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Frontiers in Oncology 2024Administering adjuvant therapy following liver resection is crucial for patients with hepatocellular carcinoma (HCC) exhibiting high-risk recurrence factors. Immune...
Can adjuvant immune checkpoint inhibitors improve the long-term outcomes of hepatocellular carcinoma with high-risk recurrent factors after liver resection? A meta-analysis and systematic review.
BACKGROUND
Administering adjuvant therapy following liver resection is crucial for patients with hepatocellular carcinoma (HCC) exhibiting high-risk recurrence factors. Immune checkpoint inhibitors (ICIs) are effective against unresectable HCC; however, their effectiveness and safety for this specific patient group remain uncertain.
METHODS
We conducted an extensive literature search across four scholarly databases to identify relevant studies. Our primary endpoints were overall survival (OS), recurrence-free survival (RFS), and adverse events (AEs). OS and RFS were quantified using hazard ratios (HRs), whereas the 1-, 2-, and 3-year OS and RFS rates were expressed as risk ratios (RRs). Additionally, the incidence of AEs was calculated.
RESULTS
Our meta-analysis included 11 studies (N = 3,219 patients), comprising two randomized controlled trials (RCTs) and nine retrospective studies. Among these, eight studies reported HRs for OS, showing a statistically significant improvement in OS among patients receiving adjuvant ICIs (HR, 0.60; 95% confidence interval [CI], 0.45-0.80; p < 0.0001). All included studies reported HRs for RFS, indicating a favorable impact of adjuvant ICIs (HR, 0.62; 95% CI, 0.52-0.73; p < 0.0001). Moreover, aggregated data demonstrated improved 1- and 2-year OS and RFS rates with adjuvant ICIs. The incidence rate of AEs of any grade was 0.70 (95% CI, 0.49-0.91), with grade 3 or above AEs occurring at a rate of 0.12 (95% CI, 0.05-0.20).
CONCLUSION
Adjuvant ICI therapy can enhance both OS and RFS rates in patients with HCC exhibiting high-risk recurrence factors, with manageable AEs.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/#recordDetails PROSPERO, identifier CRD42023488250.
PubMed: 38854716
DOI: 10.3389/fonc.2024.1374262 -
BMC Cancer Jun 2024Poly (ADP- ribose) polymerase inhibitors (PARPi) has been increasingly adopted for metastatic castration-resistance prostate cancer (mCRPC) patients with homologous... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Poly (ADP- ribose) polymerase inhibitors (PARPi) has been increasingly adopted for metastatic castration-resistance prostate cancer (mCRPC) patients with homologous recombination repair deficiency (HRD). However, it is unclear which PARPi is optimal in mCRPC patients with HRD in 2nd -line setting.
METHOD
We conducted a systematic review of trials regarding PARPi- based therapies on mCRPC in 2nd -line setting and performed a Bayesian network meta-analysis (NMA). Radiographic progression-free survival (rPFS) was assessed as primary outcome. PSA response and adverse events (AEs) were evaluated as secondary outcomes. Subgroup analyses were performed according to specific genetic mutation.
RESULTS
Four RCTs comprised of 1024 patients (763 harbored homologous recombination repair (HRR) mutations) were identified for quantitative analysis. Regarding rPFS, olaparib monotherapy, rucaparib and cediranib plus olaparib showed significant improvement compared with ARAT. Olaparib plus cediranib had the highest surface under cumulative ranking curve (SUCRA) scores (87.5%) for rPFS, followed by rucaparib, olaparib and olaparib plus abiraterone acetate prednisone. For patients with BRCA 1/2 mutations, olaparib associated with the highest probability (98.1%) of improved rPFS. For patients with BRCA-2 mutations, olaparib and olaparib plus cediranib had similar efficacy. However, neither olaparib nor rucaparib showed significant superior effectiveness to androgen receptor-axis-targeted therapy (ARAT) in patients with ATM mutations. For safety, olaparib showed significantly lower ≥ 3 AE rate compared with cediranib plus olaparib (RR: 0.72, 95% CI: 0.51, 0.97), while olaparib plus cediranib was associated with the highest risk of all-grade AE.
CONCLUSION
PARPi-based therapy showed considerable efficacy for mCRPC patients with HRD in 2nd -line setting. However, patients should be treated accordingly based on their genetic background as well as the efficacy and safety of the selected regimen.
TRIAL REGISTRATION
CRD42023454079.
