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Clinical Epigenetics Jul 2023To systematically evaluate the efficacy and safety of FDA-approved isocitrate dehydrogenase (IDH) inhibitors in the treatment of IDH-mutated acute myeloid leukemia (AML). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To systematically evaluate the efficacy and safety of FDA-approved isocitrate dehydrogenase (IDH) inhibitors in the treatment of IDH-mutated acute myeloid leukemia (AML).
METHODS
We used R software to conduct a meta-analysis of prospective clinical trials of IDH inhibitors in the treatment of IDH-mutated AML published in PubMed, Embase, Clinical Trials, Cochrane Library and Web of Science from inception to November 15th, 2022.
RESULTS
A total of 1109 IDH-mutated AML patients from 10 articles (11 cohorts) were included in our meta-analysis. The CR rate, ORR rate, 2-year survival (OS) rate and 2-year event-free survival (EFS) rate of newly diagnosed IDH-mutated AML (715 patients) were 47%, 65%, 45% and 29%, respectively. The CR rate, ORR rate, 2-year OS rate, median OS and median EFS of relapsed or refractory (R/R) IDH-mutated AML (394 patients) were 21%, 40%, 15%, 8.21 months and 4.73 months, respectively. Gastrointestinal adverse events were the most frequently occurring all-grade adverse events and hematologic adverse events were the most frequently occurring ≥ grade 3 adverse events.
CONCLUSION
IDH inhibitor is a promising treatment for R/R AML patients with IDH mutations. For patients with newly diagnosed IDH-mutated AML, IDH inhibitors may not be optimal therapeutic agents due to low CR rates. The safety of IDH inhibitors is controllable, but physicians should always pay attention to and manage the differentiation syndrome adverse events caused by IDH inhibitors. The above conclusions need more large samples and high-quality RCTs in the future to verify.
Topics: Humans; Prospective Studies; DNA Methylation; Leukemia, Myeloid, Acute; Enzyme Inhibitors; Mutation
PubMed: 37434249
DOI: 10.1186/s13148-023-01529-2 -
The Journal of Dermatological Treatment May 2018Although BRAF inhibitors have been used to treat advanced melanoma with BRAF mutation, combination strategies are suggested due to acquired resistance to BRAF inhibitors. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although BRAF inhibitors have been used to treat advanced melanoma with BRAF mutation, combination strategies are suggested due to acquired resistance to BRAF inhibitors.
OBJECTIVE
To assess the efficacy of BRAF inhibitor-based combination therapy for the treatment of advanced melanoma with BRAF mutation.
METHODS
We conducted a systematic review and meta-analysis of studies that compared BRAF inhibitor-based combination therapy with BRAF inhibitor monotherapy. We searched MEDLINE, EMBASE, the Cochrane Library and relevant conference proceedings. The random-effects inverse variance and Mantel-Haenszel methods were used to pool the results.
RESULTS
Four randomized controlled trials and one cohort study were identified. A combination therapy with BRAF inhibitors and MEK inhibitors was used in all studies. The combined hazard ratios of overall survival (OS) and progression-free survival (PFS) comparing combination therapy with monotherapy were 0.70 [95% confidence interval (CI) 0.62-0.78] and 0.59 (95% CI 0.55-0.63), respectively. The combined risk ratio of objective response rate (ORR) was 1.30 (95% CI 1.20-1.40), which meant more patients achieved complete/partial responses in combination therapy group than those in the monotherapy group.
CONCLUSIONS
Combination therapy with BRAF inhibitors and MEK inhibitors significantly improved OS, PFS, and ORR in patients with advanced melanoma with BRAF mutation.
Topics: Databases, Factual; Disease-Free Survival; Drug Therapy, Combination; Humans; MAP Kinase Kinase Kinases; Melanoma; Polymorphism, Single Nucleotide; Protein Kinase Inhibitors; Proto-Oncogene Mas; Proto-Oncogene Proteins B-raf; Survival Rate
PubMed: 28504036
DOI: 10.1080/09546634.2017.1330530 -
Health Technology Assessment... Oct 2014Bowel cancer is the third most common cancer in the UK. Most bowel cancers are initially treated with surgery, but around 17% spread to the liver. When this happens,... (Review)
Review
BACKGROUND
Bowel cancer is the third most common cancer in the UK. Most bowel cancers are initially treated with surgery, but around 17% spread to the liver. When this happens, sometimes the liver tumour can be treated surgically, or chemotherapy may be used to shrink the tumour to make surgery possible. Kirsten rat sarcoma viral oncogene (KRAS) mutations make some tumours less responsive to treatment with biological therapies such as cetuximab. There are a variety of tests available to detect these mutations. These vary in the specific mutations that they detect, the amount of mutation they detect, the amount of tumour cells needed, the time to give a result, the error rate and cost.
