MethodsThis single-center retrospective cohort study included patients with primary hepatocellular carcinoma who received their first TACE between August 2018 and February 2019 at Zhongshan Hospital, Fudan University. Inclusion criteria were: ① pathologically or radiologically confirmed primary hepatocellular carcinoma; ② Child-Pugh grade A or B; ③ absence of extrahepatic metastasis or main portal vein tumor thrombus. Exclusion criteria were: ① other malignancies; ② prior antitumor therapy other than TACE; ③ severe organ dysfunction. The primary outcomes were disease control rate (DCR) and objective response rate (ORR) evaluated by modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria at 30 days post-treatment. Secondary outcome was adverse events. Relative risk (RR) with 95% CI was calculated, and multivariable logistic regression was performed to adjust for confounders. Subgroup analyses and interaction tests were pre-specified to explore effect modifiers. This study was approved by the Ethics Committee of Zhongshan Hospital, Fudan University (No. B2025-736). Due to the retrospective nature of the study, the Ethics Committee exempted the requirement for informed consent. The study was conducted in accordance with the principles of the Declaration of Helsinki, and patient identifiers were de-identified.ResultsA total of 190 patients were finally enrolled, including 78 in the D-TACE group and 112 in the C-TACE group. The DCR was significantly higher in the D-TACE group than in the C-TACE group (85.90% vs 72.32%, RR=1.19, 95% CI: 1.02-1.38, P=0.023). The ORR was also significantly higher in the D-TACE group (48.72% vs 32.14%, RR=1.52, 95% CI: 1.08-2.13, P=0.011). After adjustment for multivariates, D-TACE remained independently associated with disease control (adjusted OR=2.35, 95% CI: 1.12-4.93, P=0.023). Subgroup analyses showed that the superior efficacy of D-TACE was most pronounced in patients with <3 tumors (DCR: 93.33% vs 77.59%, RR=1.20). Interaction tests revealed significant effect modification by tumor number (P=0.042) and tumor diameter (P=0.038), but not by the three-way interaction (P=0.205). No significant differences were observed between the two groups in the incidence of post-embolization syndrome, infection, leukopenia, or hepatic dysfunction. No treatment-related deaths occurred in either group.ConclusionD-TACE provides superior short-term efficacy compared with C-TACE for the treatment of primary hepatocellular carcinoma, with a comparable safety profile. The benefit is particularly evident in patients with low tumor burden (<3 tumors or diameter<7 cm). This study did not provide long-term survival data, and the long-term benefits of D-TACE require further validation. Future prospective randomized controlled trials with extended follow-up are warranted.Background and purposePrimary hepatocellular carcinoma is a kind of highly prevalent and lethal malignant tumor worldwide. Transarterial chemoembolization (TACE) is a major locoregional therapy for unresectable primary hepatocellular carcinoma. Conventional TACE (C-TACE) using lipiodol has limitations including uncontrolled drug release and higher systemic toxicity. Drug-eluting beads TACE (D-TACE) allows sustained release of chemotherapeutic agents locally, potentially improving efficacy while reducing adverse events. This study aimed to compare the short-term efficacy and safety of D-TACE versus C-TACE in patients with primary hepatocellular carcinoma, and to identify subgroups that may benefit more from D-TACE.

e16296 Background: Transarterial chemoembolization (TACE) combined with ablation has been used to treat unresectable hepatocellular carcinoma (HCC) to enhance local tumor control. We initiated the TAD study of TACE in combination with ablation followed by durvalumab to evaluate the safety and efficacy in patients with unresectable HCC. Methods: This phase 2, single-arm study is designed to investigate the safety and efficacy of TACE plus ablation followed by durvalumab in patients with unresectable HCC who are unsuitable for surgical resection. Approximately 30 patients are planned for enrollment. After TACE, patients undergo ablation and then receive durvalumab 1500 mg Q4W until disease progression or death. Patients achieving complete remission (CR) after 1 year of durvalumab discontinue treatment per protocol. Treatment may be extended up to 2 years if imaging shows viable lesions. Tumor assessment is performed according to mRECIST by independent radiologists. The primary endpoint is adverse events of special interest (AESIs). The secondary endpoints are adverse events (AEs), progression-free survival (PFS), Time to progress (TTP) and overall survival (OS). Results: The interim analysis (IA) was conducted. At this IA, 30 patients (SS set) were enrolled, and the cutoff date was 10th Dec 2025. There were 24 patients (FAS and PP set) received TACE plus ablation and at least 1 cycle of durvalumab, with 12 patients receiving durvalumab for ≥1 year. The median follow-up was 27.6 months (range, 11.9-53.0). Among the 30 patients (SS set), 14 (46.7%) reported grade 1–2 AESIs possibly related to durvalumab: 7 (23.3%) elevated liver enzymes, 6 (20.0%) elevated lipase, 4 (13.3%) abnormal thyroid function, 2 (6.7%) elevated amylase, 2 (6.7%) rashes, and 1 (3.3%) interstitial pneumonia. However, only the 1 patient with interstitial pneumonia required oral corticosteroids for management. Additionally, 7 patients (23.3%) reported grade 3 elevated liver enzymes, attributed to TACE or ablation. No grade 4 AEs or AE-related death occurred. Serious AEs were reported in 6 patients (20.0%), none considered treatment related. No patients discontinued durvalumab due to treatment-related AEs (TRAEs). In the PP set, the objective response rate (ORR) was 100% (24/24), including CR in 70.8% (17/24) and PR in 29.2% (7/24). Additionally, the median PFS (events occurred in 15 patients) and TTP were both 12.5 months (95% CI: 9.4–15.6), with a 1-year PFS rate of 58.3%. As of the last follow-up, 2 patients had died of disease progression, and the median OS was not reached. Conclusions: TACE in combination with ablation followed by durvalumab demonstrated an manageable safety profile without unexpected toxicity, and a promising early efficacy in this interim analysis. The trial is ongoing, and OS benefits will be reported with further follow-up. Clinical trial information: NCT04517227 .

