23-2.0) and significantly reduce grade 3/4 AEs (RR:0.5, 95% CI 0.34-0.75; subgroup-RR: 0.53, 95% CI 0.26-1.08). The OS of the NTT arm is slightly higher, but the difference is not significant (hazards ratio [HR]: 0.74, 95% CI: 0.43-1.27; subgroup-HR: 0.64 95% CI 0.40-1.03). No difference in PFS was found (HR: 0.81, 95% CI 0.27-2.44). In neoadjuvant setting, targeted therapy has a definitive effect on patients with EGFR mutation-positive stage IIIA NSCLC and is even better than chemotherapy in terms of toxicity and tumor response rate. PROSPERO, identifier CRD42021221136.
PubMed: 34490338
DOI: 10.3389/fsurg.2021.715318 -
International Journal of Preventive... 2020Ethambutol (EMB) resistance is a major concern in patients with tuberculosis (TB). The aim of this study was to determine the frequency rate of mutations in 306 gene of... (Review)
Review
BACKGROUND
Ethambutol (EMB) resistance is a major concern in patients with tuberculosis (TB). The aim of this study was to determine the frequency rate of mutations in 306 gene of () resistant to EMB, based on a systematic review and meta-analysis.
METHODS
Thirty-seven original articles (1997-2015) that have been published in valid databases were considered for this research. The articles were systematically reviewed for the prevalence and rate of mutations in 306 in EMB-resistant . Data were analyzed using meta-analysis and random effects models (CI 95%, < 0.10).
RESULTS
With a 6,931 sample size in 37 original articles, the lowest rate was related to EMB resistance that was observed in 2014 with 0.05 (95% CI: 0.04-0.07) and the highest prevalence rate was 0.84 (95% CI: 0.68-1.01), observed in 1997. Lowest and highest prevalence rates of 306 gene mutation in were 0.03 (95% CI: 0.01-0.07) in 2014 and 0.78 (95% CI: 0.71-1.84) in 2005, in the USA, respectively.
CONCLUSIONS
The present study revealed the prevalence and association of mutations in the 306 gene of with resistance to EMB. Detecting EMB-resistant can help in controlling and correcting the administration of drugs for patients with TB.
PubMed: 33088440
DOI: 10.4103/ijpvm.IJPVM_114_19 -
Frontiers in Oncology 2022Gastric metastasis from lung cancer (GMLC) is a rare occurrence. The clinicopathological characteristics, outcomes, and prognostic factors remain largely elusive.
BACKGROUND
Gastric metastasis from lung cancer (GMLC) is a rare occurrence. The clinicopathological characteristics, outcomes, and prognostic factors remain largely elusive.
METHODS
We conducted a systematic review on case reports and case series of GMLC by scanning MEDLINE, Embase, and ISI Web of Knowledge. Data involving the clinicopathological features, treatment, and outcomes were extracted and analyzed. Survival analysis was performed using Kaplan-Meier method. The Cox proportional hazards regression model was used to identify potential prognostic factors associated with survival. Furthermore, a case of metastatic gastric adenocarcinoma of pulmonary origin with epidermal growth factor receptor (EGFR) L858R+T790M mutation was also described and included.
RESULTS
Seventy-eight records involving 114 cases (including ours) were finally included. The median age on admission was 65 years with a male predominance of 79.8%. Lung adenocarcinoma (42.1%), located in the right upper lobe (30.3%), was the most frequent primary tumor. Bleeding (36.7%) and abdominal pain (35.8%) were the two most common symptoms. Endoscopically, gastric lesions were typically presented as elevated lesions with or without volcano-like ulceration, or ulcerative lesions, mostly involving the gastric corpus. The median overall survival time and survival time after diagnosis of metastatic cancer were 11 months [95% confidence interval (CI): 7-14] and 4.5 months (95% CI: 3-9), respectively. The survival analyses revealed that surgical interventions (including lung surgery and/or abdominal surgery) and systemic therapy (including chemotherapy, radiotherapy, and/or targeted therapy) seemed to be positive prognostic factors for both overall survival and survival after diagnosis of metastatic cancer.
CONCLUSIONS
Clinicians should be alerted to the occurrence of gastric metastasis in lung cancer patients. Comprehensive evaluation and appropriate treatment for specific patients may improve the survival rate of GMLC patients.