OBJECTIVES
To compare the performance and cost-effectiveness of KRAS mutation tests in differentiating adults with metastatic colorectal cancer whose metastases are confined to the liver and are unresectable and who may benefit from first-line treatment with cetuximab in combination with standard chemotherapy from those who should receive standard chemotherapy alone.
DATA SOURCES
Thirteen databases, including MEDLINE and EMBASE, research registers and conference proceedings were searched to January 2013. Additional data were obtained from an online survey of laboratories participating in the UK National External Quality Assurance Scheme pilot for KRAS mutation testing.
METHODS
A systematic review of the evidence was carried out using standard methods. Randomised controlled trials were assessed for quality using the Cochrane risk of bias tool. Diagnostic accuracy studies were assessed using the QUADAS-2 tool. There were insufficient data for meta-analysis. For accuracy studies we calculated sensitivity and specificity together with 95% confidence intervals (CIs). Survival data were summarised as hazard ratios and tumour response data were summarised as relative risks, with 95% CIs. The health economic analysis considered the long-term costs and quality-adjusted life-years associated with different tests followed by treatment with standard chemotherapy or cetuximab plus standard chemotherapy. The analysis took a 'no comparator' approach, which implies that the cost-effectiveness of each strategy will be presented only compared with the next most cost-effective strategy. The de novo model consisted of a decision tree and Markov model.
RESULTS
The online survey indicated no differences between tests in batch size, turnaround time, number of failed samples or cost. The literature searches identified 7903 references, of which seven publications of five studies were included in the review. Two studies provided data on the accuracy of KRAS mutation testing for predicting response to treatment in patients treated with cetuximab plus standard chemotherapy. Four RCTs provided data on the clinical effectiveness of cetuximab plus standard chemotherapy compared with that of standard chemotherapy in patients with KRAS wild-type tumours. There were no clear differences in the treatment effects reported by different studies, regardless of which KRAS mutation test was used to select patients. In the 'linked evidence' analysis the Therascreen KRAS RGQ PCR Kit (QIAGEN) was more expensive but also more effective than pyrosequencing or direct sequencing, with an incremental cost-effectiveness ratio of £17,019 per quality-adjusted life-year gained. In the 'assumption of equal prognostic value' analysis the total costs associated with the various testing strategies were similar.
LIMITATIONS
The results assume that the differences in outcomes between the trials were solely the result of the different mutation tests used to distinguish between patients; this assumption ignores other factors that might explain this variation.
CONCLUSIONS
There was no strong evidence that any one KRAS mutation test was more effective or cost-effective than any other test.
STUDY REGISTRATION
PROSPERO CRD42013003663.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Colorectal Neoplasms; Cost-Benefit Analysis; Genetic Techniques; Humans; Liver Neoplasms; Markov Chains; Mutation; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; ras Proteins
PubMed: 25314637
DOI: 10.3310/hta18620 -
European Journal of Surgical Oncology :... Jan 2020To evaluate the benefit of risk-reducing salpingo-oophorectomy (RRSO) by estimating the pathological positive rate of occult lesions, including serous tubal... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the benefit of risk-reducing salpingo-oophorectomy (RRSO) by estimating the pathological positive rate of occult lesions, including serous tubal intraepithelial carcinoma (STIC) and occult cancers (OCCs).
METHODS
BRCA1/2 mutation carriers who underwent RRSO in a Chinese study center between 2014 and 2018 were included. A literature review was performed, followed by a meta-analysis of the literature to further validate the findings.
