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.

OBJECT:To explore the potential of dynamic contrast-enhanced MRI (DCE-MRI) and intravoxel incoherent motion MRI (IVIM-MRI) in predicting the short-term efficacy of microwave ablation (MWA) in lung tumors. METHODS:Thirty-nine patients with 47 lesions were enrolled in this study, who underwent percutaneous MWA treatment from May 2023 to July 2024. All patients underwent DCE-MRI and IVIM-MRI scanning before and after MWA procedure within 24 h. All patients underwent computed tomography (CT) examinations at 3 and 6 months after MWA. According to the CT findings during the 6-month follow-up period, all patients were classified into the local control group and the recurrence group. The pre- and post-treatment DCE-MRI parameters (Ktrans, Kep, Ve, Vp) and IVIM-MRI parameters (D, f, D*, ADC), and their percentage change (Δ) were calculated and compared between two groups. Within each group, all DCE-MRI and IVIM-MRI parameters were compared pairwise (pre vs. post). The diagnostic performance was tested using receiver operating characteristic (ROC) curves. RESULTS:Among the total of thirty-nine patients with 47 lesions, twenty-five patients with 31 lesions were classified into local control group, and fourteen patients with 16 lesions were classified into recurrence group. DCE-MRI parameters (Ktrans, Kep, Ve, Vp) and IVIM-MRI parameters (D, D*, ADC) showed a significant difference between pre-treatment and post-treatment in both groups (P < 0.05). Post-D, post-ADC, ΔD and ΔADC showed a statistically significant difference between the local control group and the recurrence group (P = 0.027, 0.018, 0.037 and 0.005, respectively). ROC analysis showed the area under the curve (AUC) values of post-D, post-ADC, ΔD and ΔADC were 0.716, 0.700, 0.688 and 0.750, respectively. CONCLUSIONS:The parameters of IVIM-MRI (D, ADC) after MWA within 24 h may be a potential early biomarker for evaluating the treatment efficacy of MWA in lung tumors.

RATIONALE AND OBJECTIVES:This study aims to investigate the impact of iodine-125 intraluminal brachytherapy on stent patency time (SPT) and overall survival (OS) in patients with advanced pancreatic cancer complicated by obstructive jaundice, which may provide evidence for optimizing multimodal interventional strategies for patients with pancreatic cancer. METHODS:This retrospective study enrolled 262 patients with advanced pancreatic cancer complicated by obstructive jaundice who had underwent metallic biliary stent implantation. Patients were stratified into the 125I group and the control group. A 1:1 propensity score matching (PSM) was performed using a caliper width of 0.2 standard deviations of the propensity score. RESULTS:After 1 month of biliary stent implantation, significant reductions of serum bilirubin, transaminases, and CA19-9 levels compared to predrainage were observed in this study. A median SPT of 7.63 months (95% CI 7.10-8.16), a stent restenosis rate of 36.2%, and a median OS of 9.40 months (95% CI 9.11-9.69) was demonstrated in the entire cohort demonstrated. After 1:1 PSM (62 patients per group), the 125 I group showed a significantly longer median SPT (9.44 months vs. 6.21 months, P < 0.001) and lower stent restenosis rate (17.7% vs. 43.5%, P = 0.002) compared to the control group. However, no significant OS difference was observed between groups (10.59 months vs. 9.07 months, P = 0.248). Cox analysis suggested that intratumoral brachytherapy (HR 0.382, P < 0.001) was an independent protective factor for SPT; post-stent Eastern Cooperative Oncology Group (ECOG) 2 score (HR 1.572, P = 0.019) was an independent risk factor for SPT. The independent risk factors for OS included post-stent ECOG 2 score (HR 1.469, P = 0.042) and post-stent CA19-9≥500 ku/L (HR 1.322, P = 0.046). CONCLUSION:Biliary stent combined with iodine-125 intraluminal brachytherapy significantly prolonged SPT compared to stent-alone in patients with advanced pancreatic cancer complicated by obstructive jaundice, although it did not significantly improve survival outcomes. Higher ECOG performance score and higher CA19-9 level after jaundice reduce were associated with poor prognosis.

