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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 Cellular and Infection... 2023The GeneXpert MTB/RIF assay (Xpert) is a diagnostic tool that has been shown to significantly improve the accuracy of tuberculosis (TB) detection in clinical settings,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The GeneXpert MTB/RIF assay (Xpert) is a diagnostic tool that has been shown to significantly improve the accuracy of tuberculosis (TB) detection in clinical settings, with advanced sensitivity and specificity. Early detection of TB can be challenging, but Xpert has improved the efficacy of the diagnostic process. Nevertheless, the accuracy of Xpert varies according to different diagnostic specimens and TB infection sites. Therefore, the selection of adequate specimens is critical when using Xpert to identify suspected TB. As such, we have conducted a meta-analysis to evaluate the effectiveness of Xpert for diagnosis of different TB types using several specimens.
METHODS
We conducted a comprehensive search of several electronic databases, including PubMed, Embase, the Cochrane Central Register of Controlled Trials, and the World Health Organization clinical trials registry center, covering studies published from Jan 2008 to July 2022. Data were extracted using an adapted version of the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies. Where appropriate, meta-analysis was performed using random-effects models. The risk of bias and level of evidence was assessed using the Quality in Prognosis Studies tool and a modified version of the Grading of Recommendations Assessment, Development, and Evaluation. RStudio was utilized to analyze the results, employing the , , and packages.
RESULTS
After excluding duplicates, a total of 2163 studies were identified, and ultimately, 144 studies from 107 articles were included in the meta-analysis based on predetermined inclusion and exclusion criteria. Sensitivity, specificity and diagnostic accuracy were estimated for various specimens and TB types. In the case of pulmonary TB, Xpert using sputum (0.95 95%CI 0.91-0.98) and gastric juice (0.94 95%CI 0.84-0.99) demonstrated similarly high sensitivity, surpassing other specimen types. Additionally, Xpert exhibited high specificity for detecting TB across all specimen types. For bone and joint TB, Xpert, based on both biopsy and joint fluid specimens, demonstrated high accuracy in TB detection. Furthermore, Xpert effectively detected unclassified extrapulmonary TB and tuberculosis lymphadenitis. However, the Xpert accuracy was not satisfactory to distinguish TB meningitis, tuberculous pleuritis and unclassified TB.
CONCLUSIONS
Xpert has exhibited satisfactory diagnostic accuracy for most TB infections, but the efficacy of detection may vary depending on the specimens analyzed. Therefore, selecting appropriate specimens for Xpert analysis is essential, as using inadequate specimens can reduce the ability to distinguish TB.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=370111, identifier CRD42022370111.
Topics: Humans; Mycobacterium tuberculosis; Rifampin; Antibiotics, Antitubercular; Tuberculosis, Pulmonary; Tuberculosis, Meningeal; Latent Tuberculosis; Sensitivity and Specificity
PubMed: 37201118
DOI: 10.3389/fcimb.2023.1149741 -
Breast (Edinburgh, Scotland) Jun 2023Patients with HER2+ breast cancer (BC) frequently develop leptomeningeal metastases (LM). While HER2-targeted therapies have demonstrated efficacy in the neoadjuvant,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with HER2+ breast cancer (BC) frequently develop leptomeningeal metastases (LM). While HER2-targeted therapies have demonstrated efficacy in the neoadjuvant, adjuvant, and metastatic settings, including for parenchymal brain metastases, their efficacy for patients with LM has not been studied in a randomized controlled trial. However, several single-armed prospective studies, case series and case reports have studied oral, intravenous, or intrathecally administered HER2-targeted therapy regimens for patients with HER2+ BC LM.
METHODS
We conducted a systematic review and meta-analysis of individual patient data to evaluate the efficacy of HER2-targeted therapies in HER2+ BC LM in accordance with PRISMA guidelines. Targeted therapies evaluated were trastuzumab (intrathecal or intravenous), pertuzumab, lapatinib, neratinib, tucatinib, trastuzumab-emtansine and trastuzumab-deruxtecan. The primary endpoint was overall survival (OS), with CNS-specific progression-free survival (PFS) as a secondary endpoint.
RESULTS
7780 abstracts were screened, identifying 45 publications with 208 patients, corresponding to 275 lines of HER2-targeted therapy for BC LM which met inclusion criteria. In univariable and multivariable analyses, we observed no significant difference in OS and CNS-specific PFS between intrathecal trastuzumab compared to oral or intravenous administration of HER2-targeted therapy. Anti-HER2 monoclonal antibody-based regimens did not demonstrate superiority over HER2 tyrosine kinase inhibitors. In a cohort of 15 patients, treatment with trastuzumab-deruxtecan was associated with prolonged OS compared to other HER2-targeted therapies and compared to trastuzumab-emtansine.
