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Oncotarget Nov 2016Estimate the epidermal growth factor receptor (EGFR) mutation prevalence in all non-small cell lung cancer (NSCLC) patients and patient subgroups. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Estimate the epidermal growth factor receptor (EGFR) mutation prevalence in all non-small cell lung cancer (NSCLC) patients and patient subgroups.
RESULTS
A total of 456 studies were included, reporting 30,466 patients with EGFR mutation among 115,815 NSCLC patients. The overall pooled prevalence for EGFR mutations was 32.3% (95% CI 30.9% to 33.7%), ranging from 38.4% (95% CI: 36.5% to 40.3%) in China to 14.1% (95% CI: 12.7% to 15.5%) in Europe. The pooled prevalence of EGFR mutation was higher in females (females vs. males: 43.7% vs. 24.0%; OR: 2.7, 95% CI: 2.5 to 2.9), non-smokers (non-smokers vs. past or current smokers: 49.3% vs. 21.5%; OR: 3.7, 95% CI: 3.4 to 4.0), and patients with adenocarcinoma (adenocarcinoma vs. non-adenocarcinoma: 38.0% vs. 11.7%; OR: 4.1, 95% CI: 3.6 to 4.8).
MATERIALS AND METHODS
PubMed, EMBASE, and the Cochrane Library were searched to June 2013. Eligible studies reported EGFR mutation prevalence and the association with at least one of the following factors: gender, smoking status and histology. Random-effects models were used to pool EGFR mutation prevalence data.
CONCLUSION
This study provides the exact prevalence of EGFR mutations in different countries and NSCLC patient subgroups.
Topics: Asian People; Carcinoma, Non-Small-Cell Lung; China; ErbB Receptors; Europe; Female; Genetic Predisposition to Disease; Humans; Lung Neoplasms; Male; Mutation; Mutation Rate; Prevalence; Risk Factors; Smoking; White People
PubMed: 27738317
DOI: 10.18632/oncotarget.12587 -
Current Oncology (Toronto, Ont.) Jan 2022Compound epidermal growth factor receptor () mutations represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) patients with uncommon mutations. We... (Review)
Review
Compound epidermal growth factor receptor () mutations represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) patients with uncommon mutations. We conducted a systematic review to investigate the available data on this patients' subgroup. Overall, we found a high heterogeneity in the incidence of compound mutations (4-26% of total mutant cases), which is dependent on the different testing methods adopted and the specific mutations considered. In addition, the relative incidence of distinct compound subclasses identified is reported with extreme variability in different studies. Preclinical and clinical data, excluding exon 20 p.T790M compound mutations, show good responses with EGFR tyrosine kinase inhibitors (TKIs) (combined common mutations: response rate (RR) ≥ 75% with either first- or second-generation TKIs; combined common plus uncommon: RR 40-80% and 100% with first-generation TKIs and afatinib, respectively; combined uncommon: RR 20-70%, ~80% and ~75% with first-generation TKIs, afatinib and osimertinib, respectively). Overall, data are consistent in supporting the use of EGFR TKIs in treating compound mutations, taking into account different sensitivity profile of accompanying mutations for selecting the most adequate EGFR TKI for individual patients.
Topics: Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Protein Kinase Inhibitors
PubMed: 35049698
DOI: 10.3390/curroncol29010024 -
Journal of Hematology & Oncology Mar 2023TP53 mutations, which are present in 5% to 10% of patients with acute myeloid leukemia (AML), are associated with treatment resistance and poor outcomes. First-line... (Meta-Analysis)
Meta-Analysis
BACKGROUND
TP53 mutations, which are present in 5% to 10% of patients with acute myeloid leukemia (AML), are associated with treatment resistance and poor outcomes. First-line therapies for TP53-mutated (TP53m) AML consist of intensive chemotherapy (IC), hypomethylating agents (HMA), or venetoclax combined with HMA (VEN + HMA).
METHODS
We conducted a systematic review and meta-analysis to describe and compare treatment outcomes in newly diagnosed treatment-naïve patients with TP53m AML. Randomized controlled trials, single-arm trials, prospective observational studies, and retrospective studies were included that reported on complete remission (CR), CR with incomplete hematologic recovery (CRi), overall survival (OS), event-free survival (EFS), duration of response (DoR), and overall response rate (ORR) among patients with TP53m AML receiving first-line treatment with IC, HMA, or VEN + HMA.
