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American Journal of Obstetrics and... Sep 2023This study aimed to: (1) identify all relevant studies reporting on the diagnostic accuracy of maternal circulating placental growth factor) alone or as a ratio with... (Meta-Analysis)
Meta-Analysis Review
Accuracy of placental growth factor alone or in combination with soluble fms-like tyrosine kinase-1 or maternal factors in detecting preeclampsia in asymptomatic women in the second and third trimesters: a systematic review and meta-analysis.
OBJECTIVE
This study aimed to: (1) identify all relevant studies reporting on the diagnostic accuracy of maternal circulating placental growth factor) alone or as a ratio with soluble fms-like tyrosine kinase-1), and of placental growth factor-based models (placental growth factor combined with maternal factors±other biomarkers) in the second or third trimester to predict subsequent development of preeclampsia in asymptomatic women; (2) estimate a hierarchical summary receiver-operating characteristic curve for studies reporting on the same test but different thresholds, gestational ages, and populations; and (3) select the best method to screen for preeclampsia in asymptomatic women during the second and third trimester of pregnancy by comparing the diagnostic accuracy of each method.
DATA SOURCES
A systematic search was performed through MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform databases from January 1, 1985 to April 15, 2021.
STUDY ELIGIBILITY CRITERIA
Studies including asymptomatic singleton pregnant women at >18 weeks' gestation with risk of developing preeclampsia were evaluated. We included only cohort or cross-sectional test accuracy studies reporting on preeclampsia outcome, allowing tabulation of 2×2 tables, with follow-up available for >85%, and evaluating performance of placental growth factor alone, soluble fms-like tyrosine kinase-1- placental growth factor ratio, or placental growth factor-based models. The study protocol was registered on the International Prospective Register Of Systematic Reviews (CRD 42020162460).
METHODS
Because of considerable intra- and interstudy heterogeneity, we computed the hierarchical summary receiver-operating characteristic plots and derived diagnostic odds ratios, β, θ, and Λ for each method to compare performances. The quality of the included studies was evaluated by the QUADAS-2 tool.
RESULTS
The search identified 2028 citations, from which we selected 474 studies for detailed assessment of the full texts. Finally, 100 published studies met the eligibility criteria for qualitative and 32 for quantitative syntheses. Twenty-three studies reported on performance of placental growth factor testing for the prediction of preeclampsia in the second trimester, including 16 (with 27 entries) that reported on placental growth factor test alone, 9 (with 19 entries) that reported on the soluble fms-like tyrosine kinase-1-placental growth factor ratio, and 6 (16 entries) that reported on placental growth factor-based models. Fourteen studies reported on performance of placental growth factor testing for the prediction of preeclampsia in the third trimester, including 10 (with 18 entries) that reported on placental growth factor test alone, 8 (with 12 entries) that reported on soluble fms-like tyrosine kinase-1-placental growth factor ratio, and 7 (with 12 entries) that reported on placental growth factor-based models. For the second trimester, Placental growth factor-based models achieved the highest diagnostic odds ratio for the prediction of early preeclampsia in the total population compared with placental growth factor alone and soluble fms-like tyrosine kinase-1-placental growth factor ratio (placental growth factor-based models, 63.20; 95% confidence interval, 37.62-106.16 vs soluble fms-like tyrosine kinase-1-placental growth factor ratio, 6.96; 95% confidence interval, 1.76-27.61 vs placental growth factor alone, 5.62; 95% confidence interval, 3.04-10.38); placental growth factor-based models had higher diagnostic odds ratio than placental growth factor alone for the identification of any-onset preeclampsia in the unselected population (28.45; 95% confidence interval, 13.52-59.85 vs 7.09; 95% confidence interval, 3.74-13.41). For the third trimester, Placental growth factor-based models achieved prediction for any-onset preeclampsia that was significantly better than that of placental growth factor alone but similar to that of soluble fms-like tyrosine kinase-1-placental growth factor ratio (placental growth factor-based models, 27.12; 95% confidence interval, 21.67-33.94 vs placental growth factor alone, 10.31; 95% confidence interval, 7.41-14.35 vs soluble fms-like tyrosine kinase-1-placental growth factor ratio, 14.94; 95% confidence interval, 9.42-23.70).
