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BMC Cancer Feb 2024The increasing number of sequential treatments complicates the evaluation of overall survival (OS) in clinical trials for hepatocellular carcinoma (HCC), therefore,...
BACKGROUND
The increasing number of sequential treatments complicates the evaluation of overall survival (OS) in clinical trials for hepatocellular carcinoma (HCC), therefore, reliable surrogate endpoints (SEs) are required. This study aimed to evaluate the surrogacy of progression-free survival (PFS) and one-year (1-yr) milestone survival for OS in HCC trials.
METHODS
We systematically searched databases for randomized clinical trials that evaluated systemic treatments for advanced HCC. Individual patient data were reconstructed to calculate the 1-yr survival rate. We adopted a two-stage meta-analytic validation model to evaluate the correlation between SEs and OS, and the correlation between treatment effects on SEs and OS. The hazard ratio (HR) was calculated to assess the treatment effects on PFS and OS, and the 1-yr survival ratio was calculated to evaluate the treatment effects on the 1-yr milestone survival.
RESULTS
Thirty-two HCC trials involving 13,808 patients were included. A weak correlation was detected between the median PFS and median OS (R2 = 0.32), whereas the correlation improved between PFS HR and OS HR (R2 = 0.58). We identified strong correlations between the 1-yr survival rate and median OS and between the 1-yr survival ratio and OS HR (R2 = 0.74 and 0.65, respectively). In subgroup analyses, PFS HR strongly correlated with OS HR in trials relevant to immune checkpoint inhibitors (ICIs). Although the correlation remained weak between PFS and OS even in trials with PFS HR ≤ 0.6, the 1-yr survival rate and 1-yr survival ratio were strong surrogates for median OS and OS HR, respectively (R2 = 0.77 and 0.75).
CONCLUSIONS
One-year milestone survival outperformed PFS as a SE for OS in HCC, indicating the application of 1-yr survival as a secondary endpoint. In particular, PFS HR was a potential SE for OS HR in the ICI trials.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Progression-Free Survival; Proportional Hazards Models; Biomarkers; Disease-Free Survival
PubMed: 38395854
DOI: 10.1186/s12885-024-12000-7 -
Medicine Feb 2024Situs inversus is a rare congenital anatomical variant that involves a group of anomalies regarding the arrangement of intrathoracic and intraabdominal organs. Being...
BACKGROUND
Situs inversus is a rare congenital anatomical variant that involves a group of anomalies regarding the arrangement of intrathoracic and intraabdominal organs. Being able to find in the abdominal region the liver, gallbladder, inferior vena cava, and head of the pancreas and ascending colon on the left side of the abdomen, while on the right side there is the spleen, the stomach, the body of the pancreas, the ligament of Treitz, descending colon among others. In this same way, the thoracic organs, lungs and heart, are changed in their position in a mirror translocation.
METHODS
We systematically searched MEDLINE, Web of Science, Google Scholar, CINAHL, Scopus, and LILACS; the search strategy included a combination of the following terms: "Situs inversus," "Situs inversus totalis," "Cancer," "Neoplasm," "Abdominopelvic regions," and "clinical anatomy."
RESULTS
Within the 41 included studies, 46 patients with situs inversus who had cancer, in addition to being found in this organ and in these regions, we also found as a result that the majority of the studies in the research were in stage II; finally, no one study could assert the direct relationship between the situs inversus totalis and the cancer.
CONCLUSION
If our hallmarks could make us think that more exhaustive follow-up of the stomach and other organs should be carried out in these patients, there could also be other predisposing factors for cancer, which is why more studies are suggested to give future diagnostic and treatment guidelines treatment.
Topics: Humans; Situs Inversus; Abdomen; Spleen; Dextrocardia; Neoplasms
PubMed: 38394506
DOI: 10.1097/MD.0000000000037093 -
Scientific Reports Feb 2024This study aimed to assess the therapeutic effect of immune checkpoint inhibitors (ICIs) in patients with unresectable hepatocellular carcinoma (uHCC) and investigate... (Meta-Analysis)
Meta-Analysis
Correlation between surrogate endpoints and overall survival in unresectable hepatocellular carcinoma patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.
