The marked heterogeneity of primary liver cancer (PLC), together with the dynamic influence of the tumor microenvironment (TME), remains a major challenge to precision oncology. As currently available therapies provide limited benefit for many patients and robust preclinical platforms for rapid, patient-specific treatment stratification are lacking, there is an urgent need for models that faithfully preserve individual tumor architecture and cellular diversity. We established three-dimensional bioprinted primary liver cancer (3DP-PLC) models comprising 61 patient-derived monocultures and 34 co-culture models with patient-matched cancer-associated fibroblasts (CAFs). To explore the correlation between ex vivo models and clinical drug response, we developed a clinically anchored hybrid stratification framework for response classification. In parallel, the 3DP-PLC/CAF co-culture biobank was used to investigate stromal regulation of therapeutic response. These 3DP-PLC constructs preserved the histological features, biomarker expression patterns, mutational landscapes, and transcriptomic profiles of their corresponding parental tumors. Drug-sensitivity profiling across the biobank revealed substantial intertumoral heterogeneity in therapeutic responses. The clinically anchored hybrid stratification framework integrating ex vivo pharmaceutical profiles with external clinical benchmark data enabled interpretable response classification and demonstrated clinical relevance in patients receiving neoadjuvant or adjuvant targeted therapy. In parallel, the 3DP-PLC/CAF co-culture biobank, combined with single-cell transcriptomic analysis, recapitulated fibrous ring-like architecture and revealed CAF-associated drug-resistant states. These findings support 3DP-PLC as a high-fidelity and scalable platform for personalized therapeutic stratification and mechanistic investigation of tumor–stroma interactions in PLC.

Abstract Ovarian cancer is the most lethal gynecologic malignancy, characterized by tumor heterogeneity and a high recurrence rate. Patient-derived in vitro tumor models offer a promising strategy for individualized drug screening to overcome limitations of systemic therapy. Among existing modeling methodologies, 3D bioprinting exhibits advantages including high-throughput, high fidelity, and a drug screening timeline of 8 days. Here, we present experimental data of a cohort of novel 3D bioprinted patient-derived ovarian cancer (3DP-OC) models. We established 3DP-OC models by mixing primary ovarian cancer cells with Gelatin Methacryloyl (GelMA) and photoinitiator, and bioprinting in a layer-by-layer manner. In total, 3DP-OC from 79 patients were successfully established, including 61 high-grade serous ovarian cancer patients, 9 ovarian clear cell carcinoma patients, 4 ovarian sarcoma patients, 4 ovarian endometrioid carcinoma patients, and 1 ovarian neuroendocrine cancer patient. 113 3DP-OC models were constructed from different tissue origins (primary lesion and metastatic sites) with high cell viability maintained throughout bioprinting and prolonged in vitro culture. Bulk RNA sequencing and immunohistochemistry confirmed that key molecular markers and Ki-67 levels in 3DP-OC models closely resembled those of their paired tumor tissues, demonstrating that 3DP-OC can serve as a patient avatar for drug sensitivity testing. On days in vitro 5, 3DP-OC models were exposed to gradient concentrations of 15 frequently used chemotherapeutic and targeted drugs in ovarian cancer including paclitaxel, carboplatin, olaparib, etc. Cell viability was quantified to calculate IC50 values of different anti-tumor drugs. Drug sensitivity testing revealed substantial interpatient heterogeneity in therapeutic responses. To further investigate whether this response heterogeneity has clinical relevance, we conducted a prospective observational cohort study that enrolled 41 stage III/IV newly diagnosed ovarian cancer patients. Patients were divided into “3DP-OC identified sensitive group” or “3DP-OC identified resistant group” according to 3DP-OC IC50 values of anti-tumor drugs they received. The median follow-up time for all patients was 580.5 days. The 3DP-OC identified sensitive group exhibited significantly prolonged progression-free survival compared to the 3DP-OC identified resistant group (P < 0.05), with disease progression observed in 16.7% (4/24) and 52.9% (9/17) of patients, respectively. In this study, we established a 3D bioprinted patient-derived cancer model with high success rate of establishment, low intra-batch heterogeneity, and high biological fidelity. 3DP-OC model holds promise for predictive utility in precision oncology as well as the potential to serve as an innovative platform that bridges fundamental cancer research and clinical practice. Citation Format: Jiangang Zhang, Huiyu Yang, Ying Shan, Zihan Zhong, Ziren Kong, Yuning Sun, Huayu Yang, Lingya Pan, Yilei Mao, Ying Jin. Predicting therapy efficacy and revealing tumor heterogeneity using patient-derived 3D bioprinted ovarian cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4860.

