Background and Aims: HCC remains a leading cause of cancer mortality in China. Anti-angiogenic drugs (AADs) plus immune checkpoint blockade (ICB) combination therapy shows considerable promise for HCC; however, its efficacy is hampered by immunosuppression within the tumor microenvironment. High endothelial venules (HEVs) facilitate lymphocyte migration and tumor infiltration. The aim was to study the formation, functional mechanisms, and clinical relevance of HEVs in the treatment of HCC with combination therapy. Approach and Results: Single-nucleus RNA sequencing, flow cytometry, and immunohistochemistry revealed increased HEV expression and higher CD3 ⁺ T-cell infiltration in HCC tissue after a combination of AAD and ICB therapy. Multiplex immunohistochemistry and spatial analysis demonstrated that CCR7 ⁺ CD8 ⁺ T cells were spatially associated with HEVs. Pseudotime analysis of human T cells and treatment of Hepa1-6 orthotopic liver tumor mouse models with CCR7 ⁺ CD8 ⁺ T-cell transfusions were used to show that CCR7 ⁺ CD8 ⁺ T cells can differentiate into cytotoxic effector T cells. The same models demonstrated that combination therapy activated VEGFC and non-canonical NF-κB pathways, promoting HEV formation. Kaplan–Meier analysis revealed that high HEV density correlated with improved clinical response and prolonged survival. Conclusions: HEVs are pivotal in modulating immune activity within the HCC tumor microenvironment. Targeting the VEGFC–NF-κB (non-canonical)–HEV axis could be a promising therapeutic strategy to enhance antitumor immunity and improve outcomes in patients with HCC who are receiving combination AAD plus ICB therapy.

Large hepatocellular carcinoma (HCC) exhibits heterogeneous morphologies and varied responses to treatment. We evaluated outcomes of patients with different large HCC classifications receiving surgical resection (SR) or transarterial chemoembolization plus ablation (TA). Patients with HCC ≥ 5 cm receiving SR or TA between May 2016 and December 2020 at one center were analyzed retrospectively and with propensity score matching (PSM). Overall survival (OS) and progression-free survival (PFS) of the 2 treatment groups were compared. Tumors were classified according to imaging morphology and gross pathology: Type I, simple nodular; Type II, simple nodular with extranodular growth or confluent multinodular; Type III, infiltrative. Of 644 patients, 374 met the inclusion criteria (300 received SR and 74 received TA). Before PSM, median follow-up was 51.2 (IQR 29.6-65.3) months, and the SR group had longer OS (HR 2.13, 95% CI 1.44-3.15, p<0.001) and PFS (HR 2.31, 95% CI 1.66-3.20, p0.05). Infiltrative HCC (Type III) was an independent negative prognostic factor for OS and PFS. Within both treatment groups, patients with infiltrative HCC had shorter OS and PFS than patients with non-infiltrative HCC (Types I and II) (all p<0.001). For patients with HCC ≥ 5 cm, tumor classification is an important prognostic factor. In patients with non-infiltrative HCC, TA and SR had comparable OS after PSM. For patients with infiltrative HCC, TA and SR had limited efficacy.

Introduction: For patients with large unresectable hepatocellular carcinoma (HCC), the effectiveness of conventional transarterial chemoembolization (cTACE) remains suboptimal. This study investigated the efficacy and safety of modified TACE using low-dose chemotherapy with blank microspheres (BMS-TACE) plus low-dose lenvatinib (LD-LEN) and microwave ablation (MWA) in patients with large unresectable HCC. Methods: In this prospective, single-arm, phase 2 study, patients with unresectable HCC exceeding the up-to-seven criteria, with maximum tumor diameter ≥7 cm, and without macrovascular invasion or extrahepatic metastases, received initial BMS-TACE (lipiodol, low-dose doxorubicin, and lobaplatin up to 30 mg each, and blank microspheres; subsequently modified and repeated in most patients) plus LD-LEN (4–8 mg/day) and MWA. The primary endpoint was downstaging rate (DSR); secondary endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events. Results: From November 2019 to March 2022, 43 patients were enrolled. Median follow-up was 21.2 months. Median largest tumor diameter was 11.2 cm (interquartile range [IQR], 7–25). Following BMS-TACE and LD-LEN, downstaging occurred in 37 (86.0%) patients, 32 of whom received MWA, and 8 of whom had a complete response (CR) without MWA. ORR was 93.0% (CR in 32 [74.4%] and partial response in 8 [18.6%] patients). The 1-, 2-, and 3-year PFS rates were 57.5%, 25.9%, and 18.1%, respectively (median PFS, 14.7 months [95% CI: 8.1–19.5]). The 1-, 2-, and 3-year OS rates were 85.8%, 67.7%, and 61.6%, respectively (median OS, 36.4 months [95% CI: 26.8-not reached]). After BMS-TACE, a significant decline in CD11b+/CD33+/HLA-DR- myeloid-derived suppressor cells and early elevation in CXCR5+/CD8+ and CXCR5+/CD4+ T cells were observed (both p < 0.05). Conclusion: BMS-TACE plus LD-LEN and MWA resulted in promising efficacy and tolerable toxicity in patients with large unresectable HCC exceeding the up-to-seven criteria with a maximum tumor diameter ≥7 cm and without macrovascular invasion or extrahepatic metastases.