Topics: Humans; Poly(ADP-ribose) Polymerase Inhibitors; Bayes Theorem; Prostatic Neoplasms, Castration-Resistant; Mutation; Male; Phthalazines; Network Meta-Analysis; Piperazines; BRCA2 Protein; Recombinational DNA Repair; Antineoplastic Combined Chemotherapy Protocols; Randomized Controlled Trials as Topic; Progression-Free Survival; Indoles; BRCA1 Protein; Treatment Outcome; Quinazolines
PubMed: 38851712
DOI: 10.1186/s12885-024-12388-2 -
BMC Gastroenterology Jun 2024Despite transarterial chemoembolization (TACE) was recommended as first line therapy for intermediate hepatocellular carcinoma (HCC), the efficacy of transarterial... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite transarterial chemoembolization (TACE) was recommended as first line therapy for intermediate hepatocellular carcinoma (HCC), the efficacy of transarterial embolization (TAE) has not been widely recognized. This work was to determine whether TAE was as effective and safe as TACE for unresectable HCC.
METHODS
We performed a systematic search of electronic databases and other sources for randomized controlled studies (RCTs) comparing TAE with TACE for unresectable HCC. Results were expressed as Hazard Ratio (HR) for survival and Odds Ratio (OR) for dichotomous outcomes using RevMan 5.4.1.
RESULTS
We included 6 trials with 683 patients. The risk of bias of included RCTs was from unclear to high risk. There were no significant differences between TACE and TAE for progression-free survival (HR 0.83, 95% CI 0.45-1.55; p = 0.57), overall survival (HR 1.10, 95% CI 0.90-1.35; p = 0.36), and objective response rate (OR 1.17, 95% CI 0.80-1.71; p = 0.42) without obvious publication bias. Sensitivity analyses confirmed the robustness of the results. TAE group reported similar or less adverse effects than TACE group in all the studies.
CONCLUSIONS
Our study demonstrated that TAE was as effective as TACE. Since TAE was simpler, cheaper and had less adverse effects than TACE, TAE should be a better choice in most cases where TACE was indicated for unresectable HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Chemoembolization, Therapeutic; Randomized Controlled Trials as Topic; Embolization, Therapeutic; Treatment Outcome
PubMed: 38849765
DOI: 10.1186/s12876-024-03282-z -
Medicine Jun 2024The study aimed to predict the risk factors of deep vein thrombosis of lower extremity after traumatic fracture of lower extremity, so as to apply effective strategies... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The study aimed to predict the risk factors of deep vein thrombosis of lower extremity after traumatic fracture of lower extremity, so as to apply effective strategies to prevent deep vein thrombosis of lower extremity, improve survival rate, and reduce medical cost.
METHODS
The English and Chinese literatures published from January 2005 to November 2023 were extracted from PubMed, Embase, Willey Library, Scopus, CNKI, Wanfang, and VIP databases. Statistical analysis was performed using Stata/SE 16.0 software.
RESULTS
A total of 13 articles were included in this paper, including 2699 venous thromboembolism (VTE) patients and 130,507 normal controls. According to the meta-results, 5 independent risk factors can be identified: history of VTE was the most significant risk factor for deep vein thrombosis after traumatic lower extremity fracture (risk ratio [RR] = 6.45, 95% confidence interval [CI]: 1.64-11.26); age (≥60) was the risk factor for deep vein thrombosis after traumatic lower extremity fracture (RR = 1.60, 95% CI: 1.02-2.18); long-term braking was a risk factor for deep vein thrombosis after traumatic lower extremity fracture (RR = 1.52, 95% CI: 1.11-1.93); heart failure was a risk factor for deep vein thrombosis after traumatic lower extremity fracture (RR = 1.92, 95% CI: 1.51-2.33); obesity was a risk factor for deep vein thrombosis after traumatic lower extremity fracture (RR = 1.59, 95% CI: 1.35-1.83).
CONCLUSION
The study confirmed that the history of deep vein thrombosis, age (60 + years), previous history of VTE, obesity, prolonged bed rest, and heart failure are all associated with an increased risk of VTE. By identifying these significant risk factors, we can more intensively treat patients at relatively high risk of VTE, thereby reducing the incidence of VTE. However, the limitation of the study is that the sample may not be diversified enough, and it fails to cover all potential risk factors, which may affect the universal applicability of the results. Future research should include a wider population and consider more variables in order to obtain a more comprehensive risk assessment.
