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Radiotherapy and Oncology : Journal of... Jul 2024We performed this systematic review and meta-analysis to investigate the performance of ML in detecting genetic mutation status in NSCLC patients. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
We performed this systematic review and meta-analysis to investigate the performance of ML in detecting genetic mutation status in NSCLC patients.
MATERIALS AND METHODS
We conducted a systematic search of PubMed, Cochrane, Embase, and Web of Science up until July 2023. We discussed the genetic mutation status of EGFR, ALK, KRAS, and BRAF, as well as the mutation status at different sites of EGFR.
RESULTS
We included a total of 128 original studies, of which 114 constructed ML models based on radiomic features mainly extracted from CT, MRI, and PET-CT data. From a genetic mutation perspective, 121 studies focused on EGFR mutation status analysis. In the validation set, for the detection of EGFR mutation status, the aggregated c-index was 0.760 (95%CI: 0.706-0.814) for clinical feature-based models, 0.772 (95%CI: 0.753-0.791) for CT-based radiomics models, 0.816 (95%CI: 0.776-0.856) for MRI-based radiomics models, and 0.750 (95%CI: 0.712-0.789) for PET-CT-based radiomics models. When combined with clinical features, the aggregated c-index was 0.807 (95%CI: 0.781-0.832) for CT-based radiomics models, 0.806 (95%CI: 0.773-0.839) for MRI-based radiomics models, and 0.822 (95%CI: 0.789-0.854) for PET-CT-based radiomics models. In the validation set, the aggregated c-indexes for radiomics-based models to detect mutation status of ALK and KRAS, as well as the mutation status at different sites of EGFR were all greater than 0.7.
CONCLUSION
The use of radiomics-based methods for early discrimination of EGFR mutation status in NSCLC demonstrates relatively high accuracy. However, the influence of clinical variables cannot be overlooked in this process. In addition, future studies should also pay attention to the accuracy of radiomics in identifying mutation status of other genes in EGFR.
Topics: Humans; Lung Neoplasms; Machine Learning; Mutation; Carcinoma, Non-Small-Cell Lung; Positron Emission Tomography Computed Tomography; ErbB Receptors; Proto-Oncogene Proteins p21(ras)
PubMed: 38734145
DOI: 10.1016/j.radonc.2024.110325 -
Frontiers in Pharmacology 2024The European League of Rheumatology(EULAR)guidelines recommend Janus kinase (JAK) inhibitors for patients with moderate to severe rheumatoid arthritis (RA) who are... (Review)
Review
Comparative efficacy of five approved Janus kinase inhibitors as monotherapy and combination therapy in patients with moderate-to-severe active rheumatoid arthritis: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUND
The European League of Rheumatology(EULAR)guidelines recommend Janus kinase (JAK) inhibitors for patients with moderate to severe rheumatoid arthritis (RA) who are insensitive or under-responsive to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). But there was no recommendation for which one was preferred in five currently approved JAK inhibitors. The objective of this network meta-analysis study was to evaluate the efficacy of five JAK inhibitors as monotherapy and combination therapy in patients with moderate-to-severe active rheumatoid arthritis.
METHODS
The randomized controlled trials (RCTs) of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy or combined with csDMARD in the treatment of active RA were searched in database of PubMed, Embase, Web of Science and Cochrane Library, up to December 2023. The control group included placebo or csDMARD. Outcome indicators included American College of Rheumatology 20% response (ACR20), ACR50, ACR70 and the percentage of patients achieving 28-joint disease activity score using C-reactive protein (DAS28(CRP))<2.6 at 12 weeks and 24 weeks. The statistical analysis was performed by Stata14 and RevMan5.4. Data processing, network evidence plots, surface under the cumulative ranking curve (SUCRA) ranking, league plots and funnel plots were generated. Risk ratio (RR) and 95% confidence interval (95%CI) as effect sizes to analyze the statistics.
RESULTS
This study included thirty-six RCTs with 16,713 patients. All JAK inhibitors were more effective than placebo in ACR20 (RRs ranging between 1.74 and 3.08), ACR50 (RRs ranging between 2.02 and 7.47), ACR70 (RRs ranging between 2.68 and 18.13), DAS28(CRP) < 2.6 (RRs ranging between 2.70 and 7.09) at 12 weeks. Upadacitinib 30 mg and upadacitinib 15 mg showed relatively good efficacy according to their relative SUCRA ranking. All JAK inhibitors were more effective than csDMARD or placebo in ACR20 (RRs ranging between 1.16 and 1.86), ACR50 (RRs ranging between 1.69 and 2.84), ACR70 (RRs ranging between 1.50 and 4.47), DAS28(CRP) < 2.6 (RRs ranging between 2.28 and 7.56) at 24 weeks. Upadacitinib 15 mg + csDMARD and baricitinib 4 mg + csDMARD showed relatively good efficacy according to their relative SUCRA ranking. The safety analysis results such as serious infection, malignancy, major adverse cardiovascular event (MACE), and venous thromboembolic events (VTE) showed no statistical difference.