CONCLUSION
Placental growth factor with maternal factors ± other biomarkers determined in the second trimester achieved the best predictive performance for early preeclampsia in the total population. However, in the third trimester, placental growth factor-based models had predictive performance for any-onset preeclampsia that was better than that of placental growth factor alone but similar to that of soluble fms-like tyrosine kinase-1-placental growth factor ratio. Through this meta-analysis, we have identified a large number of very heterogeneous studies. Therefore, there is an urgent need to develop standardized research using the same models that combine serum placental growth factor with maternal factors ± other biomarkers to accurately predict preeclampsia. Identification of patients at risk might be beneficial for intensive monitoring and timing delivery.
Topics: Female; Humans; Pregnancy; Biomarkers; Cross-Sectional Studies; Placenta Growth Factor; Pre-Eclampsia; Pregnancy Trimester, Third; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1
PubMed: 36990308
DOI: 10.1016/j.ajog.2023.03.032 -
Biochimica Et Biophysica Acta. Reviews... Nov 2023This study aimed to explore the efficacy and safety of trastuzumab plus tyrosine kinase inhibitors (TKIs) compared with those of trastuzumab monotherapy in patients with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This study aimed to explore the efficacy and safety of trastuzumab plus tyrosine kinase inhibitors (TKIs) compared with those of trastuzumab monotherapy in patients with human epidermal growth factor receptor (HER2)-positive breast cancer.
METHODS
The PubMed, Embase, Cochrane, and Web of Science databases were systematically searched for relevant articles from inception until September 2022. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Subgroup analyses were performed based on disease status, TKI type, and hormone receptor status.
RESULTS
Sixteen studies were included in the current analysis. Trastuzumab plus TKI significantly improved OS and PFS compared to trastuzumab monotherapy. In the neoadjuvant setting, trastuzumab plus TKI significantly increased the pathologic complete response (pCR) rate compared to trastuzumab monotherapy. Moreover, a higher objective response rate (ORR) was observed with trastuzumab plus TKI. Patients who received the combination therapy had a higher incidence of discontinuation, all-grade diarrhea, and grade ≥ 3 diarrhea.
CONCLUSIONS
Trastuzumab plus TKI was better than trastuzumab monotherapy for treating different stages of HER2-positive breast cancer. The safety of trastuzumab plus TKI anti-HER2 therapy was controllable. The different efficacies of TKIs combined with trastuzumab may be related to the mechanism of action of the different TKIs, needing further investigations.
Topics: Humans; Female; Trastuzumab; Breast Neoplasms; Tyrosine Kinase Inhibitors; Receptor, ErbB-2; Protein Kinase Inhibitors; Diarrhea
PubMed: 37640146
DOI: 10.1016/j.bbcan.2023.188969 -
Radiotherapy and Oncology : Journal of... Sep 2023In recent years, the treatment landscape for breast cancer has undergone significant advancements, with the introduction of several new anticancer agents. One such agent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
In recent years, the treatment landscape for breast cancer has undergone significant advancements, with the introduction of several new anticancer agents. One such agent is trastuzumab emtansine (T-DM1), an antibody drug conjugate that has shown improved outcomes in both early and advanced breast cancer. However, there is currently a lack of comprehensive evidence regarding the safety profile of combining T-DM1 with radiation therapy (RT). In this study, we aim to provide a summary of the available data on the safety of combining RT with T-DM1 in both early and metastatic breast cancer settings.
MATERIALS AND METHODS
This systematic review and meta-analysis project is part of the consensus recommendations by the European Society for Radiotherapy and Oncology (ESTRO) Guidelines Committee on integrating RT with targeted treatments for breast cancer. A thorough literature search was conducted using the PUBMED/MedLine, Embase, and Cochrane databases to identify original studies focusing on the safety profile of combining T-DM1 with RT.
RESULTS
After applying eligibility criteria, nine articles were included in the meta-analysis. Pooled data from these studies revealed a high incidence of grade 3 + radionecrosis (17%), while the rates of grade 3 + radiation-related pneumonitis (<1%) and skin toxicity (1%) were found to be very low.
CONCLUSION
Although there is some concern regarding a slight increase in pneumonitis when combining T-DM1 with postoperative RT, the safety profile of this combination was deemed acceptable for locoregional treatment in non-metastatic breast cancer. However, caution is advised when irradiating intracranial sites concurrently with T-DM1. There is a pressing need for international consensus guidelines regarding the safety considerations of combining T-DM1 and RT for breast cancer.
