Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Comprehensive analysis of the cancer driver genes in breast cancer demonstrates their roles in cancer prognosis and tumor microenvironment.

BACKGROUND: Breast cancer is the most common malignancy in women. Cancer driver gene-mediated alterations in the tumor microenvironment are critical factors affecting the biological behavior of breast cancer. The purpose of this study was to identify the expression characteristics and prognostic value of cancer driver genes in breast cancer. METHODS: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets are used as the training and test sets. Classified according to cancer and paracancerous tissues, we identified differentially expressed cancer driver genes. We further screened prognosis-associated genes, and candidate genes were submitted for the construction of a risk signature. Functional enrichment analysis and transcriptional regulatory networks were performed to search for possible mechanisms by which cancer driver genes affect breast cancer prognosis. RESULTS: We identified more than 200 differentially expressed driver genes and 27 prognosis-related genes. High-risk group patients had a lower survival rate compared to the low-risk group (P<0.05), and risk signature showed high specificity and sensitivity in predicting the patient prognosis (AUC 0.790). Multivariate regression analysis suggested that risk scores can independently predict patient prognosis. Further, we found differences in PD-1 expression, immune score, and stromal score among different risk groups. CONCLUSION: Our study confirms the critical prognosis role of cancer driver genes in breast cancer. The cancer driver gene risk signature may provide a novel biomarker for clinical treatment strategy and survival prediction of breast cancer.

Effect of vitamin B supplementation on cancer incidence, death due to cancer, and total mortality: A PRISMA-compliant cumulative meta-analysis of randomized controlled trials.

BACKGROUND: Observational studies have suggested that vitamin B supplementation is associated with cancer risk, but this association remains controversial. A pooled data-based meta-analysis was conducted to summarize the evidence from randomized controlled trials (RCTs) investigating the effects of vitamin B supplementation on cancer incidence, death due to cancer, and total mortality. METHODS: PubMed, EmBase, and the Cochrane Library databases were searched to identify trials to fit our analysis through August 2015. Relative risk (RR) was used to measure the effect of vitamin B supplementation on the risk of cancer incidence, death due to cancer, and total mortality using a random-effect model. Cumulative meta-analysis, sensitivity analysis, subgroup analysis, heterogeneity tests, and tests for publication bias were also conducted. RESULTS: Eighteen RCTs reporting the data on 74,498 individuals were included in the meta-analysis. Sixteen of these trials included 4103 cases of cancer; in 6 trials, 731 cancer-related deaths occurred; and in 15 trials, 7046 deaths occurred. Vitamin B supplementation had little or no effect on the incidence of cancer (RR: 1.04; 95% confidence interval [CI]: 0.98-1.10; P = 0.216), death due to cancer (RR, 1.05; 95% CI: 0.90-1.22; P = 0.521), and total mortality (RR, 1.00; 95% CI: 0.94-1.06; P = 0.952). Upon performing a cumulative meta-analysis for cancer incidence, death due to cancer, and total mortality, the nonsignificance of the effect of vitamin B persisted. With respect to specific types of cancer, vitamin B supplementation significantly reduced the risk of skin melanoma (RR, 0.47; 95% CI: 0.23-0.94; P = 0.032). CONCLUSION: Vitamin B supplementation does not have an effect on cancer incidence, death due to cancer, or total mortality. It is associated with a lower risk of skin melanoma, but has no effect on other cancers.