CONCLUSION
This NMA study indicated that all JAK inhibitors performed better than placebo. Based on the results of this study, upadacitinib 30 mg, upadacitinib 15 mg, upadacitinib 15 mg + csDMARD and baricitinib 4 mg + csDMARD were recommended treatment options with relatively good efficacy and safety. However, attention should be paid to monitoring the occurrence of adverse events in high-risk RA patients with medication. Combination therapy with csDMARD might be more suitable for the maintenance of long-term efficacy. However, in clinical practice, it is still necessary to select the appropriate therapeutic regimen based on the actual clinical situation.
PubMed: 38725657
DOI: 10.3389/fphar.2024.1387585 -
International Journal of Molecular... Apr 2024Non-alcoholic fatty liver disease (NAFLD) is the predominant cause of chronic liver conditions, and its progression is marked by evolution to non-alcoholic steatosis,... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) is the predominant cause of chronic liver conditions, and its progression is marked by evolution to non-alcoholic steatosis, steatohepatitis, cirrhosis related to non-alcoholic steatohepatitis, and the potential occurrence of hepatocellular carcinoma. In our systematic review, we searched two databases, Medline (via Pubmed Central) and Scopus, from inception to 5 February 2024, and included 73 types of research (nine clinical studies and 64 pre-clinical studies) from 2854 published papers. Our extensive research highlights the impact of Berberine on NAFLD pathophysiology mechanisms, such as Adenosine Monophosphate-Activated Protein Kinase (AMPK), gut dysbiosis, peroxisome proliferator-activated receptor (PPAR), Sirtuins, and inflammasome. Studies involving human subjects showed a measurable reduction of liver fat in addition to improved profiles of serum lipids and hepatic enzymes. While current drugs for NAFLD treatment are either scarce or still in development or launch phases, Berberine presents a promising profile. However, improvements in its formulation are necessary to enhance the bioavailability of this natural substance.
Topics: Berberine; Non-alcoholic Fatty Liver Disease; Humans; Animals; Liver Cirrhosis; Liver
PubMed: 38673787
DOI: 10.3390/ijms25084201 -
Archives of Gynecology and Obstetrics Jun 2024Gynecologic perivascular epithelioid cell (PEC) tumors, or 'PEComas,' represent a rare and intriguing subset of tumors within the female reproductive tract. This... (Review)
Review
Gynecologic perivascular epithelioid cell (PEC) tumors, or 'PEComas,' represent a rare and intriguing subset of tumors within the female reproductive tract. This systematic literature review aims to provide an updated understanding of gynecologic PEComas based on available literature and data. Although PEComa is rare, there are varied tumor-site presentations across gynecologic organs, with uterine PEComas being the most prevalent. There is scarce high-quality literature regarding gynecologic PEComa, and studies on malignant PEComa underscore the challenges in diagnosis. Among the diverse mutations, mTOR alterations are the most prominent. Survival analysis reveals a high rate of local recurrence and metastatic disease, which commonly affects the lungs. Treatment strategies are limited, however mTOR inhibitors have pivotal role when indicated and chemotherapy may also be used. with some cases demonstrating promising responses. The paucity of data underscores the need for multicentric studies, an international registry for PEComas, and standardized reporting in case series to enhance clinical and pathological data.