Topics: Humans; Female; Ado-Trastuzumab Emtansine; Trastuzumab; Receptor, ErbB-2; Antibodies, Monoclonal, Humanized; Maytansine; Treatment Outcome; Breast Neoplasms
PubMed: 37437610
DOI: 10.1016/j.radonc.2023.109805 -
Frontiers in Endocrinology 2023Noonan syndrome (NS) is a genetic multisystem disorder characterised by variable clinical manifestations including dysmorphic facial features, short stature, congenital...
BACKGROUND
Noonan syndrome (NS) is a genetic multisystem disorder characterised by variable clinical manifestations including dysmorphic facial features, short stature, congenital heart disease, renal anomalies, lymphatic malformations, chest deformities, cryptorchidism in males.
METHODS
In this narrative review, we summarized the available data on puberty and gonadal function in NS subjects and the role of the RAS/mitogen-activated protein kinase (MAPK) signalling pathway in fertility. In addition, we have reported our personal experience on pubertal development and vertical transmission in NS.
CONCLUSIONS
According to the literature and to our experience, NS patients seem to have a delay in puberty onset compared to the physiological timing reported in healthy children. Males with NS seem to be at risk of gonadal dysfunction secondary not only to cryptorchidism but also to other underlying developmental factors including the MAP/MAPK pathway and genetics. Long-term data on a large cohort of males and females with NS are needed to better understand the impact of delayed puberty on adult height, metabolic profile and well-being. The role of genetic counselling and fertility related-issues is crucial.
Topics: Male; Child; Adult; Female; Humans; Noonan Syndrome; Cryptorchidism; Gonads; Puberty; Mitogen-Activated Protein Kinases
PubMed: 37576960
DOI: 10.3389/fendo.2023.1213098 -
Acta Oncologica (Stockholm, Sweden) Dec 2023Patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) often experience cutaneous adverse events, such as rashes and pruritus. In... (Meta-Analysis)
Meta-Analysis
Comparison of cutaneous adverse events between second-generation tyrosine kinase inhibitors and imatinib for chronic myeloid leukemia: a systematic review and meta-analysis.
BACKGROUND
Patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) often experience cutaneous adverse events, such as rashes and pruritus. In this study, we aimed to compare the risks of cutaneous adverse events between imatinib- and second-generation TKI-treated patients with CML.
MATERIAL AND METHODS
Paired reviewers independently obtained studies from PubMed, Embase, and Cochrane Library published until 15 March 2022. The following terms were searched: (Leukemia, Myelogenous, Chronic and BCR-ABL Positive), chronic myeloid leukemia, tyrosine kinase inhibitor, TKI, imatinib, dasatinib, nilotinib, bosutinib, and radotinib. Two independent reviewers screened the results and selected articles on cutaneous adverse events. RevMan 5.4 and the Cochrane Collaboration tool were used to perform the meta-analysis and risk of bias assessment.
RESULTS AND CONCLUSION
Eleven trials involving 4502 patients were analyzed in this study. Patients treated with second-generation TKIs were significantly more likely to experience cutaneous adverse events than those treated with imatinib with a relative risk (RR) of 1.62 (95% confidence interval [CI], [1.25-2.09]). Except dasatinib (RR [95% CI], 1.39 [0.75-2.56]), the risk of adverse events was more with second-generation TKIs than with imatinib as follows: nilotinib (2.11 [1.53-2.90]), bosutinib (1.41 [1.07-1.86]), and radotinib (1.87 [1.33-2.63]). Rash was the most common cutaneous adverse event that was observed in 21.6% of cases across all grades, followed by pruritus (5.7%) and alopecia (4.3%). In conclusion, our findings suggest that cutaneous adverse events occur more frequently with second-generation TKIs than with imatinib. Therefore, effective management of the cutaneous outcome is necessary to achieve high patient adherence to medication and successful treatment with TKIs.