e16251 Background: Postoperative recurrence remains a major challenge in hepatocellular carcinoma (HCC), particularly among patients with high-risk pathological features. Currently, no globally accepted standard adjuvant therapy exists after curative resection. This study reports an interim analysis evaluating the efficacy and safety of adjuvant donafenib combined with transarterial chemoembolization (TACE) in patients with high-risk HCC following surgery. Methods: This prospective, single-arm, single-center study enrolled patients with hepatocellular carcinoma who underwent curative resection and had predefined high-risk recurrence features, including tumor size > 5 cm, microvascular invasion, satellite lesions, or portal vein tumor thrombus. Patients received donafenib (200 mg BID) combined with a fixed single session of postoperative transarterial chemoembolization for a planned duration of 6 months. The primary endpoint was 12-month recurrence-free survival rate, with secondary endpoints including recurrence-free survival, overall survival, time to recurrence, and safety. This study was registered at ClinicalTrials.gov (NCT05161143). Results: As of December 10, 2025, 25 patients were enrolled, with a median follow-up of 9.7 months. High-risk features included tumor size ≥5 cm (56.0%), MVI (56.0%), satellite lesions (20.0%), and multiple concurrent high-risk factors (36.0%), and notably, the inclusion of patients with concomitant PVTT (n = 2). At data cut-off, 4 patients experienced recurrence, including one death. The 6-month RFS rate was 95.2% (95% CI, 86.6-100), and the estimated 12-month RFS rate was 74.9% (95% CI, 56.0-100); median RFS was not reached. In subgroup analyses, 12-month RFS rates were 81.5% and 66.7% in patients with tumor size ≥5 cm and < 5 cm, respectively. Patients without MVI showed a numerically higher 12-month rate than those with MVI (80.8% vs 66.7%). No stable subgroup-specific differences were observed according to satellite lesions or PVTT. Overall survival data remain immature. Treatment-emergent adverse events (TEAEs) occurred in 84.0% of patients, with grade ≥3 TEAEs reported in 36.0%. No grade 4 or 5 treatment-related adverse events were observed. ALBI scores remained stable during treatment, with no significant difference between baseline and end of treatment (median −3.12 vs −3.14, p = 0.68), indicating preserved liver function. Conclusions: This interim analysis suggests that adjuvant donafenib combined with a single session of postoperative TACE demonstrates encouraging antitumor activity and a manageable safety profile in patients with high-risk HCC after curative resection. Longer follow-up and larger studies are warranted to confirm the durability of benefit. Clinical trial information: NCT05161143 .

H2S-mediated protein S-sulfhydration is an emerging post-translational modification that regulates key biological processes via regulating enzyme activities, controlling protein–protein interactions, and modulating signal transduction. Lipid metabolism represents an important target of S-sulfhydration–mediated regulation, which fine-tunes lipid metabolic networks including fatty acid turnover, triglyceride metabolism, and cholesterol homeostasis. This review aims to systematically summarize current knowledge on the regulation of lipid metabolism with a focus on S-sulfhydration, and highlight novel molecular targets identified in recent research. By integrating emerging evidence, we demonstrate how S-sulfhydration acts as a regulatory module linking redox signaling and lipid homeostasis, which may be leveraged therapeutically to treat lipid-associated disorders, either using H2S donors or sulfhydrated protein–targeted medications.

INTRODUCTION:Prostate cancer (PCa) is one of the most prevalent malignancies in men and frequently progresses to bone metastasis. Understanding the interactions between PCa cells and the bone microenvironment, as well as their impact on therapeutic response, is therefore of critical clinical relevance. OBJECTIVES:This study aimed to investigate the effects of the osteogenic microenvironment on prostate cancer cells by constructing three-dimensional (3D) bioprinted in vitro co-culture models, and to evaluate how the osteogenic niche influences tumor malignant phenotypes. METHODS:This study employed extrusion-based 3D bioprinting (3DP) to construct in vitro co-culture models of the PCa osteogenic microenvironment. Two 3D-PCa models based on LNCaP and PC-3 cells were each co-cultured with osteogenically differentiated adipose-derived stem cells (ADSCs) to generate corresponding osteogenic niche models. Tumor phenotypes and drug responses were evaluated using functional assays, histological and immunofluorescence analyses, molecular profiling, and RNA sequencing. RESULTS:The 3D bioprinted constructs exhibited structural stability and high reproducibility, providing a 3D growth environment that mimics key aspects of the in vivo tumor niche. The 3D-PCa models showed enhanced drug resistance, invasive potential, and adaptation to androgen-deprivation. Meanwhile, ADSCs exhibited robust osteogenic differentiation within 3D scaffolds. Under co-culture conditions, 3D-PCa cells exhibited enhanced malignant-like phenotypes, including increased proliferation and reduced drug sensitivity. Multi-level analyses further indicated that these phenotypic changes were associated with coordinated activation of epithelial-mesenchymal transition (EMT)-, hypoxia-, and mitogen-activated protein kinase (MAPK)-related signaling programs, accompanied by alterations in drug transporter expression and cell cycle distribution. CONCLUSION:The 3D co-culture model provides a biomimetic platform for simulating the PCa bone-metastatic microenvironment. This system enables investigation of the effects of the osteogenic niche on tumor behavior and therapeutic responses, and may serve as a useful tool for preclinical drug screening and evaluation of combination treatment strategies for bone-metastatic prostate cancer.