e15531 Background: Hepatic arterial infusion (HAI) chemotherapy combined with systemic therapy may better control the progression of liver lesions. Up to the present, there have been no relevant reports on the application of liposomal paclitaxel formulation in combined systemic treatment of gastrointestinal cancer with liver metastasis. Here, we assessed the safety and primary efficacy of HA131 (a novel cationic liposomal paclitaxel formulation) administered via HAI plus systemic chemotherapy for gastrointestinal cancer with liver metastases. Methods: This open-label dose escalation and dose expansion phase I clinical trial was conducted at two centers in China. Based on accelerated titration followed by a 3+3 design with five planned HA131 dose levels, the initial dose of HA131 was 11 mg/m 2 followed by 22, 33, 44, and 55 mg/m 2 administered on Day 15 every 3 weeks for about 6–8 cycles. XELOX (±bevacizumab) administration was repeated every 3 weeks accordingly. The primary endpoint of the study was safety; secondary endpoints included pharmacokinetics (PK) charactertics, overall response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), which were assessed using the RECIST v1.1/mRECIST criteria. Results: Twenty-three patients were enrolled between March 13, 2023, and December 12, 2025. Evaluation of five HA131 dose levels revealed no dose-limiting toxicities. All patients experienced treatment-emergent adverse events (TEAEs), with 87.0% experiencing TEAEs of grade 3 or higher. The most common HA131-related TEAEs were thrombocytopenia, elevated procalcitonin, lymphopenia, neutrophilia, and leukocytosis. No drug-related fatal TEAEs have been reported to date. Among the 20 evaluable patients, ORR was 85.0% per RECIST and 90.0% per mRECIST; in patients with colorectal liver metastases (n = 18), ORR was 88.9% and 94.4% accordingly; both with a DCR of 100.0%. All patients exhibited tumor shrinkage following treatment. After a median follow-up of 13.3 months, the median PFS has not been reached (6 patients had disease progression). The estimated 18-month PFS rate was 65.7%. In addition, nonlinear pharmacokinetic properties were observed. Conclusions: This regimen demonstrated manageable safety and notably primary efficacy, warranting further exploration in patients with gastrointestinal cancer and liver metastases. Clinical trial information: ChiCTR2300069012.

Primary hepatic carcinosarcoma is an exceptionally rare and highly aggressive malignancy, and ectopic β-hCG production and paraneoplastic leukemoid reaction are both uncommon findings in solid tumors. We report the case of a 47-year-old woman who initially presented with abnormal vaginal bleeding and elevated serum β-hCG, raising concern for a pregnancy-related disorder. Diagnostic curettage showed no evidence of pregnancy or trophoblastic disease, yet the β-hCG level continued to rise. At the same time, she developed extreme leukocytosis, and bone marrow examination favored a leukemoid reaction rather than hematologic malignancy. Imaging subsequently revealed a rapidly enlarging mass in the right hepatic lobe with necrosis, satellite lesions, vascular involvement, and hilar nodal disease. Surgical resection was performed because the lesion was considered resectable and tissue diagnosis was required. Histopathology demonstrated a poorly differentiated primary hepatic carcinosarcoma with β-hCG expression in a subset of tumor cells. After surgery, the white blood cell count, serum β-hCG, and PIVKA-II levels all fell markedly, supporting their paraneoplastic origin. However, the tumor recurred rapidly, and the patient died approximately 1 month after surgery. This case shows that persistent β-hCG elevation and marked leukocytosis, when unexplained by gynecologic or hematologic disease, may rarely be the presenting clues to an aggressive primary hepatic malignancy. Importantly, persistent β-hCG elevation and marked leukocytosis should not be interpreted in isolation as gynecologic or hematologic disease when imaging reveals a rapidly enlarging liver mass.

