There is still no noninvasive, automated, and accurate model for guiding physicians in the decision-making of transarterial chemoembolization combined with microwave ablation (TACE-MWA) in intermediate-stage hepatocellular carcinoma (HCC).

To develop a prognostic score based on the tumor burden and radiomic features for the prediction of the long-term survival of patients with intermediate-stage HCC after TACE-MWA.

From June 2008 to October 2022, a total of 2189 consecutive patients from seven tertiary-care hospitals with intermediate-stage HCC who received initial TACE combined with MWA were enrolled. Among them, 2189 were divided into training cohort (N = 1753), and internal test cohort (N = 436) in a single center, and 316 patients were assigned to external test cohort in another 6 centers. A prognostic scoring system was constructed using tumor burden and radiologic features (TBR) and compared with conventional predicting systems.

In training cohort, multivariate Cox regression analysis suggested that tumor burden (hazard ratio (HR), 0.693; 95% confidence interval (CI): 0.505, 0.814; 1 point per 1.0 increase, p = 0.024), radiologic features (HR, 0.349; 95% CI: 0.236, 0.517; p < 0.001), and alpha-fetoprotein (HR, 1.629; 95% CI: 1.280, 2.073; p < 0.001) were independent prognostic factors for OS. A prognostic model that comprises TBR was built, which showed significantly higher AUC values than other clinical stagings in all three cohorts. Moreover, the TBR score provided greater net benefit across the range of reasonable threshold probabilities than other models. Based on cutoff values of 32 and 74 centiles of the TBR score, the cohort was divided into low-, middle-, and high-risk strata, which provide consistent performance in survival discrimination across different patient subgroups.

The TBR score serves as an efficient instrument for risk stratification, guiding the course of adjuvant targeted and immunotherapies for HCC patients undergoing TACE-MWA combined treatment.

A retrospective, multi-institutional study.

With advancements in drug therapy, local treatments, and evolving concepts, conversion therapy has shown benefits for patients initially diagnosed with unresectable hepatocellular carcinoma (HCC). Over the past 10 years, the conversion therapy field has accumulated a vast amount of underutilized data, necessitating in-depth bibliometric evaluation.

This cross-sectional retrospective study collected a substantial amount of research on conversion therapy published between 2014 and 2023, adhering to strict search criteria. The primary outcomes were publication volume, citation count, and interstudy relationships. Comprehensive analysis was conducted using unsupervised hierarchical clustering, spatiotemporal analysis, regression model, and the Walktrap algorithm.

Over the past decade, conversion therapy has demonstrated significant progress, with an annual growth rate of 23.0%. Post-2020, these metrics saw a marked increase, reaching 116 publications and 1943 citations by 2023. Cluster analysis grouped 244 authors into 17 clusters, highlighting early and sustained contributions from Western authors compared with later-emerging Eastern authors. Research characteristics in HCC conversion therapy were classified into 5 clusters, with Cluster 2 (Target Therapy and Immunotherapy) emerging as a new focus. Thematic analysis categorized research characteristics into 4 quadrants, identifying "immune checkpoint inhibitor" and "combination therapy" as highly relevant and rapidly developing themes, while "hepatic arterial infusion chemotherapy" and "radioembolization" show high potential for future research.

This study highlights key contributors and emerging trends and provides important predictions for future research directions. To achieve effective conversion therapy for HCC, researchers may prioritize immunotherapy and locoregional treatments such as hepatic arterial infusion chemotherapy or radioembolization.

For advanced hepatocellular carcinoma (HCC), effective treatment options remain scarce. The risks of surgery and the likelihood of tumor residue restrict the use of liver resection. However, the combination of systemic therapy with locoregional treatments has recently demonstrated promising anti-tumor efficacy, offering new avenues for advanced HCC.