FGFR2 fusion is a common alteration in malignancies, including intrahepatic cholangiocarcinoma (iCCA). While FGFR2 fusion has oncogenic properties, iCCA patients harboring this alteration demonstrate favorable prognosis, remaining a paradox. Here, we delineated the transcriptomic landscape of FGFR2 fusion-positive iCCA. We observed transcriptional features related to PI3K-AKT signaling in tumor cells and reduced neutrophil infiltration, particularly of the PD-L1+ neutrophil subtype. Mechanistically, FGFR2 fusion was associated with reduced H3K27ac enrichment at the CXCL3 promoter and decreased CXCL3 expression in tumor cells, which may contribute to impaired neutrophil recruitment to tumor tissues. In preclinical models, pharmacological FGFR inhibition increased CXCL3 levels and neutrophil infiltration. Combining neutrophil blockade with clinically available FGFR inhibitors enhanced antitumor activity. In conclusion, this study provides mechanistic insights into the paradox between the oncogenic properties of FGFR2 fusion and favorable clinical outcomes in FGFR2 fusion-positive iCCA, and suggests a potential strategy to optimize FGFR2-targeted therapies.

INTRODUCTION:Gastrointestinal cancers remain a major global health issue, with tobacco use as a key factor. Understanding the impact of tobacco use on these cancers and its regional trends is essential for effective prevention strategies. METHODS:Using data from the Global Burden of Disease (GBD) study, we analyzed mortality and disability-adjusted life years (DALYs) related to tobacco from 1990 to 2021. Joinpoint regression estimated average annual percent change (AAPC), and ARIMA predicted disease burden up to 2036. Two-sample Mendelian randomization (MR) analysis with GWAS data, applied methods such as inverse variance weighting (IVW) and MR-Egger for causal inference. RESULTS:Esophageal cancer had the highest burden in 2021, with a mortality rate of 2.54 deaths per 100000 population and a DALY rate of 58.49 DALYs per 100000 population. Stomach cancer showed the most significant decrease, with mortality dropping from 2.81 to 1.25 deaths per 100000 population (AAPC= -2.58; 95% uncertainty interval, UI: -2.61- -2.55) and DALY rates decreasing from 71.71 to 29.01 DALYs per 100000 population (AAPC= -2.87; 95% UI: -2.90 - -2.84). The disease burden was higher in older males. ARIMA analysis showed a general decline in disease burden, though some regions had an increasing trend. MR analysis did not provide genetic evidence supporting an association between tobacco use and these cancers. CONCLUSIONS:From 1990 to 2021, the global burden of gastrointestinal cancers linked to tobacco use showed a declining trend. However, mortality and DALY rates remain high, with significant regional, age, and gender differences, highlighting the need for continued tobacco control efforts.

BACKGROUND:Sympathetic signalling plays a critical role in the initiation and progression of various malignancies. However, its specific contribution to intrahepatic cholangiocarcinoma (iCCA) remains poorly understood. OBJECTIVE:This study aimed to investigate the effects and underlying mechanisms of sympathetic signalling on tumour and immune cells, and to explore the potential efficacy of targeting sympathetic pathways in iCCA characterised by perineural invasion (PNI). DESIGN:Single-cell RNA sequencing was employed to elucidate the impact of PNI on iCCA. In vivo and in vitro experiments were conducted to decipher the molecular mechanisms. Preclinical models were used to investigate the therapeutic potential of targeting sympathetic signalling. RESULTS:Tyrosine hydroxylase-positive sympathetic nerve fibres were detected in PNI+ iCCA, accompanied by elevated norepinephrine (NE). We constructed an atlas of PNI+ iCCA at single-cell transcriptional level, characterised by MDK overexpression and reduced infiltration of CD56dimCD16+ natural killer (NK) cells. Mechanistically, NE was found to upregulate MDK expression via the ADRB2/PI3K-AKT/p65 axis, thereby promoting tumour progression of PNI+ iCCA. Furthermore, NE might induce NK cell ferroptosis by triggering an imbalance in glutamate/cysteine metabolism in PNI+ iCCA via ADRB2. Loss of sympathetic innervation in mice reduced NE concentrations and MDK expression, while increasing NK cell infiltration and inhibiting tumour growth. Preliminary results suggested that blockers of β-adrenergic receptors suppressed iCCA progression. CONCLUSION:This study uncovers a novel neuro-immune-tumour axis in iCCA and provides a mechanistic rationale for targeting β-adrenergic signalling as a possible therapeutic strategy for PNI+ iCCA.