4133 Background: Subsequent treatment options for advanced cholangiocarcinoma (CCA) after failure of chemotherapy and FGFR inhibitors (FGFRi) are limited. Tinengotinib (TT-00420), a novel FGFRi, potently inhibited FGFR2 fusion/rearrangement and acquired resistant/FGFR2 kinase domain mutations. The FIRST-08 study is an open-label, multicenter Phase II study in Chinese patients (pts) with advanced/metastatic CCA (NCT06057571). Methods: Eligible pts with advanced/metastatic CCA harboring FGFR2 fusion or arrangement, who had failed prior chemotherapy and one FGFRi, received tinengotinib 10 mg orally once daily in 21-day cycles. The primary endpoint was objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included progression free survival (PFS), disease control rate (DCR), duration of response (DoR), overall survival (OS), safety, PK and quality of life (QOL) per EORTC QLQ-C30. Results: As of June 27, 2025, 50 pts were enrolled (median age 56.5 years; 52.0% male; ECOG of 1: 44.0%). Median follow-up was 8.5 months. Forty percent had ≥ 3 prior systemic regimens, 66.0% had prior immunotherapy, and 42.0% had received other targeted therapies beyond FGFRi. The ORR by BICR was 28.0% (95%CI, 17.5~41.7) with 14 confirmed partial responses, and median DoR was 7.9 (5.6~ -) months. The disease control rate (DCR) was 82.0%. The median PFS was 5.7 (4.3~8.3) months. The median OS had not reached, with the 18 months survival rate 66.9% (47.3~80.6). Common Gr3/4 TRAEs (≥15%) included hypertension (42.0%), palmar-plantar erythrodysesthesia syndrome (16.0%), No Gr 5 TRAE was observed. 41 out of 50 pts had biomarker ctDNA samples collected at baseline, 82.9% pts had FGFR2 fusion and 48.8% had FGFR2 mutation (SNV). 28 pts had biomarker ctDNA samples collected at both baseline and C3D1. A significant decrease in maximum variant allele frequencies (MaxVAF) from baseline to C3D1 by a median relative VAF reduction of 83.7% (p<0.0001), indicating strong molecular response to tinengotinib. Conclusions: Tinengotinib demonstrated durable clinical anti-tumor activity and a manageable safety profile in heavily pretreated CCA pts with FGFR2 fusion/rearrangement following prior chemotherapy and FGFRi therapy. Clinical trial information: NCT06057571 . Efficacy outcomes by BICR and investigator. BICR Investigator ORR, % (95%CI) 28.0 (17.5~41.7) 20.0 (11.2~33.0) DCR, % (95%CI) 82.0 (69.2~90.2) 78.0 (64.8~87.3) mPFS, months (95%CI) 5.7 (4.3~8.3) 6.9 (4.3~8.5) mDoR, months (95%CI) 7.9 (5.6~ -) 6.6 (2.4~ -)

OBJECTIVES:To establish and validate a preoperative MRI-based model to predict very early recurrence (VER, ≤6 months) of intrahepatic mass-forming cholangiocarcinoma (IMCC) following curative resection. MATERIALS AND METHODS:This multicenter study enrolled 228 patients who underwent curative resection for IMCC between May 2019 and January 2024. Participants were randomly allocated to a training cohort (n = 160) and a validation cohort (n = 68). Independent predictors of VER were identified using Cox regression analysis and integrated into a prediction nomogram. The discriminative performance was evaluated and recurrence-free survival (RFS) between low-and high-risk groups was compared using Kaplan-Meier analysis. RESULTS:VER was observed in 52 patients (32.5%) and 28 patients (41.2%) in the training and validation cohorts. Tumor multiplicity (HR: 1.858, 95% CI: 1.017-3.394, p = 0.044), arterial edge enhancement ratio (HR: 0.012, 95% CI: 0.001-0.423; p = 0.015), and intrahepatic duct dilatation (HR: 2.367, 95% CI: 1.332-4.205; p = 0.003) were identified as independent predictors of VER. The area under the curve (AUC) of nomogram was 0.815 (95 % CI: 0.746-0.894) and 0.827 (95% CI: 0.726-0.927) in the training and validation cohorts. RFS rate was significantly lower in the high-risk group compared to the low-risk group in the training cohort (27.8% vs. 79.0%; p < 0.001) and the validation cohort (18.8% vs. 71.2%; p < 0.001). CONCLUSION:The preoperative MRI-based model, incorporating tumor multiplicity, arterial edge enhancement ratio, and intrahepatic duct dilatation can effectively predict VER with risk stratification in IMCC patients.