RESULTS
Searches of EMBASE and MEDLINE identified 3006 abstracts, and 17 publications describing 12 studies met the inclusion criteria. Random-effects models were used to pool response rates, and time-related outcomes were analyzed with the median of medians method. IC was associated with the greatest CR rate of 43%, and CR rates were 33% for VEN + HMA and 13% for HMA. Rates of CR/CRi were comparable for IC (46%) and VEN + HMA (49%) but were lower for HMA (13%). Median OS was uniformly poor across treatments: IC, 6.5 months; VEN + HMA, 6.2 months; and HMA, 6.1 months. For IC, the EFS estimate was 3.7 months; EFS was not reported for VEN + HMA or HMA. The ORR was 41% for IC, 65% for VEN + HMA, and 47% for HMA. DoR was 3.5 months for IC, 5.0 months for VEN + HMA, and was not reported for HMA.
CONCLUSIONS
Despite improved responses seen with IC and VEN + HMA compared to HMA, survival was uniformly poor, and clinical benefits were limited across all treatments for patients with newly diagnosed, treatment-naïve TP53m AML, demonstrating a significant need for improved treatment for this difficult-to-treat population.
Topics: Humans; Retrospective Studies; Treatment Outcome; Leukemia, Myeloid, Acute; Progression-Free Survival; Mutation; Tumor Suppressor Protein p53; Observational Studies as Topic
PubMed: 36879351
DOI: 10.1186/s13045-023-01417-5 -
Acta Obstetricia Et Gynecologica... Oct 2021Ovarian granulosa cell tumor (GCT) is a rare, low-grade malignant tumor that accounts for 70% of the sex cord-stromal tumors. It has two histopathologic types with...
Ovarian granulosa cell tumor (GCT) is a rare, low-grade malignant tumor that accounts for 70% of the sex cord-stromal tumors. It has two histopathologic types with different clinical and biologic features: adult GCT and juvenile GCT. Most women diagnosed with the adult GCT have a favorable prognosis, with a 5-year survival rate of 97%-98%, but adult GCT has a feature of late relapse; the recurrence time could be more than 20 years after diagnosis. Juvenile GCT has a survival rate of 97% in stage I and a 5-year survival rate of 0%-22% in advanced stage with earlier recurrence than adult GCT. Consequently, the scenario emphasizes the need for early diagnosis, standardized treatment protocols, and long-term follow up. However, there is a lack of consensus regarding accurate diagnosis of GCT and adjuvant treatment. Furthermore, GCT tends to occur in young women, which emphasizes the viability of fertility-sparing surgery. The current review performed a systematic literature review of 60 articles to summarize the latest advances in GCT, with an emphasis on the molecular pathogenesis and survival after fertility-sparing surgery. We found that young women with fertility-sparing surgery had a desirable reproductive and survival outcome compared with those undergoing radical surgery.
Topics: Female; Fertility Preservation; Granulosa Cell Tumor; Humans; Neoplasm Recurrence, Local; Ovarian Neoplasms; Survival Analysis
PubMed: 34027996
DOI: 10.1111/aogs.14189 -
Clinical Lung Cancer Sep 2023MET exon 14 (METex14) skipping is a rare oncogenic driver in non-small-cell lung cancer (NSCLC) for which targeted therapy with MET tyrosine kinase inhibitors (TKIs) was... (Review)
Review
INTRODUCTION
MET exon 14 (METex14) skipping is a rare oncogenic driver in non-small-cell lung cancer (NSCLC) for which targeted therapy with MET tyrosine kinase inhibitors (TKIs) was recently approved. Given the heterogeneity in published data of METex14 skipping NSCLC, we conducted a systematic literature review to evaluate its frequency, patient characteristics, and outcomes.
METHODS
On June 13, 2022 we conducted a systematic literature review of publications and conference abstracts reporting frequency, patient characteristics, or outcomes of patients with METex14 skipping NSCLC.