Three-dimensional (3D) bioprinting is an emerging strategy for constructing tissues and organsin vitro. Here, we achieved long-term expansion of primary mouse hepatocytes using a defined medium and constructed liver tissue using 3D bioprinting. The 3D-printed liver tissue demonstrated several essential liver functions and was able to prolong the survival of mice with acute liver failure due to extreme hepatectomy afterin vivotransplantation, and the transplanted artificial liver tissue showed distinct functional partitioning. Overall, our results develop a method for long-termin vitroculture of primary hepatocytes and demonstrate the potential of 3D bio-printed liver tissue for clinical translational applications.

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy with a dismal prognosis, and pronounced interpatient heterogeneity severely limits the efficacy of systemic therapies, underscoring the need for rapid and accurate functional platforms to guide individualized drug selection. Here, we develop a clinically oriented, patient-derived, 3D bioprinted in vitro model for personalized drug sensitivity assessment in ICC. Using a compositionally defined and cost-effective GelMA/HAMA composite hydrogel, we reconstruct a tumor microenvironment that supports rapid self-organization and sustained viability of primary ICC cells. Histological analyses, marker expression profiling, and bright-field imaging demonstrate close similarity to matched patient tumor tissues. Genomic and transcriptomic fidelity are further confirmed by whole-exome and RNA sequencing, revealing preserved driver mutations and transcriptional programs. Drug sensitivity testing was performed on tumor samples from 21 ICC patients using clinically relevant agents. Notably, in patients receiving neoadjuvant therapy, in vitro drug responses were fully consistent with clinical outcomes. Longitudinal follow-up further showed that recurrence occurred exclusively in patients who did not receive the predicted sensitive therapies. Importantly, clinically actionable drug response profiles were generated within 10 days. Collectively, this platform provides a rapid, reproducible, and patient-specific functional drug testing strategy with strong potential for clinical translation.

Cholangiocarcinoma (CCA) is an aggressive biliary tract cancer with limited treatment options, underscoring the need for breakthrough precision therapies. Neoantigen-based therapy is a promising novel strategy for cancer treatment. This study investigates the potential of neoantigen peptides in CCA, emphasizing their role in personalized immunotherapy and providing insights for vaccine design. Paired samples from 33 CCA patients underwent whole-exome sequencing and RNA sequencing to profile the mutational and neoantigen landscape. Besides, personalized neoantigen peptides were synthesized and immunogenicity was validated through enzyme-linked immunospot assay. Meanwhile, corresponding T cell receptor (TCR) sequences were predicted by bioinformatics. TP53 was the most frequently mutated gene (57.58

INTRODUCTION:The age-male-albumin-bilirubin-platelets (AMAP) score serves as a specific model for assessing liver fibrosis among individuals with chronic hepatitis B. However, there remains ambiguity regarding its ability to reliably predict the long-term outcomes for patients diagnosed with intrahepatic cholangiocarcinoma (ICC) after undergoing radical surgical interventions. METHODS:This retrospective multicenter investigation included 681 participants diagnosed with ICC who had undergone radical surgical procedures. The AMAP risk score was computed according to the following equation: (0.06 × age + 0.48 × ALBI - 0.01 × platelet + 7.4)/14.77 × 100. To assess the clinical significance of the AMAP score on survival outcomes, Kaplan-Meier methods, log-rank tests, and Cox proportional hazards regression models were utilized. In addition, a nomogram was created utilizing the outcomes of the multivariate analysis. RESULTS:The AMAP model demonstrated a significant correlation with the rates of disease-free survival (DFS) and overall survival (OS) in individuals diagnosed with ICC. Patients in the low-risk group exhibited significantly longer DFS (P = 0.002) and OS (P < 0.001) compared to those in the high-risk group. In addition, a nomogram was constructed to predict DFS, achieving a C-index of 0.705, and for OS, a C-index of 0.753. The nomogram based on AMAP demonstrates strong predictive performance. CONCLUSIONS:The AMAP score functions as a prospective prognostic indicator for individuals diagnosed with ICC. A nomogram incorporates the AMAP score proves valuable in recognizing patients with ICC who are at high risk and supports the creation of adjuvant treatment plans.