BACKGROUND:This real-world study aimed to evaluate and compare the efficacy and safety of two treatment strategies for advanced hepatocellular carcinoma (HCC): transarterial chemoembolisation (TACE) combined with camrelizumab and apatinib versus camrelizumab and apatinib alone. METHODS:In this nationwide, multi-centre retrospective cohort study, data were collected on patients with advanced HCC who received either TACE combined with camrelizumab and apatinib (T-C-A) or camrelizumab and apatinib alone (C-A) between January 2018 and December 2022. To reduce potential bias, stabilised inverse probability of treatment weighting (sIPTW) was applied. The primary outcome was overall survival (OS), while secondary outcomes included progression-free survival (PFS), objective response rate (ORR) based on RECIST v1.1 criteria, and safety. RESULTS:A total of 252 HCC patients were included (T-C-A group, n = 183; C-A group, n = 69). Among them, 210 were males and 42 were females, with a median age of 54 years. After sIPTW, the median OS was significantly longer in the T-C-A group compared to the C-A group (24.2 months [95% CI: 21.4-33.4] vs. 15.2 months [95% CI: 9.8-21.0]; p < 0.001). The T-C-A group also demonstrated a significantly improved median PFS of 10.1 months [95% CI: 8.8-12.2], compared to 4.9 months [95% CI: 4.0-12.5] in the C-A group (p < 0.001). Further, the ORR was higher in the T-C-A group. Grade 3/4 adverse events were reported in 12.0% of patients in the T-C-A group and 14.5% in the C-A group. CONCLUSION:The combination of TACE with camrelizumab and apatinib suggests potential survival advantages for patients with advanced HCC while maintaining an acceptable safety profile.(Study series number CHANCE 2311).

Background and Aim:Unresectable hepatocellular carcinoma (u-HCC) is highly heterogeneous, with limited survival expectancy. The aim of this study was to reappraise the efficacy and safety of locoregional hepatic arterial infusion chemotherapy (HAIC)combined with systemic treatment in initially diagnosed u-HCC. Methods:A total of 302 treatment-naive patients with u-HCC who received HAIC and systemic treatment therapy between December 2018 and November 2023 were enrolled. The cumulative progression-free survival (PFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. Factors affecting survival were analyzed via Cox regression analysis. Results:The median PFS and OS were 11.5 (95% CI: 8.7-14.3) months and 30.0 (95% CI: 20.7-39.2) months, respectively. The estimated PFS rates were 66.2%, 47.9% and 35.2% at 0.5, 1 and 2 years, respectively, and the estimated OS rates were 68.0%, 52.5% and 41.7% at 1, 2, and 3 years, respectively. Aspartate aminotransferase (AST), alkaline phosphatase (ALP), neutrophil to lymphocyte ratio (NLR), extrahepatic metastasis (EHM), metabolic comorbidity and treatment allocation were identified as factors associated with patient survival. The treatment regimen was well tolerated. Conclusion:Locoregional HAIC combined with systemic immune checkpoint inhibitors (ICIs) and targeted therapy represents an effective and safe treatment modality for initially diagnosed u-HCC. Favorable survival outcomes were associated with AST ≤ 56.5 U/L, ALP ≤ 174.5 U/L, NLR ≤ 1.77, absence of extrahepatic metastasis, presence of metabolic comorbidity, and HAIC combined with ICI plus targeted/anti-VEGF therapy. These findings require further validation in external and prospective cohorts.