Topics: Humans; Imatinib Mesylate; Dasatinib; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Pyrimidines; Pruritus; Exanthema; Antineoplastic Agents
PubMed: 37787749
DOI: 10.1080/0284186X.2023.2263152 -
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 -
Inflammation Research : Official... Sep 2023The therapeutic efficacy of systemic Janus kinase (JAK) inhibitors in moderate-to-severe atopic dermatitis (AD) is well established. However, the associated risk of... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The therapeutic efficacy of systemic Janus kinase (JAK) inhibitors in moderate-to-severe atopic dermatitis (AD) is well established. However, the associated risk of incident acne, which is a prevalent adverse event in AD patients treated with systemic JAK inhibitors, has yet to be systematically analyzed.
METHODOLOGY
To evaluate the risk of incident acne in AD patients treated with systemic JAK inhibitors, an extensive database search (clinicaltrials.gov, PubMed) was performed to identify publications eligible for inclusion from January 2020 to October 2022. Five randomized clinical trials (RCTs) of abrocitinib, four RCTs of upadacitinib, and one RCT of baricitinib, encompassing a total of 7901 participants, were included in the analysis. The risk difference for incident acne between systemic JAK inhibitors and controls was assessed using Review Manager, version 5.3, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Meta-analysis elucidated a significant difference in the risk of incident acne between AD participants receiving 200 mg abrocitinib (Mantel-Haenszel risk difference, 3.69; 95% CI 1.60-8.48; P < 0.01), 15 mg upadacitinib (Mantel-Haenszel risk difference, 4.61; 95% CI 2.79-7.62; P < 0.00001), and 30 mg upadacitinib (Mantel-Haenszel risk difference, 6.82; 95% CI 4.59-10.13; P < 0.00001) compared with controls receiving placebo or dupilumab. In contrast, no significant difference was found in the risk of incident acne between participants receiving 100 mg abrocitinib, 2 mg baricitinib, and 4 mg baricitinib, as compared with controls.
CONCLUSIONS
Based on the current evidence, there is an increased risk of acne related to systemic JAK inhibitors, particularly with abrocitinib and upadacitinib. For patients predisposed to acne, the balance between the benefits of symptomatic relief from AD and the potential risk of acne may need to be carefully considered. This study contributes to a nuanced understanding of the risk profile of systemic JAK inhibitors and has the potential to guide personalized treatment decisions for AD patients.
Topics: Humans; Dermatitis, Atopic; Janus Kinase Inhibitors; Acne Vulgaris; Janus Kinase 1
PubMed: 37707560
DOI: 10.1007/s00011-023-01789-x -
European Journal of Medical Research Aug 2023The aim of this study was to evaluate the efficacy and safety of osimertinib for the treatment of leptomeningeal metastases (LM) from epidermal growth factor receptor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this study was to evaluate the efficacy and safety of osimertinib for the treatment of leptomeningeal metastases (LM) from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC).
METHODS
We conducted a systematic review and meta-analysis to aggregate the clinical outcomes of patients with LM from EGFR-mutant NSCLC treated with osimertinib. A comprehensive literature search for published and unpublished studies was implemented in April 2021 of PubMed, EMBASE, the Cochrane Library, and several international conference databases, in accordance with the PRISMA guidelines. Meta-analysis of proportions was conducted to calculate the pooled rate of overall response rate (ORR), disease control rate (DCR), one-year overall survival (OS), and adverse events (AEs).
RESULTS
A total of eleven studies (five prospective and six retrospective) including 353 patients were included. The majority of patients (346/353, 98.0%) received osimertinib as ≥ 2nd-line treatment for LM, either at a dosage of 80 mg (161/353, 45.6%) or 160 mg (191/353, 54.1%). The pooled rates of ORR and DCR were 42% (95% CI 24% to 59%) and 93% (95% CI 88% to 97%), respectively. The pooled one-year OS rate was 59% (95% CI 53% to 65%) in 233 patients from five studies. The highest incidence of AEs of all grades was rash (53%), followed by diarrhea (45%), paronychia (35%), decreased appetite (35%), and dry skin (27%), based on data from four studies.
CONCLUSIONS
Our study highlighted and confirmed the meaningful efficacy and a manageable safety profile of osimertinib for the treatment of LM from EGFR-mutant advanced NSCLC.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Retrospective Studies; Prospective Studies; Antineoplastic Agents; ErbB Receptors; Protein Kinase Inhibitors; Mutation
PubMed: 37542339
DOI: 10.1186/s40001-023-01219-y -
Radiotherapy and Oncology : Journal of... Oct 2023The addition of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) to endocrine therapy in hormone receptor-positive (HR+) human epidermal growth factor 2-negative (HER2-)... (Meta-Analysis)
Meta-Analysis
Safety and feasibility of CDK4/6 inhibitors treatment combined with radiotherapy in patients with HR-positive/HER2-negative breast cancer. A systematic review and meta-analysis.
