Aims To investigate the efficacy and safety of lenvatinib and idarubicin‐loaded drug‐eluting beads transarterial chemoembolization (IDADEB‐TACE) in primary advanced hepatocellular carcinoma (HCC). Methods This retrospective study included patients with primary advanced HCC who received either lenvatinib monotherapy or lenvatinib plus IDADEB‐TACE as first‐line treatment from September 2019 to September 2020 at three institutes. Overall survival (OS), time to progression (TTP), objective response rate (ORR), and adverse events were compared. Propensity score‐matching was used to reduce the influence of confounding factors on the outcomes. Results The study reviewed 118 patients who received lenvatinib plus IDADEB‐TACE (LIDA group) and 182 who received lenvatinib alone (LEN group). After propensity score‐matching, 78 pairs of patients remained. Compared to patients in the LEN group, those in the LIDA group had better post‐treatment ORR (57.7% vs. 25.6%, p < 0.001, respectively), median OS and TTP (15.7 vs. 11.3 months, hazard ratio [HR] = 0.50, p < 0.001; 8.0 vs. 5.0 months, HR = 0.60, p = 0.003, respectively), 6‐ and 12‐month OS rates (88.5% vs. 71.4%; 67.6% vs. 43.4%, respectively), and progression‐free rates at 6 and 12 months (60.3% vs. 42.3%; 21.1% vs. 10.3%, respectively). Vascular invasion, α‐fetoprotein level, and treatment type were independent OS predictors, and vascular invasion and treatment type were independent TTP predictors. Incidences of nausea/vomiting, fever, abdominal pain, and increased ALT/AST were higher in the LIDA group than in the LEN group. Conclusions Lenvatinib plus IDADEB‐TACE is well‐tolerated and more effective than lenvatinib monotherapy in patients with advanced HCC.
Background. Transarterial chemoembolization (TACE) is recommended for intermediate-stage HCC patients. Owing to substantial variation in its efficacy, indicators of patient responses to TACE need to be determined. Methods. A Gene Expression Omnibus (GEO) dataset consisting of patients of different TACE-response status was retrieved. Differentially expressed genes (DEGs) were calculated and variable gene ontology analyses were conducted. Potential drugs and response to immunotherapy were predicted using multiple bioinformatic algorithms. We built and compared 5 machine-learning models with finite genes to predict patients’ response to TACE. The model was also externally validated to discern different survival outcomes after TACE. Tumor-infiltrating lymphocytes (TILs) and tumor stemness index were evaluated to explore potential mechanism of our model. Results. The gene set variation analysis revealed enhanced pathways related to G2/M checkpoint, E2F, mTORC1, and myc in TACE nonresponders. TACE responders had better immunotherapy response too. 373 DEGs were detected and the upregulated DEGs in nonresponders were enriched in IL-17 signal pathway. 5 machine-learning models were constructed and evaluated, and a linear support vector machine (SVM)-based model with 10 genes was selected (AQP1, FABP4, HERC6, LOX, PEG10, S100A8, SPARCL1, TIAM1, TSPAN8, and TYRO3). The model achieved an AUC and accuracy of 0.944 and 0.844, respectively, in the development cohort. In the external validation cohort comprised of patients receiving adjuvant TACE and postrecurrence TACE treatment, the predicted response group significantly outlived the predicted nonresponse counterparts. TACE nonresponders tend to have more macrophage M0 cells and lower resting mast cells in the tumor tissue and the stemness index is also higher than responders. Those characteristics were successfully captured by our model. Conclusion. The model based on expression data of 10 genes could potentially predict HCC patients’ response and prognosis after TACE treatment. The discriminating power was TACE-specific.
10600 Background: Blood or saliva DNA generally considered to be representative of germline genome in genetic cancer risk assessment. However white blood cells from these samples may also include somatic origin DNA due to postzygotic variation or, most commonly, clonal hematopoiesis (CH). Low variant allele fraction (VAF) found in germline genetic testing suggest the possibility of somatic variant and may lead to misinterpretation of genetic risk. TP53, of which germline pathogenic variants are associated with Li-Fraumeni syndrome (LFS), is frequently mutated in CH. This analysis investigated characteristics of TP53 pathogenic variants with low VAF. Methods: We reviewed the prevalence and distribution of TP53 pathogenic variants(PVs) detected in 11,277 advanced cancer patients who underwent clinical testing with a clinical NGS pan-cancer panel. Potential somatic PVs were defined as variants with low VAF from 10% to 35%. The VAF were evaluated in matched tumor tissue samples if available. Results: TP53 pathogenic variants were detected in 36 (0.32%) patients from blood or saliva samples, VAF between 10% and 35% were identified in 8(22.22%) patients and 7 of them were performed NGS sequencing in matched tumor tissue samples. The average VAF of tissue samples were 9.31times lower than blood or saliva samples(21.69% vs 3.88%). Conclusions: TP53 pathogenic variants with low allele fraction in blood or saliva samples indicate the possibility of somatic variant, a reduced VAF in matched tumor tissue samples may contribute to confirmation for suspicion of somatic origin.
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