PubMed: 35875072
DOI: 10.3389/fonc.2022.922016 -
Cureus Dec 2021The presence of mitral valve prolapse (MVP) varies from asymptomatic to life-threatening arrhythmias. Catheter ablation (CA) is widely used to treat ventricular... (Review)
Review
The presence of mitral valve prolapse (MVP) varies from asymptomatic to life-threatening arrhythmias. Catheter ablation (CA) is widely used to treat ventricular arrhythmias (VAs) associated with MVP. Despite having high procedural success, outcome data after CA is limited, especially in a long-term setting. Therefore, this systematic review and meta-analysis were performed. Literature searching was conducted in Pubmed, EuropePMC, Proquest, and Ebsco from inception to December 2020 using keywords: ventricular arrhythmia, premature ventricular complex, ventricular tachycardia, ventricular fibrillation, mitral valve prolapse, and catheter ablation. A total of 407 potential articles were retrieved for further review. The final review resulted in six articles for systematic review and meta-analysis. The study was registered in PROSPERO (CRD42020219144). The most common origin of VAs was papillary muscle. The acute success rate of CA in the MVP group varies between 66% and 94%. Follow-up studies reported a higher percentage of VAs recurrence after CA in the MVP group (22.22%) compared with the non-MVP group (11.38%). However, the difference is not significant (P-value = 0.16). Other studies reported a 12.5%-36% rate and 40% of repeat ablation in the medium term and the long term, respectively. Episodes of sudden cardiac death during exertion could still occur following CA in patients with MVP. Distinct origin of VAs was observed during repeated ablation procedures, which may explain arrhythmic substrate progression. Diffuse left ventricular fibrosis around papillary muscle rather than local fibrosis was observed among older patients. Furthermore, the presence of mitral annular disjunction (MAD) and Filamin C mutation might increase the risk of recurrent VAs. CAn has been done as the treatment of VAs associated with MVP. The acute success rate of CA varies between studies and the number of patients requiring repeat CA varied from 12.5% to 40%. Sudden cardiac death could still occur after CA. Older age during CA, genetic predisposition, deep arrhythmic foci, multifocal VAs origin, diffuse fibrosis, and the presence of MAD may contribute to the recurrence of VAs. Further studies, stratification, and evaluation are needed to prevent fatal outcomes in VA associated with MVP, even after CA.
PubMed: 35024259
DOI: 10.7759/cureus.20310 -
Frontiers in Immunology 2021Immune checkpoint inhibitors (ICIs) have improved survival for advanced wild-type non-small cell lung cancer (NSCLC) significantly, but few studies compared single ICI... (Meta-Analysis)
Meta-Analysis
Comparison of Efficacy and Safety of Single and Double Immune Checkpoint Inhibitor-Based First-Line Treatments for Advanced Driver-Gene Wild-Type Non-Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis.
BACKGROUND
Immune checkpoint inhibitors (ICIs) have improved survival for advanced wild-type non-small cell lung cancer (NSCLC) significantly, but few studies compared single ICI (SICI)-based treatments and double ICIs (DICI)-based treatments. We summarized the general efficacy of ICI-related treatments, compared the efficacy and safety of SICI-based [programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) or cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors ± chemotherapy (CT)] and DICI-based (PD-1/PD-L1 inhibitors+CTLA-4 inhibitors ± chemotherapy) treatments . CT in the first-line treatment.
METHODS
We included phase II/III randomized controlled trials (RCTs), including patients with histologically confirmed stage IIIB-IV driver-gene wild-type NSCLC who received first-line ICI-related therapy in at least one arm. PubMed, Embase, and Cochrane Library were searched from January 1, 2005, to December 31, 2020. This network meta-analysis was performed in a Bayesian framework using GEMTC and JAGS package in R.3.6.1. The research was registered with PROSPERO (CRD42020184534).
RESULTS
Twenty RCTs were involved, including 13,032 patients and 17 treatment regimens. The results showed that ICI-based therapies could provide a pooled median overall survival (mOS) (POS) of 15.79 (95% CI: 14.85-16.73) months, and there were no significant differences in OS, progression-free survival (PFS), objective response rate (ORR), and grade 3 or higher adverse events (≥3AEs) between DICI-based treatments (POS: 14.81, 12.11-17.52 months) and SICI-based treatments (POS: 16.17, 14.59-17.74 months) in overall patients. However, DICI-based treatments had significantly prolonged the OS over SICI-based treatments in squamous and PD-L1 <1% subgroups. The ranking of OS benefit by Bayesian surface under the cumulative ranking curve (SUCRA) spectrum showed that DICI+chemotherapy ranked first for overall population and subgroups including squamous, non-squamous, any level of PD-L1 expression, smoking, male, Eastern Cooperative Oncology Group performance status (ECOG PS) = 0/1, age < 65/≥65 while SICI+CT for low tumor mutation burden (TMB), non-smoking, and female subgroups, and DICI for high TMB subgroups.