We detail the case of a 61-year-old male who is free of viral hepatitis and alcohol consumption, but overweight with a body mass index (BMI) of 25.2 kg/m2. A magnetic resonance imaging (MRI), ultrasound, and blood tests were conducted, leading to a diagnosis of HCC associated with steatohepatitis, along with a combined portal vein tumor thrombus. Following four rounds of hepatic artery infusion chemotherapy combined with transarterial chemoembolization (HAIC-TACE), 7 cycles of sintilimab treatment, and lenvatinib, there was marked tumor reduction and thrombus retraction to a peripheral branch. The patient subsequently underwent curative liver resection. Pathology revealed extensive necrosis within the tumor region and chronic hepatitis with steatosis in the adjacent liver tissue. No viable tumor tissue was identified. Now about 6 months after the operation, the patient is still in a tumor-free state.

In this instance, we detail the effective transition of an HCC patient, with underlying steatohepatitis, to a treatment regimen that included HAIC-TACE along with sintilimab and lenvatinib. This approach yielded potent antitumor activity and was notably devoid of severe side effects. The outcome of this case expands the therapeutic horizon for managing HCC in the context of steatohepatitis.

To assess the cost-effectiveness of combining camrelizumab with rivoceranib versus sorafenib as initial treatment options for advanced hepatocellular carcinoma (HCC) across different developmental regions in China.

Utilizing TreeAge Pro and data from the phase III randomized CARES-310 clinical trial, a model based on Markov state transitions was developed. Health state utility values were derived from the CARES-310 trial, and direct medical costs were obtained from relevant literature and local pricing data. The primary outcome measured was the incremental cost-effectiveness ratio (ICER), defined as the cost per additional quality-adjusted life year (QALY) gained per person. The ICERs were compared against the willingness-to-pay (WTP) thresholds of different regions in China, including low-income ($16,426.80), medium-income ($34,319.01), and high-income regions ($81,036.63). Sensitivity analyses were also conducted to assess the robustness and reliability of the model under various assumptions. A tornado diagram was used to illustrate the impact of parameter variations on the model's cost-effectiveness.

For base case analysis, QALYs per person for the cohort receiving sorafenib were 0.91, with a corresponding cost of $8,860.97. For the cohort receiving camrelizumab plus rivoceranib, the QALYs per person were 1.71, with a corresponding cost of $16,190.72. The camrelizumab plus rivoceranib treatment group exhibited an increase of 0.80 QALYs and an additional expenditure of $7,329.75. The calculated ICER was $9,150.75 per QALY, which is below the WTP thresholds for all regions in China. The camrelizumab plus rivoceranib regimen is regarded as highly cost-effective in medium-income areas of China, with a probability of 99.9%. In high-income regions, the probability reaches 100.0%. Even in low-income regions, this regimen is considered 95.6% cost-effective. Sensitivity analysis further verified that these findings were robust across various assumptions.

The combination of camrelizumab and rivoceranib as a treatment strategy not only improves health outcomes but also represents a cost-effective option across different developmental regions in China.

The combination of transarterial chemoembolization (TACE), lenvatinib, and programmed cell death 1 (PD-1) inhibitor has been widely used in the treatment of advanced hepatocellular carcinoma (HCC) and has achieved promising results. However, there are few studies comparing whether drug-eluting beads TACE (D-TACE) can bring more survival benefits to patients with large HCC compared to conventional TACE (C-TACE) in this triplet therapy.

To compare the efficacy and adverse events (AEs) of triple therapy comprising D-TACE, PD-1 inhibitors, and lenvatinib (D-TACE-P-L) and C-TACE, PD-1 inhibitors, and lenvatinib (C-TACE-P-L) in patients with large HCC (maximum diameter ≥ 5 cm), and analyze the prognostic factors.

Following a comprehensive review of our hospital's medical records, this retrospective study included 104 patients: 50 received D-TACE-P-L, and 54 received C-TACE-P-L. We employed Kaplan-Meier estimation to assess the median progression-free survival (PFS) between the two groups, utilized Cox multivariate regression analysis to identify prognostic factors, and applied the χ 2 test to evaluate AEs.

