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Cancer Reports (Hoboken, N.J.) Feb 2024Tumor mutational load (TML) has emerged as a potential biomarker for multiple solid tumors. However, data on its prognostic impact on upper gastrointestinal (UGI) cancer... (Meta-Analysis)
Meta-Analysis
Tumor mutation load better predicts the prognosis of patients treated with immune checkpoint inhibitors in upper gastrointestinal cancers: A systematic review and meta-analysis.
BACKGROUND
Tumor mutational load (TML) has emerged as a potential biomarker for multiple solid tumors. However, data on its prognostic impact on upper gastrointestinal (UGI) cancer are limited. Therefore, the aim of this systematic review and meta-analysis was to assess the prognostic value of TML for the survival of patients with UGI cancer.
METHOD
A comprehensive search of the PubMed, Embase, Cochrane Library, and Web of Science databases was conducted up to February 13, 2023. Eleven studies met our inclusion criteria. Hazard ratios (HRs) for progression-free survival and overall survival and their 95% confidence intervals (CIs) were calculated. Subsequently, the combined HR and its 95% CI were calculated for UGI tract cancers in the high and low TML groups. I statistics and p-values were used to evaluate heterogeneity. Publication bias, sensitivity, and subgroup analyses were performed to determine sources of heterogeneity.
RESULTS
In total, 932 patients with UGI tract cancer from 11 publications were included. The high TML group treated with immunotherapy showed significantly improved overall survival (HR = 0.68; 95% CI: 0.53, 0.86; p = .001) and progression-free survival (HR = 0.74; 95% CI: 0.58, 0.95; p = .020) compared with the low TML group.
CONCLUSION
Our study demonstrated that patients with UGI tumors and higher TML have a better prognosis with immunotherapy, suggesting that TML is a promising predictive biomarker for immunotherapy.
REGISTRATION
The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO Registration No: CRD42023405596).
Topics: Humans; Immune Checkpoint Inhibitors; Gastrointestinal Neoplasms; Prognosis; Mutation; Biomarkers
PubMed: 38204354
DOI: 10.1002/cnr2.1959 -
Pharmacological Research Feb 2024To assess the efficacy and safety of FDA-approved KRAS inhibitors in patients with KRAS-mutated solid tumors. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the efficacy and safety of FDA-approved KRAS inhibitors in patients with KRAS-mutated solid tumors.
METHODS
We searched PubMed, EMBASE, Cochrane Library, and major international conferences for clinical trials published in English up to March 6, 2023. Clinical trials investigating sotorasib or adagrasib and reporting the clinical outcomes of the objective response rate (ORR), disease control rate (DCR), or incidence rate of grade ≥ 3 adverse events (AEs) were eligible. The primary endpoint was the ORR. Secondary endpoints included the DCR, incidence rate of grade ≥ 3 AEs, and odds ratio (OR) of the ORR between patients with or without co-mutation. The Random-effects model was applied for the outcomes of interest.
RESULTS
18 studies with 1224 patients were included in this meta-analysis. The pooled ORR, DCR, and incidence rate of grade ≥ 3 AEs were 31 % (95 % CI, 25-37 %), 86 % (95 % CI, 82-89 %), and 29 % (95 % CI, 23-36 %), respectively. KRAS-mutated NSCLC patients with a co-mutation of KEAP1 exhibited a worse ORR than those with wild-type KEAP1 (OR: 0.35, 95 % CI: 0.16-0.77).
CONCLUSIONS
This study provided a comprehensive understanding of the efficacy and safety of KRAS inhibitors in treating solid tumors and identified KEAP1 mutation as a potential predictive biomarker of inferior response in patients treated with KRAS inhibitors. These findings may assist in the design of future clinical trials for identifying populations that may benefit from KRAS inhibitor treatment.
Topics: Humans; Kelch-Like ECH-Associated Protein 1; Proto-Oncogene Proteins p21(ras); NF-E2-Related Factor 2; Carcinoma, Non-Small-Cell Lung; Mutation; Lung Neoplasms
PubMed: 38185210
DOI: 10.1016/j.phrs.2024.107060 -
BMC Urology Jan 2024The incidence rate of malignant tumors after solid organ transplantation is higher than the normal population. The aim of our study is to identify the risk of renal cell... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The incidence rate of malignant tumors after solid organ transplantation is higher than the normal population. The aim of our study is to identify the risk of renal cell carcinoma (RCC) after liver, kidney, heart and lung transplantation, respectively, and suggest that transplant patients can be screened early for tumors to avoid risk.
