-
World Journal of Gastroenterology Feb 2024Most patients with advanced pancreatic neuroendocrine tumors (pNETs) die due to tumor progression. Therefore, identifying new therapies with low toxicity and good... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Most patients with advanced pancreatic neuroendocrine tumors (pNETs) die due to tumor progression. Therefore, identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant. In this perspective, metformin is emerging as a molecule of interest. Retrospective studies have described metformin, a widely used agent for the treatment of patients with type 2 diabetes mellitus (T2DM), to be effective in modulating different tumor-related events, including cancer incidence, recurrence and survival by inhibiting mTOR phosphorylation. This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.
AIM
To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and post-treatment outcomes of pNET.
METHODS
A systematic review of the published literature was undertaken, focusing on the role of T2DM and metformin in insurgence and prognosis of pNET, measured through outcomes of tumor-free survival (TFS), overall survival and progression-free survival.
RESULTS
A total of 13 studies (5674 patients) were included in this review. Analysis of 809 pNET cases from five retrospective studies (low study heterogeneity with = 0%) confirms the correlation between T2DM and insurgence of pNET (OR = 2.13, 95%CI = 1.56-4.55; < 0.001). The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients (hazard ratio = 1.84, 95%CI = 0.78-2.90; < 0.001). The study heterogeneity was intermediate, with = 51%. A few studies limited the possibility of performing pooled analysis in the setting of metformin; therefore, results were heterogeneous, with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.
CONCLUSION
T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients. Unfortunately, a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.
Topics: Humans; Metformin; Diabetes Mellitus, Type 2; Neuroendocrine Tumors; Retrospective Studies; Pancreatic Neoplasms; Neuroectodermal Tumors, Primitive
PubMed: 38515954
DOI: 10.3748/wjg.v30.i7.759 -
Annals of Surgical Oncology Jul 2024Treatment of unresectable colorectal liver metastases (UCRLM) includes locoregional and systemic therapy. A comprehensive analysis capturing long-term outcomes of these... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Treatment of unresectable colorectal liver metastases (UCRLM) includes locoregional and systemic therapy. A comprehensive analysis capturing long-term outcomes of these treatment options has not been performed.
OBJECTIVE
A systematic review and meta-analysis was performed to calculate pooled outcomes of hepatic artery infusion with systemic chemotherapy (HAI-S), transarterial chemoembolization with systemic chemotherapy (TACE-S), transarterial radioembolization with systemic chemotherapy (TARE-S), doublet (FOLFOX, FOLFIRI), and triplet chemotherapy (FOLFOXIRI).
METHODS
Outcomes included overall survival (OS), progression-free survival (PFS), rate of conversion to resection (CTR), and response rate (RR).
RESULTS
A total of 32, 7, 9, and 14 publications were included in the HAI-S, TACE-S, and TARE-S chemotherapy arms. The 6/12/24/36-month OS estimates for HAI-S, TACE-S, TARE-S, FOLFOX, FOLFIRI, and FOLFOXIRI were 97%/80%/54%/35%, 100%/83%/40%/14%, 82%/61%/34%/21%, 96%/83%/53%/36%, and 96%/93%/72%/55%. Similarly, the 6/12/24/36-month PFS estimates were 74%/44%/19%/14%, 66%/20%/9%/3%, 57%/23%/10%/3%, 69%/30%/12%/7%, and 88%/55%/18%/11%. The corresponding CTR and RR rates were 31, 20%, unmeasurable (TARE-S), 35, 53; and 49, 45, 45, 50, 80%, respectively. The majority of chemotherapy studies included first-line therapy and liver-only metastases, whereas most HAI-S studies were pretreated. On subgroup analysis in first-line setting with liver-only metastases, the HAI-S arm had comparable outcomes to FOLFOXIRI and outperformed doublet chemotherapy regimens. Although triplet chemotherapy appeared to outperform other arms, high toxicity and inclusion of potentially resectable patients must be considered while interpreting results.
CONCLUSIONS
HAI-S and multiagent chemotherapy are effective therapies for UCRLM. To make definitive conclusions, a randomized trial with comparable patient characteristics and line of therapy will be required. The upcoming EA2222 PUMP trial may help to address this question.
Topics: Humans; Liver Neoplasms; Colorectal Neoplasms; Hepatic Artery; Antineoplastic Combined Chemotherapy Protocols; Chemoembolization, Therapeutic; Infusions, Intra-Arterial; Survival Rate; Prognosis; Fluorouracil; Leucovorin
PubMed: 38502296
DOI: 10.1245/s10434-024-15187-y -
International Journal of Surgery... Mar 2024The gradual evolution of the detection and quantification of volatile organic compounds (VOCs) has been instrumental in cancer diagnosis. The primary objective of this... (Meta-Analysis)
Meta-Analysis
Exhaled breath and urinary volatile organic compounds (VOCs) for cancer diagnoses, and microbial-related VOC metabolic pathway analysis: a systematic review and meta-analysis.