This study aimed to assess the therapeutic effect of immune checkpoint inhibitors (ICIs) in patients with unresectable hepatocellular carcinoma (uHCC) and investigate the correlation between surrogate endpoints and overall survival (OS). A systematic literature search included phase I, II, and III clinical trials comparing ICIs to placebo or other therapies for uHCC treatment. Correlations between OS and surrogate endpoints were evaluated using meta-regression analyses and calculating the surrogate threshold effect (STE). The correlation analysis showed a weak association between OS and progression-free survival (PFS), with an R value of 0.352 (95% CI: 0.000-0.967). However, complete response (CR) exhibited a strong correlation with OS (R = 0.905, 95% CI: 0.728-1.000). Subgroup analyses revealed high correlations between OS and PFS, CR, stable disease (SD), and DC in phase III trials (R: 0.827-0.922). For the ICI + IA group, significant correlations were observed between OS and SD, progressive disease (PD), and grade 3-5 immune-related adverse events (irAEs) (R: 0.713-0.969). Analyses of the correlation between survival benefit and risk of mortality across various time points showed a strong association within the first year (R: 0.724-0.868) but a weak association beyond one year (R: 0.406-0.499). In ICI trials for uHCC, PFS has limited utility as a surrogate endpoint for OS, while CR exhibits a strong correlation with OS. Subgroup analyses highlight high correlations between OS and PFS, SD, and DC in phase III trials. Notably, the ICI + IA group shows significant associations between OS and SD, PD, and grade 3-5 irAEs. These findings offer valuable insights for interpreting trial outcomes and selecting appropriate endpoints in future clinical studies involving ICIs for uHCC patients.
Topics: Humans; Carcinoma, Hepatocellular; Immune Checkpoint Inhibitors; Liver Neoplasms; Biomarkers; Progression-Free Survival
PubMed: 38383730
DOI: 10.1038/s41598-024-54945-6 -
Cancer Causes & Control : CCC Jun 2024The association between blood lipid levels and the risk of developing liver cancer remains a subject of ongoing debate. To elucidate this association, we conducted a... (Meta-Analysis)
Meta-Analysis
PURPOSE
The association between blood lipid levels and the risk of developing liver cancer remains a subject of ongoing debate. To elucidate this association, we conducted a meta-analysis by systematically incorporating data from all relevant prospective cohort studies.
METHODS
We conducted a systematic search of the PubMed, Embase, Web of Science, and Cochrane Library databases covering studies published from database inception through July 2023. This study included prospective cohort studies related to lipid profiles (e.g., total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels) that reported hazard ratios (HRs) or relative risks (RRs) with corresponding 95% confidence intervals (95% CIs) to investigate their association with the risk of liver cancer. During the analysis process, we used fixed-effects or random-effects models based on the level of heterogeneity among the studies and obtained pooled risk ratios using these models. To ensure the robustness and reliability of the study findings, we also conducted sensitivity analyses and publication bias analyses.
RESULTS
After conducting a systematic search, 12 studies were identified from a total of 11,904 articles and were included in the meta-analysis. These studies included a combined population of 10,765,221 participants, among whom 31,055 cases of liver cancer were reported. The analysis revealed that the pooled HR for the serum TC concentration (highest versus lowest) was 0.45 (95% CI = 0.35-0.58, I = 78%). For TGs, the HR was 0.67 (95% CI = 0.46-0.96, I = 86%), while for HDL-C, the HR was 0.72 (95% CI = 0.58-0.90, I = 65%). The HR for LDL-C was 0.51 (95% CI = 0.23-1.13, I = 93%).
CONCLUSION
The findings of this study indicate that serum TC, TG, and HDL-C levels are negatively associated with liver cancer risk, suggesting that higher concentrations of these lipids are associated with a reduced risk of liver cancer. However, no significant association has been found between LDL-C levels and liver cancer risk.
