537 Background: Hepatitis-associated hepatocellular carcinoma (HCC) exhibits clinical benefits from immune checkpoint inhibitors (ICIs), whereas metabolic dysfunction-associated HCC demonstrates limited therapeutic efficacy from ICI treatment. Given the rising clinical prevalence of comorbid hepatitis B virus (HBV)-associated HCC and metabolic syndrome (Mts), there is an urgent need to investigate the impact of this comorbidity on immunotherapy efficacy and safety. Methods: In this multi-center retrospective study, we included 276 advanced HBV-related HCC patients from three medical centers who received anti-PD-L1 based therapy from January 2020 to October 2024. Mts was diagnosed based on the American Heart Association/National Heart, Lung, and Blood Institute criteria. Patients were divided into two groups: Mts group and non-Mts group. Propensity score matching (PSM) was performed to mitigate baseline confounding. Results: Before PSM, there were no significant differences in OS (median OS: 39.7 months vs. Not reached, p =0.75), PFS (median PFS: 12.2 months vs. 12.9 months, p =0.64), ORR (54.05% vs. 63.6%, p =0.28) or DCR (86.49% vs. 92.05%, p =0.34) between the Mts group and non- Mts groups. After PSM, still no significant difference in OS (median OS: 39.7 months vs. Not reached, p =0.77), PFS (median PFS: 12.2 months vs. 13.8 months, p =0.98), or ORR (56.67% vs. 67.19%, p =0.30) were observed between these two groups. DCR was significantly higher in non-Mts group compared to Mts group (83.33% vs. 95.53%, p =0.027). No statistically significant difference emerged in any grade adverse events (AEs) (97.30% vs. 97.91%, p>0.05) and grade 3 or 4 AE rates between Mts group and non-Mts group (32.43% vs. 44.35%, p = 0.24). Conclusions: From our results, concomitant metabolic syndrome did not significantly affect the therapeutic efficacy and increase the incidence of treatment-related AEs of anti-PD-L1 treatment in HBV-associated HCC.

The role of adjuvant systemic therapy after resection following conversion therapy in patients with hepatocellular carcinoma (HCC) rendered resectable by transarterial therapy combined with systemic therapy remains unclear. This study aimed to evaluate the impact of adjuvant systemic therapy on survival outcomes in real-world practice. We retrospectively analyzed patients with initially unresectable HCC who underwent curative-intent resection after successful first-line transarterial therapy combined with systemic therapy between January 2018 and December 2023. Postoperative management included either adjuvant systemic therapy or active surveillance. Propensity score matching (1:2) was applied to balance baseline characteristics. Overall survival (OS) and recurrence-free survival (RFS) were evaluated using Kaplan-Meier methods and compared by log-rank tests. Subgroup and recurrence pattern analyses were also performed. Among 496 eligible patients, 120 received adjuvant systemic therapy and 376 underwent active surveillance. After matching, 326 patients were included (116 vs. 210). Adjuvant systemic therapy was associated with significantly improved OS (HR 0.58, 95

BACKGROUND The CRAPT-M model, which comprises C-reactive protein, albumin, protein induced by vitamin K absence or antagonist-II, total bilirubin, and macrovascular invasion, is recognized to serve as a prognostic indicator in patients with hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab. However, its ability to predict survival in HCC patients receiving locoregional-bevacizumab-immunotherapy (L-Bev-IO) has not been fully elucidated. AIM To evaluate the performance of the CRAPT-M model in predicting the efficacy of first-line L-Bev-IO in HCC patients. METHODS This study enrolled HCC patients receiving L-Bev-IO between 2020 and 2023. According to the CRAPT-M model, patients were stratified into low (≤ 4), intermediate (5-12), or high (≥ 13) risk groups. The primary endpoint was defined as overall survival (OS), and secondary endpoints included progression-free survival (PFS) and tumor response rate. RESULTS Median OS was 13.4 months (95%CI: 11.3-16.8) in the high-risk group and was not reached in the low- and intermediate-risk groups. Median PFS was 17.5 months (95%CI: 11.3-not reached), 15.6 months (95%CI: 13.8-21.1), and 8.2 months (95%CI: 7.0-10.0) in the low-, intermediate-, and high-risk groups, respectively (P < 0.01). The C-index of the CRAPT-M model was 0.637 for OS and 0.593 for PFS. The Simple-CRAPT-M model ultimately retained effective risk stratification and strong predictive performance compared with the original CRAPT-M model. CONCLUSION The CRAPT-M model was an independent prognostic indicator in HCC patients receiving L-Bev-IO and demonstrated favorable predictive performance. In addition, the Simple-CRAPT-M model may facilitate risk stratification, enabling physicians to rapidly identify HCC patients likely to gain therapeutic benefit from L-Bev-IO.