RESULTS
We included 139 studies reporting frequency or patient characteristics (350,997 patients), and 39 studies reporting clinical outcomes (3989 patients). Median METex14 skipping frequency was 2.0% in unselected patients with NSCLC, with minimal geographic variation. Median frequency was 2.4% in adenocarcinoma or nonsquamous subgroups, 12.0% in sarcomatoid, and 1.3% in squamous histology. Patients with METex14 skipping NSCLC were more likely to be elderly, have adenocarcinoma histology; there was no marked sex or smoking status distribution. In first line of treatment, median objective response rate ranged from 50.7% to 68.8% with targeted therapies (both values correspond to MET TKIs), was 33.3% with immunotherapy, and ranged from 23.1% to 27.0% with chemotherapy.
CONCLUSIONS
Patients with METex14 skipping are more likely to have certain characteristics, but no patient subgroup can be ruled out; thus, it is crucial to test all patients with NSCLC to identify suitable candidates for MET inhibitor therapy. MET TKIs appeared to result in higher efficacy outcomes, although no direct comparison with chemotherapy or immunotherapy regimens was found.
Topics: Aged; Humans; Adenocarcinoma; Carcinoma, Non-Small-Cell Lung; Exons; Lung Neoplasms; Mutation; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-met
PubMed: 37451931
DOI: 10.1016/j.cllc.2023.06.008 -
Cancer Apr 2023This study compares the safety and efficacy of first-line treatments for anaplastic lymphoma kinase (ALK)-mutated non-small cell lung cancer (NSCLC). (Meta-Analysis)
Meta-Analysis
Efficacy and safety of first-line treatments for patients with advanced anaplastic lymphoma kinase mutated, non-small cell cancer: A systematic review and network meta-analysis.
BACKGROUND
This study compares the safety and efficacy of first-line treatments for anaplastic lymphoma kinase (ALK)-mutated non-small cell lung cancer (NSCLC).
METHODS
A comprehensive literature search was conducted in PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases. Abstracts related to lung cancer presented at important international conferences were also reviewed. Randomized clinical trials that qualified the inclusion criteria were subjected to Bayesian network meta-analysis and systematically reviewed.
RESULTS
The authors included a total of nine studies including 2441 patients and seven first-line treatments (ensartinib, brigatinib, crizotinib, lorlatinib, alectinib, ceritinib, and pemetrexed-based chemotherapy). Overall, lorlatinib appeared to confer the best progression-free survival (PFS) (probability of being the best [Prbest], 90%; surface under the cumulative ranking curve [SUCRA], 98%), and the same conclusion was obtained on paired comparisons (lorlatinib vs. ceritinib [hazard ratio (HR), 0.31; 95% confidence interval (CI), 0.20-0.47); lorlatinib vs. chemotherapy [HR, 0.17; 95% CI, 0.12-0.23]; crizotinib vs. lorlatinib [HR, 3.6; 95% CI, 2.4-5.2]; and brigatinib vs. lorlatinib [HR, 1.7; 95% CI, 1.0-2.8]). Alectinib conferred the best overall survival (OS) and safety profile. In the Asian population, ensartinib conferred the best PFS (Prbest 50%, SUCRA 87%), and for patients with brain metastases at baseline, lorlatinib showed the best PFS (Prbest 70%, SUCRA 93%).
CONCLUSIONS
For first-line treatment of patients with ALK-positive NSCLC, lorlatinib was associated with the best PFS and objective response rate, but poorer safety profile, whereas alectinib demonstrated the best OS and safety profile. In Asians, ensartinib conferred the best PFS benefit, and in the brain baseline metastasis population, lorlatinib conferred the best PFS benefit.