Background:This study aimed to assess the clinical outcomes of transarterial chemoembolization (TACE) with immune checkpoint inhibitors (ICIs) plus vascular endothelial growth factor (VEGF) inhibitors or tyrosine kinase inhibitors (TKIs) (combination therapy) versus TACE monotherapy as a first-line treatment for intermediate-stage hepatocellular carcinoma (HCC). Methods:This nationwide, retrospective cohort study employed a target trial emulation framework with a cloning-censoring-weighting approach. Patients with intermediate-stage HCC receiving either combination therapy or TACE monotherapy between January 2018 and December 2022 in China were included. Co-primary outcomes were overall survival (OS) and progression-free survival (PFS) per modified Response Evaluation Criteria in Solid Tumors (mRECIST), assessed using restricted mean survival time (RMST). Hazard ratio (HR) was additionally estimated using Cox proportional hazards models for reference. For both RMST and HR, 95% CIs were obtained by bootstrapping. Secondary outcomes included PFS per RECIST 1.1, objective response rate (ORR) per both mRECIST and RECIST 1.1, and safety. This study is registered at ClinicalTrials.gov (NCT05332496). Findings:A total of 941 patients were included in the study, with 308 (32.7%) receiving combination therapy, and 633 (67.3%) receiving TACE monotherapy. Median OS was 32.9 with combination therapy versus 23.0 months with TACE monotherapy, with an RMST difference of 9.2 months (95% CI 4.5-14.3, bootstrapped p < 0.001; HR 0.57 [95% CI 0.43-0.70]). Median PFS was 18.0 and 12.9 months in the respective groups, with an RMST difference of 6.7 months (95% CI 3.3-10.7, bootstrapped p = 0.001; HR 0.70 [95% CI 0.58-0.82]). Combination therapy also yielded a higher ORR per mRECIST (60.5% versus 44.3%; p < 0.001). Similar results for PFS and ORR were observed when assessed using RECIST 1.1. Grade ≥3 adverse events occurred in 64 (20.8%) and 43 (6.8%) patients, respectively. Interpretation:Combining TACE with ICIs and VEGF inhibitors or TKIs was associated with improved OS and PFS than TACE monotherapy, with an acceptable safety profile, supporting its potential as a first-line treatment strategy for intermediate-stage HCC. Funding:National Natural Science Foundation of China (82130060, 82502493), China Postdoctoral Science Foundation (2025M772071), Jiangsu Provincial Basic Research ProgramNatural Science Foundation-Frontier Leading Technology Basic Research Project (BK20232008), Jiangsu Provincial Medical Innovation Center (CXZX202219), Postdoctoral Fellowship Program of CPSF (GZC20251385), and Natural Science Foundation of Jiangsu Province (BK20251687).

The ataxia telangiectasia and Rad3-related (ATR) kinase plays a pivotal role in the DNA damage response (DDR), serving as a critical regulator of replication stress and genomic stability. As a central mediator of cell cycle checkpoint signaling, ATR activation enables cancer cells to survive under conditions of DNA damage, making it an attractive therapeutic target, particularly in tumors with high replication stress or DDR deficiencies. This review outlines a comprehensive overview of the biological functions of ATR, highlighting its mechanistic roles in DNA repair, cell cycle control, and cancer cell survival. It further examines the clinical-stage ATR inhibitors (ATRi) and discusses the structure-activity relationships of preclinical compounds, aiming to offer insights for developing next-generation ATRi or degraders. The emergence of ATR dual inhibitors has also injected new vitality into targeted therapy. We also present combination strategies of ATRi with other anti-tumor agents and assess their feasibility, offering a fresh perspective on the clinical application of ATRi.

BackgroundChronic venous insufficiency (CVI) is a common vascular disorder that substantially impairs quality of life. Endovenous laser ablation (EVLA) and radiofrequency ablation (RFA) have largely replaced conventional surgery; however, their comparative efficacy and safety—particularly across follow-up time points and EVLA wavelengths—remain debated.MethodsWe conducted a systematic review and meta-analysis of PubMed, Scopus, Web of Science, the Cochrane Library, and Google Scholar from inception to September 2024. Thirty-three comparative studies (9 randomized controlled trials and 24 non-randomized studies) involving 22,814 patients (8,144 EVLA and 14,670 RFA) were included. Analyses were performed at the patient level. The single primary outcome was complete occlusion of the treated vein; all other endpoints were secondary. Secondary outcomes included procedural success, recanalization, partial occlusion, reflux-free rate, postoperative pain, recurrence, return to work or daily activities, patient satisfaction, and complications, with stratified analyses by follow-up time and EVLA wavelength.ResultsRFA was associated with significantly lower postoperative pain at 6 weeks (mean difference [MD] = −3.00; 95% CI: −3.42 to −2.58) and 6 months (MD = −1.00; 95% CI: −1.85 to −0.14), and a reduced risk of paresthesia at 1 month (odds ratio [OR] = 0.52; 95% CI: 0.28–0.95). Non-randomized studies suggested lower recurrence rates with RFA compared with EVLA (OR = 0.42; 95% CI: 0.29–0.62), although randomized trials showed no significant difference. Complete occlusion rates were lower with RFA than with EVLA in pooled analyses (OR = 0.07; 95% CI: 0.04–0.14), particularly at early follow-up (1 day: OR = 0.01; 95% CI: 0.00–0.11), with differences diminishing over time. Variation in outcome definitions and imaging timing likely contributed to these early effects. Reflux-free rates and patient-reported outcomes, including Aberdeen Varicose Vein Questionnaire scores, did not differ significantly between groups.ConclusionBoth EVLA and RFA are effective and safe treatments for CVI. RFA provides advantages in short-term postoperative comfort and selected complications, whereas EVLA—particularly with 1,470-nm wavelengths—achieves more consistent early technical occlusion. However, these differences do not translate into clear differences in reflux-free status or patient-reported quality-of-life outcomes, supporting individualized treatment selection. When performed competently, neither modality offers a clinically meaningful advantage for patient-centered outcomes.