The objective response rate (ORR) and median PFS were significantly higher in the D-TACE-P-L group compared to the C-TACE-P-L group (ORR: 66.0% vs 44.4%, P = 0.027; median PFS: 6.8 months vs 5.0 months, P = 0.041). Cox regression analysis identified treatment option, portal vein tumor thrombus, and hepatic vein invasion as protective factors for PFS. AEs were comparable between the two groups.

D-TACE-P-L may have significantly better PFS and ORR for large HCC, while exhibiting similar AEs to C-TACE-P-L.

This editorial reviews advances in hepatocellular carcinoma (HCC) treatment, focusing on a triple therapy approach and biomarker discovery. Zhang et al discuss the synergistic potential of transarterial chemoembolization combined with tyrosine kinase inhibitors and PD-1 inhibitors. Meanwhile, Li et al identify protein tyrosine phosphatase non-receptor II (PTPN2) as a biomarker for poor prognosis and immune evasion in HCC. The studies highlight the importance of combined therapies and biomarkers in improving HCC treatment efficacy and patient outcomes, with PTPN2 emerging as a potential therapeutic target. This article supplements the aforementioned studies with more recent research advancements, focusing on the molecular mechanisms and clinical applications of biomarkers.

Locoregional treatment with transarterial chemoembolization (TACE) or hepatic artery infusion chemotherapy (HAIC) and systemic targeted immunotherapy with tyrosine kinase inhibitors (TKI) and programmed cell death protein-1 (PD-1) inhibitors in the treatment of unresectable hepatocellular carcinoma (uHCC) have achieved promising efficacy. The retrospective study aimed to evaluate the efficacy and safety of TACE and HAIC plus TKI with or without PD-1 for uHCC.

From November 2020 to February 2024, the data of 44 patients who received TACE-HAIC + TKI + PD-1 (THKP group) and 34 patients who received TACE-HAIC + TKI (THK group) were retrospectively analyzed. Primary outcomes were overall survival (OS) and progress-free survival (PFS), and secondary outcomes were objective response rate (ORR), disease control rate (DCR), conversion rates, and adverse events (AEs).

A total of 78 patients were recruited in our single-center study. The patients in THKP group had prolonged median OS [25 months, 95% confidence interval (CI) 24.0-26.0 vs 18 months, 95% CI 16.1-19.9; p = 0.000278], median PFS [16 months, 95% CI 14.1-17.9 vs 12 months 95% CI 9.6-14.4; p = 0.004] and higher ORR (38.6% vs 23.5%, p = 0. 156) and DCR (88.6% vs 64.7%, p = 0.011) compared with those in THK group. Multivariate analysis showed that treatment option and alpha-fetoprotein (AFP) level were independent prognostic factors of OS and PFS. The frequency of AEs were similar between the two groups.

The THKP group had better efficacy for uHCC than the THK group, with acceptable safety.

This study aimed to evaluate how the timing of transarterial chemoembolization (TACE) relative to systemic therapy (tyrosine-kinase inhibitors [TKIs] and immune checkpoint inhibitors [ICIs]) influences oncological outcomes in patients with hepatocellular carcinoma (HCC). A retrospective analysis was conducted on HCC patients treated with TACE plus TKIs and ICIs from January 2018 to February 2023. We compared objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) between patients receiving TACE before versus after systemic therapies. Multivariate Cox regression analyses identified potential prognostic factors. Of the 194 patients enrolled, 111 received TACE before systemic therapies, and 83 after. The median age at diagnosis was 52.8 years. There were no significant differences in ORR (40.72% vs. 30.41%, p = 0.989) or DCR (48.45% vs. 35.57%, p = 0.770) between the groups. Likewise, OS (18.73 vs. 18.20 months, p = 0.091) and PFS (11.53 vs. 10.05 months, p = 0.336) were similar regardless of treatment sequence. In the result of Cox analysis, a 20% decrease in AFP from baseline at one month was associated with improved OS (HR = 0.35, 95% CI 0.17-0.70, p = 0.003) and PFS (HR = 0.69, 95% CI 0.49-0.96, p = 0.028). Large tumor size (≥ 10 cm) was a poor prognostic factor for OS (HR = 2.12, 95% CI 1.07-4.21, p = 0.032), and the presence of portal vein tumor thrombus adversely affected PFS (HR = 2.31, 95% CI 1.47-3.62, p < 0.001). The sequencing of TACE and systemic therapies does not significantly impact the prognosis of advanced HCC. A 20% reduction in AFP within one month of treatment commencement emerges as a protective prognostic factor for HCC.