Apoptosis undergoes dynamic changes during tumor progression and treatment and has complex effects on tumor development. Apoptotic cell-derived extracellular vesicles (Apo-EVs) have recently been recognized as key mediators of intercellular communication, but their role in hepatocellular carcinoma (HCC) remains unclear. We performed a series of in vitro and in vivo experiments to investigate the effects of tumor-derived Apo-EVs on HCC cell proliferation, apoptosis, and metabolic remodeling. Additional mechanistic studies were conducted to identify the functional cargo molecules carried by Apo-EVs and to determine their roles in ATP synthesis and metabolic regulation. Tumor-derived Apo-EVs suppressed HCC cell proliferation and increased apoptosis. Mechanistically, Apo-EVs promoted apoptotic cell death by shifting cellular metabolism from aerobic glycolysis to oxidative phosphorylation. Notably, transmembrane protein 70 (TMEM70), which is transported by Apo-EVs, was identified as a key mediator of this process. TMEM70 participated in ATP synthesis and contributed to metabolic reprogramming in HCC cells. Our study reveals a potential mechanism by which tumor-derived Apo-EVs promote apoptosis and metabolic remodeling in HCC. Apo-EV-associated TMEM70 may contribute to this process through its involvement in mitochondrial metabolism. These findings suggest that Apo-EVs and selected cargo molecules may represent promising therapeutic targets for HCC. Engineered apoptotic vesicles inhibit hepatocarcinoma proliferation by disrupting mitochondrial function. Tumor growth is suppressed while energy metabolism is altered. Incresed Tmem70 expression promotes oxidative phosphorylation over glycolysis. A metabolic reprogramming strategy enables potent suppression of hepatocarcinoma.

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:The efficacy of immune checkpoint inhibitors (ICIs) in advanced gastrointestinal (GI) cancers, especially microsatellite-stable tumors, is limited. Stereotactic body radiation therapy (SBRT) may enhance ICIs' antitumor immune response by promoting immunogenic cell death. This meta-analysis evaluated the efficacy, safety, and abscopal effect of combining SBRT and ICIs in advanced GI malignancies. Methods:A literature search across PubMed, Embase, and Cochrane Library up to November 23, 2025, was conducted. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS); secondary outcomes included overall survival (OS), disease control rate (DCR), grade ≥3 treatment-related adverse events (TRAEs), and abscopal effect rate. Random-effects models and I² statistics were used for analysis. Results:Twenty-five studies were included in the final analysis. Risk of bias assessment indicated generally high methodological quality across included studies. SBRT+ICIs significantly improved the objective response rate (OR 5.30, 95% CI: 2.19-12.84) compared to controls. The combination therapy robustly reduced the risk of death (HR 0.43, 95% CI: 0.33-0.55) and disease progression (HR 0.43, 95% CI: 0.35-0.54). Importantly, the risk of grade ≥3 treatment-related adverse events was not significantly increased compared to control groups (pooled RD -0.09, 95% CI: -0.35 to 0.18). The reported abscopal effect rate varied across studies, with a mean of 26.2%. Conclusion:SBRT+ICIs improves efficacy and survival in advanced GI cancers, with manageable safety, especially in hepatocellular carcinoma. Further validation in randomized trials and optimization for less responsive tumors is needed.

Tumor collagen is vital in chemotherapy resistance of pancreatic cancer (PC), but its non-invasive evaluation remains challenging. This study aims to investigate the association of variables derived from dual-energy CT with the collagen ratio (CR) of PC and to determine the prognostic value of CR in unresectable diseases. A total of 83 patients with resected PC and 71 patients with unresectable PC were enrolled. In the resected group, the correlation between the tumor CR and variables of dual-energy CT was analyzed. In the unresectable group, Cox regression analyses were conducted to investigate the prognostic value of dual-energy CT-predicted CR and other clinicoradiological indicators. The patients with resected PC were divided into low and high-CR sets with a threshold of 55

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.