CONCLUSIONS
The results of this meta-analysis, comprising the limited data available, suggest that intrathecal administration of HER2-targeted therapy for patients with HER2+ BC LM confers no additional benefit over oral and/or IV treatment regimens. Although the number of patients receiving trastuzumab deruxtecan in this cohort is small, this novel agent offers promise for this patient population and requires further investigation in prospective studies.
Topics: Female; Humans; Ado-Trastuzumab Emtansine; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Prospective Studies; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Trastuzumab; Meningeal Neoplasms
PubMed: 37156650
DOI: 10.1016/j.breast.2023.04.008 -
The Turkish Journal of Gastroenterology... Jun 2023Rifaximin is an oral antimicrobial drug with a broad-spectrum effect. It locally regulates the function and structure of intestinal bacteria and decreases intestinal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Rifaximin is an oral antimicrobial drug with a broad-spectrum effect. It locally regulates the function and structure of intestinal bacteria and decreases intestinal endotoxemia. We aimed to investigate the preventive role of rifaximin in recurrent episodes of hepatic encephalopathy in cases with a history of hepatic diseases.
METHODS
We searched PubMed, Scopus, and Web of Science for the relevant studies using the following search strategy: "(Rifaximin) OR (Xifaxan) AND (cirrhosis) OR (encephalopathy)." We assessed the risk of bias using Cochrane's risk of bias tool. We included the following outcomes: recurrence of hepatic encephalopathy, adverse events, mortality rate, and time to the first episode of hepatic encephalopathy from the time of randomization (days). We performed the analysis of homogeneous data under the fixed-effects model, while analysis of heterogeneous data was performed under the random-effects model.
RESULTS
We analyzed data obtained from 999 patients from 7 included trials. The overall risk ratio proved that the rifaximin group was associated with a lower recurrence rate than the control group (risk ratio [RR] = 0.61[0.50, 0.73], P = .001). We found no significant variation in both groups regarding adverse events (RR = 1.08 [0.89, 1.32], P = .41), and mortality rates (RR = 0.98 [0.61, 1.57], P = .93). The overall risk of bias results was low.
CONCLUSION
The meta-analysis showed that in patients allocated to the rifaximin group, the incidence rate of hepatic encephalopathy was significantly lower when compared with those in the control group with no difference in both groups regarding adverse events and mortality rates.
Topics: Humans; Rifaximin; Hepatic Encephalopathy; Liver Diseases; Liver Cirrhosis; Bias; Rifamycins
PubMed: 37051626
DOI: 10.5152/tjg.2023.22575 -
Journal of Gastrointestinal and Liver... Apr 2023Transjugular intrahepatic portosystemic shunt (TIPS) is often used in patients with cirrhosis to manage portal hypertension-related complications. Unfortunately, 35-50%... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Transjugular intrahepatic portosystemic shunt (TIPS) is often used in patients with cirrhosis to manage portal hypertension-related complications. Unfortunately, 35-50% of patients develop overt hepatic encephalopathy (HE) after TIPS. However, data on lactulose and rifaximin to prevent post-TIPS HE is limited. Therefore, we aimed to perform a network meta-analysis to investigate the efficacy of multiple pharmacological regimens in the prevention of post-TIPS HE.
METHODS
A comprehensive search strategy to identify reports of studies of rifaximin use on post-TIPS hepatic encephalopathy was constructed using truncated keywords, phrases, and subject headings developed in Embase. This strategy was translated to MEDLINE, Cochrane Central Register of Controlled Trials, and the Web of Science Core Collection, with all searches performed on 10 February 2022. No publication date or language limits were used.
RESULTS
The initial search identified 72 studies, and 56 studies were screened after removing duplicates. Five studies, two randomized controlled trials (RCTs) and three retrospective studies, met our inclusion criteria and were included in the final analysis. A total of 840 patients were included, with 65% male. Our meta- analysis did not find a statistically significant difference between lactulose vs placebo/no prophylaxis, nor rifaximin vs placebo/no prophylaxis, nor rifaximin plus lactulose vs placebo/no prophylaxis in the reduction of post-TIPS HE.