Hepatocellular carcinoma (HCC) is a common type of tumor worldwide. The development of systemic treatment of advanced HCC has remained stagnant for a considerable period. During the last years, a series of new treatment regimens based on the combination of immunotherapeutic drugs and targeted drugs have been gradually developed, increased the objective response rate (ORR), overall survival (OS), and progression free survival (PFS) of HCC patients. Among the different combination therapy groups, atezolizumab plus bevacizumab and sintilimab plus IBI-305 seem to have unique advantages, while head-to-head comparisons are still needed. A comprehensive understanding of the developments, the ongoing clinical trials and the mechanisms of combination of immunotherapy and targeted therapy might lead to the development of new combination strategies and solving current challenges such as the molecular biomarkers, the clinical administration order of drugs and the second-line treatments after combination therapy.

Though atezolizumab plus bevacizumab (A+B) offer promise for unresectable hepatocellular carcinoma (uHCC) treatment, the response rate remains suboptimal. Our previous studies highlighted the potential of transarterial chemoembolization (TACE) when combined with FOLFOX-based hepatic arterial infusion chemotherapy (HAIC) in HCC treatment. This study aims to evaluate the safety and efficacy of A+B plus TACE-HAIC for high tumor burden uHCC (HTB-uHCC).

This three-center retrospective study involved 82 HTB-uHCC patients administered with TACE-HAIC followed by A+B. We characterized HTB-uHCC patients as those surpassing the up-to-11 criteria, exhibiting VP 3-4, or presenting extrahepatic metastases. The primary outcomes were the objective response rate (ORR) and progression-free survival (PFS). Secondary outcomes encompassed the incidence of treatment-related adverse events (TRAEs) and overall survival (OS).

Employing the mRECIST criteria, the ORR was 62.2 %, wherein 18 (22.0 %) patients achieved complete response, 33 (40.2 %) demonstrated partial response, 21 (25.6 %) maintained stable disease, and 10 (12.2 %) exhibited disease progression. Impressively, 11 (13.4 %) patients were converted to resectable HCC and underwent curative hepatectomy. The median PFS was 10.1 months (95 % CI, 8.4 to NA), and the median OS was still pending. At the one-year mark, the OS and PFS rates were 92.8 % (95 % CI, 86.1 to 100.0) and 42.9 % (95 % CI, 31.3 to 58.7), respectively. 79 (96.3 %) experienced TRAEs, and 39 (47.6 %) had grade 3-4 TRAEs, though no treatment-related death was recorded.

The findings underscore the potential of the A+B and TACE-HAIC combined treatment for HTB-uHCC patients, marking it as a viable therapeutic option, given its potent efficacy and tolerable safety profile.

Pediatric abdominal infection is a common but serious disease that requires timely and effective treatment. In surgical treatment, accurate diagnosis and rational application of antibiotics are the keys to improving treatment effects.

To investigate the effect of broad-spectrum bacterial detection on postoperative antibiotic therapy.

A total of 100 children with abdominal infection who received surgical treatment in our hospital from September 2020 to July 2021 were grouped. The observation group collected blood samples upon admission and sent them for broad-spectrum bacterial infection nucleic acid testing, and collected pus or exudate during the operation for bacterial culture and drug sensitivity testing; the control group only sent bacterial culture and drug sensitivity testing during the operation.

White blood cell count, C-reactive protein, procalcitonin, 3 days after surgery, showed better postoperative index than the control group (P < 0.05). The hospital stay in the observation group was significantly shorter than that in the control group. The hospitalization cost in the observation group was significantly lower than that in the control group, and the difference between the two groups was statistically significant (P < 0.05).

