Hepatocellular Carcinoma (HCC)

We propose to construct and validate an early HCC risk prediction model in a multicenter retrospective cohort of hepatitis B-related fibrosis/cirrhosis patients, using multimodal data encompassing longitudinal clinical data, serum glycomics profiles, and liver biopsy histopathological images.

At four major centers in Korea, patients with hepatocellular carcinoma (HCC) that exceed the up-to-7 criteria yet remain locally confined will undergo ablative radioembolization using Yttrium-90 glass microspheres, guided by a standardized dosimetry method. Their treatment response, survival outcomes, and adverse events will be monitored for two years following the procedure.

This study is to evaluate the safety and tolerability to determine (i) the recommended Phase 2 dose (RP2D) of VMD-102 (Phase 1), and (ii) preliminary anti-tumor efficacy (Phase 2), in participants with advanced HCC, metastatic uveal melanoma (MUM), renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and colorectal cancer (CRC). The pharmacokinetics (PK), preliminary anti-tumor activity, and potential biomarkers of VMD-102 will also be assessed. VMD-102 will be the first selective PKC epsilon (PKCε or PKCe) kinase inhibitor to enter human clinical testing. Preclinical VMD-102 anti-tumor activities in mouse liver/HCC tumor models and preclinical toxicology and pharmacology studies support this study.

The purpose of this study is to evaluate the safety and tolerability of Pumitamig alone or in combination with Ipilimumab in participants with first-line advanced or unresectable Hepatocellular Carcinoma (HCC)

In patients who has no sign suggesting high lung shunt fraction (TIPS, hepatic vein invasion, hepatic vein enhancement on arterial phase, dysmorphic intratumoral vessel, tumor size \< 5cm), radioembolization is performed without MAA scan with SIR-Spheres. This prospective registry will prove that the selection criteria is accurate and streamlining radioembolization is feasible and safe.

In patients who has no sign suggesting high lung shunt fraction (TIPS, hepatic vein invasion, hepatic vein enhancement on arterial phase, dysmorphic intratumoral vessel), planning angiography, MAA scan, and radioembolization are performed in a single day with SIR-Spheres. This prospective registry will prove that the selection criteria is accurate and same-day radioembolization is feasible and safe.

This is a Phase 2, open-label, single-arm, multicenter study designed to evaluate the safety and efficacy of atezolizumab, bevacizumab, and tocilizumab in patients with locally advanced, metastatic, and/or unresectable hepatocellular carcinoma (HCC). Approximately 51 patients will be enrolled at 6 study sites and will receive combination therapy consisting of atezolizumab, bevacizumab, and tocilizumab. Patients assigned to the study will receive atezolizumab 1,200 mg intravenously and bevacizumab 15 mg/kg intravenously on Day 1 of each 21-day cycle, alongside tocilizumab 4 mg/kg intravenously on Day 1 of each 42-day cycle for up to 5 doses. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-defined discontinuation criteria are met. The study population includes adult patients with locally advanced, metastatic, and/or unresectable HCC who have received no prior systemic therapy for hepatocellular carcinoma. Eligible patients must have histologically, cytologically, or radiologically confirmed diagnosis, at least one measurable lesion according to RECIST version 1.1, Child-Pugh class A liver function, ECOG performance status 0 or 1, and adequate organ function. The primary objective is to assess the incidence of Grade 3 or higher immune-related adverse events (irAEs) occurring within 24 weeks after treatment initiation according to NCI CTCAE version 5.0. Secondary objectives include evaluation of objective response rate (ORR) and disease control rate (DCR) according to RECIST v1.1, progression-free survival, overall survival, and the rate of treatment discontinuation due to adverse events. Safety evaluations will include assessment of adverse events, serious adverse events, laboratory parameters, vital signs, and other clinical assessments. Exploratory objectives include evaluation of the correlation between treatment response and serum inflammatory markers (such as IL-6 and CRP) and immune cell profiles using blood samples collected at protocol-defined intervals. Tumor assessments will be performed at protocol-defined intervals using radiologic imaging every 6 weeks from Cycle 1 Day 1 up to Week 54, and every 9 weeks thereafter. The primary efficacy analysis will be based on the Full Analysis Set according to RECIST v1.1. This study is intended to evaluate the clinical activity and safety profile of prophylactic tocilizumab in combination with atezolizumab and bevacizumab in this patient population and to generate data to inform future clinical development.