CONCLUSIONS
Rifaximin alone, lactulose alone, and rifaximin plus lactulose did not significantly reduce the development of post-TIPS HE. Based on the P-scores of the three treatment groups, the combination of rifaximin plus lactulose showed the most promising trend towards preventing post-TIPS HE. More studies, especially large RCTs, are warranted.
Topics: Male; Humans; Female; Hepatic Encephalopathy; Lactulose; Rifaximin; Network Meta-Analysis; Liver Cirrhosis
PubMed: 37004220
DOI: 10.15403/jgld-4508 -
Cancer Apr 2023This study compares the safety and efficacy of first-line treatments for anaplastic lymphoma kinase (ALK)-mutated non-small cell lung cancer (NSCLC). (Meta-Analysis)
Meta-Analysis
Efficacy and safety of first-line treatments for patients with advanced anaplastic lymphoma kinase mutated, non-small cell cancer: A systematic review and network meta-analysis.
BACKGROUND
This study compares the safety and efficacy of first-line treatments for anaplastic lymphoma kinase (ALK)-mutated non-small cell lung cancer (NSCLC).
METHODS
A comprehensive literature search was conducted in PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases. Abstracts related to lung cancer presented at important international conferences were also reviewed. Randomized clinical trials that qualified the inclusion criteria were subjected to Bayesian network meta-analysis and systematically reviewed.
RESULTS
The authors included a total of nine studies including 2441 patients and seven first-line treatments (ensartinib, brigatinib, crizotinib, lorlatinib, alectinib, ceritinib, and pemetrexed-based chemotherapy). Overall, lorlatinib appeared to confer the best progression-free survival (PFS) (probability of being the best [Prbest], 90%; surface under the cumulative ranking curve [SUCRA], 98%), and the same conclusion was obtained on paired comparisons (lorlatinib vs. ceritinib [hazard ratio (HR), 0.31; 95% confidence interval (CI), 0.20-0.47); lorlatinib vs. chemotherapy [HR, 0.17; 95% CI, 0.12-0.23]; crizotinib vs. lorlatinib [HR, 3.6; 95% CI, 2.4-5.2]; and brigatinib vs. lorlatinib [HR, 1.7; 95% CI, 1.0-2.8]). Alectinib conferred the best overall survival (OS) and safety profile. In the Asian population, ensartinib conferred the best PFS (Prbest 50%, SUCRA 87%), and for patients with brain metastases at baseline, lorlatinib showed the best PFS (Prbest 70%, SUCRA 93%).
CONCLUSIONS
For first-line treatment of patients with ALK-positive NSCLC, lorlatinib was associated with the best PFS and objective response rate, but poorer safety profile, whereas alectinib demonstrated the best OS and safety profile. In Asians, ensartinib conferred the best PFS benefit, and in the brain baseline metastasis population, lorlatinib conferred the best PFS benefit.
PLAIN LANGUAGE SUMMARY
Among the many molecularly targeted drugs currently used to treat anaplastic lymphoma kinase mutation-positive non-small cell lung cancer, lorlatinib may be one of the most effective targeted drugs. Lung cancer has long been at the top of cancer rankings in terms of incidence and mortality. Today, the treatment of lung cancer has moved into the era of precision therapy. In this article, we use a statistical approach to compare the efficacy and safety of targeted drugs that have been used in the first-line treatment of anaplastic lymphoma kinase mutations to improve the reference for clinicians to make treatment decisions in the real world.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Crizotinib; Anaplastic Lymphoma Kinase; Network Meta-Analysis; Bayes Theorem; Lactams, Macrocyclic; Protein Kinase Inhibitors
PubMed: 36748799
DOI: 10.1002/cncr.34664 -
The American Journal of Gastroenterology Feb 2023Patients with hepatic encephalopathy (HE) suffer from significant symptoms and impaired quality of life. Improved understanding on the potential benefits of first-line... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Patients with hepatic encephalopathy (HE) suffer from significant symptoms and impaired quality of life. Improved understanding on the potential benefits of first-line HE therapies may aid patient-provider discussions regarding expected benefits of HE treatments. We aimed to perform a systematic review to assess the effects of lactulose and rifaximin on patient-reported outcomes (PROs).
METHODS
We searched MEDLINE, EMBASE, and Cochrane Library databases for randomized trials or prospective cohort studies using lactulose and/or rifaximin for the management of HE and assessing changes in PRO using PRO instruments. Physician reviewers independently reviewed titles, abstracts, and full texts and extracted data independently. We performed random-effects meta-analyses to examine the effects of lactulose and rifaximin on PROs.
