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Frontiers in Immunology 2024Neoadjuvant immunotherapy has demonstrated beneficial outcomes in various cancer types; however, standardized protocols for neoadjuvant immunotherapy in hepatocellular... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neoadjuvant immunotherapy has demonstrated beneficial outcomes in various cancer types; however, standardized protocols for neoadjuvant immunotherapy in hepatocellular carcinoma (HCC) are currently lacking. This systematic review and meta-analysis aims to investigate the reliability of neoadjuvant immunotherapy's efficacy and safety in the context of HCC.
METHODS
A systematic search was conducted across PubMed (MEDLINE), EMBASE, the Web of Science, the Cochrane Library, and conference proceedings to identify clinical trials involving resectable HCC and neoadjuvant immunotherapy. Single-arm meta-analyses were employed to compute odds ratios and 95% confidence intervals (CIs). Heterogeneity analysis, data quality assessment, and subgroup analyses based on the type of immunotherapy drugs and combination therapies were performed. This meta-analysis is registered in PROSPERO (identifier CRD42023474276).
RESULTS
This meta-analysis included 255 patients from 11 studies. Among resectable HCC patients, neoadjuvant immunotherapy exhibited an overall major pathological response (MPR) rate of 0.47 (95% CI 0.31-0.70) and a pathological complete response (pCR) rate of 0.22 (95% CI 0.14-0.36). The overall objective response rate (ORR) was 0.37 (95% CI 0.20-0.69), with a grade 3-4 treatment-related adverse event (TRAE) incidence rate of 0.35 (95% CI 0.24-0.51). Furthermore, the combined surgical resection rate was 3.08 (95% CI 1.66-5.72). Subgroup analysis shows no significant differences in the efficacy and safety of different single-agent immunotherapies; the efficacy of dual ICIs (Immune Checkpoint Inhibitors) combination therapy is superior to targeted combined immunotherapy and monotherapy, while the reverse is observed in terms of safety.
DISCUSSION
Neoadjuvant immunotherapy presents beneficial outcomes in the treatment of resectable HCC. However, large-scale, high-quality experiments are warranted in the future to provide robust data support.
Topics: Humans; Carcinoma, Hepatocellular; Immune Checkpoint Inhibitors; Liver Neoplasms; Neoadjuvant Therapy; Reproducibility of Results
PubMed: 38440727
DOI: 10.3389/fimmu.2024.1352873 -
Reproductive Sciences (Thousand Oaks,... Jun 2024The definition of the association between ovarian cancer and endometriosis was first reported by Sampson in 1925. He identified the following criteria: (a) clear... (Meta-Analysis)
Meta-Analysis
The definition of the association between ovarian cancer and endometriosis was first reported by Sampson in 1925. He identified the following criteria: (a) clear evidence of endometriosis in proximity to the tumour, (b) exclusion of a metastatic tumour to the ovary, (c) presence of tissue resembling endometrial stroma surrounding epithelial glands. The naming of these cancers is "endometriosis-associated ovarian cancer" (EAOC). Scott proposed an additional stringent criterion: evidence of histological transition from endometriosis to cancer is to define "ovarian cancer arising in endometriosis" (OCAE). The aim of this systematic review is to analyse the distribution of different ovarian cancer histotypes in EAOC and OCAE to understand their similarities and differences. A total of 31 studies were included. Four studies added data for both EAOC and OCAE. Twenty-three studies were selected for EAOC, with a total of 800 patients, and 12 studies were selected for OCAE, with a total of 375 patients. The results show no significant differences in the distribution of histotypes in the two populations analysed. Clear cell carcinoma (CCC) and endometrioid carcinoma (EC) were the most common subtypes and were less frequent in EAOC compared to OCAE; the odd ratios were 0.58 (0.26-1.29) and 0.65 (0.33-1.26) respectively, although the difference was not statistically significant. The other histotypes were present in small proportions. This analysis shows that the histological profiles of EAOC and OCAE are similar, suggesting a similar aetiopathological mechanism, which requires further research to investigate whether EAOC and OCAE may be in the same way but at different points of the process to malignancy or have different pathways of progression to malignancy.
Topics: Humans; Endometriosis; Ovarian Neoplasms; Female; Carcinoma, Endometrioid; Adenocarcinoma, Clear Cell
PubMed: 38438776
DOI: 10.1007/s43032-024-01489-9 -
World Journal of Gastrointestinal... Feb 2024Gastric cancer is the third most common cause of cancer related death worldwide. Surgery with or without chemotherapy is the most common approach with curative intent;...