The purpose of this multicenter pragmatic randomized controlled trial is to determine whether AI-assisted interpretation of multiphasic liver contrast-enhanced computed tomography (CE-CT) is non-inferior to standard radiology reporting with respect to missed clinically significant malignant focal liver lesions, \*\*with the non-inferiority margin prespecified in the statistical analysis plan before enrollment\*\*, and whether it improves lesion detection, diagnostic characterization, downstream clinical management, and reporting efficiency. On AI-assisted center-days, AI results will be revealed only after the first-line radiologist has saved an unaided initial assessment and may be used to revise the final report. On control center-days, examinations will be interpreted using the standard radiology workflow without access to AI tools.

This is a multicenter, randomized, open-label, controlled Phase 2 study in patients with unresectable hepatocellular carcinoma (uHCC). The purpose of this study is to compare the efficacy and safety of GKL-006 Injection in combination with transarterial chemoembolization (TACE) versus TACE alone.

This is a multicenter Phase 1b, open label, dose-escalation and cohort-expansion study, evaluating the safety, tolerability, pharmacokinetics (PK), preliminary antitumor activity, and effect of biomarkers of zanzalintinib administered alone, and in combination with nivolumab (doublet), nivolumab + ipilimumab (triplet) and nivolumab + relatlimab (triplet) and in combination with docetaxel and prednisone in participants with advanced solid tumors. In addition, the study will evaluate the effect of multiple dose administration of zanzalintinib on the single-dose pharmacokinetics of sensitive CYP3A4, CYP2C9, CYP2C19, or CYP1A2 substrates in participants with advanced solid tumors. In the Expansion Stage, the safety and efficacy of zanzalintinib as monotherapy and in combination therapy will be further evaluated in tumor-specific Expansion Cohorts.

Subcapsular hepatocellular carcinoma (HCC) has unique anatomical characteristics that may influence treatment selection and clinical outcomes. Surgical resection and liver transplantation are potentially curative treatments but may be limited by liver function, tumor characteristics, and perioperative risks. Microwave ablation has become an important minimally invasive treatment option for patients with HCC, particularly for lesions that are difficult to treat surgically. This prospective observational cohort study aims to compare the therapeutic efficacy, safety, and long-term outcomes of no-touch microwave ablation, tumor-puncture microwave ablation and surgical resection in patients with subcapsular HCC. Treatment outcomes, including local tumor control, treatment-related complications, recurrence, and survival outcomes, will be evaluated to provide evidence for individualized treatment strategies for patients with subcapsular HCC.

This study is a prospective, randomized, single-center randomized controlled clinical trial to investigate the safety and efficacy of ondansetron in reducing the toxicity associated with immune checkpoint inhibitor treatment. This study plans to enroll 134 patients with hepatocellular carcinoma who are scheduled to receive standard ICI treatment. This study will adopt the 2023 CSCO Guidelines for the Management of Immune checkpoint inhibitor-related toxicity as the main assessment criterion, and take the incidence and severity of irAEs as the main observation indicators to evaluate the effectiveness of ondansetron in reducing the toxicity related to immune checkpoint inhibitor treatment in patients with hepatocellular carcinoma.