536 Background: Hepatic arterial infusion chemotherapy (HAIC), and immune checkpoint inhibitors showed promising results for advanced hepatocellular carcinoma. Considering different anti-malignancy mechanisms, combining these two treatments may improve outcomes. This study aimed to evaluate the efficacy and safety of toripalimab (a PD-1 inhibitor) in combination with HAIC for advanced hepatocellular carcinoma (HCC). Methods: In this single-center, single-arm, biomolecular exploratory, prospective phase II trial, HCC patients of BCLC stage C underwent the treatment of toripalimab in combination of FOLFOX-HAIC. The primary endpoint was progression-free survival (PFS) per RECIST v1.1. It has been more than 48 months since the last patient was enrolled, with long-term follow-up to fully assess the benefit of this combination treatment. Luminex cytokine microarray examined 48 most common human cytokines in pre-treatment plasma specimens from enrolled patients to explore molecular markers for predicting efficacy. Results: Between May 20, 2019 and April 26, 2021, twenty-one patients were enrolled. The primary endpoint was a median PFS of 11.93 months [95% confidence interval (CI), 4.57–37.57], and the median overall survival (OS) was 27.57 months (95% CI, 15.63–NA). The objective response rate was 61.90% per RECIST v1.1 and 66.67% per mRECIST, respectively. The most common adverse events were neutropenia and increased alanine aminotransferase level. Exploratory analyses of luminex cytokine microarray suggested that patients with low level of leukemia inhibit factor (LIF) were more likely to be benefit from this combination therapy. Conclusions: Toripalimab in combination with FOLFOX-HAIC demonstrated promising antitumor activity with favorable tolerability as first-line therapy in HCC of BCLC stage C. LIF expression level may be a promising molecular marker for predicting the efficacy of this combination therapy. Clinical trial information: NCT03851939 . Best observed treatment response. All patients (n=21) RECISTv1.1 (n=21) mRECIST (n=21) CR 0 4 (19.05%) PR 13 (61.90%) 10 (47.62%) SD 4 (19.05%) 3 (14.29%) PD 4 (19.05%) 4 (19.05%) ORR, n (%) 13 (61.90%) 14 (66.67%)