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.

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.”

Nasopharyngeal carcinoma (NPC) is a prominent head and neck malignancy, yet the mechanisms underlying its occurrence, progression, recurrence, metastasis, drug resistance, and radiation resistance have not been fully understood. This knowledge gap is partly due to the lack of preclinical NPC models for research. Compared to traditional 2D cell cultures, 3D bioprinting (3DP) offers significant advantages in replicating the tumor microenvironment. However, no studies to date have used 3DP technology to model NPC. In this study, we used extrusion-based 3DP to develop a new preclinical NPC model (3DP-HK1) using the emerging bio-ink gelatin methacryloyl. The model successfully demonstrated the ability to sustain long-term tumor cell activity. Immunohistochemistry and immunofluorescence analyses demonstrated that 3DP-HK1 largely retained the histopathological features and tumor-related protein expression of NPC. In addition, we conducted a wound healing experiment, which indicated that tumor cells in 3DP-HK1 have stronger migration ability than 2D-cultured cells (2D-HK1), highlighting differences in cellular phenotype. The different responses of 3DP-HK1 and 2D-HK1 to various anti-tumor drugs and radiation reflect the advantages of 3DP-HK1 for preclinical drug screening and exploring mechanisms of radiotherapy in NPC. Transcriptome sequencing revealed that 3DP-HK1 has a distinct gene expression profile compared to 2D-HK1, with significantly upregulated expression of malignant genes, such as keratin 6B (KRT6B), S100 calcium-binding protein A8 (S100A8), and crystallin alpha B (CRYAB). Meanwhile, genes associated with drug resistance (e.g., lysine demethylase 5B [KDM5B]) and radiation resistance (e.g., carnitine palmitoyltransferase 1A [CPT1A]) were also upregulated, confirming findings from other experimental analyses at the RNA level. In conclusion, this study successfully constructed a 3DP-based preclinical model for NPC research and proved its reliability and significant potential for advancing drug screening and mechanistic studies.

BACKGROUND:Gastrointestinal stromal tumors (GISTs) exhibit significant heterogeneity, posing substantial challenges for personalized treatment strategies. Patients often display varied responses to different therapeutic agents and dosages. Currently, the absence of robust and physiologically relevant in vitro models for GISTs impedes accurate prediction of therapeutic efficacy, thereby constraining the advancement of effective treatment strategies. Traditional 2D cell cultures fail to replicate the tumor microenvironment (TME) and lack patient-specific characteristics, limiting their predictive value. In contrast, three-dimensional bioprinting (3DP) technology faithfully recapitulates key histological architecture and molecular features of their parental tumors, enhancing the physiological relevance of in vitro models. METHODS:We employed patient-derived 3DP-GIST models via 3D bioprinting technology, followed by comprehensive histopathological, genomic, and transcriptomic analyses. Subsequently, we applied clinically approved targeted therapeutic agents to perform drug screening and response prediction on the 3DP-GIST models. The drug sensitivity profiles obtained from these models were then correlated with retrospective clinical data and patient follow-up records to assess the models' potential in guiding the selection and prediction of effective GIST therapies. RESULTS:In our study, we successfully constructed 12 patient-derived 3DP-GIST models. Histopathological assessments, whole-exome sequencing (WES), and transcriptomic analyses confirmed that these models accurately recapitulate the histological architecture, biomarker expression, and molecular features of their corresponding parental tumors. Transcriptomic profiling further revealed gene expression signatures associated with GIST recurrence risk and imatinib resistance. Importantly, the 3DP-GIST models demonstrated the capacity to provide precise, individualized treatment recommendations within 10 days post-surgery, potentially reducing treatment delays and improving patient outcomes. CONCLUSIONS:Overall, the 3DP-GIST model represents a robust and efficient platform for evaluating patient-specific drug sensitivities in vitro, thereby guiding personalized therapeutic strategies for GIST patients.

