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Cancer Medicine Sep 2019Melanoma is a potentially fatal malignancy with poor prognosis. Several recent studies have demonstrated that combination therapy of BRAF and MEK inhibition achieved... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Melanoma is a potentially fatal malignancy with poor prognosis. Several recent studies have demonstrated that combination therapy of BRAF and MEK inhibition achieved better curative effect and appeared less toxic effects. We conducted a meta-analysis to evaluate the efficacy and safety between BRAF inhibition plus MEK inhibition combination therapy and BRAF inhibition monotherapy in melanoma patients.
METHODS
We performed the search in PubMed, EMBASE, and the Cochrane Library from January 2010 to January 2019. Inclusion and exclusion of studies, assessment of quality, outcome measures, data extraction, and synthesis were independently accomplished by two reviewers. Revman 5.3 software was used for the meta-analysis.
RESULTS
Totally, seven randomized controlled trials involving 3146 patients met our inclusion criteria. Comparing the results of combination therapy and monotherapy, combination therapy significantly improved OS (RR = 1.13; 95% CI, 1.08, 1.19; P < 0.00001), ORR (RR = 1.36; 95% CI, 1.28, 1.45; P < 0.00001), PFS (RR = 0.57; 95% CI, 0.52, 0.63; P < 0.00001) and reduced deaths (RR = 0.78; 95% CI, 0.69, 0.88; P < 0.0001). Skin-related adverse events such as hyperkeratosis, cutaneous squamous-cell carcinoma were less compared with monotherapy. However, gastrointestinal events like nausea, diarrhea, and vomiting were at a higher frequency.
CONCLUSION
Doublet BRAF and MEK inhibition achieved better survival outcomes over single-agent BRAF inhibition and occurred less skin-related events, but gastrointestinal events were more in combination therapy.
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; MAP Kinase Kinase Kinases; Melanoma; Molecular Targeted Therapy; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Randomized Controlled Trials as Topic; Survival Analysis; Treatment Outcome
PubMed: 31393083
DOI: 10.1002/cam4.2248 -
Journal of Immunotherapy (Hagerstown,... May 2024The therapeutic landscape for patients with advanced or metastatic non-small cell lung cancer (NSCLC) is rapidly evolving due to advances in molecular testing and the...
Clinical Outcomes of PD-1/PD-L1 Inhibitors Among Patients With Advanced or Metastatic Non-Small Cell Lung Cancer With BRAF, ERBB2/HER2, MET , or RET Alterations: A Systematic Literature Review.
The therapeutic landscape for patients with advanced or metastatic non-small cell lung cancer (NSCLC) is rapidly evolving due to advances in molecular testing and the development of new targeted therapies and immunotherapies. However, the efficacy of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors in advanced or metastatic patients with NSCLC whose tumors harbor BRAF V600E mutation, HER2/ERBB2 alteration, MET exon 14 skipping mutation, or RET rearrangement is not completely understood. A systematic literature review was performed to summarize evidence from clinical trials and observational studies on objective response rate, progression-free survival, and overall survival in patients whose tumors express these biomarkers and who were treated with PD-1/PD-L1 inhibitors. Searches of Embase, MEDLINE, conference abstracts, and a clinical trial registry identified a total of 12 unique studies: 4 studies included patients with BRAF V600E mutation, 6 studies included patients with HER2/ERBB2 alteration, 7 studies included patients with MET exon 14 skipping mutation, and 5 studies included patients with RET rearrangement. Across studies, there was heterogeneity in treatment and patient characteristics and a lack of reporting on many important predictive and prognostic factors, including treatment regimens, patients' line of therapy, and tumor PD-L1 expression, which may explain the wide variation in objective response rate, progression-free survival, and overall survival across studies. Therefore, additional studies prospectively evaluating clinical outcomes of PD-1/PD-L1 inhibitors among patients with advanced or metastatic NSCLC whose tumors harbor emerging predictive or prognostic biomarkers are needed to determine whether this class of immunotherapy can provide additional survival benefits for these patients.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Immune Checkpoint Inhibitors; Proto-Oncogene Proteins B-raf; B7-H1 Antigen; Programmed Cell Death 1 Receptor; Proto-Oncogene Proteins c-ret; Receptor, ErbB-2
PubMed: 38112201
DOI: 10.1097/CJI.0000000000000500 -
Frontiers in Endocrinology 2023Evidence suggests that patients with Hashimoto thyroiditis (HT) are at significantly higher risk of developing papillary thyroid cancer (PTC). However, the course of PTC... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence suggests that patients with Hashimoto thyroiditis (HT) are at significantly higher risk of developing papillary thyroid cancer (PTC). However, the course of PTC in patients with both diseases concomitantly has been found to be more indolent than conventional PTC. Additionally, it has been well proven that BRAF mutation results in an aggressive course of PTC. The aims of this meta-analysis were to identify prevalence of BRAF mutation and its impact on clinicopathological features in patients with concomitant PTC-HT.