RESULTS
Twenty-four BRCA1/2 mutation carriers who underwent RRSO were identified; one patient (4.2%) had STIC, and one patient (4.2%) had occult fallopian tube cancer complicated by STIC. Thirty-four articles were ultimately included in the meta-analysis. Of the reported cases of OCC, 61.3% occurred in the fallopian tubes and 32.3% in the ovaries, and 81.5% were in the early stages. The estimated rate of overall pathological positive events was 5%. The estimated rates of overall STIC events and OCC were 1% and 3%, respectively. The rates of STIC and OCC were 1% and 3%, respectively, for BRCA1 mutation carriers and 1% and 1%, respectively, for BRCA2 mutation carriers. No significant difference was observed between the results of a routine examination of pathological sections and those of the Sectioning and Extensively Examining the Fimbriae (SEE-FIM) protocol.
CONCLUSIONS
This study is the first report of RRSO results in China. In this systematic review, the positive rates of STIC or OCC after RRSO were no more than 3%, which are 200-fold higher than the risk of the general population. The use of a strict SEE-FIM protocol would likely increase positive results.
Topics: Cystadenocarcinoma, Serous; Fallopian Tube Neoplasms; Fallopian Tubes; Female; Genes, BRCA1; Genes, BRCA2; Genetic Predisposition to Disease; Humans; Mutation; Neoplasm Staging; Ovarian Neoplasms; Ovary; Salpingo-oophorectomy
PubMed: 31521389
DOI: 10.1016/j.ejso.2019.09.002 -
International Journal of Molecular... Nov 2023Studying primary melanoma and its corresponding metastasis has twofold benefits. Firstly, to better understand tumor biology, and secondly, to determine which sample... (Meta-Analysis)
Meta-Analysis Review
Studying primary melanoma and its corresponding metastasis has twofold benefits. Firstly, to better understand tumor biology, and secondly, to determine which sample should be examined in assessing drug targets. This study systematically analyzed all the literature on primary melanoma and its matched metastasis. Following PRISMA guidelines, we searched multiple medical databases for relevant publications from January 2000 to December 2022, assessed the quality of the primary-level studies using the QUIPS tool, and summarized the concordance rate of the most reported genes using the random-effects model. Finally, we evaluated the inter-study heterogeneity using the subgroup analysis. Thirty-one studies investigated the concordance of and in 1220 and 629 patients, respectively. The pooled concordance rate was 89.4% [95% CI: 84.5; 93.5] for and 97.8% [95% CI: 95.8; 99.4] for . When high-quality studies were considered, only mutation status consistency increased. Five studies reported the concordance status of c (93%, 44 patients) and promoter (64%, 53 patients). Lastly, three studies analyzed the concordance of cancer genes involved in the signaling pathways, apoptosis, and proliferation, such as (25%, four patients), (44%, nine patients), and (20%, five patients). Our study found that the concordance of known drug targets (mainly ) during melanoma progression is higher than in previous meta-analyses, likely due to advances in molecular techniques. Furthermore, significant heterogeneity exists in the genes involved in the melanoma genetic makeup; although our results are based on small patient samples, more research is necessary for validation.
Topics: Humans; Melanoma; Skin Neoplasms; Proto-Oncogene Proteins B-raf; Mutation; Melanoma, Cutaneous Malignant
PubMed: 38003476
DOI: 10.3390/ijms242216281 -
Human Pathology Jul 2016Medullary carcinoma (MC) is a very rare variant of colorectal carcinoma (CRC). Its clinicopathologic findings are not fully elucidated. The aim of this study was to... (Meta-Analysis)
Meta-Analysis Review
Medullary carcinoma (MC) is a very rare variant of colorectal carcinoma (CRC). Its clinicopathologic findings are not fully elucidated. The aim of this study was to investigate the clinicopathological characteristics of MC in the colorectum through a systematic review and meta-analysis. The meta-analysis examined the incidence, age, sex, site, mismatch repair deficiency (MMRd), MMR protein expression, ARID1A expression, BRAF(V600E) mutation, KRAS mutation, and survival rate of MC. The 21469 CRCs included 462 MCs in 16 eligible studies, representing an estimated incidence of MC of 0.027 (95% confidence interval [CI] 26 0.016-0.045). MC frequently occurred in female patients and in the right colon. Lymph node metastasis of MC was significantly lower than that of poorly differentiated adenocarcinoma/undifferentiated adenocarcinoma (PDA/UDA). In addition, MC had a higher MMRd rate (0.892, 95% CI 0.758-0.956), higher BRAF(V600E) mutation rate (0.652, 95% CI 0.143-0.954) and lower KRAS mutation rate (0.171, 95% CI 0.065-0.378) than PDA/UDA and conventional adenocarcinoma. Patients with MC had significantly better overall survival rate compared to patients with PDA/UDA (hazard ratio 0.441, 95% CI 0.262-0.742). However, there was no significant difference of overall survival rate between MC and conventional adenocarcinoma patients. MC predominantly occurred in females and in the right colon, and had different molecular characteristics and behaviors compared to PDA/UDA and conventional adenocarcinoma.
