Hepatecellular Carcinoma

1.1. Main Objectives The objective response rate (ORR) determined by the researchers based on RECIST v1.1 was used to evaluate the efficacy of systemic therapy (carrycept combined with apatinib) in combination with or without local treatment (surgery, radiotherapy, or ablation therapy) for patients with advanced hepatocellular carcinoma with pulmonary metastases. 1.2. Secondary objectives Through efficacy indicators such as progression-free survival (PFS) and objective response rate (ORR) determined by researchers based on RECIST v1.1 and mRECIST, evaluate the efficacy of systemic therapy (carrietumab combined with apatinib) combined or not with local treatment (surgery, radiotherapy, or ablation therapy) for patients with advanced hepatocellular carcinoma with pulmonary metastases. Evaluate the safety of combining systemic therapy (caretuximab-rbsm in combination with apatinib) with or without local treatment (surgery, radiotherapy, or ablation therapy) for patients with advanced hepatocellular carcinoma with pulmonary metastases. 1.3. Exploratory Purpose Evaluate the cumulative duration (the sum of the time spent in a NED state) and the safety of local treatments for patients who have undergone comprehensive treatment and have no detectable active lesions on imaging studies (NED). Explore the correlation between biomarkers and the efficacy of combined treatment regimens. Explore the relationship between the number, diameter, and treatment outcomes of pulmonary metastases in hepatocellular carcinoma.

Primary liver tumors, with hepatocellular carcinoma (HCC) accounting for 80%, represent 6% of global cancer incidence and 9% of global cancer-associated mortality.HCC remains the leading causes of cancer-related deaths worldwide, due to late diagnosis. Although local-stage liver tumors are curable with tumor resection or livertransplantation, 65-70% of diagnosed cases are not suitable for resection due to large or multifocal lesions. For these patients, local therapies such as transcatheterarterial chemoembolization (TACE) or selective internal radiation therapy (SIRT) are appropriate at intermediate stages. In cases of advanced and metastatic livertumors, systemic therapies like sorafenib are the standard approach. Selective Intra-arterial Radionuclide Therapy (SIRT) offers a promising treatment for inoperableliver tumors by delivering beta-emitting radiolabeled microspheres directly to tumor sites through the liver's dual blood supply. However, the high cost of standard90Y-microspheres has limited accessibility for patients. This current project aims to develop, optimize, and validate the indigenously prepared microspheres forradiolabeling with 188Re from commercially available generator and indigenously produced radionuclide 177Lu (BARC Mumbai) for SIRT in liver cancer. With hightransformational impact, the current multicentric research will lead to a potentially safe, effective, and promising low-cost SIRT solution for low-income settings.Through collaboration across multiple centers, the study will evaluate the efficacy of microspheres labelled with both radionuclides. By establishing these accessibleSIRT options, this project strives to reduce financial barriers to treatment, advancing the goals of "Jai Anusandhan" towards building innovative therapeutics throughcollaborative research project and improving outcomes for patients with limited options.

The goal of this prospective, single-arm, multi-center Phase II clinical trial is to evaluate the clinical efficacy and safety of QL1706 combined with bevacizumab and RALOX hepatic artery infusion chemotherapy in treating liver cancer patients with VP3/4 portal vein tumor thrombus. It will also explore molecular biomarkers that predict the efficacy of this combined therapy. The main questions it aims to answer are: What is the progression-free survival (PFS) of patients treated with this regimen? What are the objective response rate (ORR), disease control rate (DCR), and overall survival (OS) of these patients? What is the safety and tolerability profile of this combined treatment? Which molecular biomarkers can predict the efficacy of this therapy? Eligible subjects (who have signed informed consent) will receive RALOX hepatic artery infusion chemotherapy plus QL1706 (7.5mg, intravenous infusion every 3 weeks) and bevacizumab (15mg/kg, intravenous infusion every 3 weeks), with 3 weeks as one treatment cycle. Treatment will continue until a protocol-specified discontinuation event occurs. After treatment, subjects will undergo post-treatment safety follow-up and survival follow-up; those who discontinue treatment for reasons other than disease progression or death will also have tumor progression follow-up.

This observational study aims to validate a deep learning model for predicting aggressive recurrence patterns in patients with early-stage liver cancer (HCC) after surgery. The main question it aims to answer is: Can the AI model accurately identify patients at high risk of cancer recurrence within 2 years after surgery? Participants will provide clinical data and undergo standard surgery, followed by 2-year imaging surveillance. Their data will be used for both AI prediction and validation of recurrence patterns.