PLAIN LANGUAGE SUMMARY
Among the many molecularly targeted drugs currently used to treat anaplastic lymphoma kinase mutation-positive non-small cell lung cancer, lorlatinib may be one of the most effective targeted drugs. Lung cancer has long been at the top of cancer rankings in terms of incidence and mortality. Today, the treatment of lung cancer has moved into the era of precision therapy. In this article, we use a statistical approach to compare the efficacy and safety of targeted drugs that have been used in the first-line treatment of anaplastic lymphoma kinase mutations to improve the reference for clinicians to make treatment decisions in the real world.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Crizotinib; Anaplastic Lymphoma Kinase; Network Meta-Analysis; Bayes Theorem; Lactams, Macrocyclic; Protein Kinase Inhibitors
PubMed: 36748799
DOI: 10.1002/cncr.34664 -
Journal of Oral Pathology & Medicine :... Sep 2023The objective of this systematic review with meta-analysis was to critically evaluate the available data on the association of the BRAF V600E mutation and recurrence... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The objective of this systematic review with meta-analysis was to critically evaluate the available data on the association of the BRAF V600E mutation and recurrence rate of ameloblastomas.
MATERIALS AND METHODS
This systematic review was registered in Prospero (CRD42020183645) and performed based on the PRISMA statement. A comprehensive search in PubMed, Web of Science, Scopus and Cochrane Library databases was performed in order to answer the question "Does BRAF V600E mutation affect recurrence rate of ameloblastomas?" Methodological quality and risk of bias of the selected studies were assessed with JBI Critical Appraise Tool. Meta-analysis of quantitative data was conducted with RevMan 5.3 and Jamovi 2.3.
RESULTS
The initial search identified 302 articles, and 21 met the inclusion criteria. A total of 855 subjects with ameloblastoma were included in the analysis. The pooled measures for frequency of BRAF V600E mutation was 65.30% (95% CI: 0.56-0.75; p < .001; I = 90.85%; τ = 0.205; p < .001), and the pooled recurrence rate was 25.30% (95% CI: 0.19-0.31; p < .001; I = 79.44%; τ = 0.118; p < .001). No differences in recurrence rate were observed between the BRAF V600E and wild type BRAF ameloblastomas, with a pooled Odds Ratio of 0.93 (95% CI: 0.56-1.54; p = .78; I = 31%; p = .09).
CONCLUSIONS
BRAF V600E mutation is a frequent event in ameloblastomas, but does not increase nor reduce its recurrence rate, and thus have a limited value in predicting its prognosis.
Topics: Humans; Ameloblastoma; Proto-Oncogene Proteins B-raf; Mutation; Prognosis
PubMed: 37364158
DOI: 10.1111/jop.13458 -
Oral Surgery, Oral Medicine, Oral... Sep 2022This systematic review aimed to identify the molecular alterations of head and neck rhabdomyosarcomas (HNRMS) and their prognostic values. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This systematic review aimed to identify the molecular alterations of head and neck rhabdomyosarcomas (HNRMS) and their prognostic values.
STUDY DESIGN
An electronic search was performed using PubMed, Embase, Scopus, and Web of Science with a designed search strategy. Inclusion criteria comprised cases of primary HNRMS with an established histopathological diagnosis and molecular analysis. Forty-nine studies were included and were appraised for methodological quality using the Joanna Briggs Institute Critical Appraisal tools. Five studies were selected for meta-analysis.
RESULTS
HNRMS predominantly affects pediatric patients (44.4%), and the parameningeal region (57.7%) is the most common location. The alveolar variant (43.2%) predominates over the embryonal and spindle cell/sclerosing types, followed by the epithelioid and pleomorphic variants. PAX-FOXO1 fusion was observed in 103 cases of alveolar RMS (79.8%). MYOD1 mutation was found in 39 cases of sclerosing/spindle cell RMS (53.4%). FUS/EWSR1-TFCP2 gene fusions were identified in 21 cases of RMS with epithelioid and spindle cell morphologies (95.5%). The 5-year overall survival rate of patients was 61.3%, and MYOD1 mutation correlated with significantly higher mortality.
CONCLUSION
The genotypic profile of histologic variants of HNRMS is widely variable, and MYOD1 mutation could be a potential prognostic factor, but more studies are required to establish this.
Topics: Child; DNA-Binding Proteins; Humans; Mutation; Rhabdomyosarcoma; Transcription Factors
PubMed: 35840496
DOI: 10.1016/j.oooo.2021.12.128 -
International Journal of Surgery... Apr 2023Colorectal cancer (CRC) is the second most common cause of cancer-related death (9.4% of the 9.9 million cancer deaths). However, CRC develops slowly, and early...
