Online risk scores for pre- and postoperative prediction of early recurrence in hepatocellular carcinoma patients undergoing conversion liver resection after tyrosine kinase inhibitors and immune checkpoint inhibitors therapy.

Background: Conversion therapy with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) offers the potential for curative resection in unresectable hepatocellular carcinoma (HCC). However, early recurrence (≤2 years) after conversion liver resection remains a major concern. This study aimed to develop and validate online preoperative and postoperative risk scores to predict early recurrence in patients undergoing conversion liver resection.

GUIDE: a prospective cohort study for blood-based early detection of gastrointestinal cancers using targeted DNA methylation and fragmentomics sequencing.

Background: Gastrointestinal (GI) cancers are among the most prevalent and lethal malignancies worldwide. Early, non-invasive detection is essential for timely intervention and improved survival. To address this clinical need, we developed GutSeer, a blood-based assay combining DNA methylation and fragmentomics for multi-GI cancer detection.

The MASTL/YBX1/PAK4 axis regulated by stress-activated STK24 triggers lenvatinib resistance and tumor progression in HCC.

Background And Aims: Many patients with HCC present inadequate responses to lenvatinib therapy. Therefore, it is important to elucidate the underlying mechanisms of resistance and to formulate effective reversal strategies.

Approach And Results: We conducted transcriptome and proteome sequencing analyses of lenvatinib-resistant cell lines and patient-derived tissues, identifying microtubule-associated serine/threonine kinase-like (MASTL) as a critical factor associated with lenvatinib resistance in HCC.

Adjuvant Lenvatinib for High-Risk CNLC IIb/IIIa Hepatocellular Carcinoma After Curative Hepatectomy: A Prospective Exploratory Study.

Objective: The risk of hepatocellular carcinoma (HCC) recurrence following surgical resection remains high, approaching 50%-70% at 5 years, with the highest risk occurring in the first year after resection. This study aimed to evaluate the efficacy and safety of lenvatinib as adjuvant therapy for HCC.

Methods: In this open-label, single-arm, prospective, multicenter Phase II clinical study, a total of 51 hCC patients with China Liver Cancer (CNLC) stage IIb/IIIa (ie tumor number ≥ 4 or vascular invasion, equivalent to BCLC B/C) who underwent R0 resection 4-6 weeks after curative surgery were enrolled.

Efficacy and safety of combined targeted therapy and immunotherapy versus targeted monotherapy in older patients with uHCC.

Background: The prevalence of hepatocellular carcinoma (HCC) among older patients is rising due to the aging population. This study aimed to compare the efficacy and safety of targeted therapy alone versus its combination with immunotherapy in older patients (≥ 65 years old) with unresectable HCC (uHCC).

Methods: We retrospectively analyzed 158 patients aged ≥ 65 diagnosed with uHCC who received targeted therapy alone or in combination with immunotherapy from the CLEAP database between March 2019 and July 2023.

FMO2 cancer-associated fibroblasts sensitize anti-PD-1 therapy in patients with hepatocellular carcinoma.

Background: The efficacy of immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) is limited by heterogeneity in individual responses to therapy. The heterogeneous phenotypes and crucial roles of cancer-associated fibroblasts (CAFs) in immunotherapy resistance remain largely unclear.

Methods: A specific CAF subset was identified by integrating comprehensive single-cell RNA sequencing, spatial transcriptomics and transcriptome profiling of patients with HCC with different responses to antiprogrammed cell death protein 1 (anti-PD-1) therapy.

CXCL6 Reshapes Lipid Metabolism and Induces Neutrophil Extracellular Trap Formation in Cholangiocarcinoma Progression and Immunotherapy Resistance.

The chemokine CXCL6 is identified as a pivotal regulator of biological processes across multiple malignancies. However, its function in cholangiocarcinoma (CCA) is underexplored. Tumor profiling for CXCL6 is performed using a public database.