BACKGROUND & AIMS:Systemic therapy for hepatocellular carcinoma (HCC) has evolved rapidly with the introduction of tyrosine kinase inhibitors (TKI), immune checkpoint inhibitors (ICIs), anti-vascular endothelial growth factor (anti-VEGF) antibodies, and their combinations. This multicenter study aimed to characterize real-world systemic treatment patterns and clinical outcomes in treatment-naïve patients with HCC in China. METHODS:Patients initiating systemic therapy for HCC between 2017 and 2023 across five centers were retrospectively enrolled. Four systemic treatment categories were analyzed: TKI monotherapy, ICIs monotherapy, TKI plus ICIs, and anti-VEGF plus ICIs. Baseline clinical characteristics, treatment patterns across lines, survival outcomes, tumor response, and adverse events (AEs) were analyzed. RESULTS:A total of 4,250 patients were included (median age, 53 years), predominantly male (88.7%) with hepatitis B virus infection (86.3%); 81.3% had Barcelona Clinic Liver Cancer stage C disease. In the first-line setting, 92.3% of patients received systemic therapy combined with transarterial therapy. Median overall survival (OS) was 20.7 months (95% CI, 19.1-22.3), and median progression-free survival (PFS) was 9.7 months (95% CI, 8.2-11.2). Baseline characteristics differed across systemic treatment groups, including demographic and disease characteristics and treatment patterns involving transarterial therapy, and were accounted for using inverse probability of treatment weighting and multivariable Cox regression. Median OS was 17.0, 21.4, 21.6, and 22.4 months in the TKI monotherapy, ICIs monotherapy, TKI plus ICIs, and anti-VEGF plus ICIs groups, respectively. Grade ≥3 AEs occurred in 28.3% of patients. CONCLUSIONS:In this multicenter cohort, ICIs-based systemic regimens combined with transarterial therapy were frequently applied in patients with HCC and associated with favorable survival outcomes and acceptable safety profiles. These findings provide contemporary real-world insights into systemic treatment patterns and outcomes. IMPACT AND IMPLICATIONS:The therapeutic landscape of hepatocellular carcinoma (HCC) has evolved rapidly, whereas treatment patterns in routine clinical practice may differ substantially from those represented in randomized clinical trials, particularly in regions with a high burden of hepatitis B-related disease. This large multicenter real-world study delineates contemporary systemic treatment strategies in China and describes clinical outcomes associated with the use of immune checkpoint inhibitor-containing regimens, particularly when integrated with transarterial therapy, in routine clinical practice. These findings provide additional real-world context regarding multidisciplinary treatment approaches for HCC and may help inform future prospective evaluation of systemic and locoregional treatment integration. Although limited by its observational design, this study generates hypotheses for future prospective studies evaluating multimodal treatment strategies and patient selection for immunotherapy-based approaches in HCC.

Lenvatinib is the first-line therapy for advanced hepatocellular carcinoma (HCC). Nevertheless, drug resistance is a challenge for improving the outcomes of these patients. Discs Large Homolog Associated Protein 5 (DLGAP5) belongs to cell-cycle-regulated proteins, associated with poor prognosis in cancer. However, its biological roles and mechanisms in lenvatinib sensitivity of HCC remain unclear. We analyzed the expression level of DLGAP5 by public database. A sixty HCC patients’ cohort was used to investigate the prognostic potential after lenvatinib treatment. Cell growth, metastasis, apoptosis, and animal experiments were used to explore the specific function of DLGAP5. Differentially expressed genes of DLGAP5-knockdown cells were analyzed by RNA-seq data. DLGAP5 was upregulated in HCC tissues, especially in lesions of patients with metastasis. Overexpression of DLGAP5 correlated with poor prognosis and lower response to lenvatinib treatment. We found that the downregulation of DLGAP5 inhibited malignancy and increased the sensitivity of HCC cells to lenvatinib both in vitro and in vivo. Mechanistically, DLGAP5 might function by regulating AKT/mTOR/NF-κB signaling pathway. DLGAP5 promotes malignancy of HCC and reduces cell lenvatinib sensitivity by positively regulating the AKT/mTOR/NF-κB pathway, indicating that DLGAP5 functions as a potential biomarker for clinical prognosis and lenvatinib treatment in HCC.

Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal malignancy with limited therapeutic options. The spatial architecture and functional diversity of tertiary lymphoid structures (TLSs) in iCCA remain unclear. Here, we present a multimodal spatial atlas of TLSs and identified intratumoral TLSs (iTLSs) as independent prognostic markers. Bulk proteomic profiling of 214 discovery and 155 validation cases identified a four-tier TLS-based tumor microenvironment classification system and supported development of a TLS-predictive random forest classifier. Imaging mass cytometry revealed that iTLS + tumors harbor structured immune architectures, where M1-like tissue-resident macrophages (RTMs), dendritic cells, and CXCL13 + CD4 + T cells colocalize to form antigen-presenting neighborhoods (apc-CNs) spatially coupled to TLS core regions (TLScore-CNs). Single-cell spatial transcriptomics further resolved 61 TLSs into 14 spatial niches and defined a pseudotemporal maturation continuum: aggregated, activated, and postactivated. Intraniche communication, primarily mediated by ifnCAFs, iCAFs, and CXCL12 + macrophages, evolved dynamically with maturation. Single-nucleus RNA sequencing combined with Tangram-based spatial mapping revealed CXCL12 + macrophages and iCAFs forming a peripheral band in aggregated TLSs, whereas ifnCAFs infiltrated TLS interiors during activation. These findings define TLS heterogeneity and provide insights for stroma-directed immunotherapy.

Despite numerous available treatment options, the overall prognosis for patients with unresectable hepatocellular carcinoma (uHCC) remains poor. This study aimed to evaluate the efficacy and safety of combining hepatic arterial infusion chemotherapy with FOLFOX (FOLFOX-HAIC), lenvatinib, and the PD-L1 inhibitor durvalumab in this population, with all uHCC patients receiving the triple-combination regimen as initial therapy. The primary objective was progression-free survival (PFS), and secondary outcomes included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. From August 2021 to September 2023, 40 uHCC patients were enrolled, with a median follow-up of 23.1 months (95% confidence interval [CI], 19.0-23.8); 3 deaths and 12 disease progressions were recorded. The median PFS was 15.8 months (95% CI, 8.3-23.3) with a 6-month PFS rate of 77.5% (95% CI, 63-90%), and 1- and 2-year OS rates were 97.5% and 94.0%, respectively. Per modified RECIST criteria, ORR was 75.0% (9 CR/pCR, 21 PR) and DCR was 95.0% (8 SD); median time to response (TTR) was 2.2 months and median duration of response (DOR) was 10.4 months. Seven patients (17.5%) underwent R0 conversion surgery, 3 (42.9%) achieving pCR. Safety was favorable: 85.0% had grade 1-2 adverse events, with grade 3 elevated alanine aminotransferase and thrombocytopenia each occurring in 2 patients (5.0%). No grade 4 adverse events were observed. Collectively, the triple-combination therapy of FOLFOX-HAIC, lenvatinib, and durvalumab exhibits promising therapeutic efficacy, favorable disease control, and a well-tolerated safety profile, providing a potential new treatment option for patients with uHCC. Trial number: NCT04961918.

The role of hilar lymph node metastasis (LNM) in intrahepatic cholangiocarcinoma (ICC) was investigated and a simple postoperative risk-stratification system combining LNM and preoperative anemia was established to predict the outcome of patients with ICC after curative resection. A retrospective analysis was conducted on 384 patients who underwent hepatectomy for ICC. Both postoperative clinical outcomes and long-term oncological outcomes were systematically evaluated. Subsequently, predictive models were developed to assess the risks of tumor recurrence, overall survival (OS) and recurrence-free survival (RFS). The primary cohort demonstrated 65.2