The role of the gut microbiome in the development and progression of liver cancer has long been recognized. However, the presence of microbes in tumors that were previously considered sterile has only recently been discovered. The intratumor microbiome in liver cancer likely originates from various sources, including the gut, hematogenous spread from other mucosal locations, adjacent non-cancerous tissues, and co-metastasis with the tumor cells. As a newly discovered component of the tumor microenvironment, it regulates host immune responses, promotes chronic inflammation, modulates metabolic pathways, and exerts other influences in liver cancer. These unique features offer potential new biomarkers for liver cancer prognosis and treatment response. Exploring the complex interactions between intratumor microbiome and the host to modulate or target the intratumor microbiome may provide new avenues for liver cancer treatment. This article provides a comprehensive review of our current understanding regarding the potential origins of the intratumor microbiome in liver cancer, its unique characteristics, and the underlying mechanisms by which it affects liver cancer. Furthermore, we discuss the promising clinical implications and potential challenges that remain before this knowledge can be fully integrated into clinical practice.

BACKGROUND:Although several PD-1 or PD-L1 inhibitors combined with antiangiogenic agents have been approved as first-line treatment of advanced hepatocellular carcinoma, treatment needs remain unmet given the high incidence and mortality of hepatocellular carcinoma and due to factors such as regional approval status, medical insurance restrictions, and cost considerations. In this phase 3 HEPATORCH study, we aimed to compare the efficacy and safety of toripalimab plus bevacizumab versus sorafenib in patients with previously untreated advanced hepatocellular carcinoma. METHODS:We did a randomised, open-label, phase 3 study in 57 hospitals across mainland China, Taiwan, and Singapore. Using a central interactive web response system, eligible patients aged 18-75 years with unresectable or metastatic hepatocellular carcinoma were randomly assigned (1:1) through a stratified block randomisation method to receive 240 mg toripalimab (intravenously, once every 3 weeks) plus 15 mg/kg bevacizumab (intravenously, once every 3 weeks) or 400 mg sorafenib (oral, twice daily). Randomisation was stratified by macrovascular invasion or extrahepatic spread (presence vs absence), ECOG performance status score (0 vs 1), and history of locoregional therapy (yes vs no). The co-primary endpoints were progression-free survival (assessed by the Independent Review Committee per Response Evaluation Criteria in Solid Tumors, version 1.1) and overall survival. Efficacy analysis was performed in the intention-to-treat population (ie, all patients randomly assigned to a treatment group). Safety was assessed in all patients who received at least one dose of study treatment. The study is registered with ClinicalTrials.gov, NCT04723004, and is completed. FINDINGS:Between Nov 23, 2020, and Jan 21, 2022, 545 patients were screened for study inclusion, of whom 219 did not meet the screening criteria. 326 patients were randomly assigned to receive an intervention: 162 patients were assigned to the toripalimab plus bevacizumab group and 164 were assigned to the sorafenib group, with median age 58·0 years (IQR 50·0-66·0) and 56·0 years (49·0-61·0) years, respectively. All 326 patients were included in the intention-to-treat population and the safety population. 282 (87%) patients were male and 44 (14%) were female. At the primary analysis of progression-free survival (data cutoff Aug 10, 2022), median follow-up was 9·4 months (IQR 7·0-12·0). Toripalimab plus bevacizumab significantly prolonged progression-free survival compared with sorafenib (median 5·8 months [95% CI 4·6-7·2] vs 4·0 months [2·8-4·2]; hazard ratio [HR] 0·69 [95% CI 0·53-0·91; p=0·0086). At the final analysis of overall survival (May 31, 2024), median follow-up was 16·4 months (IQR 7·1-29·5). Toripalimab plus bevacizumab significantly improved overall survival compared with sorafenib (median 20·0 months [95% CI 15·3-23·4] vs 14·5 months [11·4-18·8]; HR 0·76 [95% CI 0·58-0·99; p=0·039). Grade 3 or higher adverse events occurred in 102 (63%) patients in the toripalimab plus bevacizumab group compared with 100 (61%) in the sorafenib group, and led to discontinuation of treatment in 21 (13·0%) participants in the toripalimab plus bevacizumab group and 20 (12%) participants in the sorafenib group. The incidence of treatment-related fatal adverse events (two [1%] vs one [1%]) was similar between the toripalimab plus bevacizumab and sorafenib groups. The most common (incidence ≥5% in the toripalimab plus bevacizumab group) grade 3-4 adverse events were hypertension (26 [16%] in the toripalimab plus bevacizumab group vs 19 [12%] in the sorafenib group), thrombocytopenia (16 [10%] vs four [2%]), upper gastrointestinal haemorrhage (ten [6%] vs one [1%]), anaemia (nine [6%] vs seven [4%]), and abnormal hepatic function (nine [6%] vs five [3%]). The most common (incidence ≥2% in the toripalimab plus bevacizumab group) serious adverse events were upper gastrointestinal haemorrhage (12 [7%] vs one [1%]), abnormal hepatic function (eight [5%] vs five [3%]), ascites (six [4%] vs three [2%]), and gastrointestinal haemorrhage (four [2%] vs three [2%]). INTERPRETATION:Among patients with previously untreated advanced hepatocellular carcinoma, toripalimab plus bevacizumab resulted in significantly longer progression-free survival and overall survival than did sorafenib, with an acceptable safety profile. Based on these results, the regimen has been approved for use in China by the National Medical Products Administration. FUNDING:Shanghai Junshi Biosciences. TRANSLATION:For the Chinese translation of the abstract see Supplementary Materials section.