BACKGROUND
The gradual evolution of the detection and quantification of volatile organic compounds (VOCs) has been instrumental in cancer diagnosis. The primary objective of this study was to assess the diagnostic potential of exhaled breath and urinary VOCs in cancer detection. As VOCs are indicative of tumor and human metabolism, our work also sought to investigate the metabolic pathways linked to the development of cancerous tumors.
MATERIALS AND METHODS
An electronic search was performed in the PubMed database. Original studies on VOCs within exhaled breath and urine for cancer detection with a control group were included. A meta-analysis was conducted using a bivariate model to assess the sensitivity and specificity of the VOCs for cancer detection. Fagan's nomogram was designed to leverage the findings from our diagnostic analysis for the purpose of estimating the likelihood of cancer in patients. Ultimately, MetOrigin was employed to conduct an analysis of the metabolic pathways associated with VOCs in relation to both human and/or microbiota.
RESULTS
The pooled sensitivity, specificity and the area under the curve for cancer screening utilizing exhaled breath and urinary VOCs were determined to be 0.89, 0.88, and 0.95, respectively. A pretest probability of 51% can be considered as the threshold for diagnosing cancers with VOCs. As the estimated pretest probability of cancer exceeds 51%, it becomes more appropriate to emphasize the 'ruling in' approach. Conversely, when the estimated pretest probability of cancer falls below 51%, it is more suitable to emphasize the 'ruling out' approach. A total of 14, 14, 6, and 7 microbiota-related VOCs were identified in relation to lung, colorectal, breast, and liver cancers, respectively. The enrichment analysis of volatile metabolites revealed a significant enrichment of butanoate metabolism in the aforementioned tumor types.
CONCLUSIONS
The analysis of exhaled breath and urinary VOCs showed promise for cancer screening. In addition, the enrichment analysis of volatile metabolites revealed a significant enrichment of butanoate metabolism in four tumor types, namely lung, colorectum, breast and liver. These findings hold significant implications for the prospective clinical application of multiomics correlation in disease management and the exploration of potential therapeutic targets.
Topics: Humans; Volatile Organic Compounds; Prospective Studies; Breath Tests; Liver Neoplasms; Metabolic Networks and Pathways
PubMed: 38484261
DOI: 10.1097/JS9.0000000000000999 -
Frontiers in Immunology 2024It is unclear whether the systemic inflammation response index (SIRI) can predict the prognosis of patients with hepatocellular carcinoma (HCC). Consequently, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It is unclear whether the systemic inflammation response index (SIRI) can predict the prognosis of patients with hepatocellular carcinoma (HCC). Consequently, the present study focused on systematically identifying the relationship between SIRI and the prognosis of patients with HCC through a meta-analysis.
METHODS
Systematic and comprehensive studies were retrieved from PubMed, Web of Science, Embase, and the Cochrane Library from their inception to August 10, 2023. The role of SIRI in predicting overall survival (OS) and progression-free survival (PFS) in HCC was determined using pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Odds ratios (ORs) and 95% CIs were pooled to analyze the correlations between SIRI and the clinicopathological features of HCC.
RESULTS
Ten articles involving 2,439 patients were included. An elevated SIRI was significantly associated with dismal OS (HR=1.75, 95% CI=1.52-2.01, p<0.001) and inferior PFS (HR=1.66, 95% CI=1.34-2.05, p<0.001) in patients with HCC. Additionally, according to the combined results, the increased SIRI was significantly related to multiple tumor numbers (OR=1.42, 95% CI=1.09-1.85, p=0.009) and maximum tumor diameter >5 cm (OR=3.06, 95% CI=1.76-5.30, p<0.001). However, the SIRI did not show any significant relationship with sex, alpha-fetoprotein content, Child-Pugh class, or hepatitis B virus infection.
CONCLUSION
According to our results, elevated SIRI significantly predicted OS and PFS in patients with HCC. Moreover, the SIRI was significantly associated with tumor aggressiveness.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com/inplasy-2023-9-0003/, identifier INPLASY202390003.
Topics: Humans; Carcinoma, Hepatocellular; Prognosis; Liver Neoplasms; Progression-Free Survival; Inflammation
PubMed: 38469315
DOI: 10.3389/fimmu.2024.1291840 -
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 -
Journal of Cellular and Molecular... Mar 2024Deep learning is gaining importance due to its wide range of applications. Many researchers have utilized deep learning (DL) models for the automated diagnosis of cancer...
Deep learning is gaining importance due to its wide range of applications. Many researchers have utilized deep learning (DL) models for the automated diagnosis of cancer patients. This paper provides a systematic review of DL models for automated diagnosis of cancer patients. Initially, various DL models for cancer diagnosis are presented. Five major categories of cancers such as breast, lung, liver, brain and cervical cancer are considered. As these categories of cancers have a very high percentage of occurrences with high mortality rate. The comparative analysis of different types of DL models is drawn for the diagnosis of cancer at early stages by considering the latest research articles from 2016 to 2022. After comprehensive comparative analysis, it is found that most of the researchers achieved appreciable accuracy with implementation of the convolutional neural network model. These utilized the pretrained models for automated diagnosis of cancer patients. Various shortcomings with the existing DL-based automated cancer diagnosis models are also been presented. Finally, future directions are discussed to facilitate further research for automated diagnosis of cancer patients.