Early detection of broad-spectrum bacterial infection nucleic acids in pediatric abdominal infections can help identify pathogens sooner and guide the appropriate use of antibiotics, improving treatment outcomes and reducing medical costs to some extent.

Surgical resection (SR) following transarterial chemoembolization (TACE)-based downstaging is a promising treatment for unresectable hepatocellular carcinoma (uHCC), and identification of patients at high-risk of postoperative recurrence may assist individualized treatment.

To develop and externally validate preoperative and postoperative prognostic models integrating multimodal CT and digital subtraction angiography features as well as clinico-therapeutic-pathological features for predicting disease-free survival (DFS) after TACE-based downstaging therapy.

From March 2008 to August 2022, 488 consecutive patients with Barcelona Clinic Liver Cancer (BCLC) A/B uHCC receiving TACE-based downstaging therapy and subsequent SR were included from four tertiary-care hospitals. All CT and digital subtraction angiography images were independently evaluated by two blinded radiologists. In the derivation cohort ( n =390), the XGBoost algorithm was used for feature selection, and Cox regression analysis for developing nomograms for DFS (time from downstaging to postoperative recurrence or death). In the external testing cohort ( n =98), model performances were compared with five major staging systems.

The preoperative nomogram included over three tumors [hazard ratio (HR), 1.42; P =0.003], intratumoral artery (HR, 1.38; P =0.006), TACE combined with tyrosine kinase inhibitor (HR, 0.46; P <0.001) and objective response to downstaging therapy (HR, 1.60; P <0.001); while the postoperative nomogram included over three tumors (HR, 1.43; P =0.013), intratumoral artery (HR, 1.38; P =0.020), TACE combined with tyrosine kinase inhibitor (HR, 0.48; P <0.001), objective response to downstaging therapy (HR, 1.69; P <0.001) and microvascular invasion (HR, 2.20; P <0.001). The testing dataset C-indexes of the preoperative (0.651) and postoperative (0.687) nomograms were higher than all five staging systems (0.472-0.542; all P <0.001). Two prognostically distinct risk strata were identified according to these nomograms (all P <0.001).

Based on 488 patients receiving TACE-based downstaging therapy and subsequent SR for BCLC A/B uHCCs, the authors developed and externally validated two nomograms for predicting DFS, with superior performances than five major staging systems and effective survival stratification.

Primary liver cancer is a major health problem being the sixth most frequent cancer in the world and the third cause of cancer-related death in the world. The most common histological type of liver cancer is hepatocellular carcinoma (HCC, 75-80%).

Based on primary literature, this review provides an updated analysis of studies of genetic characterization of HCC at the level of gene mutation profiling, copy number alterations, and gene expression, with the definition of molecular subgroups and the identification of some molecular biomarkers and therapeutic targets. Recent therapeutic developments are also highlighted.

Deepening the understanding of the molecular complexity of HCC is progressively paving the way for the development of more personalized treatment approaches. Two important strategies involve the definition and validation of molecularly defined therapeutic targets in a subset of HCC patients and the identification of suitable biomarkers for approved systematic therapies (multikinase inhibitors and immunotherapies). The extensive molecular characterization of patients at the genomic and transcriptomic levels and the inclusion of detailed and relevant translational studies in clinical trials will represent a fundamental tool for improving the benefit of systemic therapies in HCC.

Locoregional treatment combined with systemic therapy is expected to play a synergistic anticancer role. We conducted this systemic meta-analysis to examine the efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib with or without programmed cell death protein-1 (PD-1) inhibitors (TLP group) compared with TACE + lenvatinib (TL group) for unresectable hepatocellular carcinoma (uHCC).

From the inception date to April 2024, the data from PubMed, EMBASE, the Cochrane Library, Ovid, Web of Science, and Clinical Trials. gov were used for meta-analysis. All clinical outcomes of interest included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). The hazard ratio (HR) and risk ratio (RR) with 95% confidence intervals (CI) were used to measure the pooled effect.