The BILLIONSTARS study is a prospective, single arm observational study inviting patients diagnosed with hepatocellular carcinoma (HCC) or cholangiocarcinoma (CCC) who are to be recommended locoregional intervention by surgery, ablation or transarterial chemoembolization and/or antitumoral medical treatment. The aim is to investigate how tumor- and individual-related factors affect response to treatment. To this end, circulating tumor DNA, immune cells and various proteins will be analyzed in repeated blood samples taken before, during and after completion of systemic treatment. When applicable, analyses will also be performed on tumor tissue from resected tumors and biopsies, and in some cases also from autopsies

The purpose of this study is to assess the safety and effectiveness of treating a tumor using a different planning method called MCD for the FDA-Approved device, TheraSphere. TheraSphere Microspheres are microscopic radioactive glass spheres that deliver radiation therapy in the liver tissue where they are placed. This study investigates a procedure called multicompartment dosimetry (MCD). When using a multicompartment dosimetry approach, the doctor will look at images of the liver to see where there is tumor to determine where to treat. That area will be divided into "compartments" where the dose to tumor and the healthy liver are calculated separately. The goal of MCD is to give the tumor a higher radiation dose while protecting more of the healthy part of the liver. Traditional planning for the TheraSphere Microspheres procedure uses single compartment dosimetry (SCD) which treats the tumor and the healthy liver as one area so the dose is more evenly distributed and the dose to the tumor may be lower than with the MCD approach. The single compartment approach is standard and is well established however this research study is to see if giving TheraSphere Microspheres with an MCD planning method is safe and effective by evaluating the effect of radiation on the liver as well as how the tumor responds to higher doses

This is a Phase 1, open-label, first-in-human study of CTX-10726 monotherapy in patients with metastatic or locally advanced malignancies. The study will be conducted in 2 Cohorts: Cohort 1 Dose Escalation and Cohort 2 Dose Expansion.

This is a single-arm, single-center, prospective trial designed to evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with ipalimab/tuvonralimab (QL1706) in the peri-operative setting for resectable hepatocellular carcinoma exceeding the Milan criteria, and to explore biomarkers predictive of therapeutic response.

This single-center prospective observational cohort study aims to evaluate the predictive value of peripheral blood-based biomarkers for treatment response in patients with hepatocellular carcinoma (HCC) receiving first-line atezolizumab plus bevacizumab (T+A) therapy. Residual peripheral blood samples obtained during routine clinical testing will be analyzed without additional blood draws. The study hypothesizes that baseline and longitudinal peripheral blood biomarkers are associated with treatment response and can be used to identify patients more likely to benefit from T+A therapy. Treatment response will be evaluated based on the best overall response (BOR) during treatment. The primary efficacy assessment will be performed according to RECIST 1.1, while modified RECIST (mRECIST) will be used as a supportive assessment. Predictive models based on peripheral blood biomarkers will be developed using RECIST 1.1-defined treatment response as the primary analysis, with mRECIST used for supportive and sensitivity analyses.

This is a multicenter, retrospective study planned to enroll patients with unresectable hepatocellular carcinoma (uHCC) who received first-line donafenib combined with an anti-PD-1/L1 monoclonal antibody and either TACE or HAIC at 8 sites between June 1, 2021 and November 30, 2024. The study consists of two cohorts: Cohort A consists of patients who received donafenib + PD-1/L1 inhibitor + TACE, and Cohort B consists of patients who received donafenib + PD-1/L1 inhibitor + HAIC, with a planned enrollment of 200 patients per cohort. Relevant data will be collected to evaluate the efficacy and safety of donafenib combined with an anti-PD-1/L1 monoclonal antibody and either TACE or HAIC in the treatment of uHCC in real-world clinical practice.