Topics: Humans; Age Factors; Fractures, Bone; Heart Failure; Lower Extremity; Risk Factors; Venous Thrombosis; Middle Aged
PubMed: 38847716
DOI: 10.1097/MD.0000000000038439 -
Annals of Medicine and Surgery (2012) Jun 2024Although conversion arthroplasty of fused hips can relieve pain and provide patient satisfaction, long-term outcomes of total hip arthroplasty (THA) after hip fusion...
BACKGROUND
Although conversion arthroplasty of fused hips can relieve pain and provide patient satisfaction, long-term outcomes of total hip arthroplasty (THA) after hip fusion remain a subject of debate. This meta-analysis aimed to assess the effectiveness of THA for fused hips over a long period with concerns over potential complications.
METHODS
A systematic search of five databases from 2000 until 2023 identified English studies evaluating THA for fused hips with at least 100 months of follow-up. Meta-analyses were conducted using random-effect models via the comprehensive meta-analysis software. Sensitivity analysis, in-depth meta-regression, Egger's test, and the trim-and-fill method were performed appropriately.
RESULTS
The meta-analysis assessed 790 patients and 889 hips with a mean follow-up of 11 years. At the final follow-up, the mean Harris Hip Score (HHS) and leg length discrepancy (LLD) improved by 34.755 and 2.3 cm from the baseline, respectively. Regarding survival of hip fusion conversion to THA, most studies (88.8%) reported a 5-year implant survival rate of at least 90%, and the 15-year and 20-year implant survival rates, ranged between 80-90% and 70-90%, respectively. Subjective dissatisfaction with the conversion of hip fusion to THA was only 5.3%. Composite rates of revision, instability, and aseptic loosening were 13.6%, 3.8%, and 8.8%, respectively.
CONCLUSIONS
Conversion of fused hips to THA results in favourable long-term outcomes regarding HHS, LLD, survival rates, and subjective satisfaction, leading to improved quality of life in properly selected patients. However, the presence of complications should be considered when evaluating the overall success of the procedure.
PubMed: 38846831
DOI: 10.1097/MS9.0000000000002024 -
JTO Clinical and Research Reports Jun 2024The available approved anticancer drugs for Chinese patients are relatively limited because of China's low participation rate in international clinical trials....
Efficacy and Safety of Anti-Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Antibodies Plus Chemotherapy as First-Line Treatment for NSCLC in the People's Republic of China: a Systematic Review and Meta-Analysis.
INTRODUCTION
The available approved anticancer drugs for Chinese patients are relatively limited because of China's low participation rate in international clinical trials. Therefore, a focus on approved anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) drugs in China is needed. This study aims to assess the heterogeneity of anti-PD-1/PD-L1 antibodies manufactured in China (domestic PD-1/PD-L1) and overseas (imported PD-1/PD-L1) when combined with chemotherapy as the first-line treatment of NSCLC.
METHODS
A systematic search was performed using PubMed, EMBASE, and Cochrane Library of publications up to July 13, 2023. Meta-analysis was applied to compare the efficacy and safety profile between anti-PD-1/PD-L1 antibodies plus chemotherapy (PD-1/PD-L1+Chemo) and chemotherapy alone using STATA software. Pooled hazard ratios for progression-free survival and overall survival, odds ratios for objective response rate, and incidence rate of grade greater than or equal to three treatment-related adverse events with 95% confidence intervals were calculated in the domestic group and imported group by a random-effects model, and the heterogeneity between the two estimates was assessed.
RESULTS
There were 14 eligible clinical studies with a total of 3951 patients involved in this analysis, including eight studies of domestic PD-1/PD-L1+Chemo and six studies of imported PD-1/PD-L1+Chemo. The study revealed that there was no significant difference between domestic and imported PD-1/PD-L1+Chemo in overall survival ( = 0.80), progression-free survival ( = 0.53), and incidence rate of grade greater than or equal to three treatment-related adverse events ( = 0.10). Nevertheless, the objective response rate of imported PD-1/PD-L1+Chemo was significantly higher than that of domestic PD-1/PD-L1+Chemo ( = 0.03).
CONCLUSIONS
Domestic anti-PD-1/PD-L1 antibodies plus chemotherapy were found to have comparable efficacy and safety to those combined with imported anti-PD-1/PD-L1 antibodies based on current evidence.