This study included 10 retrospective cohort studies, including 1128 patients. The OS (HR=0.51; 95% CI: 0.43-0.60, P < 0.05), PFS (HR=0.52; 95% CI: 0.45-0.61, P < 0.05), ORR (RR = 1.58; 95% CI: 1.37-1.83; P < 0.05) and DCR (RR = 1.31; 95% CI: 1.20-1.43; P < 0.05) were significantly higher in TLP group than in the TL group. The incidence of AEs was acceptable. Prognostic factor analysis identified that ECOG PS (1/0), Child-Pugh class (B/A), BCLC stage (C/B) and main portal vein invasion (yes/no) were independent prognostic factors for OS. BCLC stage (C/B) and main portal vein invasion (yes/no) were independent prognostic factors for PFS.

The TLP group had better efficacy for uHCC than that of the TL group, with acceptable safety.

PROSPERO, identifier (CRD42023420093).

Systemic conversion therapy provides patients with initially unresectable hepatocellular carcinoma (HCC) the chance to salvage radical liver resection and superior survival outcomes, but the optimal conversion strategy is unclear.

A systematic literature search was conducted on PubMed, EMBASE, Web of Science, Scopus, and the Cochrane Library between 2007 and 2024 focusing on studies reporting conversion therapy for HCC. The treatment groups were divided into Tyrosine kinase inhibitors (TKI), TKI plus loco-regional therapy (LRT), TKI plus anti-PD-1 therapy (TKI + PD-1), TKI + PD-1 + LRT, immune checkpoint inhibitors (ICI) plus LRT, and Atezolizumab plus bevacizumab (A + T) groups. The conversion to surgery rate (CSR), objective response rate (ORR), grade ≥ 3 treatment-related adverse events (AEs), overall survival (OS) and progression-free survival (PFS) were analyzed.

38 studies and 4,042 patients were included. The pooled CSR were 8% (95% CI, 5-12%) in TKI group, 13% (95% CI, 8-19%) in TKI + LRT group, 28% (95% CI, 19-37%) in TKI + PD-1 group, 33% (95% CI, 25-41%) in TKI + PD-1 + LRT group, 23% (95% CI, 1-46%) in ICI + LRT group, and 5% (95% CI, 3-8%) in A + T group, respectively. The pooled HR for OS (0.45, 95% CI, 0.35-0.60) and PFS (0.49, 95% CI, 0.35-0.70) favored survival benefit of conversion surgery. Subgroup analysis revealed that lenvatinib + PD-1 + LRT conferred higher CSR of 35% (95% CI, 26-44%) and increased ORR of 70% (95% CI, 56-83%).

The current study indicates that TKI + PD-1 + LRT, especially lenvatinib + PD-1 + LRT, may be the superior conversion therapy with a manageable safety profile for patients with initially unresectable HCC. The successful conversion therapy favors the superior OS and PFS compared with systemic treatment alone.

International prospective register of systematic reviews (PROSPERO) (registration code: CRD 42024495289).

Combination therapy has emerged as the focus of research for unresectable hepatocellular carcinoma (HCC). In recent years, several studies have explored the clinical efficacy and safety of the combination therapies of transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs).

To conduct an updated meta-analysis verifying the clinical benefits and adverse effects of the triple combination therapy for unresectable HCC.

All eligible cohort, non-randomized controlled, and randomized controlled trial studies from the PubMed, Web of Science, Embase, Cochrane Library, and MedLine databases up to March 20, 2024 were screened for the present meta-analysis. The study endpoints included complete response (CR), objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Stata 16/18 software was used for this meta-analysis, and a P value of <0.05 was considered statistically significant.