METHODS
PubMed, Embase and the Cochrane Library from their inception until August 16,2023. Retrospective and cohort studies which focus on the statistical data of standardized incidence ratios (SIRs) of RCC after solid organ transplantation (SOT) more than one year have been included and extracted. The study was registered with PROSPERO, CRD4202022343633.
RESULTS
Sixteen original studies have been included for meta-analysis. Liver transplantation could increase the risk of RCC (SIR = 0.73, 95%CI: 0.53 to 0.93) with no heterogeneity(P = 0.594, I = 0.0%). And kidney transplantation could increase the risk of RCC(8.54, 6.68 to 10.40; 0.000,90.0%). Besides, heart and lung transplantation also could increase the risk of RCC(SIR = 0.73, 95%CI: 0.53 to 0.93; SIR = 1.61, 95%CI:0.50 to 2.71). Moreover, significance could also be found in most subgroups, especially the European group and retrospective study group. What's more, after removing studies which have a greater impact on the overall outcome in RCC rate after kidney transplantation, heterogeneity did not solve and significant different was also observed in the European group (7.15, 5.49 to 8.81; 0.000, 78.6%).
CONCLUSION
Liver, kidney, heart and lung transplantation patients have an increased risk of processing RCC compared to the general population and most subgroups, especially in geographic location of European subgroup, which suggested that patients should be screened frequently after transplantation.
Topics: Humans; Carcinoma, Renal Cell; Incidence; Retrospective Studies; Kidney Transplantation; Kidney Neoplasms
PubMed: 38184525
DOI: 10.1186/s12894-023-01389-1 -
PloS One 2023Endocytoscopy (EC) is a nuclei and micro-vessels visualization in real-time and can facilitate "optical biopsy" and "virtual histology" of colorectal lesions. This study... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Endocytoscopy (EC) is a nuclei and micro-vessels visualization in real-time and can facilitate "optical biopsy" and "virtual histology" of colorectal lesions. This study aimed to investigate the significance of employing artificial intelligence (AI) in the field of endoscopy, specifically in diagnosing colorectal lesions. The research was conducted under the supervision of experienced professionals and trainees.
METHODS
EMBASE, PubMed, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI) database, and other potential databases were surveyed for articles related to the EC with AI published before September 2023. RevMan (5.40), Stata (14.0), and R software (4.1.0) were used for statistical assessment. Studies that measured the accuracy of EC using AI for colorectal lesions were included. Two authors independently assessed the selected studies and their extracted data. This included information such as the country, literature, total study population, study design, characteristics of the fundamental study and control groups, sensitivity, number of samples, assay methodology, specificity, true positives or negatives, and false positives or negatives. The diagnostic accuracy of EC by AI was determined by a bivariate random-effects model, avoiding a high heterogeneity effect. The ANOVA model was employed to determine the more effective approach.
RESULTS
A total of 223 studies were reviewed; 8 articles were selected that included 2984 patients (4241 lesions) for systematic review and meta-analysis. AI assessed 4069 lesions; experts diagnosed 3165 and 5014 by trainees. AI demonstrated high accuracy, sensitivity, and specificity levels in detecting colorectal lesions, with values of 0.93 (95% CI: 0.90, 0.95) and 0.94 (95% CI: 0.73, 0.99). Expert diagnosis was 0.90 (95% CI: 0.85, 0.94), 0.87 (95% CI: 0.78, 0.93), and trainee diagnosis was 0.74 (95% CI: 0.67, 0.79), 0.72 (95% CI: 0.62, 0.80). With the EC by AI, the AUC from SROC was 0.95 (95% CI: 0.93, 0.97), therefore classified as excellent category, expert showed 0.95 (95% CI: 0.93, 0.97), and the trainee had 0.79 (95% CI: 0.75, 0.82). The superior index from the ANOVA model was 4.00 (1.15,5.00), 2.00 (1.15,5.00), and 0.20 (0.20,0.20), respectively. The examiners conducted meta-regression and subgroup analyses to evaluate the presence of heterogeneity. The findings of these investigations suggest that the utilization of NBI technology was correlated with variability in sensitivity and specificity. There was a lack of solid evidence indicating the presence of publishing bias.