METHODS
Medline, Cochrane Library, Scopus, and Web of Science were searched until 16.09.2022, resulting in 227 articles, of which nine studies were included. Summary estimates, comparing patients with (A) BRAF (+) PTC-HT versus BRAF (+) PTC, and (B) BRAF (+) PTC-HT versus BRAF (-) PTC-HT, were generated with Review Manager 5.0.
RESULTS
In total, 6395 patients were included in this review. PTC-HT patients had significantly less BRAF mutation than PTC patients (Odds Ratio (OR) (95% Confidence Interval (CI))=0.45 (0.35-0.58), P<0.001). BRAF (+) PTC-HT patients were significantly more likely to have multifocal lesions (OR (95% CI)=1.22 (1.04-1.44), P=0.01) but less likely to have lymph node metastasis (OR (95% CI)=0.65 (0.46-0.91), P=0.01) and extrathyroidal extension (OR (95% CI)=0.55 (0.32-0.96), P=0.03) compared to BRAF (+) PTC patients. BRAF (+) PTC-HT patients were more likely to have multifocal lesions (OR (95% CI)=0.71 (0.53-0.95), P=0.02), lymph node metastasis (OR (95% CI)=0.59 (0.44-0.78), P<0.001) and extrathyroidal extension (OR (95% CI)=0.72 (0.56-0.92), P=0.01) compared to BRAF (-) PTC-HT patients.
CONCLUSION
This meta-analysis highlights that the lower prevalence of BRAF mutation in patients with PTC-HT than conventional PTC may explain the indolent clinicopathological course in this cohort.
Topics: Humans; Thyroid Cancer, Papillary; Hashimoto Disease; Proto-Oncogene Proteins B-raf; Thyroid Neoplasms; Lymphatic Metastasis; Prevalence; Carcinoma, Papillary; Mutation
PubMed: 38047109
DOI: 10.3389/fendo.2023.1273498 -
Endocrine Jan 2020The association between telomerase reverse transcriptase (TERT) promoter mutations and some clinical behaviors in thyroid cancer remains controversial and requires... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The association between telomerase reverse transcriptase (TERT) promoter mutations and some clinical behaviors in thyroid cancer remains controversial and requires additional investigation. This study aimed to evaluate the association between TERT promoter mutations and clinical behaviors (including clinicopathological features and prognosis) in differentiated thyroid carcinomas (DTC).
METHODS
We performed an up-to-date systematic review and current comprehensive meta-analysis. We searched three electronic databases for relevant studies. We used fixed- or random-effect models to calculate pooled estimated odds ratios (ORs) or standardized mean differences (SMDs) and corresponding 95% confidence intervals (CIs).
RESULTS
We included 51 eligible studies incorporating 11,382 cases. Average frequencies of TERT promoter mutations in DTC, papillary (PTC), and follicular (FTC) thyroid carcinomas were 10.9%, 10.6%, and 15.1%, respectively. In DTC and PTC, TERT promoter mutations were significantly associated with sex, age, tumor size, vascular invasion, extrathyroidal extension, lymph node and distant metastases, advanced tumor, nodes, and metastasis (TNM) stage, persistence/recurrence, and disease-specific mortality. In FTC, TERT promoter mutations were significantly associated with age, distant metastases, advanced TNM stage, persistence/recurrence, and disease-specific mortality.
CONCLUSIONS
TERT promoter mutations could be considered as biomarkers assisting in risk stratification, prognostic prediction, and individualizing therapeutic options for DTC (PTC and FTC).