Topics: Humans; Deep Learning; Lung; Neural Networks, Computer; Tomography, X-Ray Computed; Neoplasms; Diagnosis, Computer-Assisted
PubMed: 38426930
DOI: 10.1111/jcmm.18144 -
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 -
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 -
Advances in Therapy Apr 2024This literature review and exploratory network meta-analysis (NMA) aimed to compare the clinical effectiveness and tolerability of selective internal radiation therapy... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
This literature review and exploratory network meta-analysis (NMA) aimed to compare the clinical effectiveness and tolerability of selective internal radiation therapy (SIRT) using yttrium-90 (Y-90) resin microspheres, regorafenib (REG), trifluridine-tipiracil (TFD/TPI), and best supportive care (BSC) in adult patients with chemotherapy-refractory or chemotherapy-intolerant metastatic colorectal cancer (mCRC).
METHODS
In light of recently published data, the literature was searched to complement and update a review published in 2018. Studies up to December 2022 comparing two or more of the treatments and reporting overall survival (OS), progression-free survival (PFS), or incidence of adverse events (AE) were included. The NMA compared hazard ratios (HRs) for OS and PFS using Markov chain Monte Carlo techniques.
RESULTS
Fifteen studies were included, with eight studies added (none addressing SIRT). All active treatments improved OS in relation to BSC. SIRT had the longest OS among all treatments, although without statistically significant differences (HR [95% credible interval] for SIRT, 0.48 [0.27, 0.87]; TFD/TPI, 0.62 [0.46, 0.83]; REG, 0.78 [0.57, 1.05]) in a fixed effects model. Information regarding SIRT was insufficient for PFS analysis, and TFD/TPI was the best intervention (HR 2.26 [1.6, 3.18]). One SIRT study reported radioembolization-induced liver disease in > 10% of the sample; this was symptomatically managed. Non-haematological AEs (hand-foot skin reaction, fatigue, diarrhoea, hypertension, rash or desquamation) were more common with REG, while haematological events (neutropoenia, leukopenia, and anaemia) were more common with TFD/TPI.
CONCLUSION
Current evidence supports SIRT treatment in patients with chemotherapy-refractory or chemotherapy-intolerant mCRC compared to newer oral agents, with comparable OS and low incidence of AEs.
Topics: Adult; Humans; Yttrium Radioisotopes; Colorectal Neoplasms; Network Meta-Analysis; Microspheres; Colonic Neoplasms; Pyrrolidines; Antineoplastic Combined Chemotherapy Protocols; Phenylurea Compounds; Pyridines
PubMed: 38407790
DOI: 10.1007/s12325-024-02800-5 -
Cancer Medicine Feb 2024While evidence of hyperprogressive disease (HPD) continues to grow, the lack of a consensual definition obscures a proper characterization of HPD incidence. We examined... (Meta-Analysis)
Meta-Analysis
BACKGROUND
While evidence of hyperprogressive disease (HPD) continues to grow, the lack of a consensual definition obscures a proper characterization of HPD incidence. We examined how HPD incidence varies by the tumor type or the type of definition used.
METHODS
We searched PubMed, Embase, the Cochrane Library of Systematic Reviews, and Web of Science from database inception to June 21, 2022. Observational studies reporting HPD incidence, in patients diagnosed with solid malignant tumors and treated with immune checkpoint inhibitors (ICI), were included. Random-effects meta-analyses were performed, and all statistical tests were 2-sided.
RESULTS
HPD incidence was 12.4% (95% CI 10.2%-15.0%) with evidence of heterogeneity (Q = 119.32, p < 0.001). Meta-regression showed that the risk of developing HPD was higher in patients with advanced gastric cancer (adjusted odds ratio [OR], 10.83; 95% CI, 2.14-54.65; p < 0.001), hepatocellular carcinoma (adjusted OR, 7.99; 95% CI, 1.68-38.13; p = 0.006), non-small cell lung cancer (adjusted OR, 7.14; 95% CI, 1.58-32.29; p = 0.005), and mixed or other types (adjusted OR, 5.09; 95% CI, 1.12-23.14, p = 0.018) than in patients with renal cell carcinoma. Across definitions, HPD defined as a tumor growth kinetics ratio ≥ 2 (adjusted OR, 1.82; 95% CI, 1.08-3.07; p = 0.025) based on the Response Evaluation Criteria in Solid Tumors (RECIST) reported higher incidence than when HPD was defined as RECIST-defined progressive disease and a change in the tumor growth rate (TGR) exceeding 50% (∆TGR > 50).
CONCLUSIONS
The incidence of immunotherapy-related HPD may vary across tumor types and definitions used, supporting the argument for a uniform and improved method of HPD evaluation for informed clinical decision-making.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Incidence; Immunotherapy; Liver Neoplasms; Kidney Neoplasms; Disease Progression
PubMed: 38400685
DOI: 10.1002/cam4.6970