Depth of Radiographic Response as an Independent Prognostic Factor for Patients with Initially Unresectable Hepatocellular Carcinoma Receiving Hepatectomy following Targeted Therapy plus Immunotherapy.

Introduction: Surgical resection following systemic therapy is feasible in patients with initially unresectable hepatocellular carcinoma (HCC). However, postoperative tumor recurrence is common after surgery, and the factors affecting this recurrence remain unclear. This study aimed to assess factors influencing postoperative outcomes in patients with initially unresectable HCC undergoing hepatectomy after systemic therapy.

Sintilimab plus bevacizumab followed by resection in intermediate-stage hepatocellular carcinoma: a phase Ib clinical trial with biomarker analysis.

Objective: This phase Ib trial aimed to assess the safety and efficacy of sintilimab plus bevacizumab (sintilimab/bev), followed by resection in patients with potentially resectable intermediate-stage hepatocellular carcinoma (HCC) and explore the clinical implications of circulating tumour DNA (ctDNA) and T cell receptor (TCR) repertoire.

Methods And Analysis: Eligible patients with intermediate-stage HCC received sintilimab/bev treatment. Patients with partial response or stable disease for at least two consecutive evaluations and technically resectable received hepatectomy.

Systemic Treatment for Unresectable Hepatocellular Carcinoma: A Surgeon's Perspective.

In recent years, the standard treatment for hepatocellular carcinoma (HCC) has changed dramatically due to the emergence of potent systemic treatment options. These advanced therapies have led to increased survival benefits for patients with advanced or intermediate-stage HCC. Advancements in HCC treatments also offer the possibility of conversion therapy for initially unresectable HCC.

Imaging-based prediction of early recurrence and neoadjuvant therapy outcomes for resectable beyond Milan HCC.

Purpose: To develop and validate an MRI-based model for predicting postoperative early (≤2 years) recurrence-free survival (RFS) in patients receiving upfront surgical resection (SR) for beyond Milan hepatocellular carcinoma (HCC) and to assess the model's performance in separate patients receiving neoadjuvant therapy for similar-stage tumors.

Method: This single-center retrospective study included consecutive patients with resectable BCLC A/B beyond Milan HCC undergoing upfront SR or neoadjuvant therapy. All images were independently evaluated by three blinded radiologists.

The prognostic value of systemic immune-inflammation index in patients with unresectable hepatocellular carcinoma treated with immune-based therapy.

Background: Predicting the efficacy of immune-based therapy in patients with unresectable hepatocellular carcinoma (HCC) remains a clinical challenge. This study aims to evaluate the prognostic value of the systemic immune-inflammation index (SII) in forecasting treatment response and survival outcomes for HCC patients undergoing immune-based therapy.

Methods: We analyzed a cohort of 268 HCC patients treated with immune-based therapy from January 2019 to March 2023.

A plain language summary of the results from the phase 2b HERIZON-BTC-01 study of zanidatamab in participants with HER2-amplified biliary tract cancer.

What Is This Summary About?: Researchers wanted to study whether the research drug zanidatamab could help people with a type of cancer called biliary tract cancer. In some people, biliary tract cancer cells make extra copies of a gene called HER2 (also called ERBB2). This is known as being HER2-amplified.

Deubiquitination of CIB1 by USP14 promotes lenvatinib resistance via the PAK1-ERK1/2 axis in hepatocellular carcinoma.

Lenvatinib is the most common multitarget receptor tyrosine kinase inhibitor for the treatment of advanced hepatocellular carcinoma (HCC). Acquired resistance to lenvatinib is one of the major factors leading to the failure of HCC treatment, but the underlying mechanism has not been fully characterized. We established lenvatinib-resistant cell lines, cell-derived xenografts (CDXs) and patient-derived xenografts (PDXs) and obtained lenvatinib-resistant HCC tumor tissues for further study.

The pattern of tumor progression on first-line immune checkpoint inhibitor-based systemic therapy for Chinese advanced hepatocellular carcinoma -CLEAP 004 study.