Background: A significant portion of primary liver cancer patients in China are diagnosed at intermediate-to-advanced stages, often making them ineligible for curative surgery. Furthermore, high postoperative recurrence rates, reaching up to 70%, pose a major challenge for long-term survival. The emergence of novel systemic treatments, such as immune checkpoint inhibitor combinations, and advancements in locoregional therapies have created new opportunities for conversion and perioperative strategies. This updated consensus aims to standardize the clinical application of these therapies based on the latest evidence, with the objective of improving patient prognosis. Methods: A multidisciplinary committee of 97 experts was convened to revise previous guidelines. The process involved a comprehensive search of medical databases and conference proceedings, with evidence graded according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Consensus statements were finalized through a formal electronic voting process, requiring at least 80% agreement for approval, resulting in 18 updated statements. Results: The consensus provides refined definitions for conversion and perioperative therapy. It recommends various strategies for oncological conversion, including systemic therapy with anti-angiogenic drugs plus immunotherapy, and locoregional approaches like precision transarterial chemoembolization (TACE) and hepatic artery infusion chemotherapy (HAIC). The document strongly affirms surgical resection as a crucial step for achieving long-term survival after successful conversion and offers guidance on surgical timing and adjuvant therapy. For resectable patients with high-risk features, neoadjuvant and adjuvant treatments are outlined to mitigate recurrence. The consensus also advocates for using dynamic enhanced magnetic resonance imaging ( MRI) and the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria for efficacy assessment and underscores the essential role of a multidisciplinary team in management. Conclusions: This updated consensus offers standardized, evidence-based guidance for clinicians on implementing conversion and perioperative strategies to optimize patient-centered care and highlights the need for continued research to further refine these promising approaches.

RATIONALE AND OBJECTIVES: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). MATERIALS AND METHODS: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. RESULTS: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, p<0.001) than the TA group; after PSM these differences were not significant (all p>0.05). 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). CONCLUSION: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.

Hepatocellular carcinoma (HCC), which accounts for approximately 75–85% of primary liver cancers, ranks 4th in newly diagnosed cases among various types of cancer in China, and is the 2nd leading cause of cancer-related mortality, thereby posing a significant threat to the life and health of the Chinese population. Since the publication of the “Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China” in June 2017, which were updated by the China’s National Health Commission in December 2019 and December 2021, additional high-quality evidence from researchers worldwide regarding the diagnosis, staging, and treatment of HCC has emerged, necessitating another update to the guidelines. The new edition (2024 Edition) was written by more than 120 multidisciplinary experts in the field of HCC in China, which not only reflects the real-world situation in China but also may reshape the nationwide diagnosis and treatment of HCC. The new guideline aims to encourage the implementation of evidence-based practice and improve the national average 5-year survival rate for patients with HCC, as proposed in the “Healthy China 2030: A Vision for Health Care.”

Introduction: Transarterial chemoembolization (TACE) is an optional treatment for hepatocellular carcinoma (HCC) patients with macrovascular invasion (MVI) and without extrahepatic metastasis (EHM). As a recently emerging approach, the efficacy of hepatic arterial infusion chemotherapy (HAIC) compared with TACE in this group of patients is unclear. Methods: Between December 2016 and June 2020, patients diagnosed with HCC with MVI and without EHM who underwent TACE (n=91) or HAIC (n=190) as their initial treatment were included. Propensity score matching (PSM) was used to reduce selection bias and other imbalances. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS), rate of subsequent resection, and safety were compared between groups. Results: Seventy-seven pairs of patients were matched after PSM. The ORR was higher in the HAIC group than that in the TACE group (29.9% vs. 9.1%, P = 0.013). The median PFS of patients in the HAIC group was longer than that of the patients in the TACE group (4.7 vs. 1.4 months, P = 0.002), but there was no significant difference in the median OS between the groups (19.6 vs. 18.1 months, P = 0.122). HAIC also showed a better safety profile than TACE. Conclusions: HAIC is an effective and safe option for treating HCC patients with MVI and without EHM compared to TACE.