Background: Anaplastic lymphoma kinase-targeted tyrosine kinase inhibitors (ALK-TKIs) have revolutionized the treatment of non-small-cell lung cancer (NSCLC). However, several key issues remain unresolved. Specifically, the impact of prior chemotherapy on ALK-TKI efficacy is unclear, the impact of MET overexpression on ALK-TKI efficacy remains unclear, and the dynamic changes in programmed death ligand 1 (PD-L1) expression during the development of TKI resistance are not fully understood. Objective: This study aimed to evaluate the efficacy of ALK-TKIs across different treatment lines, analyze the impact of MET expression on treatment outcomes, and investigate changes in PD-L1 expression before and after the development of resistance. Design: Retrospective cohort study. Methods: A retrospective analysis was conducted on 259 patients with ALK-positive NSCLC treated at Zhejiang Cancer Hospital between 2011 and 2022 to compare the efficacy of ALK-TKIs administered as first-line therapy versus after chemotherapy. Immunohistochemical staining was used to assess MET and PD-L1 expression. Survival analysis was performed using the Kaplan–Meier method and the log-rank test. Results: Crizotinib showed no significant difference in progression-free survival (PFS) or overall survival (OS) between first-line and post-chemotherapy use (PFS: p = 0.803; OS: p = 0.761). For second-generation ALK-TKIs, first-line treatment had numerically longer PFS compared to post-chemotherapy (alectinib: 41 vs 24 months; ceritinib: 30 vs 8 months), but these differences were not statistically significant after adjustment ( p = 0.120 and 0.284, respectively). OS did not differ significantly between the two treatment sequences for either drug. Notably, among patients treated with alectinib, those with MET overexpression had significantly shorter PFS (12 vs 42 months; p = 0.011) and OS (41 months vs not reached; p = 0.001) compared with MET-negative patients. There was no significant change in PD-L1 expression following resistance ( p = 0.248). Conclusion: ALK-TKIs have shown a tendency to improve patient survival in both first-line and post-chemotherapy settings. Among patients treated with alectinib, there appears to be a trend toward shorter PFS and OS in those with MET overexpression. In a limited number of matched samples, PD-L1 expression did not change significantly after TKI resistance, although a slight increase was observed.

Congenital extrahepatic portosystemic shunt (CEPS), known as Abernethy malformation, is a rare vascular anomaly involving aberrant communication between the portal vein (PV) and the inferior vena cava (IVC). In this case, a 51-year-old man with chronic comorbidities presented primarily with symptoms of heart failure rather than hepatic dysfunction. Following endovascular coil embolization of the shunt, the patient's heart failure symptoms improved significantly. This report outlines the diagnostic process and treatment strategy, highlighting the safety and feasibility of a single-session embolization in patients without elevated portal pressure.

To compare the efficacy and safety between thermal ablation combined with synchronous TACE and TACE in patients with liver metastasis of neuroendocrine tumors of different pathologic grades and different primary sites. A retrospective analysis was performed on patients with liver metastases of neuroendocrine tumors in this study. The patients were divided into simultaneous ablation group and TACE group according to treatment mode and subgroups. The endpoints of prognosis were progression-free survival (PFS) and overall survival (OS). A total of 108 patients with neuroendocrine tumors were collected, including 46 patients in the simultaneous ablation group and 62 patients in the TACE group. According to WHO classification, 21 patients with G1 grade, 55 patients with G2 grade and 32 patients with G3 grade were included. The median OS and the median PFS showed no statistically significant differences between the TACE group and the simultaneous ablation group. Among G2 stage, the TACE group and the synchronous ablation group showed no difference in the median OS but statistically difference in the median PFS. For G1 2 stage patients, synchronous ablation showed longer median PFS than TACE. In pNET patients, although median OS showed no significant difference between the two groups, the synchronous ablation group achieved longer median PFS compared to the TACE group. Both the TACE group and the synchronous ablation group showed improved median OS in G1 2 stage patients relative to G3 stage patients. Simultaneous ablation can delay disease progression in patients with liver metastasis of neuroendocrine tumors to a certain extent, and has a good safety, especially for patients with liver metastases of neuroendocrine tumors of intermediate or low grade or pancreatic origin.

Background:Neuroendocrine tumors (NETs) are a group of heterogeneous diseases which have liver dominant involvement potency. The value of transcatheter arterial chemoembolization (TACE) treatment for NET patients in the era of somatostatin analogues (SSAs) and anti-proliferation agents needs further study. The study aimed to investigate the value of TACE-based treatment for NETs involving the liver. Methods:A group of 29 NET patients received TACE-based multimodal treatment in the Department of Hepatic Oncology of Zhongshan Hospital, Fudan University was retrospectively collected. Baseline characteristics of included patients were analyzed. Kaplan-Meier analysis and Cox proportional hazards regression were used to investigate clinical and pathological parameters on overall survival (OS) and progression free-survival (PFS) in NET patients. Results:The median OS and PFS were 20.0 [95% confidence interval (CI): 13.4-26.5] months and 11.0 (95% CI: 7.7-14.3) months, respectively. Tumor grade (P=0.001), number of TACE treatments (P=0.003), neutrophil to lymphocyte ratio (NLR) (P=0.005) and systemic treatment mode (P=0.007) were significantly associated with OS while tumor grade (P<0.001), number of TACE treatments (P=0.002), aspartate aminotransferase (AST) (P=0.01) and systemic treatment mode (P=0.001) were of significance to PFS in multivariate Cox regression analyses. Conclusions:TACE-based multimodal treatment is beneficial for NETs involving the liver. The sequence and timing of local treatment and systemic treatment allocation need further investigation.