Topics: Carcinoma, Papillary; Humans; Mutation; Neoplasm Recurrence, Local; Prognosis; Proto-Oncogene Proteins B-raf; Telomerase; Thyroid Neoplasms
PubMed: 31655978
DOI: 10.1007/s12020-019-02117-2 -
PloS One 2017Studies of anti-angiogenic agents (AAs), combined with chemotherapy (chemo) or as monotherapy in metastatic oesophago-gastric cancer (mOGC), have reported mixed... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Studies of anti-angiogenic agents (AAs), combined with chemotherapy (chemo) or as monotherapy in metastatic oesophago-gastric cancer (mOGC), have reported mixed outcomes. We undertook systematic review and meta-analysis to determine their overall benefits and harms.
METHODS
Randomized controlled trials in mOGC were sought investigating the addition of AAs to standard therapy (best supportive care or chemo). The primary endpoint was overall survival (OS) with secondary endpoints progression-free survival (PFS), overall response rate (ORR) and toxicity. Estimates of treatment effect from individual trials were combined using standard techniques. Subgroup analyses were performed by line of therapy, region, age, performance status, histological type, number of metastatic sites, primary site, mechanism of action and HER2 status.
RESULTS
Fifteen trials evaluating 3502 patients were included in quantitative analysis. The addition of AAs was associated with improved OS: HR 0·81 (95% CI 0·75-0·88, p<0·00001) and improved PFS: HR 0·68 (95% CI 0·63-0·74, p<0·00001). Subgroup analyses favoured greater benefit for OS in 2nd/3rd line settings (HR 0·74) compared to 1st-line settings (HR 0·91) (X2 = 6·00, p = 0·01). OS benefit was seen across all regions-Asia (HR 0·83) and rest of world (HR 0·75)-without significant subgroup interaction. Results from 8 trials evaluating 2602 patients were pooled for toxicity > = Grade 3: with OR 1·39 (95% CI 1·17-1·65).
CONCLUSIONS
The addition of AAs to standard therapy in mOGC improves OS. Improved efficacy was only observed in 2nd- or 3rd-line setting and not in 1st-line setting. Consistent OS benefit was present across all geographical regions. This benefit is at the expense of increased overall toxicity.
Topics: Angiogenesis Inhibitors; Antineoplastic Agents; Carcinoma; Disease-Free Survival; Esophageal Neoplasms; Genes, erbB-2; Humans; Publication Bias; Quality of Life; Randomized Controlled Trials as Topic; Stomach Neoplasms; Survival Analysis; Treatment Outcome
PubMed: 28222158
DOI: 10.1371/journal.pone.0172307 -
Hematology/oncology and Stem Cell... Mar 2017Acute myeloid leukemia (AML) is defined as leukemic blast reproduction in bone marrow. Chromosomal abnormalities form different subgroups with joint clinical... (Review)
Review
OBJECTIVE/BACKGROUND
Acute myeloid leukemia (AML) is defined as leukemic blast reproduction in bone marrow. Chromosomal abnormalities form different subgroups with joint clinical specifications and results. t(8;21)(q22;q22) and inv(16)(p13;q22) form core binding factor-AML (CBF-AML). c-kit mutation activation occurs in 12.8-46.1% of adults with CBF leukemia. These mutations occur in 20-25% of t(8;21) and 30% of inv(16) cases.
METHODS
In this systematic review, we searched different databases, including PubMed, Scopus, and Embase. Selected articles were measured based on the inclusion criteria of this study and initially compared in terms of titles or abstracts. Finally, articles relevant to the subject of this review were retrieved in full text. Twenty-two articles matched the inclusion criteria and were selected for this review.
RESULTS
In this study, c-kit mutations were associated with poor prognosis in AML patients with t(8;21) and inv(16). In addition, these mutations had better prognostic effects on AML patients with inv(16) compared with those with t(8;21).
CONCLUSION
According to the results of this study, c-kit mutations have intense, harmful effects on the relapse and white blood cell increase in CBF-AML adults. However, these mutations have no significant prognostic effects on patients.