A total of 29 studies with 1754 patients were included. Among the patients who received the TACE therapy with TKIs and ICIs, the tumor response results revealed a pooled CR, ORR, and DCR of 14% [95%CI (0.11-0.18)], 61% [95%CI (0.55-0.66)], and 85% [95%CI (0.83-0.87)], respectively. In terms of the survival outcomes, the pooled median PFS and OS were 10.25 months [95%CI (9.31-11.18)] and 20.47 months [95%CI (18.98-21.97)], respectively. The pooled prevalence of all-grade AEs during the triple treatment was 90% [95%CI (0.84-0.94)] and that of grade ≥ 3 AEs was 32% [95%CI (0.24-0.42)].

The combination therapy of TACE, TKIs, and ICIs exhibits great clinical benefits for unresectable HCC in terms of tumor responses and survival outcomes without increasing the risk of severe AEs.

Our aim was to explore whether programmed death receptor-1 (PD-1) inhibitors would improve the prognosis of unresectable hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) plus lenvatinib. In this single-center retrospective study, patients with unresectable HCC who underwent TACE and were administered lenvatinib with or without PD-1 inhibitors were enrolled and divided into the TACE + lenvatinib group and TACE + lenvatinib + PD-1 group. Overall survival (OS), progression-free survival (PFS) and tumor response were assessed by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1 and mRECIST). Treatment-related adverse events (AEs) were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). In total, 35 eligible patients with unresectable HCC were included; 82.9% of patients had Hepatitis B virus (HBV) infection, and 88.6% of patients had liver cirrhosis. A total of 88.6% of patients had multiple tumors, and the median diameter of the largest tumor was 10.1 cm. A total of 14.3% of patients had extrahepatic metastasis, and 51.4% of patients had portal vein tumor thrombus. The percentages of BCLC stages A, B and C were 5.7%, 28.6% and 65.7%, respectively. There were 16 patients in the TACE + lenvatinib group and 19 patients in the TACE + lenvatinib + PD-1 group. The median follow-up time was 7.7 months (ranging from 1.7 to 31.6 months). Neither group reached the median overall survival. Under RECIST v1.1 criteria, the median PFS was 10.4 and 7.9 months in the TACE + lenvatinib and TACE + lenvatinib + PD-1 groups (HR, 1.13; 95% CI 0.45-2.84; p = 0.80), the objective response rates (ORR) were 31.3% and 31.6% (p > 0.05), and the disease control rates (DCR) were 93.8% and 78.9% (p > 0.05), respectively. Under mRECIST criteria, the median PFS was 10.4 and 10.1 months (HR, 0.98; 95% CI 0.38-2.54, p = 0.97), the ORR was 62.5% and 63.2% (p > 0.05), and the DCR was 93.8% and 73.7% (p > 0.05), respectively. Overall, AEs were relatively similar between the two groups. PD-1 inhibitors did not improve the PFS and tumor response of unresectable HCC treated with TACE plus lenvatinib. Hepatitis B infection, liver cirrhosis, portal vein tumor thrombus, multiple tumors and large tumor diameter may be potential factors that affect the efficacy of PD-1 inhibitors but need further validation.

The prognosis of hepatocellular carcinoma (HCC) with macrovascular invasion(MaVI)is poor, and the treatment is limited. This study aims to explore the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC), combined with lenvatinib and programmed cell death-1(PD-1) inhibitor in the first-line treatment of HCC with MaVI.

From July 2020 to February 2022, we retrospectively analyzed consecutive patients with HCC with MaVI who received hepatic arterial infusion FOLFOX(oxaliplatin, 5-fluorouracil, and leucovorin)combined with lenvatinib and PD-1 inhibitor. The efficacy was evaluated by RECIST 1.1. Kaplan-Meier was used to explore the overall survival and progression-free survival (PFS), and the COX regression model was used to analyze the risk factors of PFS. Adverse events (AEs) were evaluated according to CTCAE5.0.