Topics: Humans; Liver Neoplasms; Risk Factors; Lipids
PubMed: 38376693
DOI: 10.1007/s10552-024-01853-9 -
World Journal of Surgical Oncology Feb 2024Whether radiofrequency ablation (RFA) and liver resection (LR) are comparable treatments for early-stage hepatocellular carcinoma (HCC) is controversial. We conducted... (Meta-Analysis)
Meta-Analysis
Comparison of liver resection and radiofrequency ablation in long-term survival among patients with early-stage hepatocellular carcinoma: a meta-analysis of randomized trials and high-quality propensity score-matched studies.
BACKGROUND
Whether radiofrequency ablation (RFA) and liver resection (LR) are comparable treatments for early-stage hepatocellular carcinoma (HCC) is controversial. We conducted this study to provide ample clinical evidence for the argument.
METHODS
The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched to identify randomized controlled trials (RCTs) and propensity score-matched (PSM) studies that compared long-term outcomes of both RFA and LR for patients with early-stage HCC. The hazard ratios (HRs) with 95% confidence intervals (95% CI) of overall survival (OS) and disease-free survival (DFS) were calculated.
RESULTS
Thirty-six studies consisting of six RCTs and 30 PSM studies were included in this study, and a total of 7384 patients were involved, with 3694 patients being treated with LR and 3690 patients with RFA. Meta-analysis showed that LR provided better OS and DFS than RFA (HR: 1.22, 95% CI: 1.13-1.31; HR: 1.56, 95% CI: 1.39-1.74, respectively). A sensitivity analysis indicated that the results were stable. For the subgroup of patients with BCLC 0 stage, RFA and LR resulted in similar OS and DFS. For the subgroup of patients with single tumor sizes less than 3 cm, RFA reached similar OS (HR: 1.19, 95% CI: 0.90-1.58) but worse DFS compared with LR (HR: 1.45, 95% CI: 1.11-1.90). For the subgroup of ablation margin larger than 0.5 cm, LR still resulted in better OS than RFA (HR: 1.29, 95% CI: 1.09-1.53); while the ablation margin was larger than 1 cm, both RFA and LR resulted in similar OS. The modality of RFA was also a factor that affected results. Subgroup analysis showed that patients receiving ultrasound-guided RFA had worse OS and DFS than LR (HR: 1.24, 95% CI: 1.14-1.36; HR: 1.44, 95% CI: 1.25-1.66, respectively).
CONCLUSIONS
Meta-analysis showed that LR provided better OS and DFS for patients with early-stage HCC. However, RFA and LR had similar effects on long-term survival in patients with BCLC 0 stage HCC. RFA and LR probably had similar effects on OS in patients with solitary HCC less than 3 cm or when the ablation margin was larger than 1 cm which need more studies to confirm. The effects of different modalities of RFA on long-term survival are needed for further assessment.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Propensity Score; Treatment Outcome; Catheter Ablation; Randomized Controlled Trials as Topic; Radiofrequency Ablation; Hepatectomy; Retrospective Studies
PubMed: 38369480
DOI: 10.1186/s12957-024-03330-8 -
Clinical Colorectal Cancer Jun 2024A survey of medical oncologists (MOs), radiation oncologists (ROs), and surgical oncologists (SOs) who are experts in the management of patients with metastatic...
BACKGROUND
A survey of medical oncologists (MOs), radiation oncologists (ROs), and surgical oncologists (SOs) who are experts in the management of patients with metastatic colorectal cancer (mCRC) was conducted to identify factors used to consider metastasis-directed therapy (MDT).
MATERIALS AND METHODS
An online survey to assess clinical factors when weighing MDT in patients with mCRC was developed based on systematic review of the literature and integrated with clinical vignettes. Supporting evidence from the systematic review was included to aid in answering questions.
RESULTS
Among 75 experts on mCRC invited, 47 (response rate 62.7%) chose to participate including 16 MOs, 16 ROs, and 15 SOs. Most experts would not consider MDT in patients with 3 lesions in both the liver and lung regardless of distribution or timing of metastatic disease diagnosis (6 vs. 36 months after definitive treatment). Similarly, for patients with retroperitoneal lymph node and lung and liver involvement, most experts would not offer MDT regardless of timing of metastatic disease diagnosis. In general, SOs were willing to consider MDT in patients with more advanced disease, ROs were more willing to offer treatment regardless of metastatic site location, and MOs were the least likely to consider MDT.