Topics: Chromosome Inversion; Databases, Factual; Humans; Leukemia, Myeloid, Acute; Mutation; Prognosis; Proto-Oncogene Proteins c-kit; Survival Rate; Translocation, Genetic
PubMed: 27613372
DOI: 10.1016/j.hemonc.2016.08.005 -
British Journal of Haematology Aug 2015'Double-hit lymphomas' (DHL), defined by concurrent MYC and BCL2 (or, alternatively, BCL6) rearrangements, have a very poor outcome compared to standard-risk, diffuse... (Meta-Analysis)
Meta-Analysis Review
Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis.
'Double-hit lymphomas' (DHL), defined by concurrent MYC and BCL2 (or, alternatively, BCL6) rearrangements, have a very poor outcome compared to standard-risk, diffuse large B-cell lymphomas (DLBCL). Consequently, dose-intensive (DI) therapies and/or consolidation with high-dose therapy and transplant have been explored in DHL, although benefit has been debated. This meta-analysis compared survival outcomes in DHL patients receiving dose-escalated regimens [DI: R-Hyper-CVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone) or R-CODOX-M/IVAC (rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, high dose cytarabine); or intermediate-dose: R-EPOCH (rituximab, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone)] versus standard-dose regimens (R-CHOP; rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) in the first-line setting. Data were synthesized to estimate hazard ratios of dose-escalated treatments versus R-CHOP using a Weibull proportional hazards model within a Bayesian meta-analysis framework. Eleven studies examining 394 patients were included. Patients were treated with either front-line R-CHOP (n = 180), R-EPOCH (n = 91), or R-Hyper-CVAD/rituximab, methotrexate, cytarabine (R-M/C), R-CODOX-M/R-IVAC (DI) (n = 123). Our meta-analysis revealed that median progression-free survival (n = 350) for the R-CHOP, R-EPOCH and DI groups was 12·1, 22·2, and 18·9 months, respectively. First-line treatment with R-EPOCH significantly reduced the risk of a progression compared with R-CHOP (relative risk reduction of 34%; P = 0·032); however, overall survival (n = 374) was not significantly different across treatment approaches. A subset of patients might benefit from intensive induction with/without transplant. Further investigation into the role of transplant and novel therapy combinations is necessary.
Topics: Antineoplastic Combined Chemotherapy Protocols; DNA-Binding Proteins; Disease-Free Survival; Humans; Lymphoma, Large B-Cell, Diffuse; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-bcl-6; Proto-Oncogene Proteins c-myc; Survival Rate
PubMed: 25907897
DOI: 10.1111/bjh.13463 -
Journal of Clinical Periodontology Mar 2015The aim was to evaluate the effects of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and recombinant human fibroblast growth factor-2 (rhFGF-2) on... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
The aim was to evaluate the effects of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and recombinant human fibroblast growth factor-2 (rhFGF-2) on treating periodontal intra-bony defects, compared to the control (carrier alone).
METHODS
Electronic and hand searches were performed to identify eligible studies. The weighed mean differences of linear defect fill (LDF), probing depth (PD) reduction, clinical attachment level (CAL) gain and gingival recession (GR) were calculated using random effect meta-analysis.
RESULTS
The searches yielded 1018 articles, of which seven studies were included. Only one included study was considered at low risk of bias. The outcomes that reached statistical significance in comparison to carriers alone included: LDF (0.95 mm, 95% CI: 0.62-1.28 mm or 20.17%, 95% CI: 11.81-28.54%) and CAL gain (0.34 mm, 95% CI: 0.03-0.65 mm) for PDGF, and LDF (21.22%, 95% CI: 5.82-36.61%) for FGF-2.
CONCLUSIONS
Within the limits of this review, rhPDGF-BB demonstrated significantly more LDF and CAL gain; rhFGF-2 resulted in significantly higher percentage of LDF.
Topics: Alveolar Bone Loss; Becaplermin; Bone Regeneration; Fibroblast Growth Factor 2; Gingival Recession; Guided Tissue Regeneration, Periodontal; Humans; Periodontal Attachment Loss; Periodontal Pocket; Proto-Oncogene Proteins c-sis; Treatment Outcome
PubMed: 25605424
DOI: 10.1111/jcpe.12354 -
Journal of Clinical Laboratory Analysis Dec 2020The current research was conducted to study the association between the SNP309 and del1518 polymorphisms with the breast cancer in the patients with the Kurdish ethnic...
OBJECTIVE
The current research was conducted to study the association between the SNP309 and del1518 polymorphisms with the breast cancer in the patients with the Kurdish ethnic background from western Iran. Also, a systematic review of the relevant case-control studies on the MDM2 polymorphisms in the patients with breast cancer was performed.