Topics: Adenocarcinoma; Age Distribution; Biomarkers, Tumor; Carcinoma, Medullary; Cell Differentiation; Colorectal Neoplasms; Female; Genetic Predisposition to Disease; Humans; Incidence; Lymphatic Metastasis; Male; Phenotype; Risk Factors; Sex Distribution; Survival Analysis; Time Factors
PubMed: 27001432
DOI: 10.1016/j.humpath.2016.02.018 -
Cancer Feb 2013The authors conducted a systematic review and meta-analysis to examine whether patients who had metastatic colorectal cancer (mCRC) with the v-Ki-ras2 Kirsten rat... (Meta-Analysis)
Meta-Analysis Review
KRAS p.G13D mutation and codon 12 mutations are not created equal in predicting clinical outcomes of cetuximab in metastatic colorectal cancer: a systematic review and meta-analysis.
BACKGROUND
The authors conducted a systematic review and meta-analysis to examine whether patients who had metastatic colorectal cancer (mCRC) with the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G13D mutation (an amino acid substitution at position 13 in KRAS from a glycine to an aspartic acid) and received cetuximab treatment had better clinical outcomes than patients who had mCRC tumors with KRAS codon 12 mutations.
METHODS
Relevant studies were identified by a search of MEDLINE, EMBASE, the Chinese Biomedical Database, and Wan Fang Digital Journals from inception to October 2011. The primary clinical outcomes included the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The pooled relative risk (RR) or hazard ratio (HR) was estimated by using fixed-effects or random-effects models according to heterogeneity between studies.
RESULTS
Ten studies were considered eligible that included 1487 patients with mCRC. Patients who had tumors with the KRAS p.G13D mutation had a significantly higher ORR (10 studies; RR, 1.642; 95% confidence interval [CI], 1.131-2.384), longer PFS (1 study; HR, 0.54; 95% CI, 0.36-0.81), and longer OS (1 study; HR, 0.52; 95% CI, 0.33-0.80) than patients who had tumors with KRAS codon 12 mutations. Compared with patients who had KRAS wild-type tumors, patients with the p.G13D mutation had a significantly lower ORR (9 studies; RR, 0.540; 95% CI, 0.381-0.765) and nonsignificantly shorter PFS (1 study; HR, 0.99; 95% CI, 0.68-1.45) and OS (1 study; HR, 1.01; 95% CI, 0.66-1.54).
CONCLUSIONS
Patients who had mCRC with the KRAS p.G13D mutation appeared to benefit more from cetuximab than patients who had tumors with KRAS codon 12 mutations. However, because of the limited sample sizes in the current meta-analysis, these results should be interpreted with caution.
Topics: Adult; Aged; Aged, 80 and over; Amino Acid Substitution; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Aspartic Acid; Cetuximab; Codon; Colorectal Neoplasms; Disease-Free Survival; Female; Glycine; Humans; Male; Middle Aged; Mutation; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); Treatment Outcome; ras Proteins
PubMed: 22972628
DOI: 10.1002/cncr.27804 -
International Immunopharmacology Nov 2022To investigate the clinical benefits of combination therapy with immune checkpoint inhibitors (ICIs) and best combination regimen for people with advanced hepatocellular... (Meta-Analysis)
Meta-Analysis Review
Benefits of combination therapy with immune checkpoint inhibitors and predictive role of tumour mutation burden in hepatocellular carcinoma: A systematic review and meta-analysis.
OBJECTIVES
To investigate the clinical benefits of combination therapy with immune checkpoint inhibitors (ICIs) and best combination regimen for people with advanced hepatocellular carcinoma (HCC) and to explore the predictive performance of tumour mutation burden (TMB).