Transarterial chemoembolization (TACE) is commonly used to treat patients with unresectable hepatocellular carcinoma (HCC); however, TACE alone has demonstrated unsatisfactory survival benefits. Our previous studies suggested that TACE plus oral medication of thalidomide, carmofur and compound mylabris capsule (TCC cocktail) may be a better therapeutic option. In this randomized, open-label, multicenter clinical trial, 72 treatment-naive HCC patients were randomly assigned to receive cTACE alone or cTACE plus oral TCC cocktail between July 2018 and October 2019. The primary endpoint of this trial was the 1-, 2- and 3-year overall survival (OS) rates. The second endpoints of this trial included 1-, 2- and 3-year progression-free survival (PFS) rates, objective response rates (ORR) according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), and safety with adverse events (AEs). The 1-, 2- and 3-year OS rates were significantly higher in the cTACE plus TCC group than in the cTACE group (83.2 https://www.chictr.org.cn/showproj.html?proj=27493 as ChiCTR1800016335 on 25th May 2018 named an open-label, multicenter, randomized, prospective clinical trial of thalidomide based triple oral regimen for low-dose maintenance therapy after TACE in advanced hepatocellular carcinoma.

The safety of immunotherapy in patients undergoing transplant remains unclear due to rejection risks. This study assessed the safety and efficacy of programmed death-1 (PD-1) inhibitors in patients with recurrent tumors who had undergone liver transplantation, emphasizing the value of using graft programmed death-ligand 1 expression as a predictor of rejection to guide patient selection. This single-center, open-label, prospective, single-arm study was conducted from July 2019 to May 2024 at Zhongshan Hospital, Fudan University (Shanghai, China). Eligible participants included patients with recurrent or metastatic liver cancer who had undergone liver transplantation and were unresponsive to locoregional or systemic therapies. The primary endpoints were the incidence and clinical outcomes of acute rejection. Secondary endpoints were overall survival and objective response rate. Twenty consecutive patients received PD-1 inhibitor therapy. Of these, 18 had HCC, and 2 had intrahepatic cholangiocarcinoma. Liver graft biopsies confirmed negative programmed death-ligand 1 expression in all participants before PD-1 inhibitor therapy. Three patients (15%) experienced acute rejection, with a 95% CI of 3.2%-37.9%. The 1-year and 2-year survival probabilities after PD-1 inhibitor treatment were 0.55 (95% CI: 0.33-0.77) and 0.24 (95% CI: 0.05-0.43), respectively. The median survival time after tumor recurrence was 24.6 months, exceeding the historically reported median survival time of 16.3 months. These exploratory findings suggest that, in selected recipients of liver transplant, PD-1 inhibitors may be associated with reduced rejection risk and potential survival benefit, although further validation is needed.

This research aimed to assess the efficacy and safety of a regimen combining lenvatinib with an anti-PD-1 antibody or chemotherapy in patients with advanced intrahepatic cholangiocarcinoma (ICC). A two-arm, open-label, phase II trial was carried out. Participants in Arm A received 240 mg of toripalimab intravenously on day 1 of each 3-week cycle, plus daily oral lenvatinib at 8 mg (< 60 kg) or 12 mg (≥60 kg). Participants in Arm B were administered the same daily lenvatinib in combination with GEMOX chemotherapy: 85 mg/m2 oxaliplatin on day 1, and 1 g/m2 gemcitabine on days 1 and 8 every 3 weeks for 6-8 cycles. The primary endpoint was the objective response rate (ORR) per RECIST 1.1, with secondary endpoints included treatment-related adverse events (AEs), overall survival (OS), and progression-free survival (PFS). Sixty one patients were recruited, with 31 in Arm A and 30 in Arm B. The ORR of Arm A was 32.3