CONCLUSIONS
The present findings indicate that using AI in EC can potentially enhance the efficiency of diagnosing colorectal abnormalities. As a valuable instrument, it can enhance prognostic outcomes in ordinary EC procedures, exhibiting superior diagnostic accuracy compared to trainee-level endoscopists and demonstrating comparability to expert endoscopists. The research is subject to certain constraints, namely a limited number of clinical investigations and variations in the methodologies used for identification. Consequently, it is imperative to conduct comprehensive and extensive research to enhance the precision of diagnostic procedures.
Topics: Humans; Artificial Intelligence; Endoscopy; Software; Sensitivity and Specificity; Colorectal Neoplasms
PubMed: 38113199
DOI: 10.1371/journal.pone.0294930 -
BMC Cancer Dec 2023The clinical relevance of circulating tumor cell-white blood cell (CTC-WBC) clusters in cancer prognosis is a subject of ongoing debate. This study aims to unravel their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The clinical relevance of circulating tumor cell-white blood cell (CTC-WBC) clusters in cancer prognosis is a subject of ongoing debate. This study aims to unravel their contentious predictive value for patient outcomes.
METHODS
We conducted a comprehensive literature search of PubMed, Embase, and Cochrane Library up to December 2022. Eligible studies that reported survival outcomes and examined the presence of CTC-WBC clusters in solid tumor patients were included. Hazard ratios (HR) were pooled to assess the association between CTC-WBC clusters and overall survival (OS), as well as progression-free survival (PFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/recurrence-free survival (RFS). Subgroup analyses were performed based on sampling time, treatment method, detection method, detection system, and cancer type.
RESULTS
A total of 1471 patients from 10 studies were included in this meta-analysis. The presence of CTC-WBCs was assessed as a prognostic factor for overall survival and PFS/DFS/MFS/RFS. The pooled analysis demonstrated that the presence of CTC-WBC clusters was significantly associated with worse OS (HR = 2.44, 95% CI: 1.74-3.40, P < 0.001) and PFS/DFS/MFS/RFS (HR = 1.83, 95% CI: 1.49-2.24, P < 0.001). Subgroup analyses based on sampling time, treatment method, detection method, detection system, cancer type, and study type consistently supported these findings. Further analyses indicated that CTC-WBC clusters were associated with larger tumor size (OR = 2.65, 95% CI: 1.58-4.44, P < 0.001) and higher alpha-fetoprotein levels (OR = 2.52, 95% CI: 1.50-4.22, P < 0.001) in hepatocellular carcinoma. However, no significant association was found between CTC-WBC clusters and TNM stage, depth of tumor invasion, or lymph node metastasis in the overall analysis.
CONCLUSIONS
CTC-WBC clusters are negative predictors for OS and PFS/DFS/MFS/RFS in patients with solid tumors. Monitoring CTC-WBC levels may provide valuable information for predicting disease progression and guiding treatment decisions.
Topics: Humans; Prognosis; Neoplastic Cells, Circulating; Disease-Free Survival; Progression-Free Survival; Liver Neoplasms
PubMed: 38087278
DOI: 10.1186/s12885-023-11711-7 -
JNCI Cancer Spectrum Oct 2023Subgroup analyses in clinical trials assess intervention effects on specific patient subgroups, ensuring generalizability. However, they are usually only able to...
BACKGROUND
Subgroup analyses in clinical trials assess intervention effects on specific patient subgroups, ensuring generalizability. However, they are usually only able to generate hypotheses rather than definitive conclusions. This study examined the prevalence and characteristics of post hoc subgroup analysis in oncology.
METHODS
We systematically reviewed published subgroup analyses from 2000 to 2022. We included articles presenting secondary, post hoc, or subgroup analyses of interventional clinical trials in oncology, cancer survivorship, or cancer screening, published separately from the original clinical trial publication. We collected cancer type, year of publication, where and how subgroup analyses were reported, and funding.
RESULTS
Out of 16 487 screened publications, 1612 studies were included, primarily subgroup analyses of treatment trials for solid tumors (82%). Medical writers contributed to 31% of articles, and 58% of articles reported conflicts of interest. Subgroup analyses increased significantly over time, with 695 published between 2019 and 2022, compared to 384 from 2000 to 2014. Gastrointestinal tumors (25%) and lymphoid lineage tumors (39%) were the most frequently studied solid and hematological malignancies, respectively. Industry funding and reporting of conflicts of interest increased over time. Subgroup analyses often neglected to indicate their secondary nature in the title. Most authors were from high-income countries, most commonly North America (45%).
CONCLUSIONS
This study demonstrates the rapidly growing use of post hoc subgroup analysis of oncology clinical trials, revealing that the majority are supported by pharmaceutical companies, and they frequently fail to indicate their secondary nature in the title. Given the known methodological limitations of subgroup analyses, caution is recommended among authors, readers, and reviewers when conducting and interpreting these studies.