BACKGROUND
Gastric cancer is the third most common cause of cancer related death worldwide. Surgery with or without chemotherapy is the most common approach with curative intent; however, the prognosis is poor as mortality rates remain high. Several indexes have been proposed in the past few years in order to estimate the survival of patients undergoing gastrectomy. The preoperative nutritional status of gastric cancer patients has recently gained attention as a factor that could affect the postoperative course and various indexes have been developed. The aim of this systematic review was to assess the role of the prognostic nutritional index (PNI) in predicting the survival of patients with gastric or gastroesophageal adenocarcinoma who underwent gastrectomy with curative intent.
AIM
To investigate the role of PNI in predicting the survival of patients with gastric or gastroesophageal junction adenocarcinoma.
METHODS
A thorough literature search of PubMed and the Cochrane library was performed for studies comparing the overall survival (OS) of patients with gastric or gastroesophageal cancer after surgical resection depending on the preoperative PNI value. The PRISMA algorithm was used in the screening process and finally 16 studies were included in this systematic review. The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO).
RESULTS
Sixteen studies involving 14551 patients with gastric or esophagogastric junction adenocarcinoma undergoing open or laparoscopic or robotic gastrectomy with or without adjuvant chemotherapy were included in this systematic review. The patients were divided into high- and low-PNI groups according to cut-off values that were set according to previous reports or by using receiver operating characteristic curve analysis in each individual study. The 5-year OS of patients in the low-PNI groups ranged between 39% and 70.6%, while in the high-PNI groups, it ranged between 54.9% and 95.8%. In most of the included studies, patients with high preoperative PNI showed statistically significant better OS than the low PNI groups. In multivariate analyses, low PNI was repeatedly recognised as an independent prognostic factor for poor survival.
CONCLUSION
According to the present study, low preoperative PNI seems to be an indicator of poor OS of patients undergoing gastrectomy for gastric or gastroesophageal cancer.
PubMed: 38425390
DOI: 10.4251/wjgo.v16.i2.514 -
BMC Gastroenterology Feb 2024Treatment choices in hepatocellular carcinoma (HCC) involve consideration of tradeoffs between the benefits, toxicities, inconvenience, and costs. Stated preference...
BACKGROUND
Treatment choices in hepatocellular carcinoma (HCC) involve consideration of tradeoffs between the benefits, toxicities, inconvenience, and costs. Stated preference elicitation methods have been used in the medical field to help evaluate complex treatment decision-making. The aim of this study was to conduct a scoping review to assess the evidence base for the use of preference elicitation tools or willingness to pay/willingness to accept methods for HCC treatment decision-making from both the patient and provider perspective.
METHODS
We performed a scoping review to identify abstracts or manuscripts focused on the role preference elicitation tools or willingness to pay/willingness to accept methods for HCC treatment options among patients, caregivers, and/or providers. Two researchers independently screened full-text references and resolved conflicts through discussion. We summarized key findings, including the type and setting of preference-elicitation tools used for HCC treatment decisions.
RESULTS
Ten published abstracts or manuscripts evaluated the role of preference elicitation tools for HCC treatments. The studies revealed several attributes that are considered by patients and providers making HCC treatment decisions. Many of the studies reviewed suggested that while patients place the most value on extending their overall survival, they are willing to forgo overall survival to avoid risks of treatments and maintain quality of life. Studies of physicians and surgeons found that provider preferences are dependent on patient characteristics, provider specialty, and surgeon or hospital-related factors.
CONCLUSION
This scoping review explored both patient and physician preferences towards treatment modalities in all stages of HCC. The studies revealed a large scope of potential attributes that may be important to patients and that many patients are willing to forgo survival to maintain quality of life. Further research should explore both preference elicitation of currently available and emerging therapies for HCC as well as the use of this data to develop patient-facing tools to assist in navigating treatment options.
Topics: Humans; Carcinoma, Hepatocellular; Quality of Life; Liver Neoplasms; Surgeons; Patient Preference
PubMed: 38418997
DOI: 10.1186/s12876-024-03167-1 -
Endocrinology and Metabolism (Seoul,... Feb 2024Active surveillance (AS) has been introduced as a management strategy for low-risk papillary thyroid carcinoma (PTC) due to its typically indolent nature. Despite this,...