CONCLUSIONS
Among experts caring for patients with mCRC, significant variation was noted among MOs, ROs, and SOs in the distribution and volume of metastatic disease for which MDT would be considered. This variability highlights differing opinions on management of these patients and underscores the need for well-designed prospective randomized trials to characterize the risks and potential benefits of MDT.
Topics: Humans; Colorectal Neoplasms; Surveys and Questionnaires; Oncologists; Liver Neoplasms; Neoplasm Metastasis; Male; Female; Practice Patterns, Physicians'; Lung Neoplasms; Radiation Oncologists; Clinical Decision-Making; Middle Aged
PubMed: 38365567
DOI: 10.1016/j.clcc.2024.01.004 -
Immunity, Inflammation and Disease Feb 2024Chronic hepatitis B (CHB) virus is the most common risk factor for developing liver malignancy. Autophagy is an essential element in human cell maintenance. Several...
BACKGROUND
Chronic hepatitis B (CHB) virus is the most common risk factor for developing liver malignancy. Autophagy is an essential element in human cell maintenance. Several studies have demonstrated that autophagy plays a vital role in liver cancer at different stages. In this systematic review, we intend to investigate the role of polymorphism and mutations of autophagy-related genes (ATGs) in the pathogenesis and carcinogenesis of the hepatitis B virus (HBV).
MATERIALS AND METHODS
The search was conducted in online databases (Web of Science, PubMed, and Scopus) using Viruses, Infections, Polymorphism, Autophagy, and ATG. The study was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria.
RESULTS
The primary search results led to 422 studies. By screening and eligibility evaluation, only four studies were relevant. The most important polymorphisms in hepatocellular carcinoma were rs2241880 in ATG16L1, rs77859116, rs510432, and rs548234 in ATG5. Furthermore, some polymorphisms are associated with an increased risk of HBV infection including, rs2241880 in ATG16L1 and rs6568431 in ATG5.
CONCLUSION
The current study highlights the importance of rs2241880 in ATG16L1 and rs77859116, rs510432, and rs548234 in ATG5 for HBV-induced HCC. Additionally, some mutations in ATG16L1 and ATG5 were important in risk of HBV infection. The study highlights the gap of knowledge in the field of ATG polymorphisms in HBV infection and HBV-induced HCC.
Topics: Humans; Autophagy; Carcinoma, Hepatocellular; Genetic Predisposition to Disease; Hepatitis B virus; Liver Neoplasms
PubMed: 38353395
DOI: 10.1002/iid3.1182 -
International Journal of Surgery... May 2024
Topics: Humans; Liver Neoplasms; Carcinoma, Hepatocellular; Hepatectomy; Liver; Meta-Analysis as Topic
PubMed: 38349203
DOI: 10.1097/JS9.0000000000001154 -
Pathology Apr 2024Histopathology is the gold standard for diagnosing fibrosis, but its routine use is constrained by the need for additional stains, time, personnel and resources.... (Review)
Review
Histopathology is the gold standard for diagnosing fibrosis, but its routine use is constrained by the need for additional stains, time, personnel and resources. Vibrational spectroscopy is a novel technique that offers an alternative atraumatic approach, with short scan times, while providing metabolic and morphological data. This review evaluates vibrational spectroscopy for the assessment of fibrosis, with a focus on point-of-care capabilities. OVID Medline, Embase and Cochrane databases were systematically searched using PRISMA guidelines for search terms including vibrational spectroscopy, human tissue and fibrosis. Studies were stratified based on imaging modality and tissue type. Outcomes recorded included tissue type, machine learning technique, metrics for accuracy and author conclusions. Systematic review yielded 420 articles, of which 14 were relevant. Ten of these articles considered mid-infrared spectroscopy, three dealt with Raman spectroscopy and one with near-infrared spectroscopy. The metrics for detecting fibrosis were Pearson correlation coefficients ranging from 0.65-0.98; sensitivity from 76-100%; specificity from 90-99%; area under receiver operator curves from 0.83-0.98; and accuracy of 86-99%. Vibrational spectroscopy identified fibrosis in myeloproliferative neoplasms in bone, cirrhotic and hepatocellular carcinoma in liver, end-stage heart failure in cardiac tissue and following laser ablation for acne in skin. It also identified interstitial fibrosis as a predictor of early renal transplant rejection in renal tissue. Vibrational spectroscopic techniques can therefore accurately identify fibrosis in a range of human tissues. Emerging data show that it can be used to quantify, classify and provide data about the nature of fibrosis with a high degree of accuracy with potential scope for point-of-care use.