Topics: Humans; Neoplasms; Medical Oncology; Research Design
PubMed: 38006333
DOI: 10.1093/jncics/pkad100 -
International Journal of Surgery... Feb 2024Currently, the impact of sublobar resection versus lobectomy on the prognosis of solid-dominant stage IA lung cancer is contradictory in different studies, which... (Meta-Analysis)
Meta-Analysis
Differential efficacy of segmentectomy and wedge resection in sublobar resection compared to lobectomy for solid-dominant stage IA lung cancer: a systematic review and meta-analysis.
BACKGROUND
Currently, the impact of sublobar resection versus lobectomy on the prognosis of solid-dominant stage IA lung cancer is contradictory in different studies, which requires further exploration.
METHODS
The authors analyzed 26 studies, including one randomized controlled trial and retrospective cohort studies. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models based on heterogeneity levels.
RESULTS
The analysis included 12 667 patients, with 3488 undergoing sublobar resections and 9179 receiving lobectomies. The overall analysis revealed no statistically significant difference in overall survival (OS) (HR=1.28, 95% CI: 0.98-1.69) between sublobar resection and lobectomy, but lobectomy was associated with better recurrence-free survival (RFS) (HR=1.39, 95% CI: 1.10-1.75). Subgroup analyses revealed that, for tumors with a diameter ≤2 cm, sublobar resection versus lobectomy showed no significant difference in OS but sublobar resection had lower RFS. For 2-3 cm tumors, both OS and RFS were significantly lower in the sublobar resection group. When consolidation-to-tumor ratio (CTR) ranged from 0.5 to <1, OS did not differ significantly, but RFS was significantly lower in sublobar resection. Lung cancers with CTR=1 showed significantly lower OS and RFS in the sublobar resection group. Segmentectomy provided similar OS and RFS compared to lobectomy, while wedge resection had a detrimental effect on patient prognosis. However, wedge resection may have provided comparable outcomes for patients aged 75 years or older.
CONCLUSION
Our findings suggest that segmentectomy and lobectomy yield similar oncological outcomes. However, compared to lobectomy, wedge resection is associated with a poorer prognosis. Nevertheless, for elderly patients, wedge resection is also a reasonable surgical option.
Topics: Aged; Humans; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Pneumonectomy; Retrospective Studies; Neoplasm Staging
PubMed: 37983767
DOI: 10.1097/JS9.0000000000000896 -
The Journal of Histochemistry and... Dec 2023Fluorescence confocal microscopy (FCM) is a novel technology that enables rapid high-resolution digital imaging of non-formalin-fixed tissue specimens and offers... (Review)
Review
Fluorescence confocal microscopy (FCM) is a novel technology that enables rapid high-resolution digital imaging of non-formalin-fixed tissue specimens and offers real-time positive surgical margin identification. In this systematic review, we evaluated the accuracy metrics of ex vivo FCM for intraoperative margin assessment of different tumor types. A systematic search of MEDLINE via PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus was performed for relevant papers (PROSPERO ID: CRD42022372558). We included 14 studies evaluating four types of microscopes in six different tumor types, including breast, prostate, central nervous system, kidney, bladder, and conjunctival tumors. Using the Quality Assessment of Diagnostic Accuracy Studies tool, we identified a high risk of bias in patient selection (21%) and index test (36%) of the included studies. Overall, we found that FCM has good accuracy metrics in all tumor types, with high sensitivity and specificity (>80%) and almost perfect concordance (>90%) against final pathology results. Despite these promising findings, the quality of the available evidence and bias concerns highlight the need for adequately designed studies to further define the role of ex vivo FCM in replacing the frozen section as the tool of choice for intraoperative margin assessment.
Topics: Male; Humans; Microscopy, Confocal; Microscopy, Fluorescence; Neoplasms
PubMed: 37968920
DOI: 10.1369/00221554231212948 -
World Journal of Surgical Oncology Nov 2023The effectiveness and safety of neoadjuvant PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors is controversial. This systematic review and meta-analysis aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The effectiveness and safety of neoadjuvant PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors is controversial. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors as neoadjuvant therapy for malignant solid tumors.