BACKGRUOUND
Active surveillance (AS) has been introduced as a management strategy for low-risk papillary thyroid carcinoma (PTC) due to its typically indolent nature. Despite this, the widespread adoption of AS has encountered several challenges. The aim of this systematic review was to evaluate the safety of AS related to disease progression and its benefits compared with immediate surgery (IS).
METHODS
Studies related to AS in patients with low-risk PTC were searched through the Ovid MEDLINE, Embase, Cochrane Library, and KoreaMed databases. Studies on disease progression, surgical complication, quality of life (QoL), and cost-effectiveness were separately analyzed and narratively synthesized.
RESULTS
In the evaluation of disease progression, the proportions of cases with tumor growth ≥3 mm and a volume increase >50% were 2.2%-10.8% and 16.0%-25.5%, respectively. Newly detected lymph node metastasis was identified in 0.0%-1.4% of patients. No significant difference was found between IS and delayed surgery in surgical complications, including vocal cord paralysis and postoperative hypoparathyroidism. AS was associated with better QoL than IS. Studies on the cost-effectiveness of AS reported inconsistent data, but AS was more cost-effective when quality-adjusted life years were considered.
CONCLUSION
AS is an acceptable management option for patients with low-risk PTC based on the low rate of disease progression and the absence of an increased mortality risk. AS has additional benefits, including improved QoL and greater QoL-based cost-effectiveness.
Topics: Humans; Thyroid Cancer, Papillary; Thyroid Neoplasms; Quality of Life; Thyroidectomy; Watchful Waiting; Disease Progression
PubMed: 38417830
DOI: 10.3803/EnM.2023.1794 -
Annals of Hepatology 2024Due to organ shortages, liver transplantation (LT) using donation-after-circulatory-death (DCD) grafts has become more common. There is limited and conflicting evidence... (Meta-Analysis)
Meta-Analysis
Outcomes of liver transplantation for hepatocellular carcinoma in donation after circulatory death compared with donation after brain death: A systematic review and meta-analysis.
INTRODUCTION AND OBJECTIVES
Due to organ shortages, liver transplantation (LT) using donation-after-circulatory-death (DCD) grafts has become more common. There is limited and conflicting evidence on LT outcomes using DCD grafts compared to those using donation-after-brain death (DBD) grafts for patients with hepatocellular carcinoma (HCC). We aimed to summarize the current evidence on the outcomes of DCD-LT and DBD-LT in patients with HCC.
MATERIALS AND METHODS
Online databases were searched for studies comparing DCD-LT and DBD-LT outcomes in patients with HCC and a meta-analysis was conducted using fixed- or random-effects models.
RESULTS
Five studies involving 487 (33.4%) HCC DCD-LT patients and 973 (66.6%) DBD-LT patients were included. The meta-analysis showed comparable 1-year [relative risk (RR)=0.99, 95%CI:0.95 to 1.03, p=0.53] and 3-year [RR=0.99, 95%CI:0.89 to 1.09, p=0.79] recurrence-free survival. The corresponding 1-year [RR=0.98, 95%CI:0.93 to 1.03, p=0.35] and 3-year [RR=0.94, 95%CI:0.87 to 1.01, p=0.08] patient survival and 1-year [RR=0.91, 95%CI:0.71 to 1.16, p=0.43] and 3-year [RR=0.92, 95%CI:0.67 to 1.26, p=0.59] graft survival were also comparable. There were no significant differences between the two cohorts regarding the tumor characteristics, donor/recipient risk factors and the incidence of post-operative complications, including acute rejection, primary non-function, biliary complications and retransplantation.
CONCLUSIONS
Based on the current evidence, it has been found that comparable outcomes can be achieved in HCC patients using DCD-LT compared to DBD-LT, particularly when employing good quality graft, strict donor and recipient selection, and effective surgical management. The decision to utilize DCD-LT for HCC patients should be personalized, taking into consideration the risk of post-LT HCC recurrence. (PROSPERO ID: CRD42023445812).