METHODS
We conducted a systematic literature search to identify clinical trials. Meta-analysis and subgroup analyses were performed to estimate the benefits of combination regimens with PD-1/PD-L1 inhibitors for patients with advanced HCC and compare the effectiveness of PD-1/PD-L1 inhibitors and sorafenib as first-line therapy. Individualized analysis and Kaplan-Meier were used to assess the prognostic value of TMB.
RESULTS
A total of 29 studies with 5396 patients were included. ICIs' combination therapy had higher ORR (26 % vs 15 %) and DCR (73 % vs 55 %), longer PFS (5.5 vs 3.1 months) and OS (15.9 vs 12.6 months) compared to monotherapy. Anti-PD-1/PD-L1 agents provided improved ORR, DCR, PFS and OS compared to sorafenib. The overall ORs of ORR and DCR in subgroup analysis were 3.49 (95 % CI 2.36-5.17, p < 0.01) and 1.60 (95 % CI 1.15-2.21, p < 0.01). The overall HRs of PFS and OS were 0.68 (95 % CI 0.48-0.96, p = 0.03) and 0.73 (95 % CI 0.62-0.85, p < 0.01). PD-1/PD-L1 inhibitors plus anti-VEGF agents had an advantage in DCR (0.80 vs 0.48, meta-regression = - 0.32, P < 0.001), but an equal ORR (0.29 vs 0.26) compared to dual immune checkpoint inhibitors. The total OS in Dua-ICIs were 16.5 months (95 % CI 14.2-18.7), yet not reached in the major studies of ICI plus anti-VEGF regimen. In individualized analysis, the 1-year OS was superior for patients who had high-TMB (>10, mutations/Mb) than moderate-TMB (1-10, mutations/Mb; 28 % vs 15 %, P = 0.025).
CONCLUSION
Immune checkpoint inhibitors' combination therapy improved clinical outcomes in the management of advanced hepatocellular carcinoma. However, the overall objective response rate still did not exceed 30%. PD-1/PD-L1 inhibitors plus anti-angiogenic agents and dual immunotherapy provided significantly increased survival over sorafenib, which also pose new challenges for future research, and more appropriate and guided control regimens are required. Also, TMB may be a promising prognostic biomarker for immunotherapy in HCC. However, the validation of prospective and large sample studies is needed.
Topics: Humans; B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Carcinoma, Hepatocellular; Lung Neoplasms; Antineoplastic Agents, Immunological; Sorafenib; Prospective Studies; Liver Neoplasms; Biomarkers, Tumor; Mutation
PubMed: 36126410
DOI: 10.1016/j.intimp.2022.109244 -
Health Technology Assessment... May 2014Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Some epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutations make tumours... (Review)
Review
Epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation testing in adults with locally advanced or metastatic non-small cell lung cancer: a systematic review and cost-effectiveness analysis.
BACKGROUND
Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Some epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutations make tumours responsive to treatment with EGFR-TK inhibitors (EGFR-TKIs) but less responsive to treatment with standard chemotherapy. Patients with NSCLC are therefore tested for EGFR-TK tumour gene mutations to inform treatment decisions. There are a variety of tests available to detect these mutations. The different tests vary in the specific mutations that they attempt to detect, the amount of tumour cells needed for the test to work, the time that it takes to give a result, the error rate of the test, and the cost of the test.
OBJECTIVE
To compare the performance and cost-effectiveness of EGFR-TK mutation tests used to identify previously untreated adults with locally advanced or metastatic NSCLC, who may benefit from first-line treatment with TKIs.
DATA SOURCES
Twelve databases to August 2012 [including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations and Daily Update (OvidSP), EMBASE, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment database (HTA), Science Citation Index (SCI), Latin American and Caribbean Health Sciences Literature (LILACS), BIOSIS Previews, NIHR Health Technology Assessment programme, PROSPERO (International Prospective Register of Systematic Reviews)], research registers and conference proceedings. A web-based survey gathered data on technical performance of EGFR-TK mutation tests.
METHODS
Randomised controlled trials were assessed for methodological quality using the Cochrane risk of bias tool. Diagnostic accuracy studies were assessed using QUADAS-2. There were insufficient data for meta-analysis. For accuracy studies, we calculated sensitivity and specificity together with 95% confidence intervals (CIs). Survival data were summarised as hazard ratios and tumour response data as relative risks, with 95% CIs. The health-economic analysis considered the long-term costs and quality-adjusted life-years (QALYs) associated with different tests followed by treatment with either standard chemotherapy or a TKI. Direct sequencing was taken as the comparator. The de novo model consisted of a decision tree and a Markov model.