Topics: Humans; Perivascular Epithelioid Cell Neoplasms; Female; Genital Neoplasms, Female; MTOR Inhibitors; Uterine Neoplasms; TOR Serine-Threonine Kinases; Neoplasm Recurrence, Local
PubMed: 38664269
DOI: 10.1007/s00404-024-07510-5 -
Annals of Hematology Jun 2024Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between... (Meta-Analysis)
Meta-Analysis
Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between JAK2V617F allele burden (also known as variant allele frequency) and the relevant clinical characteristics. Numerous studies have reported associations between allele burden and both hematologic and clinical features. While there are strong indications linking high allele burden in PV patients with symptoms and clinical characteristics, not all associations are definitive, and disparate and contradictory findings have been reported. Hence, this study aimed to synthesize existing data from the literature to better understand the association between JAK2V617F allele burden and relevant clinical correlates. Out of the 1,851 studies identified, 39 studies provided evidence related to the association between JAK2V617F allele burden and clinical correlates, and 21 studies were included in meta-analyses. Meta-analyses of correlation demonstrated that leucocyte and erythrocyte counts were significantly and positively correlated with JAK2V617F allele burden, whereas platelet count was not. Meta-analyses of standardized mean difference demonstrated that leucocyte and hematocrit were significantly higher in patients with higher JAK2V617F allele burden, whereas platelet count was significantly lower. Meta-analyses of odds ratio demonstrated that patients who had higher JAK2V617F allele burden had a significantly greater odds ratio for developing pruritus, splenomegaly, thrombosis, myelofibrosis, and acute myeloid leukemia. Our study integrates data from approximately 5,462 patients, contributing insights into the association between JAK2V617F allele burden and various hematological parameters, symptomatic manifestations, and complications. However, varied methods of data presentation and statistical analyses prevented the execution of high-quality meta-analyses.
Topics: Polycythemia Vera; Janus Kinase 2; Humans; Alleles; Gene Frequency; Amino Acid Substitution; Mutation, Missense
PubMed: 38652240
DOI: 10.1007/s00277-024-05754-4 -
Translational Lung Cancer Research Mar 2024International guidelines recommend the use of local therapy (LT) to limited progression in patients with epidermal growth factor receptor (EGFR)-mutated advanced...
BACKGROUND
International guidelines recommend the use of local therapy (LT) to limited progression in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). However, the use of LT before disease progression has not been extensively analyzed. This meta-analysis evaluates the efficacy and safety of administering additional LT in conjunction with first-line EGFR-tyrosine kinase inhibitors (TKIs) before disease progression in patients with EGFR-mutated advanced NSCLC.
METHODS
We systematically searched PubMed, Embase, and the Cochrane Library for studies published up until May 31, 2023. The LT group consisted of patients who received first-line EGFR-TKIs in conjunction with additional LT, while the TKI group comprised participants treated with first-line EGFR-TKIs alone. Studies comparing the survival outcomes of the LT and TKI groups were included in this analysis. The primary outcomes were progression-free survival (PFS) and overall survival (OS). This review was registered on PROSPERO (registration number CRD42023439913).
RESULTS
Among the 11 investigated studies covering 1,313 patients, the LT modalities included radiotherapy, surgery, and ablation therapy, which accounted for 91%, 27%, and 27% of the studies, respectively. The pooled hazard ratios of median PFS and OS were 0.34 [95% confidence interval (CI): 0.22-0.53; P<0.001] and 0.42 (95% CI: 0.36-0.48; P<0.001), respectively, which indicated significant benefits for the LT group compared to the TKI group. There was no significant difference between the LT and TKI groups (P=0.473) regarding the incidence of grade 3 or higher adverse events.
CONCLUSIONS
This study suggests that the strategic use of additional LT before disease progression is a promising approach for the treatment of EGFR-mutated advanced NSCLC.
PubMed: 38601443
DOI: 10.21037/tlcr-23-830 -
Cancer Control : Journal of the Moffitt... 2024Combination therapy with multiple tyrosine kinase inhibitors (multi-TKIs) and immune checkpoint inhibitors (ICIs) has been increasingly tested in clinical studies. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Combination therapy with multiple tyrosine kinase inhibitors (multi-TKIs) and immune checkpoint inhibitors (ICIs) has been increasingly tested in clinical studies. This study aimed to investigate the effect of the addition of ICI to multi-TKIs on the profile of treatment-related adverse events.
METHODS
An electronic database search was performed using PubMed and Web of Science to identify published clinical studies on multi-TKI monotherapy and multi-TKI plus ICI combination therapy from July 20, 2005 to July 1, 2023. The incidence rate of common adverse events caused by multi-TKI monotherapy and multi-TKI plus ICI combination therapy was obtained and compared from the viewpoints of (1) relative risk for the combination therapy vs sunitinib, (2) adverse event incidence rate by clinical trial, and (3) pooled incidence rate. The quality of the evidence was assessed with the Cochrane risk of bias tool. Meta-analysis used random effects models.