Topics: Humans; Liver Transplantation; Carcinoma, Hepatocellular; Liver Neoplasms; Brain Death; Graft Survival; Tissue and Organ Procurement; Tissue Donors; Treatment Outcome; Risk Factors
PubMed: 38417629
DOI: 10.1016/j.aohep.2024.101484 -
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 -
Current Oncology (Toronto, Ont.) Feb 2024Surgical management of gastric adenocarcinoma can have a drastic impact on a patient's quality of life (QoL). There is high variability among surgeons' preferences for... (Review)
Review
Surgical management of gastric adenocarcinoma can have a drastic impact on a patient's quality of life (QoL). There is high variability among surgeons' preferences for the type of resection and reconstructive method. Peri-operative and cancer-specific outcomes remain equivalent between the different approaches. Therefore, postoperative quality of life can be viewed as a deciding factor for the surgical approach. The goal of this study was to interrogate patient QoL using patient-reported outcomes (PROs) following gastrectomy for gastric cancer. This systematic review was registered at Prospero and followed PRISMA guidelines. Medline, Embase, and Scopus were used to perform a literature search on 18 January 2020. A set of selection criteria and the data extraction sheet were predefined. Covidence (Melbourne, Australia) software was used; two reviewers (P.C.V. and E.J.) independently reviewed the articles, and a third resolved conflicts (A.B.F.). The search yielded 1446 studies; 308 articles underwent full-text review. Ultimately, 28 studies were included for qualitative analysis, including 4630 patients. Significant heterogeneity existed between the studies. Geography was predominately East Asian (22/28 articles). While all aspects of quality of life were found to be affected by a gastrectomy, most functional or symptom-specific measures reached baseline by 6-12 months. The most significant ongoing symptoms were reflux, diarrhoea, and nausea/vomiting. Generally, patients who undergo a gastrectomy return to baseline QoL by one year, regardless of the type of surgery or reconstruction. A subtotal distal gastrectomy is preferred when proper oncologic margins can be obtained. Additionally, no one form of reconstruction following gastrectomy is statistically preferred over another. However, for subtotal distal gastrectomy, there was a trend toward Roux-en-Y reconstruction as superior to abating reflux.
Topics: Humans; Quality of Life; Stomach Neoplasms; Gastroenterostomy; Gastrectomy; Anastomosis, Roux-en-Y
PubMed: 38392059
DOI: 10.3390/curroncol31020065 -
Frontiers in Immunology 2024Although immune checkpoint inhibitors (ICIs) show a significant overall survival advantage over standard advanced renal cell carcinoma (aRCC) therapies, tumor response... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although immune checkpoint inhibitors (ICIs) show a significant overall survival advantage over standard advanced renal cell carcinoma (aRCC) therapies, tumor response to these agents remains poor. Some studies have shown that combination therapy including an ICI appears to be the best treatment; however, the overall benefit in terms of efficacy and toxicity still needs to be assessed. Thus, we performed a network meta-analysis to evaluate the differences in the efficacy of several combinations that include an ICI to provide a basis for clinical treatment selection.
METHODS
We conducted a thorough search of PubMed, EMBASE, and the Cochrane Library for articles from January 2010 to June 2023. R 4.4.2 and STATA 16.0 were used to analyze data; hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CI) were used to assess the results.
RESULTS
An indirect comparison showed that nivolumab plus cabozantinib and pembrolizumab plus lenvatinib were the most effective treatments for progression-free survival (PFS), with no significant differences between the two interventions (HR, 1.31; 95% CI, 0.96-1.78; P=0.08); rank probability showed that pembrolizumab plus lenvatinib had a 57.1% chance of being the preferred treatment. In the absence of indirect comparisons between pembrolizumab plus axitinib, nivolumab plus ipilimumab, avelumab plus axitinib, nivolumab plus cabozantinib, and pembrolizumab plus lenvatinib, pembrolizumab plus axitinib (40.2%) was the best treatment option for overall survival (OS). Compared to pembrolizumab plus lenvatinib, nivolumab plus ipilimumab (OR, 0.07; 95% CI, 0.01-0.65; P=0.02) and pembrolizumab plus axitinib (OR, 0.05; 95% CI, 0.00-0.78; P<0.001) had a lower incidence of overall adverse events (AEs).
CONCLUSION
Pembrolizumab plus lenvatinib and pembrolizumab plus axitinib resulted in the highest PFS and OS rates, respectively. Pembrolizumab plus axitinib may be the best option when AEs are a concern.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com/, identifier INPLASY202410078.
Topics: Humans; Carcinoma, Renal Cell; Axitinib; Nivolumab; Immune Checkpoint Inhibitors; Ipilimumab; Network Meta-Analysis; Kidney Neoplasms; Anilides; Phenylurea Compounds; Pyridines; Quinolines
PubMed: 38390328
DOI: 10.3389/fimmu.2024.1255577 -
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