BACKGROUND
Colorectal cancer (CRC) is the second most common cause of cancer-related death (9.4% of the 9.9 million cancer deaths). However, CRC develops slowly, and early detection and intervention can effectively improve the survival rate and quality of life. Although colonoscopy can detect and diagnose CRC, it is unsuitable for CRC screening in average-risk populations. Some commercial kits based on DNA mutation or methylation are approved for screening, but the low sensitivity for advanced adenoma or early-stage CRC would limit the applications.
MAIN RESULTS
Recently, researchers have focused on developing noninvasive or minimally invasive, easily accessible biomarkers with higher sensitivity and accuracy for CRC screening. Numerous reports describe advances in biomarkers, including DNA mutations and methylation, mRNA and miRNA, gut microbes, and metabolites, as well as low-throughput multiomics panels. In small cohorts, the specificity and sensitivity improved when fecal immunochemical testing combined with other biomarkers; further verification in large cohorts is expected. In addition, the continuous improvement of laboratory technology has also improved the sensitivity of detection technology, such as PCR, and the application of CRISPR/Cas technology. Besides, artificial intelligence has extensively promoted the mining of biomarkers. Machine learning was performed to construct a diagnosis model for CRC screening based on the cfDNA fragment features from whole-genome sequencing data. In another study, multiomics markers, including cfDNA, epigenetic, and protein signals, were also discovered by machine learning. Finally, advancements in sensor technology promote the applicability of volatile organic compounds in CRC early detection.
CONCLUSION
Here, the authors review advances in early detection and screening of CRC based on different biomarker types. Most studies reported optimistic findings based on preliminary research, and prospective clinical studies are ongoing. These promising biomarkers are expected to more accurately identify early-stage patients with CRC and be applied in the future.
Topics: Humans; Prospective Studies; Artificial Intelligence; Quality of Life; Biomarkers, Tumor; Early Detection of Cancer; DNA; Cell-Free Nucleic Acids; Colorectal Neoplasms
PubMed: 36974713
DOI: 10.1097/JS9.0000000000000260 -
JCO Precision Oncology Aug 2022Non-V600 mutations comprise approximately 35% of all BRAF mutations in cancer. Many of these mutations have been identified as oncogenic drivers and can be classified... (Meta-Analysis)
Meta-Analysis
PURPOSE
Non-V600 mutations comprise approximately 35% of all BRAF mutations in cancer. Many of these mutations have been identified as oncogenic drivers and can be classified into three classes according to molecular characteristics. Consensus treatment strategies for class 2 and 3 BRAF mutations have not yet been established.
METHODS
We performed a systematic review and meta-analysis with published reports of individual patients with cancer harboring class 2 or 3 BRAF mutations from 2010 to 2021, to assess treatment outcomes with US Food and Drug Administration-approved mitogen-activated protein kinase (MAPK) pathway targeted therapy (MAPK TT) according to BRAF class, cancer type, and MAPK TT type. Coprimary outcomes were response rate and progression-free survival.
RESULTS
A total of 18,167 studies were screened, identifying 80 studies with 238 patients who met inclusion criteria. This included 167 patients with class 2 and 71 patients with class 3 BRAF mutations. Overall, 77 patients achieved a treatment response. In both univariate and multivariable analyses, response rate and progression-free survival were higher among patients with class 2 compared with class 3 mutations, findings that remain when analyses are restricted to patients with melanoma or lung primary cancers. MEK ± BRAF inhibitors demonstrated greater clinical activity in class 2 compared with class 3 BRAF-mutant tumors than BRAF or EGFR inhibitors.
CONCLUSION
This meta-analysis suggests that MAPK TTs have clinical activity in some class 2 and 3 BRAF-mutant cancers. BRAF class may dictate responsiveness to current and emerging treatment strategies, particularly in melanoma and lung cancers. Together, this analysis provides clinical validation of predictions made on the basis of a mutation classification system established in the preclinical literature. Further evaluation with prospective clinical trials is needed for this population.
Topics: Humans; Lung Neoplasms; Melanoma; Mitogen-Activated Protein Kinases; Prospective Studies; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; United States
PubMed: 35977349
DOI: 10.1200/PO.22.00107