Integration of Imaging, Molecular, Pathological, and Clinical Outcome Data in Hepatocellular Carcinoma. (IMPACT)

Integration of Multidimensional Imaging, Molecular, Pathological, And Clinical Outcome Data in Hepatocellular Carcinoma: Collection of the Prospective IMPACT Cohort.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death globally. Surgical resection is the mainstay of curative-intent treatment, but the 5-year postoperative recurrence rate can be as high as 70%. Tumor heterogeneity is a major driver of recurrence and continues to complicate individualized treatment decision-making. For example, extended resection may improve radicality but risks hepatic decompensation, whereas limited resection preserves liver function but may leave microscopic invasive foci. Therefore, accurate preoperative evaluation of tumor invasiveness is critical to achieving a delicate balance between radicality and safety, and to improving long-term survival.

Multiparametric MRI is the most comprehensive noninvasive modality for assessing HCC invasiveness. However, most existing models are primarily data-driven and lack histopathological or molecular validation of their underlying mechanisms. They also lack precise spatial localization, limiting their direct application to surgical planning. A bottleneck is the lack of precise imaging-pathology correspondence, resulting from mismatches between macroscopic imaging and microscopic histology in both spatial registration and sampling adequacy. This gap also makes it difficult to establish a coherent link between imaging phenotypes and postoperative recurrence risk.

Therefore, this prospective observational cohort study aims to construct a multidimensional Imaging, Molecular, Pathological, And Clinical Outcome (IMPACT) database in patients undergoing curative resection for single BCLC 0/A HCC. The study has three major objectives:

1. Cross-scale imaging-pathology-molecular correlations: to spatially correlate multiparametric MRI and photon-counting CT (PCCT) imaging features with pathologic and molecular features, as well as with prognosis, thereby elucidating the biological mechanisms underlying imaging markers and phenotypes.
2. Prospective validation of prognostic models: to validate the predictive performance of the MERP, SPAN, and related models for recurrence-free survival (RFS), overall survival (OS), and other endpoints;
3. Imaging-guided individualized surveillance: to explore the role of abbreviated MRI (AMRI)-based surveillance in the postoperative follow-up of patients at high risk of recurrence.

By integrating imaging phenotypes, pathological immune microenvironment, genomic alterations, and clinical outcomes into a four-dimensional radiogenomic framework, this database will support a shift towards the "imaging-as-virtual-biopsy" paradigm, inform individualized surgical planning, perioperative treatment, and postoperative surveillance.

Study Overview

• Status: Not yet recruiting
• Conditions: Resectable Hepatocellular Carcinoma (HCC)
• Intervention / Treatment: Procedure: Resection

• Study Type: Observational
• Enrollment (Estimated): 380

Contacts and Locations

• Study Contact: Name: Hanyu Jiang; Phone Number: +86 18608008770; Email: hanyu_jiang@foxmail.com

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital of Sichuan University
      • Contact: Hanyu Jiang; Phone Number: +86 18608008770; Email: hanyu_jiang@foxmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

This prospective observational cohort will enroll adult patients with preserved liver function who undergo curative-intent resection for single BCLC 0/A HCCs.

Description

Inclusion Criteria:

1. Able to understand the study requirements, provide written informed consent, and comply with radiological examinations, biospecimen collection, and follow-up schedules.

2. Age ≥18 years at the time of signing Informed Consent Form.

3. Newly diagnosed HCC either clinically in accordance with the version 2026 Liver Imaging Reporting and Data System (LI-RADS) or pathologically via core-needle biopsy.

4. Single BCLC 0/A HCC.

5. HCC that is amenable to R0 surgical resection with curative intent in the opinion of the multidisciplinary tumor board involved in the care of the participant.

6. No prior antitumor therapy.

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

8. Child-Pugh class A liver function.

9. No contraindications to contrast-enhanced CT or MRI, such as contrast-media allergy, claustrophobia, or incompatible metallic implants.

10. No evidence of clinically significant portal hypertension (CSPH) or minor CSPH (HVPG <12 mmHg) in candidates for minor resection (fewer than 3 segments). Clinically significant portal hypertension (CSPH) can be defined either by its gold standard measurement, a hepatic venous pressure gradient (HVPG) ≥10 mmHg, or by the presence of surrogate markers such as a platelet count <100 × 109/L combined with splenomegaly.

11. Adequate major organ function, with laboratory values obtained within 7 days before enrollment meeting the following criteria:

    Hematology: absolute neutrophil count ≥ 1.0 × 10⁹/L, platelet count ≥ 75 × 10⁹/L, hemoglobin ≥ 90 g/L ((no blood transfusion, no use of granulocyte colony-stimulating factor [G-CSF], and no medication correction within 2 weeks prior to screening, except for hemoglobin).

    Blood chemistry: total bilirubin ≤1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 × ULN; albumin ≥ 30 g/L (no albumin or branched-chain amino acid supplementation within 14 days prior to screening); serum creatinine (Cr) ≤1.5 × ULN or Cr clearance > 50 mL/min (Cockcroft-Gault formula); and urine protein ≤1+ ((if urine protein is ≥2+, 24-hour urine protein quantification can be performed, and patients with 24-hour urine protein quantification < 1.0 g can be enrolled).

    Coagulation: prothrombin time (PT) exceeding the normal range ≤2 s; international normalized ratio (INR) or activated partial thromboplastin time (APTT) ≤1.5 × ULN.