RESULTS
This systematic review identified 83 clinical studies involving 7951 patients. The combination therapy of multi-TKI and ICI was associated with an increased risk of diarrhea (relative risk [RR]: 1.24, 95% confidence interval [CI]: 1.15-1.33, < .001), hypothyroidism (RR: 1.44, 95% CI: 1.11-1.87, = .0064) and rash (RR: 1.71, 95% CI: 1.18-2.47, = .0045) compared with multi-TKI monotherapy. The addition of ICI was suggested to decrease the risk of adverse events related to performance status.
CONCLUSION
Our study identified an increased risk of treatment-related adverse events associated with multi-TKI plus ICI combination therapy. This would help optimize the management of toxicities caused by multi-TKI plus ICI combination therapy.
Topics: Humans; Immune Checkpoint Inhibitors; Tyrosine Kinase Inhibitors; Combined Modality Therapy; Protein Kinase Inhibitors; Databases, Factual
PubMed: 38581169
DOI: 10.1177/10732748241244586 -
Clinical Breast Cancer Jul 2024Poly-ADP ribose polymerase inhibitor (PARPi) is approved for HER2-negative advanced breast cancer with BRCA1/2 mutation. In recent years, many studies have explored the... (Meta-Analysis)
Meta-Analysis
Poly-ADP ribose polymerase inhibitor (PARPi) is approved for HER2-negative advanced breast cancer with BRCA1/2 mutation. In recent years, many studies have explored the application of PARPi in neoadjuvant therapy, but failed to reach a unified conclusion. PubMed, Clinicaltrials.gov, Cochrane CENTRAL, Embase, and key oncological meetings for trials were searched for studies reporting neoadjuvant regimens with PARPi in HER2-negative breast cancer. Pathological complete response (pCR), residual cancer burden (RCB), breast-conservation surgery rate (BCSR), clinical response, and adverse events were extracted and pooled in a meta-analysis using the Mantel Haenszel random/fixed effects model. Subgroup analyses of pCR were conducted according to BRCA1/2 status, and hormone receptor (HR) status. Five studies (N = 1223) were included, the addition of PARPi to neoadjuvant regimens significantly increased pCR rates (HR 1.45, 95%CI 1.09-1.92, P = .01, I = 86%). In subgroup analysis, the addition of PARPi increased the pCR rate both in HR-positive (n = 383) and HR-negative (n = 431) subgroups, which showed a dominant effect of PARPi regardless of HR status (HR 2.07, 95%CI 1.33-3.23, P = .001, I = 0%; HR 1.85, 95%CI 1.39-2.26, P < .0001, I = 0%, respectively). However, when we performed a subgroup analysis based on the status of BRCA1/2, no further benefit for PARPi was found. Adverse reactions were generally tolerable. Other outcome indexes, including RCB, clinical response, BCSR, and PARPi did not show a clinical benefit. Regardless of BRCA1/2 status, PARPi in neoadjuvant therapy, can improve the pCR rate of HER2-negative breast cancer, especially in HR-positive patients. Thus, we should have performed larger randomized trials and provided a stronger evidence-based basis.
Topics: Female; Humans; BRCA1 Protein; BRCA2 Protein; Breast Neoplasms; Neoadjuvant Therapy; Poly(ADP-ribose) Polymerase Inhibitors; Receptor, ErbB-2; Treatment Outcome
PubMed: 38580572
DOI: 10.1016/j.clbc.2024.02.020 -
Frontiers in Pharmacology 2024This study aimed to assess the efficacy and safety of saponin (PNS) injection, when combined with conventional treatment (CT), for acute myocardial infarction (AMI)....