ABSTRACT Background Hepatocellular carcinoma (HCC) is the second leading cause of cancer‐related death in China. The rapid progress in systemic therapies has led to the approval of many therapeutic methods that have quickly changed clinical guidelines and practices. Because of the high heterogeneity of HCC, there are still some gaps between the guidelines and real‐world clinical practice. The present study surveyed experts in China to investigate the current treatment concepts and clinical practice regarding HCC. Methods A questionnaire survey on the treatment concepts and clinical practice of HCC was administered to 310 experts with senior professional titles in 2020 and 312 experts in 2021. The results were analyzed and compared. Results For treating patients with resectable HCC, 28% of hepatobiliary surgeons indicated neoadjuvant therapy, and 7% chose systemic therapy ± locoregional therapy as 1 L therapy in 2021 compared with 20% and 1% in 2020. More experts chose adjuvant treatment within 1 month in 2021 compared with 2020, and 6 months and 12 months were the leading choices for the duration of adjuvant treatment. In 2021, 79% of surgeons and 19% of interventionalists were willing to conduct downstaging/conversion therapy for patients with potentially resectable HCC, and 78% chose tyrosine kinase inhibitors (TKI) + immunotherapy (IO) + locoregional therapy for cases in which R0 resection could not be achieved. For completely unresectable HCC, more experts preferred TKI + IO‐based therapy as 1 L therapy in 2021 compared with 2020 (78% vs. 55%). The proportion of experts who indicated TKI + IO‐based therapy as 2 L therapy increased from 32% in 2020 to 40% in 2021. Conclusion The survey results indicated that in 2021, compared with 2020, more experts opted to administer IO + TKI for the treatment of liver cancer, and more experts and patients were willing to participate in clinical research.

Background:Hepatocellular carcinoma (HCC) with microvascular invasion (MVI) is associated with high recurrence risk after curative resection. While adjuvant immune checkpoint inhibitors (ICIs) have shown potential in improving outcomes, there is no consensus on their optimal duration, and the comparative effectiveness versus transcatheter arterial chemoembolization (TACE) remains unclear. Methods:We conducted a retrospective multicenter cohort study of 399 patients with microvascular invasion-positive hepatocellular carcinoma who underwent curative resection between 2017 and 2024. Patients receiving adjuvant ICIs or TACE were compared. Propensity score matching (PSM) was used to adjust baseline differences. The primary endpoint was recurrence-free survival (RFS); overall survival (OS) was assessed as a secondary endpoint. Subgroup analysis evaluated the impact of ICI treatment duration. Results:Among 399 patients, 132 received TACE alone, and 129 received ICI-based therapy. Median RFS was significantly longer in the ICI group than in the TACE group (35 months vs 16 months; HR = 0.50, 95% CI: 0.34-0.72; p = 0.00015). After PSM, ICI remained associated with improved RFS (HR = 0.54, 95% CI: 0.36-0.82; p = 0.0042), while the OS difference was not statistically significant. In the ICI subgroup, treatment duration ≥12 months was associated with superior RFS (HR = 0.46, 95% CI: 0.21-0.99; p = 0.041). Conclusion:Among patients with HCC and MVI following curative resection, adjuvant ICIs therapy provides a significant recurrence-free survival advantage over TACE. Treatment durations shorter than 12 months may be insufficient, supporting the benefit of prolonged therapy.