PubMed: 38846810
DOI: 10.1016/j.jtocrr.2024.100678 -
Oncology Letters Jul 2024The present study compared the differences in effectiveness and safety between segmentectomy (ST) and wedge resection (WR) in patients with operable non-small cell lung...
Effectiveness and safety of segmentectomy vs. wedge resection for the treatment of patients with operable non‑small cell lung cancer: A meta‑analysis and systematic review.
The present study compared the differences in effectiveness and safety between segmentectomy (ST) and wedge resection (WR) in patients with operable non-small cell lung cancer (NSCLC). The PubMed, EMBASE, Cochrane Library and Web of Science databases were searched for papers published from inception until July 2023. The inclusion criteria were based on the population, intervention, comparator, outcomes and study designs. ROBINS-I was selected to assess the risk of bias and quality of evidence in the included non-randomised studies. Appropriate effect sizes were selected, and subgroup analyses, heterogeneity tests, sensitivity analyses and publication bias were applied. A total of 18 retrospective studies were included, involving 19,381 patients with operable NSCLC. The 5-year overall survival rate [hazard ratio (HR), 0.19; 95% confidence interval (CI), 0.04, 0.34; P=0.014; I=76.3%], lung cancer-specific survival rate (HR, 0.3; 95% CI, 0.21, 0.38; P<0.01; I=13.8%) and metastasis rate [odds ratio (OR), 1.56; 95% CI, 1.03, 2.38; P=0.037] in patients with operable NSCLC treated with WR were worse than those in patients treated with ST. The incidence of postoperative complications (OR, 0.44; 95% CI, 0.23, 0.82) in the WR group was lower than in the ST treatment group. There was no difference in postoperative recurrence (OR, 2.15; 95% CI, 0.97, 4.74; P=0.058) and mortality (risk difference, 0.04; 95% CI, -0.03, 0.11; P=0.287) between groups. Based on current evidence, patients with NSCLC treated with ST surgery have better postoperative survival but more complications than those patients treated with WT, while the effect of WR and ST on the recurrence rate and distant metastasis rate remains controversial.
PubMed: 38846430
DOI: 10.3892/ol.2024.14469 -
European Journal of Physical and... Jun 2024Spinal cord injuries have a considerable impact on healthcare in terms of mortality and morbidity. To address the difficulties faced by people affected by this condition...
INTRODUCTION
Spinal cord injuries have a considerable impact on healthcare in terms of mortality and morbidity. To address the difficulties faced by people affected by this condition and to raise awareness among stakeholders and policymakers, it is crucial to understand factors impacting survival. The purpose of this study is to systematically review the literature on life expectancy in people with traumatic spinal cord injury (tSCI), identifying key factors influencing mortality and survival.
EVIDENCE ACQUISITION
We conducted a systematic review, searching the literature for articles published up to July 2023 in PubMed, Web of Science, Cochrane Library, Google Scholar, and PEDro. Study outcomes had to be one of survival rate, life expectancy, standardized mortality ratio, or mortality rate. Only original research articles published in English were included. The quality of evidence was evaluated with the MINORS scale. The level of evidence was categorized according to the OCEBM model.
EVIDENCE SYNTHESIS
A comprehensive literature search yielded 102 articles, after the selection process 20 studies were included in our review. The main factors negatively influencing survival and life expectancy included higher neurological level of injury (NLI), completeness of the lesion, need for mechanical ventilation, increasing age, and male gender. The development of SCI-related comorbidities also negatively impacted survival as well as the lack of specialized care, especially in low-income countries. Additionally, pre-injury health status and personal income may affect survival.
CONCLUSIONS
Current literature shows that people affected by tSCI have a shorter life expectancy compared to the general population, highlighting some factors as possible predictors. It is difficult to compare available evidence due to the methodological heterogeneity across studies, which makes it challenging to draw generalizable conclusions on life expectancy in people with tSCI. Further studies are required to address these issues and accurately estimate life expectancy accounting for gaps in the management of people affected by tSCI to improve their care.
PubMed: 38842067
DOI: 10.23736/S1973-9087.24.08462-4 -
Frontiers in Immunology 2024A single immune checkpoint inhibitor (ICI) regimen has limited value in treating advanced bile tract cancer (BTC); therefore, ICI combination therapy is often applied.... (Meta-Analysis)
Meta-Analysis
Clinical outcomes of immune checkpoint inhibitor combined with other targeted or immunological therapy regimens for the treatment of advanced bile tract cancer: a systematic review and meta-analysis.