Topics: Humans; Point-of-Care Systems; Spectroscopy, Near-Infrared; Spectrum Analysis, Raman; Skin; Fibrosis
PubMed: 38341306
DOI: 10.1016/j.pathol.2023.11.008 -
World Journal of Surgical Oncology Feb 2024Hepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for 90% of cases worldwide and a significant contributor to cancer-related deaths.... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of laparoscopic liver resection versus radiofrequency ablation in patients with early and small hepatocellular carcinoma: an updated meta-analysis and meta-regression of observational studies.
BACKGROUND
Hepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for 90% of cases worldwide and a significant contributor to cancer-related deaths. This study comprehensively compares the safety and efficacy of laparoscopic liver resection (LLR) versus laparoscopic or percutaneous radiofrequency ablation (LRFA or PRFA) in patients with early and small HCC.
METHODS
We systematically searched Cochrane Library, PubMed, Scopus, and Web of Science databases to include studies comparing LLR versus LRFA or PRFA in patients with early HCC meets the Milan criteria (defined as solitary nodule < 5 cm or three nodules ≤ 3 cm with no extrahepatic spread or vascular invasion). Pooled results were examined for overall survival, disease-free survival, recurrence-free survival, local, intrahepatic and extrahepatic recurrence rates, and complications. We conducted subgroup analyses based on the type of RFA. Meta-regression analyzed the association between overall survival, local recurrence, and various factors. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. We analyzed the data using the R (v.4.3.0) programming language and the "meta" package of RStudio software.
RESULTS
We included 19 observational studies, compromising 3756 patients. LLR showed higher 5-year overall survival compared to RFA (RR = 1.17, 95% CI [1.06, 1.3], P > 0.01). Our subgroup analysis showed that LLR had higher 5-year survival than PRFA (RR = 1.15, 95% CI [1.02, 1.31], P = 0.03); however, there was no significant difference between LLR and LRFA (RR = 1.26, 95% CI [0.98, 1.63], P = 0.07). LLR was associated with higher disease-free survival) RR = 1.19, 95% CI [1.05, 1.35], P < 0.01; RR = 1.61, 95% CI [1.31, 1.98], P < 0.01(and recurrence-free survival) RR = 1.21, 95% CI [1.09, 1.35], P < 0.01; RR = 1.45, 95% CI [1.15, 1.84], P < 0.01(at 1 and 3 years. LLR was associated with lower local (RR = 0.28, 95% CI [0.16, 0.47], P < 0.01) and intrahepatic recurrence (RR = 0.7, 95% CI [0.5, 0.97], P = 0.03) than RFA. However, complications were significantly higher with LLR (RR = 2.01, 95% CI [1.51, 2.68], P < 0.01). Our meta-regression analysis showed that younger patients had higher risk for local recurrence (P = 0.008), while age wasn't significantly linked to overall survival (P = 0.25). Other covariates like total bilirubin, alpha-fetoprotein levels, and tumor size also showed no significant associations with either overall survival or local recurrence.
CONCLUSION
LLR offers improved long-term outcomes and lower recurrence rates than PRFA. However, no significant distinctions were observed between LRFA and LLR in overall survival, recurrence-free survival, and local recurrence. More robust well-designed RCTs are essential to validate our findings.
Topics: Humans; Carcinoma, Hepatocellular; Hepatectomy; Laparoscopy; Liver Neoplasms; Neoplasm Recurrence, Local; Radiofrequency Ablation; Retrospective Studies; Treatment Outcome
PubMed: 38326841
DOI: 10.1186/s12957-023-03292-3