Hepatocellular carcinoma, the most common type of primary liver cancer, can recur after liver resection or thermal ablation performed with curative intent. Follow-up imaging is commonly scheduled at fixed intervals, although the risk of recurrence differs among patients and may change over time. This study will test whether a locked artificial intelligence system can use routinely collected clinical, laboratory, and imaging information to recommend when the next surveillance scan should occur. Adults with no radiological evidence of viable hepatocellular carcinoma after microscopically margin-negative liver resection or complete radiofrequency or microwave ablation will be randomly assigned in a 1:1 ratio to artificial intelligence-guided risk-adapted surveillance or fixed-interval surveillance. In the artificial intelligence-guided group, participants classified as having high, intermediate, or low current recurrence risk will generally undergo the next protocol-scheduled contrast-enhanced imaging examination after 3, 4, or 6 months, respectively. Participants in the control group will undergo protocol-scheduled imaging every 4 months. The risk thresholds are designed so that the expected total number of protocol-scheduled imaging examinations is approximately comparable between the two groups over 24 months. The artificial intelligence system provides surveillance recommendations only. It does not diagnose recurrence, determine eligibility for liver transplantation, or select anticancer treatment. Clinically indicated examinations may be performed at any time in either group. When recurrence is confirmed, participants in both groups will undergo the same protocol-defined multidisciplinary evaluation, and potentially curative-intent treatment may be considered when clinically appropriate. The primary purpose is to determine whether artificial intelligence-guided surveillance increases the probability of being alive at 24 months without having a recurrence that is no longer amenable to protocol-defined curative-intent treatment. The study evaluates the timing and allocation of surveillance rather than an adjuvant anticancer treatment and is not intended to prevent the biological occurrence of recurrence.

The goal of this interventional study (clinical trial) is to evaluate the efficacy and safety of adding dapagliflozin to first-line standard therapy in patients with unresectable hepatocellular carcinoma (HCC) and comorbid metabolic syndrome. The main questions it aims to answer are: Does the addition of dapagliflozin to first-line therapy improve the objective response rate (ORR) compared with first-line therapy alone in this patient population? What are the differences between the two treatment groups in terms of overall survival (OS), progression-free survival (PFS), and safety/tolerability profiles? Researchers will compare the combination group (dapagliflozin plus first-line standard therapy) with the control group (first-line standard therapy alone) to determine whether the addition of dapagliflozin provides superior clinical benefit. Participants in the combination group will receive dapagliflozin in addition to their prescribed first-line standard therapy, while participants in the control group will receive first-line standard therapy alone. All participants will be regularly monitored for tumor response, survival outcomes, and adverse events throughout the study period. The findings of this trial are expected to provide clinical evidence supporting the use of dapagliflozin as an adjunctive therapy in patients with advanced unresectable HCC and metabolic syndrome, potentially enhancing the tumor response rate to existing standard-of-care treatments.

The investigators of this study are developing a simple breath test to help detect gastrointestinal (gut) cancers earlier, including cancers of the oesophagus (food pipe), stomach, pancreas, liver and bowel. These cancers often cause non-specific symptoms that are similar to benign conditions, making early diagnosis difficult. Delays between the onset of symptoms and referral for a diagnostic test such as an endoscopy or a scan, can allow the cancer to progress. The breath test detects small molecules called volatile organic compounds (VOCs) that are released in exhaled breath. Some of these VOCs are strongly associated with these cancers and may help identify high-risk patients who require urgent investigation. In practice, patients who come to their GP with concerning symptoms will be offered the breath test. If the test is positive, patients can be referred promptly for a diagnostic test, while those with a negative result can be reassured and offered re-testing if symptoms persist. Earlier diagnosis could improve access to curative treatment while reducing unnecessary invasive investigations. Previous studies have identified a panel of VOCs that appear to distinguish patients with gastrointestinal cancers from those without cancer. This study aims to confirm these findings in a new group of participants to determine whether the same biomarkers can be reliably identified. Participants will provide a breath sample, usually before a hospital procedure they are already scheduled to undergo, and complete a short questionnaire about their medical history and medications. Some participants will also be asked to drink a nutritional supplement before providing a second breath sample. The results will help determine whether the breath test is reliable enough for further clinical evaluation

This study tests whether it is safe and feasible to give patients with hepatocellular carcinoma (liver cancer) an infusion of their own (autologous) immune cells, called cytokine-induced killer (CIK) cells, after they have had surgery to remove their liver tumor. The patient's own blood cells are collected and grown in a laboratory to create the CIK cells, which are then given back to the patient through six intravenous infusions over about two months. Patients are followed for six months to check for side effects and early signs of whether the cancer returns.

