Publications by authors named "Huichuan Sun"

Article Synopsis
  • * Recent advancements in targeted therapy and immune-checkpoint inhibitors are now becoming available for treating unresectable HCC and preventing recurrence after curative procedures.
  • * This clinical practice guideline aims to provide updated recommendations from Asia-Pacific experts on systemic therapy for HCC, addressing key questions about patient selection, effective treatments, and management strategies for immunotherapy.
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Article Synopsis
  • Anti-PD-L1 combination immunotherapy is the first-line treatment for unresectable hepatocellular carcinoma (HCC), but its effectiveness is limited, with less than 40% of patients responding.
  • Research found that nonresponders had higher activation of the renin-angiotensin system and lower ACE2 expression, which is linked to HCC progression and resistance to treatment.
  • Targeting the ACE2 axis may improve responses to anti-PD-L1 therapy by reducing immunosuppressive factors in the tumor environment, positioning it as both a potential therapeutic target and a biomarker for predicting treatment success.
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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.

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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.

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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.

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Systemic therapy is typically the primary treatment choice for hepatocellular carcinoma (HCC) patients with extrahepatic metastases. Some patients may achieve partial response (PR) or complete response (CR) with systemic treatment, leading to the possibility of their primary tumor becoming resectable. This study aimed to investigate whether these patients could achieve longer survival through surgical resection of their primary tumor.

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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.

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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.

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Article Synopsis
  • Intrahepatic cholangiocarcinoma (iCCA) can arise from various parts of the intrahepatic biliary tree and is classified into subtypes based on their origins, such as large duct, small duct, and cholangiolocarcinoma.
  • Diagnosing these subtypes is challenging due to differences in cell structure, growth patterns, and other pathological features.
  • An expert consensus has proposed nine recommendations to standardize the diagnosis of these iCCA subtypes, referring mainly to the latest World Health Organization classification.
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Comprehensive molecular analyses of metastatic hepatocellular carcinoma (HCC) are lacking. Here, we generate multi-omic profiling of 257 primary and 176 metastatic regions from 182 HCC patients. Primary tumors rich in hypoxia signatures facilitated polyclonal dissemination.

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Article Synopsis
  • Primary liver cancer is a major health concern in China, with hepatocellular carcinoma accounting for 75-85% of cases, ranking as the fourth most common cancer and the second leading cause of cancer-related deaths in the country.
  • The Guidelines for Diagnosis and Treatment of Primary Liver Cancer were first published in 2017 and have been updated due to new research and evidence in the field, leading to the 2022 Edition written by over 100 experts.
  • The updated guidelines aim to promote evidence-based practices to enhance the 5-year survival rate of liver cancer patients in alignment with the "Health China 2030 Blueprint."
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Background: The difference in the prognoses between treatment with surgical therapy and continuation of local-plus-systemic therapy following successful down-staging of intermediate-advanced hepatocellular carcinoma (HCC) remains unclear.

Methods: Data of 405 patients with intermediate-advanced HCC treated at 30 hospitals across China from January 2017 to July 2022 were retrospectively reviewed. All patients received local-plus-systemic therapy and were divided into the surgical (n = 100) and nonsurgical groups (n = 305) according to whether they received surgical therapy.

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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.

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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.

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To explore biliary tract stone (BTS) as prognostic factors of intrahepatic cholangiocarcinoma (ICC). Clinical data of 985 ICC patients were classified into no BTS group and BTS group-subgrouped into hepatolithiasis (HL) and non-hepatolithiasis (NHL) group. Propensity score matching was utilized to mitigate baseline characteristics.

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Background: Systemic therapy is the standard care of unresectable hepatocellular carcinoma (uHCC), while transcatheter intra-arterial therapies (TRITs) were also widely applied to uHCC patients in Chinese practice. However, the benefit of additional TRIT in these patients is unclear. This study investigated the survival benefit of concurrent TRIT and systemic therapy used as first-line treatment for patients with uHCC.

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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.

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Article Synopsis
  • Advanced intrahepatic cholangiocarcinoma (ICC) has poor outcomes, but a new combination therapy of toripalimab, lenvatinib, and GEMOX shows promise as a first-line treatment.
  • In a study of 30 patients, the therapy resulted in an 80% objective response rate, with most experiencing either partial or complete responses, and an overall disease control rate of 93.3%.
  • While manageable adverse events occurred in over half of the patients, including neutropenia and leukocytopenia, the overall survival and progression-free survival were encouraging, prompting further validation in a larger clinical trial.
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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.

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Objective: Revealing the single-cell immune ecosystems in true versus de novo hepatocellular carcinoma (HCC) recurrences could help the optimal development of immunotherapies.

Design: We performed 5'and VDJ single-cell RNA-sequencing on 34 samples from 20 recurrent HCC patients. Bulk RNA-sequencing, flow cytometry, multiplexed immunofluorescence, and in vitro functional analyses were performed on samples from two validation cohorts.

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Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies in China. Most HCC patients are first diagnosed at an advanced stage, and systemic treatments are the mainstay of treatment.

Summary: In recent years, immune checkpoint inhibitors have made a breakthrough in the systemic treatment of middle-advanced HCC, breaking the single therapeutic pattern of molecular-targeted agents.

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Background: Conversion therapy is feasible in patients with oncologically unresectable hepatocellular carcinoma (HCC). However, it is challenging to prospectively identify patients who are more likely to achieve successful conversion before initiating systemic therapy, either alone or combined with locoregional therapy.

Methods: Criteria for identifying potentially resectable patients with initially oncologically unresectable HCC before treatment with lenvatinib plus an anti-PD-1 antibody were proposed based on real-world evidence.

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Background: Avatrombopag has been approved in patients who have severe thrombocytopenia (<50 × 10/L) and chronic liver disease (CLD) while receiving invasive procedures. The real-world application and effectiveness of avatrombopag in the subgroup patients with liver cancer remain unknown.

Methods: Liver cancer patients (including primary liver cancer and colorectal cancer liver metastasis) who had severe thrombocytopenia and received avatrombopag were retrospectively enrolled.

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Purpose: Probing efficacy and safety of lusutrombopag in Chinese chronic liver disease (CLD) and severe thrombocytopenia (PLT < 50 × 10/L) patients undergoing elective invasive procedures.

Methods: In this double-blind, parallel-group phase 3 study, 66 patients with CLD and severe thrombocytopenia were randomized 2:1 to lusutrombopag or placebo arm treatment regimens for seven days at 9 centers in China. Responders (PLT ≥ 50 × 10/L that increased to ≥ 20 × 10/L from the baseline and not received rescue therapy for bleeding) on Day 8 (the day after seven-day treatment) were assessed.

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