BACKGROUND AND PURPOSE
The addition of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) to endocrine therapy in hormone receptor-positive (HR+) human epidermal growth factor 2-negative (HER2-) breast cancer has led to practice-changing improvements in overall survival. However, there are conflicting data concerning the safety of CDK4/6i combination with radiotherapy, and no consensus guidelines exist to guide practice. We conducted a meta-analysis to assess the safety and feasibility of CDK4/6i treatment with radiotherapy.
MATERIALS AND METHODS
A comprehensive search was performed in PubMed/MEDLINE, Web of Science, and Scopus, for studies in advanced/metastatic breast cancer receiving CDK4/6i and radiotherapy with the provided safety data on the occurrence of toxicity. The main outcomes were safety (grade 3-5 adverse events), CDK 4/6i dose reduction, and the discontinuation rate due to toxicity.
RESULTS
Fifteen studies comprising 1133 patients with HR+/HER2- breast cancer patients were included. Among them, 617 pts received CDK4/6i and radiotherapy; the median follow-up was 17.0 months (IQR 9.2 - 18.0), and the median age was 58.8 years (IQR 55.5---62.5). The pooled prevalence of severe hematologic toxicity was 29.4% (95% CI 14.0% - 47.4%; I = 93%; τ = 0.084; p < 0.01 and severe non-hematologic toxicity was 2.8% (95% CI 1.1% - 4.8%; I = 0%; τ = 0.0; p = 0.67). The pooled prevalence of CDK4/6i dose reduction was 24.0% (95% CI 11.1% - 39.4%; I = 90%; τ = 0.052; p < 0.01) with no difference between CDK4/6i plus RT vs. CDK4/6i (odds ratio of 0.934; 95% CI 0.66 - 1.33; I = 0%; τ = 0.0; p = 0.56). The pooled prevalence of CDK4/6i discontinuation due to toxicity was 2.3% (95% CI 0.4% - 5.2%; I = 23%; τ = 0.002; p = 0.24).
CONCLUSION
The findings of this study suggest that radiotherapy in addition to CDK4/6i treatment in breast cancer patients is generally safe and well tolerated and remains a viable treatment option.
Topics: Female; Humans; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Consensus; Cyclin-Dependent Kinase 4; Epidermal Growth Factor; Feasibility Studies; Protein Kinase Inhibitors; Radiotherapy
PubMed: 37536378
DOI: 10.1016/j.radonc.2023.109839 -
Journal of Cancer Research and Clinical... Nov 2023The phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway regulates proliferation, survival and metabolism, and its dysregulation... (Review)
Review
The phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway regulates proliferation, survival and metabolism, and its dysregulation is one of the most frequent oncogenic events across human malignancies. Over the last two decades, there has been significant focus on the clinical development of PI3K pathway inhibitors. More than 40 different inhibitors of this axis have reached various stages of clinical trials, but only a few of them have been approved by the Food and Drug Administration (FDA) for cancer treatment. These clinical results, however, could be improved given the importance of PI3K signaling in cancer and its role in linking cancer growth with metabolism. In this systematic review, after a glance at PI3K/AKT/mTOR pathway and its different inhibitors, we retrieved registered clinical trials evaluating the efficacy and safety of PI3K/AKT/mTOR inhibitors on Clinicaltrials.gov. Following the extraction of the data, finally we analyzed 2250 included studies in multiple steps, beginning with an overview and moving on to the details about type of malignancies, inhibitors, and treatment strategies. We also took a closer look at more than 100 phase III-IV clinical trials to pinpoint promising therapies, hoping that presenting a comprehensive picture of current clinical trials casts a flash of light on what remains to be done in future clinical trials of PI3K/AKT/mTOR inhibitors in human malignancies.
Topics: Humans; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Sirolimus; MTOR Inhibitors; Neoplasms; TOR Serine-Threonine Kinases; Phosphoinositide-3 Kinase Inhibitors
PubMed: 37594532
DOI: 10.1007/s00432-023-05277-x