BACKGROUND AND AIMS
A single immune checkpoint inhibitor (ICI) regimen has limited value in treating advanced bile tract cancer (BTC); therefore, ICI combination therapy is often applied. This meta-analysis aimed to evaluate the effectiveness and safety of ICI combination therapy for advanced BTC.
METHODS
The study protocol was registered on PROSPERO (CRD42023452422). Data on the median progression-free survival (PFS), median overall survival (OS), objective response rate (ORR), disease control rate (DCR), and grade ≥3 adverse events (AEs) reported in relevant studies were pooled and analyzed to determine the efficacy and safety of ICI combination therapy.
RESULTS
In total, 15 studies with 665 patients were included in this meta-analysis. The overall ORR and DCR were 34.6% and 77.6%, respectively. The overall median PFS and OS were 6.06 months [95% confidence interval (CI): 4.91-7.21] and 12.11 months (95% CI: 10.66-13.55), respectively. Patients receiving ICI combination therapy in addition to other therapies had a considerably prolonged median PFS and OS (z=9.69, <0.001 and z=16.17, <0.001). Patients treated as first-line treatment had a substantially longer median PFS and OS compared to patients treated as non-first-line treatment (z=11.19, <0.001 and z=49.17, <0.001). The overall pooled grade ≥3 AEs rate was 38.2% (95% CI: 0.268-0.497) and was not influenced by whether ICI therapy was combined with other treatments or not or the treatment line.
CONCLUSION
Advanced BTC patients may benefit from ICI combination treatment without additional AEs. However, concurrent chemotherapy or radiotherapy is still needed to achieve better outcomes.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023452422.
Topics: Humans; Immune Checkpoint Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome; Biliary Tract Neoplasms; Immunotherapy
PubMed: 38840927
DOI: 10.3389/fimmu.2024.1378760 -
Cancer Immunology, Immunotherapy : CII Jun 2024Numerous randomized controlled trials (RCTs) have investigated PD-1/PD-L1 inhibitor-based combination therapies. The debate surrounding the potential additive clinical... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of anti-PD-1/PD-L1-based dual immunotherapies versus PD-1/PD-L1 inhibitor alone in patients with advanced solid tumor: a systematic review and meta-analysis.
INTRODUCTION
Numerous randomized controlled trials (RCTs) have investigated PD-1/PD-L1 inhibitor-based combination therapies. The debate surrounding the potential additive clinical benefits of combination of two immune-oncology (IO) therapies for cancer patients persists.
METHODS
Both published and grey sources of randomized clinical trials that compared anti-PD-1/PD-L1-based immunotherapy combinations with monotherapy in patients with advanced or metastatic solid tumors were encompassed. The primary outcome was progression-free survival (PFS), and secondary outcomes included objective response rate (ORR), overall survival (OS) and treatment-related adverse events (TRAEs).
RESULTS
Our analysis encompassed 31 studies comprising 10,341 patients, which covered 12 distinct immune-oncology combination regimens. Across all patients, the immunotherapy combinations exhibited the capability to enhance the ORR (OR = 1.23 [95% CI 1.13-1.34]) and extend PFS (HR = 0.91 [95% CI 0.87-0.95]). However, the observed enhancement in OS (HR = 0.96 [95% CI 0.91-1.01]) was of no significance. Greater benefits in terms of PFS (HR = 0.82 [95% CI 0.72 to 0.93]) and OS (HR = 0.85 [95% CI 0.73 to 0.99]) may be particularly pronounced in cases where PD-L1 expression is negative. Notably, despite a heightened risk of any-grade TRAEs (OR = 1.72 [95% CI 1.40-2.11]) and grade greater than or equal to 3 TRAEs (OR = 2.01 [95% CI 1.67-2.43]), toxicity was generally manageable.
CONCLUSIONS
This study suggests that incorporating an additional immunotherapy agent with PD-1/PD-L1 inhibitors can elevate the response rate and reduce the risk of disease progression, all while maintaining manageable toxicity. However, there remains a challenge in translating these primary clinical benefits into extended overall survival.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Immune Checkpoint Inhibitors; Immunotherapy; Neoplasms; Programmed Cell Death 1 Receptor; Randomized Controlled Trials as Topic
PubMed: 38834888
DOI: 10.1007/s00262-024-03734-1