METHODS
This study has been registered with the number CRD42023407275 on PROSPERO. Systematic searches were conducted in PubMed, Embase, Web of Science and Cochrane Library databases until March 17, 2023. In addition, manual searches were performed. The inclusion criteria encompassed randomized controlled trials (RCTs) that assessed the utilization of neoadjuvant PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors PD-1/PD-L1 inhibitors for patients with solid malignancies. The Cochrane Collaboration's tool for assessing risk of bias in randomized trials (ROB1) were used. Risk ratios (RRs), hazared ratios (HRs) and their respective 95% confidence intervals were calculated using Stata17.0 MP and Review Manager 5.4 software.
RESULTS
A total of 2780 records were identified, and ultimately 10 studies involving 273 patients were included. The meta-analysis showed that the addition of CTLA-4 inhibitors to PD-1/PD-L1 inhibitors did not demonstrate a significant effect on overall response rate, main pathological response, pathological complete response, surgical resection, radical resection, overall survival, progression-free survival, recurrence-free survival, grade 3-4 adverse events, all-cause mortality, and completed treatment (P > 0.05). However, further subgroup analysis indicated that the combination of PD-1 with CTLA-4 inhibitors significantly increased the occurrence of grade 3-4 adverse events in patients (P < 0.05).
CONCLUSIONS
As neoadjuvant therapy for malignant solid tumors, the addition of CTLA-4 inhibitors to PD-1/PD-L1 inhibitors does not appear to enhance efficacy.Moreover, there is a potential increase in the risk of grade 3-4 adverse events associated with this combination. However, it is important to note that the studies included in this analysis suffer from limitations such as small samples and single-center designs, which are inherent constrains with the available published literature. Further research involving large-sample and multicenter RCTs are warranted to obtain more reliable results.
Topics: Humans; Immune Checkpoint Inhibitors; Neoadjuvant Therapy; Programmed Cell Death 1 Receptor; B7-H1 Antigen; Neoplasms; Multicenter Studies as Topic
PubMed: 37926852
DOI: 10.1186/s12957-023-03212-5 -
Biomedicines Oct 2023Thymic epithelial tumors (TET) are rare neoplasms of the anterior mediastinum. Surgery is the mainstay treatment for resectable TET, whereas systemic treatments are... (Review)
Review
BACKGROUND
Thymic epithelial tumors (TET) are rare neoplasms of the anterior mediastinum. Surgery is the mainstay treatment for resectable TET, whereas systemic treatments are reserved for unresectable and metastatic tumors. The development of new treatments, such as immune checkpoint inhibitors (ICI) and targeted therapies, with promising results in other types of solid tumors, has led to the investigation of their potential efficacy in TET. The study of tumor microenvironments (TME) is another field of investigation that has gained the interest of researchers. Taking into account the complex structure of the thymus and its function in the development of immunity, researchers have focused on TME elements that could predict ICI efficacy.
MATERIALS AND METHODS
The primary objective of this systematic review was to investigate the efficacy of ICI in TET. Secondary objectives included the toxicity of ICI, the efficacy of targeted therapies in TET, and the evaluation of the elements of TME that may be predictive factors of ICI efficacy. A literature search was conducted in February 2023 using the Ovid Medline and SciVerse Scopus databases.
RESULTS
2944 abstracts were retrieved, of which 31 were retained for the systematic review. Five phase II and one retrospective study assessed ICI efficacy. The overall response rate (ORR) varied from 0% to 34%. Median progression-free survival (PFS) ranged from 3.8 to 8.6 months, being lower in thymic carcinoma (TC) (3.8-4.2 months). Median overall survival (OS) ranged from 14.1 to 35.4 months. Treatment-related adverse events occurred in 6.6% to 27.3% of patients. Sixteen studies assessed targeted therapies. The most active molecule was lenvatinib, with 38% ORR in patients with TC while no activity was detected for imatinib, erlotinib plus bevacizumab, and saracatinib. Ten studies assessed TME elements that could predict ICI efficacy. Four studies focused on the tumor-infiltrating immune cells suggesting improved outcomes in patients with TC and high tumor-infiltrating lymphocyte densities. Another study showed that CD8+, CD20+, and CD204+ tumor-infiltrating immune cells in cancer stroma might be prognostic biomarkers in TC. Another study identified the immune-related long non-coding RNAs as a predictor of response to ICI. Tumor mutational burden was identified as a predictive factor of ICI efficacy in one study.
CONCLUSIONS
Despite study heterogeneity, this review shows that ICI could be a therapeutic option for selected patients with TET that are not amenable to curative radical treatment after first-line chemotherapy.
PubMed: 37893096
DOI: 10.3390/biomedicines11102722