Background:This study aimed to identify prognostic factors and establish a nomogram for predicting overall survival (OS) in hepatitis B surface antigen-positive (HBsAg-positive) cervical cancer (CC) patients. Methods:A retrospective analysis of 149 HBsAg-positive CC patients treated at Yunnan Cancer Hospital (2015-2017) was performed. Cox regression identified independent prognostic factors for nomogram development. The nomogram's predictive accuracy and discriminative capability were evaluated through Harrell's concordance index (C-index), calibration plots, and decision curve analysis, and its performance was compared to the International Federation of Gynecology and Obstetrics (FIGO) staging system. Internal validation was conducted using the bootstrap resampling method. Results:Multivariate Cox regression analyses identified tumor stage, baseline serum AST levels, antiviral therapy, lymph node status, and treatment modality as independent prognostic factors for patients with HBsAg-positive CC, all of which were incorporated into the nomogram for OS. The Harrell's C-index of nomogram was 0.817 (95% confidence interval [CI], 0.762-0.873), which was higher than that of FIGO staging system 0.700 (95% CI, 0.637-0.764, P < 0.001). Moreover, the nomogram showed superior performance in decision curve analysis (DCA) and a higher area under the curve (AUC) compared to the FIGO staging system. The calibration curve for survival probability exhibited good consistency between the probabilities and observed values. Grouping based on the nomogram's cutoff value showed that the high-risk group experienced significantly poorer OS than the low-risk group (P < 0.001). Conclusions:This study established a nomogram for the preliminary prognostic evaluation of OS in HBsAg-positive CC patients. Further validation is required prior to its clinical application.

Objective To investigate the therapeutic effect of Huangkui capsules on targeted drug-related proteinuria in patients with hepatocellular carcinoma(HCC).Methods A retrospective analysis was conducted on clinical data of HCC patients with targeted drug-related proteinuria from June 2023 to December 2024 at Zhongshan Hospital,Fudan University.According to the treatment plan,patients were divided into the conventional treatment group and the Huangkui combination treatment group(Huangkui capsules combined with conventional treatment),and the clinical efficacy between the two groups was compared.The logistic regression analysis was used to identify the main factors affecting treatment efficacy.Results The Huangkui combination treatment group(n=29)showed a significantly higher overall effective rate(79.3%vs 42.3%,P=0.005),and an earlier proteinuria improvement(median time:3 months vs 6 months,P=0.008)than the conventional treatment group(n=26).The multivariate logistic regression analysis showed angiotensin-converting enzyme inhibitor(ACEI)or angiotensin Ⅱ receptor blocker(ARB)using(OR=0.190,95%CI 0.045-0.808,P=0.025),targeted drug adjustment(OR=0.132,95%CI 0.030-0.581,P=0.007),and Huangkui capsules using(OR=0.168,95%CI 0.039-0.730,P=0.017)were protective factors for treatment efficacy of targeted drug-related proteinuria.Conclusions On the basis of conventional treatment,additive treatment with Huangkui capsules can alleviate targeted drug-related proteinuria faster and more effectively in HCC patients.

Hepatocellular carcinoma (HCC) with major portal vein tumor thrombosis (PVTT) has a dismal survival expectancy. The treatment for HCC with major PVTT remains challenging. The aim of the study was to revisit the survival outcomes and safety of locoregional hepatic arterial infusion chemotherapy (HAIC) and systemic treatment of immune checkpoint inhibitors (ICIs) and targeted therapy for initially diagnosed HCC patients with major PVTT. For this retrospective study, we enrolled 331 initially diagnosed HCC patients with major PVTT (Vp3/4) treated with HAIC plus systemic treatment of ICIs and/or targeted therapy between December 2018 and April 2024. The demographic and laboratory data, treatment allocations, tumor response, survival, and occurrence of adverse events were recorded. Survival outcomes and safety of the treatments were analyzed. Univariable and multivariable Cox regression analyses were conducted to identify predictive factors for overall survival (OS) and progression-free survival (PFS). In the patients with Vp3/4 PVTT receiving HAIC plus ICIs and/or targeted therapy, the median PFS and OS were 10.0 [95

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.