METHODOLOGY
Two mL of peripheral blood was taken from 100 patients with breast cancer and 100 healthy individuals. The frequencies of MDM2 SNP309 and del1518 genotypes and alleles were determined using the PCR-RFLP and PCR methods, respectively.
RESULTS
The frequency of the TT, TG, and GG of MDM2-SNP309 genotypes in the patients was obtained as 23%, 52%, and 25%, and they were equal to 22%, 40%, and 38% in the control group, respectively. Also, considering the MDM2-del1518 polymorphism, the frequencies of ins/ins, ins/del, and del/del genotypes were equal to 52%, 41%, and 7% in the breast cancer group and they were equal to 62, 30, and 8% in the control group, respectively. Analysis of the results indicated that the GG genotype plays a protective role for the breast cancer in the recessive model (GG vs TT + TG) of SNP309 (χ = 3.916, P = .048, and OR = 0.54).
CONCLUSION
Our findings revealed that the GG genotype of MDM2-SNP309 can play a protective role in the breast cancer disease. Also, our systematic review indicated that the SNP309, SNP285, and del1518 of MDM2 gene in different populations mostly did not have a significant association with the risk of breast cancer.
Topics: Adult; Aged; Breast Neoplasms; Case-Control Studies; Female; Genetic Predisposition to Disease; Humans; Iran; Middle Aged; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins c-mdm2; Young Adult
PubMed: 32951271
DOI: 10.1002/jcla.23529 -
Frontiers in Endocrinology 2022The effect of iodine on papillary thyroid cancer (PTC) has been controversial for many years. Since urinary iodine is an effective indicator of iodine intake, some... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The effect of iodine on papillary thyroid cancer (PTC) has been controversial for many years. Since urinary iodine is an effective indicator of iodine intake, some recent epidemiological studies have described the relationship between urinary iodine concentration (UIC) and PTC.
METHODS
We searched PubMed, Embase, Cochrane Library, and Web of Science for case-control studies about UIC and PTC published before September 2022. Results are presented as the overall odds ratio (OR) and 95% confidence intervals (CI).
RESULTS
According to the analysis of the included studies, excessive iodine intake (UIC≥300ug/L) was positively associated with the occurrence of PTC patients compared with healthy controls (OR4.05, 95%CI 1.64-10.02, P=0.002). Meanwhile, adequate iodine exposure (100≤UIC<200ug/L) may play a protective role in the occurrence of PTC compared with healthy individuals (OR 0.36, 95%CI 0.14-0.91, P=0.03) while the difference in the prevalence of insufficient iodine intake (UIC<100ug/L) and iodine above requirements (200≤UIC<300ug/L) among the two groups were not significant (deficiency: OR 0.38, 95%CI 0.13-1.16, P=0.09; above requirements: OR 0.92, 95%CI 0.40-2.10, P=0.84). After comparing the UIC levels of PTC patients with those of other thyroid diseases, we found that there was also no significant difference in the incidence of different levels of UIC in the two groups (excessive: OR 1.25, 95%CI 0.87-1.80, P=0.22; above requirements: OR 0.93, 95%CI 0.77-1.14, P=0.49; adequate: OR 0.96, 95%CI 0.78-1.17, P=0.67; deficiency: OR 1.02, 95%CI 0.86-1.22, P=0.80). The result of this meta-analysis also did not support the relationship between UIC and the BRAF mutation and lymph node metastasis (LNM) of PTC patients. Besides, we also found that studies on the relationship between urinary iodine and PTC may be influenced by the way UIC was measured.
CONCLUSION
The 10 case-control included studies involved a total of 6,544 participants. The results of this meta-analysis showed excessive iodine intake, that is, UIC≥300ug/L was associated with the occurrence of PTC but not with BRAF mutation and LNM while adequate iodine intake (100≤UIC<200ug/L) may be one of the protective factors for PTC.
Topics: Humans; Thyroid Cancer, Papillary; Iodine; Proto-Oncogene Proteins B-raf; Thyroid Diseases; Lymphatic Metastasis; Thyroid Neoplasms
PubMed: 36387866
DOI: 10.3389/fendo.2022.1049423