The macroscopic vascular supply of liver tumors varies considerably according to histological subtype, lesion size, and disease stage. Current clinical imaging modalities primarily characterize liver tumors based on their macroscopic vascular perfusion patterns. Conventional color Doppler ultrasonography enables qualitative assessment of tumor vascularity, facilitates the differentiation of benign from malignant hepatic lesions, delineates the anatomical relationship between tumors and major intrahepatic vessels, and detects vascular invasion. Nevertheless, these macroscopic vascular characteristics arise from complex microvascular architectures, including vascular distribution patterns, microvessel density, vessel morphology and tortuosity, blood flow velocity, and flow direction. Despite the critical role of tumor microcirculation in tumor progression and therapeutic response, the heterogeneity of microvascular hemodynamics among different liver tumors remains inadequately characterized. The emergence of Super Resolution Ultrasound Imaging (SRUS) has markedly advanced ultrasound imaging by overcoming the acoustic diffraction limit, enabling visualization of microvessels with diameters as small as approximately 20 μm. Unlike conventional ultrasound techniques, SRUS preserves the inherent advantages of ultrasound, including deep tissue penetration and a large field of view, while achieving an approximately tenfold improvement in spatial resolution. This unique combination effectively bridges the long-standing gap between imaging depth and spatial resolution in vascular imaging. Furthermore, by localizing and tracking individual circulating microbubbles,SRUS enables quantitative assessment of microvascular blood flow velocity over a broad dynamic range without Doppler angle dependence. Consequently, super-resolution ultrasound imaging offers an unprecedented opportunity to characterize and compare the microvascular hemodynamic features of benign and malignant liver lesions, thereby improving the accuracy of preoperative differential diagnosis, tumor staging, therapeutic response assessment, and prognostic evaluation.

This study is testing a new imaging tracer called \[18F\]FAPI-74 with PET scans. Researchers want to find out how well this tracer shows certain diseases in the body, including several types of cancer and some non-cancer conditions like fibrosis and sarcoidosis. \[18F\]FAPI-74 attaches to a protein found on cells that are active in tumors and areas of scarring or inflammation. This may help doctors see these areas more clearly than with imaging methods used today, especially in diseases where current scans do not work well. People who join this study will get one injection of the tracer into a vein, then have one PET/CT or PET/MR scan. This takes about 2 hours in total. Researchers will compare the results with imaging the participant already had as part of their regular care, such as other PET scans, CT, or MRI. No extra treatment is given, and no other visits are needed. The study will take place at 5 hospitals in Switzerland and plans to include about 770 adults with a confirmed or suspected diagnosis of one of the conditions being studied. The main goal is to see how clearly the tracer shows up on the scan. Researchers will also look at whether this new scan changes how confident doctors feel about a diagnosis, or changes the patient's treatment plan.

Gastrointestinal (GI) cancers remain a major global health burden, largely due to the lack of effective and accessible early screening strategies. Current diagnostic approaches-including endoscopy, computed tomography (CT), and magnetic resonance imaging (MRI)-are either invasive, resource-intensive, or insufficiently sensitive for detecting early-stage disease, and are therefore not suitable for population-wide screening or for simultaneously identifying multiple GI tumor types. As a result, many patients are diagnosed at advanced stages, when therapeutic options are limited and prognosis is poor. Circulating microRNAs (miRNAs) offer a promising alternative, as they are stable in peripheral blood and reflect tumor-related molecular alterations. In this study, the investigators aim to develop and validate a robust, noninvasive miRNA-based signature capable of distinguishing GI cancers from non-malignant controls. By integrating multi-cohort datasets and applying machine learning-based feature selection and predictive modeling, the investigators will construct a screening panel optimized for reproducibility, scalability, and early-stage detection. This noninvasive miRNA signature has the potential to support accessible, cost-effective, and clinically practical population-level screening for GI cancers, ultimately facilitating earlier diagnosis and improving outcomes for participants.