This study aimed to assess the efficacy and safety of saponin (PNS) injection, when combined with conventional treatment (CT), for acute myocardial infarction (AMI). Comprehensive searches were conducted in seven databases from inception until 28 September 2023. The search aimed to identify relevant randomized controlled trials (RCTs) focusing on PNS injection in the context of AMI. This meta-analysis adhered to the PRISMA 2020 guidelines, and its protocol was registered with PROSPERO (number: CRD42023480131). Twenty RCTs involving 1,881 patients were included. The meta-analysis revealed that PNS injection, used adjunctively with CT, significantly improved treatment outcomes compared to CT alone, as evidenced by the following points: (1) enhanced total effective rate [OR = 3.09, < 0.05]; (2) decreased incidence of major adverse cardiac events [OR = 0.32, < 0.05]; (3) reduction in myocardial infarct size [MD = -6.53, < 0.05]; (4) lower ST segment elevation amplitude [MD = -0.48, < 0.05]; (5) mitigated myocardial injury as indicated by decreased levels of creatine kinase isoenzymes [MD = -11.19, < 0.05], cardiac troponin T [MD = -3.01, < 0.05], and cardiac troponin I [MD = -10.72, < 0.05]; (6) enhanced cardiac function, reflected in improved brain natriuretic peptide [MD = -91.57, < 0.05], left ventricular ejection fraction [MD = 5.91, < 0.05], left ventricular end-diastolic dimension [MD = -3.08, < 0.05], and cardiac output [MD = 0.53, < 0.05]; (7) reduced inflammatory response, as shown by lower levels of C-reactive protein [MD = -2.99, < 0.05], tumor necrosis factor-α [MD = -6.47, < 0.05], interleukin-6 [MD = -24.46, < 0.05], and pentraxin-3 [MD = -2.26, < 0.05]; (8) improved vascular endothelial function, demonstrated by decreased endothelin-1 [MD = -20.56, < 0.05] and increased nitric oxide [MD = 1.33, < 0.05]; (9) alleviated oxidative stress, evidenced by increased superoxide dismutase levels [MD = 25.84, < 0.05]; (10) no significant difference in adverse events [OR = 1.00, = 1.00]. This study highlighted the efficacy and safety of adjunctive PNS injections in enhancing AMI patient outcomes beyond CT alone. Future RCTs need to solidify these findings through rigorous methods. : (https://www.crd.york.ac.uk/PROSPERO/), identifier (CRD42023480131).
PubMed: 38576488
DOI: 10.3389/fphar.2024.1353662 -
Systematic Reviews Apr 2024Breast cancer incidence has been on the rise significantly in the Asian population, occurring at an earlier age and a later stage. The potential predictive value of... (Meta-Analysis)
Meta-Analysis
Exploring the effectiveness of molecular subtypes, biomarkers, and genetic variations as first-line treatment predictors in Asian breast cancer patients: a systematic review and meta-analysis.
BACKGROUND
Breast cancer incidence has been on the rise significantly in the Asian population, occurring at an earlier age and a later stage. The potential predictive value of molecular subtypes, biomarkers, and genetic variations has not been deeply explored in the Asian population. This study evaluated the effect of molecular subtype classification and the presence or absence of biomarkers and genetic variations on pathological complete response (pCR) after neoadjuvant treatment in Asian breast cancer patients.
METHODS
A systematic search was conducted in MEDLINE (PubMed), Science Direct, Scopus, and Cochrane Library databases. Studies were selected if they included Asian breast cancer patients treated with neoadjuvant chemotherapy and contained data for qualitative or quantitative analyses. The quality of the included studies was assessed using the Newcastle Ottawa Scale. Following the random effects model, pooled odds ratios or hazard ratios with 95% confidence intervals for pCR were analysed using Review Manager Software. Heterogeneity between studies was assessed using Cochran's Q-test and I test statistics.
RESULTS
In total, 19,708 Asian breast cancer patients were pooled from 101 studies. In the neoadjuvant setting, taxane-anthracycline (TA) chemotherapy showed better pCR outcomes in triple-negative breast cancer (TNBC) (p<0.0001) and human epidermal growth factor receptor 2 enriched (HER2E) (p<0.0001) than luminal breast cancer patients. Similarly, taxane-platinum (TP) chemotherapy also showed better pCR outcomes in TNBC (p<0.0001) and HER2E (p<0.0001). Oestrogen receptor (ER)-negative, progesterone receptor (PR)-negative, HER2-positive and high Ki-67 were significantly associated with better pCR outcomes when treated with either TA or TP. Asian breast cancer patients harbouring wildtype PIK3CA were significantly associated with better pCR outcomes when treated with TA in the neoadjuvant setting (p=0.001).
CONCLUSIONS
In the neoadjuvant setting, molecular subtypes (HER2E and TNBC), biomarkers (ER, PR, HER2, HR, Ki-67, nm23-H1, CK5/6, and Tau), and gene (PIK3CA) are associated with increased pCR rates in Asian breast cancer patients. Hence, they could be further explored for their possible role in first-line treatment response, which can be utilised to treat breast cancer more efficiently in the Asian population. However, it needs to be further validated with additional powered studies.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021246295.
Topics: Female; Humans; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Class I Phosphatidylinositol 3-Kinases; Genetic Variation; Ki-67 Antigen; Receptor, ErbB-2; Receptors, Estrogen; Taxoids; Triple Negative Breast Neoplasms
PubMed: 38576013
DOI: 10.1186/s13643-024-02520-5