RESULTS
We identified 16 studies representing 1,376 patients that met inclusion criteria. Most studies assessed treatment of covert HE. In patients with covert HE, lactulose significantly improved overall patient-reported health-related quality of life measured by the Sickness Impact Profile with an estimated pooled mean difference of 6.92 (95% confidence interval: 6.66-7.18) and showed improvements in several subscales. Conversely, rifaximin demonstrated a nonstatistically significant mean difference in the total Sickness Impact Profile of 4.76 (95% confidence interval: -4.23 to 13.76), with strong evidence of heterogeneity between these studies. Studies examining other PRO instruments showed improvements in overall health-related quality of life, social functioning, and sleep from both lactulose and rifaximin.
DISCUSSION
Patients with HE treated with lactulose or rifaximin reported improvements in important PROs. These results may inform provider-patient communication and help manage patient expectations regarding the potential benefits of HE therapies.
Topics: Humans; Rifaximin; Lactulose; Hepatic Encephalopathy; Prospective Studies; Quality of Life; Gastrointestinal Agents; Drug Therapy, Combination; Rifamycins
PubMed: 36730910
DOI: 10.14309/ajg.0000000000002008 -
World Journal of Gastroenterology Jan 2023Due to increasing resistance rates of () to different antibiotics, failures in eradication therapies are becoming more frequent. Even though eradication criteria and...
BACKGROUND
Due to increasing resistance rates of () to different antibiotics, failures in eradication therapies are becoming more frequent. Even though eradication criteria and treatment algorithms for first-line and second-line therapy against infection are well-established, there is no clear recommendation for third-line and rescue therapy in refractory infection.
AIM
To perform a systematic review evaluating the efficacy and safety of rescue therapies against refractory infection.
METHODS
A systematic search of available rescue treatments for refractory infection was conducted on the National Library of Medicine's PubMed search platform based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized or non-randomized clinical trials and observational studies evaluating the effectiveness of infection rescue therapies were included.
RESULTS
Twenty-eight studies were included in the analysis of mean eradication rates as rescue therapy, and 21 of these were selected for analysis of mean eradication rate as third-line treatment. For rifabutin-, sitafloxacin-, levofloxacin-, or metronidazole-based triple-therapy as third-line treatment, mean eradication rates of 81.6% and 84.4%, 79.4% and 81.5%, 55.7% and 60.6%, and 62.0% and 63.0% were found in intention-to-treat (ITT) and per-protocol (PP) analysis, respectively. For third-line quadruple therapy, mean eradication rates of 69.2% and 72.1% were found for bismuth quadruple therapy (BQT), 88.9% and 90.9% for bismuth quadruple therapy, three-in-one, Pylera (BQT-Pylera), and 61.3% and 64.2% for non-BQT) in ITT and PP analysis, respectively. For rifabutin-, sitafloxacin-, levofloxacin-, or metronidazole-based triple therapy as rescue therapy, mean eradication rates of 75.4% and 78.8%, 79.4 and 81.5%, 55.7% and 60.6%, and 62.0% and 63.0% were found in ITT and PP analysis, respectively. For quadruple therapy as rescue treatment, mean eradication rates of 76.7% and 79.2% for BQT, 84.9% and 87.8% for BQT-Pylera, and 61.3% and 64.2% for non-BQT were found in ITT and PP analysis, respectively. For susceptibility-guided therapy, mean eradication rates as third-line and rescue treatment were 75.0% in ITT and 79.2% in PP analysis.
CONCLUSION
We recommend sitafloxacin-based triple therapy containing vonoprazan in regions with low macrolide resistance profile. In regions with known resistance to macrolides or unavailability of bismuth, rifabutin-based triple therapy is recommended.
Topics: Humans; Helicobacter Infections; Anti-Bacterial Agents; Metronidazole; Helicobacter pylori; Bismuth; Levofloxacin; Proton Pump Inhibitors; Drug Therapy, Combination; Macrolides; Drug Resistance, Bacterial; Tetracycline; Rifabutin
PubMed: 36687120
DOI: 10.3748/wjg.v29.i2.390 -
Clinical Infectious Diseases : An... May 2023Optimal doses of first-line drugs for treatment of drug-susceptible tuberculosis in children and young adolescents remain uncertain. We aimed to determine whether... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Optimal doses of first-line drugs for treatment of drug-susceptible tuberculosis in children and young adolescents remain uncertain. We aimed to determine whether children treated using World Health Organization-recommended or higher doses of first-line drugs achieve successful outcomes and sufficient pharmacokinetic (PK) exposures.