RESULTS
The survey indicated no differences between tests in batch size, turnaround time, number of failed samples or cost. Six studies provided data on the accuracy of EGFR-TK mutation testing for predicting response to treatment with TKIs. Estimates of accuracy were similar across studies. Six analyses provided data on the clinical effectiveness of TKIs compared with standard chemotherapy. There were no clear differences in the treatment effects reported by different studies, regardless of which EGFR mutation test was used to select patients. Cost-effectiveness analysis using 'Evidence on comparative effectiveness available' and 'Linked evidence' approaches: Therascreen(®) EGFR polymerase chain reaction (PCR) Kit (Qiagen, Venlo, the Netherlands) was both less effective and less costly than direct sequencing of all exon 19-21 mutations at an incremental cost-effectiveness ratio of £32,167 (comparative) and £32,190 (linked) per QALY lost. 'Assumption of equal prognostic value' approach: the lowest total strategy cost was [commercial-in-confidence (CiC) information has been removed] [Sanger sequencing or Roche cobas EGFR Mutation Testing Kit(®) (Roche Molecular Systems, Inc., Branchburg, NJ, USA)] compared with (CiC information has been removed) for the most expensive strategy (fragment length analysis combined with pyrosequencing).
LIMITATIONS
The cost-effectiveness analysis assumed that the differences in outcomes between the results of the trials were solely attributable to the different mutation tests used to distinguish between patients; this assumption ignores other factors that might explain this variation.
CONCLUSION
There was no strong evidence that any one EGFR mutation test had greater accuracy than any other test. Re-testing of stored samples from previous studies, where patient outcomes are already known, could be used to provide information on the relative effectiveness of TKIs and standard chemotherapy in patients with EGFR mutation-positive and mutation-negative tumours, where mutation status is determined using tests for which adequate data are currently unavailable.
STUDY REGISTRATION
PROSPERO CRD42012002828.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Carcinoma, Non-Small-Cell Lung; Cost-Benefit Analysis; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Neoplasm Metastasis; Neoplasm Staging; Polymerase Chain Reaction; Protein Kinase Inhibitors; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Reproducibility of Results; Technology Assessment, Biomedical
PubMed: 24827857
DOI: 10.3310/hta18320 -
Caspian Journal of Internal Medicine 2020Mutations in the EGFR signaling pathway play an important role in the development of colorectal cancer (CRC). Mutations in these genes, like KRAS and BRAF, affect the... (Review)
Review
BACKGROUND
Mutations in the EGFR signaling pathway play an important role in the development of colorectal cancer (CRC). Mutations in these genes, like KRAS and BRAF, affect the treatment strategies and associated with poor prognosis and relative resistance to anti-EGFR therapies. Our aim was to conduct a systematic and meta-analysis on all studies that have been conducted on the prevalence of these gene mutations in Iranian CRC patients.
METHODS
Four science citation index databases (MEDLINE, EMBASE, Web of Science and Cochrane library) and local databases were searched up to March 2018 with related keywords. Two reviewers independently screened and extracted the data. Quality of all included studies was assessed using an adapted checklist from STROBE. A random-effect model was used to calculate the total prevalence of KRAS and BRAF mutations in CRC subjects by the event rate (ER). Meta-regression was utilized to explore heterogeneity causes.
RESULTS
In total, from 573 records, 23 eligible studies (2662 patients) were included for data extraction and analysis. In 18 of 23 included studies, the prevalence of KRAS mutations was 33.9% (95% CI=30.1-37.9) with I2=65.17 (p<0.001). The occurrence of KRAS mutations in codon 12 and 13 was 76.9% (95% CI = 70.4-82.3%) with I2=84.88 (p<0.001) and 23.5% (95% CI=17.9-30.3) with I2=85.85 (p<0.001), respectively. In 9 of 23 studies, the BRAF mutation rate was 3.2% (95% CI=0.003-13.6) with I2=88.61 (p<0.001).
CONCLUSION
The prevalence of these mutations in CRC patients shows a significant difference in the different regions of Iran, which is probably due to environmental and racial factors.
PubMed: 33680376
DOI: 10.22088/cjim.11.4.355