Current decision-making for the treatment of breast cancer liver metastases (BCLM) using ablation lacks strong evidence, especially for patients combined with extrahepatic metastases. To assess whether ablation plus systemic therapy (AS) improves survival outcomes in patients with BCLM compared to systemic therapy alone. This retrospective study analyzed patients with BCLM who received either AS or systemic therapy alone. Propensity score matching (PSM) and survival analysis were performed, taking into account factors like the characteristics of primary breast cancer, liver metastases and systemic therapies received. The study included 1021 female patients, with a median follow-up of 39.6 months. Of these patients, 132 underwent AS and 836 received systemic therapy alone. After PSM, among patients with BCLM (≤3 tumors, each ≤3 cm), the median overall survival (OS) for those treated with AS or systemic therapy alone was 65.5 and 40.4 months, respectively (HR = 0.48, p = .003); in the subset of patients with extrahepatic metastases, the median OS for those treated with AS and systemic therapy alone was 46.4 and 40.8 months, respectively (HR = 0.58, p = .047). Among patients with >3 cm or >3 lesions, the median OS for those treated with AS or systemic therapy alone was 45.2 and 29 months, respectively (HR = 0.67, p = .084). Among patients with BCLM (≤3 tumors, each ≤3 cm), AS provide longer survival compared to systemic therapy alone, even with extrahepatic metastases. For patients with larger or more numerous metastases (>3 cm or >3 lesions), AS may provide survival benefit, but further validation is needed.

Background: This study aimed to investigate the efficacy and safety of percutaneous ablation versus hepatectomy in an elderly population with hepatocellular carcinoma (HCC). Methods: Retrospective data on patients aged >= 65 years with very-early/early stages of HCC (<= 50 mm) were obtained from three centers in China. Inverse probability of treatment weighting analysis was performed after stratifying the patients by age (65 - 69, 70 - 74 and >= 75 years). Results: Of the 1,145 patients, 561 and 584 underwent resection and ablation, respectively. For patients aged 65 - 69 and 70 - 74 years, resection resulted in significantly better overall survival (OS) than ablation (age 65 - 69, P < 0.001, hazard ratio (HR) = 0.27; age 70 - 74, P = 0.012, HR = 0.64). However, in patients aged >= 75 years, resection and ablation resulted in a similar OS (P = 0.44, HR = 0.84). An interactive effect existed between treatment and age (effect of treatment on OS, age 65 - 69 as the reference, for age 70 - 74, P = 0.039; for age >= 75, P = 0.002). The HCC-related death rate was higher in patients aged 65 - 69, and the liver/other cause-related death rate was higher in patients aged > 69. Multivariate analyses showed that the type of treatment, number of tumors, alpha-fetoprotein level, serum albumin level and associated diabetes mellitus were independent factors associated with OS, but not hypertension or heart diseases. Conclusion: With increasing patient age, the treatment outcomes of ablation become similar to those of resection. A higher liver/other cause-related death rate in very elderly patients may shorten the life expectancy, which may lead to the same OS regardless of whether resection or ablation is chosen. World J Oncol. 2023;14(2):125-134 doi: https://doi.org/10.14740/wjon1479

Organizing free-text patient data into a structured format is labor-intensive and time-consuming. This study aims to evaluate the effectiveness of a fine-tuned lightweight language model in structuring liver cancer imaging reports. A retrospective dataset of 2,780 liver imaging reports from Sun Yat-sen University Cancer Center (2012–2022), including cases of primary liver cancer and benign liver disease, was collected. Three key entries—Number of Malignant Tumors (NMT), Diameter of the Largest Tumor (DLT), and Vascular Invasion (VI)—were annotated by three radiologists and subsequently reviewed and calibrated by a senior oncologist to ensure data reliability. The annotated dataset was randomly split into training, validation, and test sets at a ratio of 7:1:2. A T5-based lightweight model with 250 M parameters (Liver-T5) was fine-tuned using these data. Performance was evaluated using Accuracy and Macro-F1 metrics. Comparative analysis with LLMs such as ChatGLM4, Qianwen2.0, and Llama3.1 was conducted. The fine-tuned Liver-T5 model outperformed larger LLMs in Exact Match (EM) rate and key evaluation metrics, achieving an EM of 0.8907 and high accuracy for NMT (0.9355) and VI (0.9910). Specifically, for NMT extraction, Liver-T5 achieved an accuracy of 0.9355, outperforming large models such as Qianwen72B (accuracy 0.9140), LLaMA3 (accuracy 0.8961), and ChatGLM4 (accuracy 0.8226). In the VI extraction, Liver-T5 achieved the highest accuracy of 0.9910, significantly surpassing other models, with Qianwen72B, LLaMA3, and ChatGLM4 achieving accuracies of 0.9606, 0.9462, and 0.7581, respectively. A higher proportion of schema-nonconforming outputs was observed in large general-purpose models (e.g., LLaMA3), while Liver-T5 more consistently generated schema-compliant predictions. The fine-tuned lightweight language model demonstrates superior accuracy and efficiency in structuring liver cancer imaging reports compared to larger LLMs. This capability addresses critical challenges in clinical workflows by converting unstructured data into structured formats.