BACKGROUND:Patients with intrahepatic cholangiocarcinoma have a poor prognosis and high postoperative recurrence rates. Immunochemotherapy has been approved as a first-line treatment for advanced biliary tract cancer. We aimed to explore the activity and safety of camrelizumab, an anti-PD-1 immunotherapy, combined with capecitabine chemotherapy in the adjuvant treatment of patients with resected intrahepatic cholangiocarcinoma. METHODS:ACC was a single-arm, single-centre, open-label, phase 2 trial in adult patients (aged 18-75 years) with R0-resected, pathologically confirmed intrahepatic cholangiocarcinoma (staged as IA with G3 classification or IB-III per the American Joint Committee on Cancer staging system [8th edition, 2017]) done at Zhongshan Hospital, Fudan University (Shanghai, China). Eligible patients had no extrahepatic metastases, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate organ function. 4-8 weeks after surgery, patients received eight 21-day cycles of intravenous camrelizumab (200 mg on day 1 of each cycle) plus oral capecitabine (1250 mg/m2 twice daily on days 1-14, followed by a 7-day rest period). The primary endpoint was recurrence-free survival, assessed in the full analysis set (FAS), which included patients who had received at least one dose of either drug. Safety was assessed in the safety set, which included patients who received at least one dose of either drug and completed at least one post-baseline safety assessment following enrolment. This study is registered with ClinicalTrials.gov (NCT04295317) and is currently ongoing but no longer recruiting new patients. FINDINGS:Between Sept 7, 2020, and Nov 18, 2022, 65 patients were enrolled (median age 64 years [IQR 54-70]) and included in the FAS and safety set. 40 (62%) patients were male and 25 (38%) were female. At the data cutoff of Nov 19, 2024, the median follow-up duration was 33·73 months (IQR 24·86-40·38) and 36 (55%) of 65 patients had recurrence (24 [67%] with intrahepatic recurrence only, six [17%] with both intrahepatic and extrahepatic recurrence, and six [17%] with extrahepatic recurrence only). Median recurrence-free survival was 24·29 months (95% CI 13·54-not reached). The most common treatment-related adverse events (occurring in ≥10% of patients) were reactive cutaneous capillary endothelial proliferation (45 [69%] patients), nausea (21 [32%] patients), hand-foot syndrome (19 [29%] patients), pruritus (11 [17%] patients), fatigue (11 [17%] patients), and dizziness (nine [14%] patients). Grade 3 treatment-related adverse events occurred in 15 (23%) patients, the most common of which was elevated bilirubin (two [3%] patients). Serious treatment-related adverse events were reported in four (6%) patients, including one case each of myocarditis, myalgia, type 1 diabetes, and hypothyroidism. No grade 4 treatment-related adverse events or treatment-related deaths occurred. INTERPRETATION:The combination of camrelizumab and capecitabine showed promising activity with an acceptable safety profile in the adjuvant setting for patients with resected intrahepatic cholangiocarcinoma. Further validation of this immunochemotherapy regimen is warranted in larger, multicentre trials. FUNDING:Clinical Research Special Fund, Zhongshan Hospital, Fudan University.

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.”

BackgroundGastrointestinal neuroendocrine tumor (GI-net) is a rare heterogeneous tumor, and there is a lack of models to predict its prognosis. Our study aims to develop and validate two new nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of GI-net patients and investigate their application value.MethodsSEER*Stat 8.4.4 software was used to download clinicopathological information of GI-net patients between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. These patients were randomly divided into a training group (n=3007) and an internal-validation group (n=1289) at a 7:3 ratio. Patients from the Fourth Hospital of Hebei Medical University were enrolled in this study to form the external-validation group (n=86). Univariate and multivariate Cox analyses were performed to explore the independent prognostic factors and establish two nomograms. The concordance index (C-index), area under the time-dependent receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the nomograms. X-tile was used to divide GI-net patients into high-, medium-, and low-risk groups. Kaplan–Meier (KM) curves and log-rank tests were used to compare survival differences among the three groups.ResultsSeven variables (age, site, size, grade, M stage, surgery, and chemotherapy) were selected to establish the nomogram for OS, and 6 variables (age, size, grade, M stage, surgery, and chemotherapy) were selected for CSS. The C indices (0.785, 0.813, and 0.936 in the training, internal-validation, and external-validation groups for OS; 0.888, 0.893, and 0.930 for CSS, respectively) and AUCs (≥0.7) indicated that the nomograms had satisfactory discriminative ability. Calibration curve analysis and DCA revealed that the nomogram had a satisfactory ability to predict OS and CSS. KM curves indicated that each of the two nomograms clearly differentiated the high-, medium-, and low-risk groups. In addition, two online risk calculators were developed to predict the OS and CSS of these patients visually.ConclusionsOur nomograms may play an important role in predicting 3- and 5-year OS and CSS for GI-net patients. Risk stratification systems and online risk calculators can be utilized in clinical practice to help doctors create personalized treatment plans.