Thirty-two patients with HCC complicated with MaVI were recruited from the Second Affiliated Hospital of Nanchang University. Among the patients treated with HAIC combined with lenvatinib and PD-1 inhibitor, ten patients (31.25%) got partial response, eighteen patients (56.25%) maintained stable disease and four patients (12.50%) suffered progressive disease during follow-up; and objective response rate was 31.25%, and disease control rate was 87.5%. The median PFS was 179 days. Univariate and multivariate Cox analysis showed that the extrahepatic metastases and Child-Pugh score were independent prognostic factors of PFS. Twenty-two (68.75%) patients suffered adverse reactions. The main AEs were elevated transaminase (46.87%), thrombocytopenia (40.63%), hypoalbuminemia (28.13%), nausea and vomiting (21.88%), leukopenia (18.76%), abdominal pain (15.63%), hypertension (15.63%) and fever (15.63%). There were seven cases (21.88%) that had grade 3 or above AEs; Among them, two cases with elevated transaminase (6.25%), leukopenia, thrombocytopenia, nausea and vomiting, abdominal pain, and diarrhea occurred in one case respectively. Moreover, no treatment-related death was observed.

Hepatic arterial infusion of FOLFOX combined with lenvatinib and PD-1 inhibitor as the first-line treatment for HCC complicated with MaVI is effective, and adverse reactions are tolerable.

Hepatocellular carcinoma (HCC) has a poor prognosis, and alpha-fetoprotein (AFP) is widely used to evaluate HCC. However, the proportion of AFP-negative individuals cannot be disregarded. This study aimed to establish a nomogram of risk factors affecting the prognosis of patients with AFP-negative HCC and to evaluate its diagnostic efficiency.

Data from patients with AFP-negative initial diagnosis of HCC (ANHC) between 2004 and 2015 were collected from the Surveillance, Epidemiology, and End Results database for model establishment and validation. We randomly divided overall cohort into the training or validation cohort (7:3). Univariate and multivariate Cox regression analysis were used to identify the risk factors. We constructed nomograms with overall survival (OS) and cancer-specific survival (CSS) as clinical endpoint events and constructed survival analysis by using Kaplan-Meier curve. Also, we conducted internal validation with Receiver Operating Characteristic (ROC) analysis and Decision curve analysis (DCA) to validate the clinical value of the model.

This study included 1811 patients (1409 men; 64.7% were Caucasian; the average age was 64 years; 60.7% were married). In the multivariate analysis, the independent risk factors affecting prognosis were age, ethnicity, year of diagnosis, tumor size, tumor grade, surgery, chemotherapy, and radiotherapy. The nomogram-based model related C-indexes were 0.762 (95% confidence interval (CI): 0.752-0.772) and 0.752 (95% CI: 0.740-0.769) for predicting OS, and 0.785 (95% CI: 0.774-0.795) and 0.779 (95% CI: 0.762-0.795) for predicting CSS. The nomogram model showed that the predicted death was consistent with the actual value. The ROC analysis and DCA showed that the nomogram had good clinical value compared with TNM staging.

The age(HR:1.012, 95% CI: 1.006-1.018, P-value < 0.001), ethnicity(African-American: HR:0.946, 95% CI: 0.783-1.212, P-value: 0.66; Others: HR:0.737, 95% CI: 0.613-0.887, P-value: 0.001), tumor diameter(HR:1.006, 95% CI: 1.004-1.008, P-value < 0.001), year of diagnosis (HR:0.852, 95% CI: 0.729-0.997, P-value: 0.046), tumor grade(Grade 2: HR:1.124, 95% CI: 0.953-1.326, P-value: 0.164; Grade 3: HR:1.984, 95% CI: 1.574-2.501, P-value < 0.001; Grade 4: HR:2.119, 95% CI: 1.115-4.027, P-value: 0.022), surgery(Liver Resection: HR:0.193, 95% CI: 0.160-0.234, P-value < 0.001; Liver Transplant: HR:0.102, 95% CI: 0.072-0.145, P-value < 0.001), chemotherapy(HR:0.561, 95% CI: 0.471-0.668, P-value < 0.001), and radiotherapy(HR:0.641, 95% CI: 0.463-0.887, P-value:0.007) were independent prognostic factors for patients with ANHC. We developed a nomogram model for predicting the OS and CSS of patients with ANHC, with a good predictive performance.