CONCLUSIONS
In the first-line therapy for advanced wild-type NSCLC, both SICI- and DICI-based treatments could bring significant overall advantages over chemotherapy, with comparable outcomes of efficacy and ≥3AEs. DICI-based treatments were more effective than SICI-based treatments in squamous and PD-L1 <1% subgroups. For most populations, DICI+chemotherapy could be the best choice with a survival benefit, while SICI+chemotherapy has established its position actually.
SYSTEMATIC REVIEW REGISTRATION
[PROSPERO], identifier [CRD42020184534].
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; CTLA-4 Antigen; Carcinoma, Non-Small-Cell Lung; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Disease Progression; Female; Humans; Immune Checkpoint Inhibitors; Lung Neoplasms; Male; Middle Aged; Mutation; Network Meta-Analysis; Programmed Cell Death 1 Receptor; Progression-Free Survival; Randomized Controlled Trials as Topic; Time Factors
PubMed: 34484242
DOI: 10.3389/fimmu.2021.731546 -
American Journal of Hematology Jul 2022Bruton tyrosine kinase inhibitors (BTKi) are important treatment options in Waldenström's macroglobulinemia (WM). Whether second-generation BTKi are associated with... (Meta-Analysis)
Meta-Analysis
Bruton tyrosine kinase inhibitors (BTKi) are important treatment options in Waldenström's macroglobulinemia (WM). Whether second-generation BTKi are associated with improved outcomes and/or better safety profile remains unclear. We did a systematic review and meta-analysis of clinical trials that reported data on the outcomes of patients with WM who received either first- or second-generation BTKi in the period between January 2010 and August 2021. Studies with twenty or fewer patients were excluded. The primary outcomes were efficacy measured by response and survival data. Eleven studies met the eligibility criteria and were included in the final analysis (n = 730 patients). A total of 298 patients received 1st-generation BTKi and 432 received a 2nd-generation BTKi. Pooled overall response rate (ORR) and major response rate (MRR) for both generations were similar (94.2% and 78.5% in 1st vs. 88.9% and 75.1% in 2nd, respectively). MRR for both generations was higher in MYD88 Mut/CXCR4 WT patients compared to MYD88 Mut/CXCR4 Mut patients (odds ratio [OR]: 3.9, 95% CI: 2.2 to 5.5). Pooled 18-mo progression-free survival (PFS) was similar for both generations (88.5% vs. 87.3%). Grade 3/4 atrial fibrillation was higher in 1st-generation BTKi (3.1% vs. 0.4%); however, grade-3/-4 infections and neutropenia were more frequent in 2nd-generarion BTKi (20.9% vs. 13.2%, 17.7% vs. 12%, respectively). The efficacy of 1st- and 2nd-generation BTKis is comparable. The 1st-generation BTKi were associated with a higher risk of atrial fibrillation, whereas infections and neutropenia occurred more frequently in 2nd-generation BTKi.
Topics: Atrial Fibrillation; Humans; Lymphoma, B-Cell; Mutation; Myeloid Differentiation Factor 88; Neutropenia; Protein Kinase Inhibitors; Pyrimidines; Waldenstrom Macroglobulinemia
PubMed: 35358350
DOI: 10.1002/ajh.26552 -
Respiratory Care May 2020Radiotherapy for breast cancer has been implicated in the development of bronchiolitis obliterans organizing pneumonia (BOOP). Patients may be asymptomatic or may have...
BACKGROUND
Radiotherapy for breast cancer has been implicated in the development of bronchiolitis obliterans organizing pneumonia (BOOP). Patients may be asymptomatic or may have pulmonary and constitutional symptoms that are moderate or severe. Postradiotherapy BOOP usually develops during the 12 months after completion of radiotherapy and is characterized by ground-glass opacities in the radiation-exposed lung and frequently in the non-irradiated lung.
METHODS
An updated literature search and review was performed to update the systematic review we conducted in 2014. Ten new publications were identified: 2 Japanese epidemiological studies, 1 Japanese case series study, 6 case reports, and 1 review article.
RESULTS
The incidence of postradiotherapy BOOP was 1.4% in both Japanese epidemiological studies. Risk factors included increasing age, cigarette smoking, and increasing central lung distance. The case reports included 7 women who had breast cancer postradiation BOOP and 1 woman who had an ataxia telangiectasia mutated () gene mutation, which may increase radiation sensitivity.
CONCLUSION
Postradiotherapy BOOP in women with breast cancer occurs at a rate of 1.0-3.0% and may occur in women with immune system dysfunction and genetic mutations.
Topics: Aged; Breast Neoplasms; Cryptogenic Organizing Pneumonia; Female; Humans; Incidence; Middle Aged; Radiation Pneumonitis
PubMed: 31892515
DOI: 10.4187/respcare.07150