METHODS
Titles, abstracts, and full-text articles were screened. We searched PubMed, EMBASE, CENTRAL, and trial registries from 2010 to 2021. We included studies in children aged <18 years being treated for drug-susceptible tuberculosis with rifampicin (RIF), pyrazinamide, isoniazid, and ethambutol. Outcomes were treatment success rates and drug exposures. The protocol for the systematic review was preregistered in PROSPERO (no. CRD42021274222).
RESULTS
Of 304 studies identified, 46 were eligible for full-text review, and 12 and 18 articles were included for the efficacy and PK analyses, respectively. Of 1830 children included in the efficacy analysis, 82% had favorable outcomes (range, 25%-95%). At World Health Organization-recommended doses, exposures to RIF, pyrazinamide, and ethambutol were lower in children than in adults. Children ≤6 years old have 35% lower areas under the concentration-time curve (AUCs) than older children (mean of 14.4 [95% CI 9.9-18.8] vs 22.0 [13.8-30.1] μg·h/mL) and children with human immunodeficiency virus (HIV) had 35% lower RIF AUCs than HIV-negative children (17.3 [11.4-23.2] vs 26.5 [21.3-31.7] μg·h/mL). Heterogeneity and small sample sizes were major limitations.
CONCLUSIONS
There is large variability in outcomes, with an average of 82% favorable outcomes. Drug exposures are lower in children than in adults. Younger children and/or those with HIV are underexposed to RIF. Standardization of PK pediatric studies and individual patient data analysis with safety assessment are needed to inform optimal dosing.
Topics: Adult; Adolescent; Child; Humans; Antitubercular Agents; Pyrazinamide; Ethambutol; Tuberculosis; Rifampin; Isoniazid; HIV; HIV Infections
PubMed: 36609692
DOI: 10.1093/cid/ciac973 -
BMC Infectious Diseases Dec 2022Countries with high TB burden have expanded access to molecular diagnostic tests. However, their impact on reducing delays in TB diagnosis and treatment has not been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Countries with high TB burden have expanded access to molecular diagnostic tests. However, their impact on reducing delays in TB diagnosis and treatment has not been assessed. Our primary aim was to summarize the quantitative evidence on the impact of nucleic acid amplification tests (NAAT) on diagnostic and treatment delays compared to that of the standard of care for drug-sensitive and drug-resistant tuberculosis (DS-TB and DR-TB).
METHODS
We searched MEDLINE, EMBASE, Web of Science, and the Global Health databases (from their inception to October 12, 2020) and extracted time delay data for each test. We then analysed the diagnostic and treatment initiation delay separately for DS-TB and DR-TB by comparing smear vs Xpert for DS-TB and culture drug sensitivity testing (DST) vs line probe assay (LPA) for DR-TB. We conducted random effects meta-analyses of differences of the medians to quantify the difference in diagnostic and treatment initiation delay, and we investigated heterogeneity in effect estimates based on the period the test was used in, empiric treatment rate, HIV prevalence, healthcare level, and study design. We also evaluated methodological differences in assessing time delays.
RESULTS
A total of 45 studies were included in this review (DS = 26; DR = 20). We found considerable heterogeneity in the definition and reporting of time delays across the studies. For DS-TB, the use of Xpert reduced diagnostic delay by 1.79 days (95% CI - 0.27 to 3.85) and treatment initiation delay by 2.55 days (95% CI 0.54-4.56) in comparison to sputum microscopy. For DR-TB, use of LPAs reduced diagnostic delay by 40.09 days (95% CI 26.82-53.37) and treatment initiation delay by 45.32 days (95% CI 30.27-60.37) in comparison to any culture DST methods.
CONCLUSIONS
Our findings indicate that the use of World Health Organization recommended diagnostics for TB reduced delays in diagnosing and initiating TB treatment. Future studies evaluating performance and impact of diagnostics should consider reporting time delay estimates based on the standardized reporting framework.
Topics: Humans; Rifampin; Tuberculosis, Pulmonary; Mycobacterium tuberculosis; Delayed Diagnosis; Time-to-Treatment; Pathology, Molecular; Sensitivity and Specificity; Tuberculosis; Tuberculosis, Multidrug-Resistant
PubMed: 36517736
DOI: 10.1186/s12879-022-07855-9