Background:The optimal adjuvant therapy after liver resection in patients with hepatocellular carcinoma (HCC) is controversial. This study aimed to revisit the efficacy of postoperative adjuvant transarterial chemoembolization (PA-TACE) in HCC patients after curative-intent hepatectomy. Methods:A total of 387 patients were divided into PA-TACE group and no adjuvant treatment control group, and follow-up data were collected. The primary endpoints of recurrence-free survival (RFS) and overall survival (OS) were assessed before and after propensity score matching (PSM) analysis. Survival data were computed by means of the Kaplan-Meier method. Multivariable Cox proportional hazards model was used to determine the independent risk factors for patients' outcomes. Results:The RFS rates were higher in patients treated with PA-TACE compared to those in the control group, with borderline statistical significance [P=0.050; hazard ratio (HR) =0.75, 95% confidence interval (CI): 0.56-1.0]. Patients in the PA-TACE group had significantly higher OS rates than those in the control group (P=0.04, HR =0.70, 95% CI: 0.50-0.99). After PSM, the impact of PA-TACE on RFS and OS remained significant (HR =0.70, P=0.04 for RFS; HR =0.65, P=0.04 for OS). On multivariate Cox regression analyses in the entire cohort, age >65 years, γ-glutamyl transferase (GGT) >40 U/L, microvascular invasion (MVI)-positive, and no PA-TACE were identified as independent predictors for HCC recurrence. In further subgroup analysis, PA-TACE significantly improved RFS and OS of HCC patients in MVI-positive group (HR =0.31, P<0.001 for RFS; HR =0.47, P=0.002 for OS). The benefit of PA-TACE on RFS and OS remained significant in MVI-positive group after PSM (HR =0.32, P<0.001 for RFS; HR =0.38, P=0.003 for OS). Furthermore, patients who received PA-TACE developed recurrent HCC with less aggressive tumor characteristics. Conclusions:PA-TACE improves RFS and OS of HCC patients after liver resection, especially in MVI-positive patients. Furthermore, PA-TACE reduces the malignancy of recurrent tumors.

Background Numerous studies have demonstrated limited survival benefits of transarterial chemoembolization (TACE) alone in the treatment of intermediate-stage hepatocellular carcinoma (HCC) beyond up-to-seven criteria. The advent of immunotherapy, particularly immune checkpoint inhibitors (ICIs), has opened new avenues for HCC treatment. However, TACE combined with ICIs has not been investigated for patients with intermediate-stage HCC beyond the up-to-seven criteria. The study aims to evaluate the efficacy and safety of this treatment strategy for such patients.Methods In this single-arm, prospective, phase II study, we enrolled eligible patients with HCC who were treated with TACE plus programmed cell death protein 1 (PD-1) inhibitors (sintilimab) from April 2021 to February 2023. The study’s primary objectives were to assess progression-free survival (PFS) and safety. Secondary objectives included measuring the objective response rate (ORR) and disease control rate (DCR) as per both Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1 and modified RECIST (mRECIST) criteria, as well as overall survival (OS). Additionally, we conducted correlation analyses to identify predictors influencing the efficacy of tumor treatment.Result 20 patients participated in this study, with a median follow-up duration of 22.0 months. Median PFS was 8.4 months (95% CI: 4.7 to 19.7) according to both RECIST V.1.1 and mRECIST. The ORR was 30.0% (95% CI: 14.6% to 51.9%) per RECIST 1.1% and 60% (95% CI: 38.7% to 78.1%) per mRECIST. DCR was 95.0% (95% CI: 76.4% to 99.1%) according to both RECIST V.1.1 and mRECIST. Median OS was not yet reached. Notably, 20% (4/20) of patients underwent successful conversion to curative surgical resection. Treatment-related adverse events (TRAEs) mainly included elevated aspartate aminotransferase levels (19/20, 95.0%), elevated alanine aminotransferase levels (18/20, 90.0%), hypothyroidism (18/20, 90.0%), and reduced appetite (10/20, 50.0%). Among all participants, only one experienced grade 3 TRAE (myocarditis). We employed the Elastic Net regression model to analyze radiomic features from tumor and peritumoral areas to predict the efficacy of this treatment strategy.Conclusion TACE plus PD-1 inhibitors demonstrated promising efficacy and an acceptable safety profile, suggesting it as a potential treatment option for patients with intermediate-stage HCC beyond up-to-seven criteria. Furthermore, our study indicates that specific image-based features may serve as predictors for patients likely to benefit from this treatment approach.Trial registration number NCT04842565.