Pyroptosis is closely associated with chemotherapeutic drugs and immune response. Here, we investigated whether oxaliplatin, a key drug in FOLFOX-hepatic artery infusion chemotherapy (FOLFOX-HAIC), induces pyroptosis in hepatoma cells and enhances antitumor immunity after tumor cell death. Hepatoma cells were treated with oxaliplatin. Pyroptosis and immunoreactivity were evaluated in vitro and in vivo. Oxaliplatin activated caspase-3-mediated gasdermin E (GSDME) cleavage and induced pyroptosis in Hep G2 and SK-Hep-1 cells in vitro. Liver cancer cells with high levels of GSDME expression are prone to pyroptosis. Bioinformatic analysis revealed that pyrolysis-related genes are closely related to immunity. In vivo experiments revealed that oxaliplatin exhibited superior antitumor efficacy in mice with normal immune function and more pronounced inhibitory effect on hepatocellular carcinoma with high GSDME levels. Higher levels of cytokines and greater CD8+ T cell infiltration were observed in tumor tissues with better efficacy. Furthermore, an in vitro coculture assay confirmed that oxaliplatin-induced pyroptosis in Hep G2 cells overexpressing GSDME and activated the p38/MAPK signaling pathway to improve the cytotoxicity of CD8+ T cells. Analysis of clinical samples of HCC suggested that the efficacy of FOLFOX-HAIC in patients with high GSDME expression was better than that in patients with low GSDME expression. Oxaliplatin induced pyroptosis in hepatoma cells by activating caspase-3-mediated cleavage of GSDME, which enhanced the cytotoxicity of CD8+ T cells by regulating the p38/MAPK signaling pathway. These results suggest that GSDME level may be used as a marker to predict the efficacy of FOLFOX-HAIC.

IntroductionImmune checkpoint inhibitors (ICIs) have been increasingly used in hepatocellular carcinoma (HCC). Despite emerging evidence indicating that concomitant medications might impact clinical outcomes, their association with ICI efficacy is undefined in HCC.MethodsThe multicenter cohort included 851 HCC patients receiving ICIs between January 2018 and December 2022 in 13 institutions. Concomitant medications given within 30 days before or after the initiation of ICIs were evaluated in association with survival, tumor response, and treatment-related adverse event (TRAE) occurrence. Concomitant medications administered within 30 days before or after the initiation of ICI therapy were identified and used to categorize patients into user and non-user groups for each medication class. The primary outcomes were overall survival (OS), and secondary outcomes included progression-free survival (PFS), time to progression (TTP), tumor response, and TRAEs. Tumor response was evaluated based on RECIST 1.1. Multivariable Cox and logistic regression models were used to adjust for confounding variables.ResultsThe median OS (13.6 vs. 20.7 months; P = 0.006) and PFS (6.6 vs. 8.9 months; P = 0.002) were significantly reduced for antibiotic users compared to non-users, while other drugs did not show an impact on patient outcomes. In multivariable analysis, antibiotic use predicted worse survival outcomes (OS: HR = 1.88, 95% CI, 1.14–3.11; P = 0.014; PFS: HR = 1.60, 95% CI, 1.20–2.13; P = 0.001). Patients who underwent glucocorticoids for early TRAE management achieved longer OS than those for prophylactic use (OS: Not reached vs. 20.3 months; HR = 0.25, 95% CI, 0.10–0.65; P = 0.042). Concomitant use of medications such as antibiotics, H2RAs, and glucocorticoids was associated with increased incidence of specific TRAEs, particularly involving hematologic, hepatic, and endocrine systems.ConclusionThis study identified antibiotic use as a negative prognostic factor in HCC treated with ICIs, while glucocorticoid for early TRAEs may indicate improved survival benefits. Concomitant medication may affect the occurrence of TRAEs and warrants careful consideration during ICI treatment.