Background: For decades, stratification criteria for first-line clinical studies have been highly uniform. However, there is no principle or consensus for restratification after systemic treatment progression based on immune checkpoint inhibitors (ICIs). The aim of this study was to assess the patterns of disease progression in patients with advanced hepatocellular carcinoma (HCC) who are not eligible for surgical intervention, following the use of immune checkpoint inhibitors.

Platelet-to-lymphocyte ratio predicts tumor response and survival of patients with hepatocellular carcinoma undergoing immunotherapies.

Background: Lymphocyte-related factors were associated with survival outcome of different types of cancers. Nevertheless, the association between lymphocytes-related factors and tumor response of immunotherapy remains unclear.

Methods: This is a retrospective study.

Proteomic and metabolomic features in patients with HCC responding to lenvatinib and anti-PD1 therapy.

Combination therapy (lenvatinib/programmed death-1 inhibitor) is effective for treating unresectable hepatocellular carcinoma (uHCC). We reveal that responders have better overall and progression-free survival, as well as high tumor mutation burden and special somatic variants. We analyze the proteome and metabolome of 82 plasma samples from patients with hepatocellular carcinoma (HCC; n = 51) and normal controls (n = 15), revealing that individual differences outweigh treatment differences.

Tumor Radiomic Features on Pretreatment MRI to Predict Response to Lenvatinib plus an Anti-PD-1 Antibody in Advanced Hepatocellular Carcinoma: A Multicenter Study.

Introduction: Lenvatinib plus an anti-PD-1 antibody has shown promising antitumor effects in patients with advanced hepatocellular carcinoma (HCC), but with clinical benefit limited to a subset of patients. We developed and validated a radiomic-based model to predict objective response to this combination therapy in advanced HCC patients.

Methods: Patients ( = 170) who received first-line combination therapy with lenvatinib plus an anti-PD-1 antibody were retrospectively enrolled from 9 Chinese centers; 124 and 46 into the training and validation cohorts, respectively.

Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study.

Background: HER2 is overexpressed or amplified in a subset of biliary tract cancer. Zanidatamab, a bispecific antibody targeting two distinct HER2 epitopes, exhibited tolerability and preliminary anti-tumour activity in HER2-expressing or HER2 (also known as ERBB2)-amplified treatment-refractory biliary tract cancer.

Methods: HERIZON-BTC-01 is a global, multicentre, single-arm, phase 2b trial of zanidatamab in patients with HER2-amplified, unresectable, locally advanced, or metastatic biliary tract cancer with disease progression on previous gemcitabine-based therapy, recruited at 32 clinical trial sites in nine countries in North America, South America, Asia, and Europe.

Radiographic and α-fetoprotein response predict pathologic complete response to immunotherapy plus a TKI in hepatocellular carcinoma: a multicenter study.

Background: Pathologic complete response (pCR) following preoperative systemic therapy is associated with improved outcomes after subsequent liver transplant/resection in hepatocellular carcinoma (HCC). However, the relationship between radiographic and histopathological response remains unclear.

Methods: We retrospectively examined patients with initially unresectable HCC who received tyrosine kinase inhibitor (TKI) plus anti-programmed death 1 (PD-1) therapy before undergoing liver resection between March 2019 and September 2021 across 7 hospitals in China.

Effectiveness and safety of lenvatinib plus anti-programmed death-1 antibodies in patients with hepatocellular carcinoma: A real-world cohort study.

Objective: Lenvatinib plus anti-programmed death-1 (anti-PD-1) antibody combinations have shown potent anti-tumor effect in phase I/II trials in advanced or unresectable hepatocellular carcinoma (HCC), but real-world data are limited.

Methods: To investigate the effectiveness and safety of lenvatinib plus anti-PD-1 antibodies in a real-world cohort, we retrospectively evaluated 210 patients with unresectable or advanced HCC treated with these regimens between October 2018 and February 2022.

Results: The objective response rate and disease control rate per Response Evaluation Criteria in Solid Tumors (RECIST) v1.