e16256 Background: For unresectable intrahepatic cholangiocarcinoma (uICC), combining targeted drugs with chemotherapy (systemic or hepatic arterial infusion chemotherapy, HAIC) and immune checkpoint inhibitors (ICIs) has become a common treatment. However, evidence-based medical evidence to choose between different targeted drugs and ICIs is lacking. This study aims to explore better therapeutic targeted drugs in combination therapy through multi-center real-world data analysis. Methods: This was a multicenter, retrospective analysis of 316 patients with uICC treated with lenvatinib/apatinib combined with HAIC plus ICIs between June 2018 and September 2024. Data were collected from three Chinese centers. Outcomes included overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier methods, overall response rate (ORR) and disease control rate (DCR) using modified RECIST (mRECIST), and adverse events (AEs) rate according to CTCAE v5.0. Propensity score matching (PSM) was performed for: age, sex, tumor size, tumor staging, and nodal staging. Results: Patients were divided into 264 patients receiving lenvatinib combined with HAIC plus ICIs (Group A) and 52 patients receiving apatinib combined with HAIC plus ICIs (Group B). Before PSM, median OS was 22.3 months (95% CI: 16.7-27.9) in Group A and 18.4 months (95% CI: 10.7-26.1) in Group B (HR: 1.483; 95% CI: 0.980-2.243; p = 0.06). Median PFS was 12.2 months (95% CI: 9.8-14.6) for Group A vs. 7.1 months (95% CI: 3.8-10.4) for Group B (HR: 1.437; 95% CI: 0.982-2.104; p = 0.06). Following PSM, 153 patients from Group A and 52 patients from Group B were included. After PSM, Group A showed a significantly higher median OS of 25.3 months (95% CI: 13.5-37.1) compared to 18.4 months in Group B (95% CI: 10.7-26.1; HR = 1.670, 95% CI: 1.066-2.617, p = 0.023). Median PFS was 15.4 months (95% CI: 8.741-22.059) for Group A vs. 7.1 months (95% CI: 3.778-10.422) for Group B, with significantly better PFS in Group A than in Group B (HR = 1.665, 95% CI: 1.105-2.508, p = 0.013). Before PSM, neither ORR (37.5% vs. 24.5%, p = 0.082) nor DCR (89.2% vs. 87.8%, p = 0.774) were significantly different between the two groups according to modified RECIST (mRECIST). After PSM, ORR was higher in Group A than in Group B (40.4% vs. 24.5%, p = 0.046), while no statistical difference was shown between DCR (91.5% vs. 87.8%, p = 0.442). Group B showed a trend towards a lower incidence of grades 3 or 4 AEs compared to Group A (16.7% vs. 9.6%, p = 0.199). Conclusions: Lenvatinib appears to be a better choice for combination therapy in uICC, demonstrating superior OS, PFS, and ORR compared to apatinib. However, apatinib may have a lower incidence of severe AEs. Further prospective studies with larger patient populations are required.

PurposeThe α-FAtE score, composed of alpha-fetoprotein, alkaline phosphatase, and eosinophil levels, has been reported as a predictor of prognosis in hepatocellular carcinoma (HCC) patients treated with atezolizumab plus bevacizumab. This study aimed to investigate the predictive ability of α-FAtE score for the efficacy and safety of locoregional immunotherapy as the treatment of HCC patients.Methods and patientsWe conducted a retrospective study of 446 HCC patients at Sun Yat-sen University Cancer Center from January 1st 2019 to January 1st 2023. The predictive performance was evaluated by the concordance index, the area under the receiver operating characteristics curve, the Kaplan-Meier curve and multiple Cox regression analysis.Results446 patients were divided into the α-FAtE 0-1 group (n=211) and α-FAtE 2-3 group (n=235). The median progression-free survival(PFS) of the α-FAtE 0-1 group and 2-3 group was 7.3 months (95%CI 6.6-8.7 months), and 12.3 months (95% CI 10.4–14.1 months; P<0.001), respectively. The median overall survival (OS) of the α-FAtE 0-1 group and 2-3 group was 16.3 months (95%CI 13.7-21.5 months) and 34.1 months (95% CI 27.6–NA months; P<0.001), respectively. HCC patients in the α-FAtE 2-3 group had higher complete response (CR) rate and experienced less drug-related adverse events than those in the α-FAtE 0-1 group. Moreover, a lower α-FAtE score was identified as an independent prognostic indicator for both OS and PFS of advanced HCC patients receiving locoregional immunotherapy.ConclusionThe α-FAtE score is a superior predictor of prognosis in HCC patients receiving locoregional immunotherapy, offering a valuable tool for patient stratification and treatment planning.

4118 Background: Currently, studies on conversion therapy for intrahepatic cholangiocarcinoma (ICC) are relatively limited. Effectiveness and optimization strategies of conversion therapy in real world remain unclear. This study aims to analyze the efficacy of locoregional combined with systematic therapy in patients with unresectable ICC, optimizing conversion therapy strategies by retrospectively. Methods: In this multicenter retrospective study, patients with unresectable ICC who received hepatic arterial infusion chemotherapy combined with ICIs and target therapy were reviewed. Overall survival (OS), progression-free survival (PFS) , objective response rate (ORR) , disease control rate(DCR)(assessed by mRECIST criteria) and safety were analyzed. Results: Between June 2018 to May 2024,a total of 341 patients from six centers were included in this study. The median follow-up time was 21.7 months.Among them, 313 patients with complete imaging evaluations are eligible for efficacy analysis. Of which, 20 patients achieved complete response (CR), 93 patients partial response (PR), 161 patients stable disease (SD), illustrating an ORR of 36.1% and a DCR of 87.5%. Among them, 65 patients successfully underwent conversion surgery, with a median duration of conversion therapy of 4.1 months. Radical resection was achieved in 39 patients within the surgical cohort, and 3 patients demonstrated pathological CR. Systemic therapy regimens with the highest conversion success rates included apatinib plus toripalimab (42.9%), lenvatinib plus tislelizumab (32.4%), and apatinib plus tislelizumab (30.8%). Patients with tumor diameters less than 10 cm and those with unilobar tumor were more likely to achieve successful conversion. After propensity score matching (PSM) to balance baseline characteristics (ratio = 1, caliper = 0.01), the surgical group exhibited better survival outcomes compared to the non-surgical group (not reached vs. 27.2 months, hazard ratio: 0.36, 95% CI: 0.61–0.81, p = 0.001). The median PFS was 13.0 months in the surgical group versus 8.0 months in the non-surgical group (hazard ratio, 0.57; 95% CI, 0.30 to 1.09; p = 0.088).Within the surgical cohort, the 2-year survival rates for patients with palliative surgery and radical resection were 51.3% and 26.9%, respectively ( p = 0.051). All patients experienced treatment-related adverse events (TRAEs), but no treatment-related deaths occurred. The incidence of Grade 3-4 TRAEs was 28.6%. Conclusions: Locoregional combined with systemic therapy is an effective strategy for conversion treatment. Conversion surgery offers substantial survival benefits, while palliative surgery may also serve as a viable therapeutic option.

Background:Clinical tools for predicting prognosis are limited for patients with hepatocellular carcinoma (HCC) undergoing hepatic arterial infusion chemotherapy (HAIC)-based hepatectomy. This study evaluated the prognostic significance of neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) in patients with HCC who received HAIC-based hepatectomy. Methods:This dual-center retrospective study included 390 patients who received HAIC-based conversion resection to investigate the relationship of NLR and LMR with survival outcomes, adverse events, and risk factors. Results:A total of 390 patients with HCC who received HAIC-based conversion liver resection were included. Patients with NLR ≥ 5 exhibited a significantly shorter overall survival (OS) and recurrence-free survival (RFS) compared to those with NLR < 5 (P = 0.0181 and P = 0.0164, respectively). Patients with LMR ≥ 3 exhibited favorable OS and RFS rates compared to those with LMR < 3 (P = 0.0195 and P = 0.0225, respectively). Similar results were observed in patients who achieved an objective response. NLR ≥ 5 and LMR < 3 were significantly associated with decreased OS and RFS compared to NLR < 5 and LMR ≥ 3 (P = 0.0131, P = 0.0104, P = 0.0055, and P = 0.0329, respectively). Conclusion:NLR and LMR have an effective predictive capability in prognosis for patients with HCC who received HAIC-based conversion surgery. These findings may help surgeons and patients make decisions regarding HAIC-based conversion hepatectomy.