12. Documented virology status of hepatitis, as confirmed by screening tests for hepatitis B virus (HBV) and/or hepatitis C virus (HCV):

    Patients with hepatitis B virus (HBV) infection, such as HBsAg positive, should be tested for HBV-DNA, and HBV-DNA must be < 2000 IU/mL (< 104 copies/mL if the site has only copy/mL testing unit); for patients with HBV-DNA ≥ 2000 IU/mL, if they have received antiviral therapy (only nucleosides such as entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide fumarate tablets are allowed) for at least 1 week ,and the viral copy number is decreased more than 10-fold (1 lg) compared with that before treatment, they also can be enrolled. For patients with HBV infection, antiviral therapy is required throughout the study.

    Patients with HCV, either with resolved infection (as evidenced by detectable antibody) or chronic infection (as evidenced by detectable HCV RNA), are eligible.

    For patients with detectable HCV RNA and for whom HCV treatment is considered appropriate by the investigator, treatment should begin no sooner than 6 months following liver resection consistent with AASLD guidelines.

13. Negative HIV test at screening with the following exception: Individuals with a positive HIV test at screening are eligible if they are stable on anti-retroviral therapy, have a CD4 count ≥ 200/cells/µL, and have an undetectable viral load.

14. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception.

For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating sperm.

Exclusion Criteria:

1. Inadequate image quality for reliable analyses (e.g., severe artifact, incomplete images).
2. Imaging evidence of tumor rupture at baseline.
3. History of hepatic encephalopathy if clinically significant within one year prior to screening.
4. Clinically symptomatic moderate-to-severe ascites.
5. History of prior malignancy.
6. Active co-infection with HBV and HCV (defined as detectable HCV RNA plus positive HBV surface antigen or HBV DNA). Patients with a history of HCV infection but who are negative for HCV RNA by Polymerase Chain Reaction (PCR) will be considered non-infected with HCV.
7. Known active co-infection with HBV and hepatitis D viral infection (HDV).
8. Active bleeding or bleeding diathesis, or those receiving ongoing thrombolytic, anticoagulant, or antiplatelet therapy.
9. High-grade esophageal or gastric fundal varices requiring intervention.
10. Inadequately controlled hypertension, defined as systolic blood pressure (BP) > 150 mmHg and/or diastolic BP > 100 mmHg (average of at least three readings at two or more sessions). Anti-hypertensive therapy to achieve these parameters is allowed.
11. History of abdominal or tracheoesophageal fistula, GI perforation, or intra-abdominal abscess within 6 months prior to screening.
12. History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction, including subocclusive or occlusive syndrome related to the underlying disease, or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding prior to screening.
13. Evidence of abdominal free air that is not explained by paracentesis or recent (< 3 months) abdominal surgical procedure.
14. Serious, non-healing, or dehiscing wound, active ulcer, or untreated bone fracture.
15. History of intra-abdominal inflammatory process within 6 months prior to screening, including but not limited to peptic ulcer disease, diverticulitis, or colitis.
16. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to screening; or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to screening; or anticipation of need for major surgical procedure, other than potentially curative liver resection, during the study; or non-recovery from side effects of any such procedure.
17. Failuere to achieve complete healing from minor surgery (e.g., simple excision, tooth extraction) must have occurred at least 7 days before screening.
18. Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID). The occasional use of NSAIDs for the symptomatic relief of medical conditions such as headache or fever is allowed.
19. Serious infection requiring oral or IV antibiotics and/or hospitalization within 4 weeks prior to screening, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that, in the opinion of the investigator, could impact participant safety.
20. Pregnancy or breastfeeding, or intention of becoming pregnant during the study. Female participants of childbearing potential must have a negative serum pregnancy test result at screening.
21. Left ventricular ejection fraction (LVEF) < 50% assessed by either transthoracic echocardiogram (TTE) or multiple-gated acquisition (MUGA) scan (TTE preferred test) within 6 months prior to screening.
22. Active tuberculosis.
23. Ongoing psychotropic substance abuse that cannot be discontinued or with a clinically significant psychiatric disorder.
24. Any serious medical condition or abnormality in clinical laboratory tests that precludes an individual's safe participation in and completion of the study.
25. Subjects considered ineligible at the investigator's discretion, with the rationale explicitly documented.
26. Non R0 resection.
27. Incomplete surgical records (e.g., missing data on whether anatomical resection was performed).
28. Unable to complete scheduled postoperative surveillance.

Study Plan

How is the study designed?

Design Details

• Observational Models: COHORT
• Time Perspectives: PROSPECTIVE

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Curative Resection HCC Cohort	Procedure: Resection; Hepatocellular carcinoma that is amenable to R0 surgical resection with curative intent in the opinion of the multidisciplinary tumor board involved in the care of the participant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free Survival (RFS)	Recurrence-free survival is defined as the time from resection of HCC to the first documented tumor recurrence or death from any cause, whichever occurs first. Participants without recurrence or death will be censored at the date of their last follow-up. Characteristics of recurrence, including but not limited to recurrence location, proximity to the surgical margin, tumor size, and number of recurrent lesions, will be collected at the time of recurrence.	From resection to the first documented recurrence or death from any cause, whichever occurs first, assessed up to 3 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall survival is defined as the time from resection of HCC to death from any cause. Participants who are alive at the last follow-up will be censored at the date of last contact. The cause of death will be adjudicated and classified as tumor-related or non-tumor-related.	From resection to death from any cause, assessed up to 3 years
Time to recurrence (TTR)	Time to recurrence is defined as the time from resection of HCC to the first documented tumor recurrence. Participants without recurrence will be censored at the date of their last follow-up. Characteristics of recurrence, including recurrence location, proximity to the surgical margin, tumor size, and number of recurrent lesions, will be collected at the time of recurrence.	From resection to the first documented recurrence, assessed up to 3 years.

Collaborators and Investigators

• Sponsor: West China Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: October 28, 2026
• First Submitted That Met QC Criteria: October 28, 2026
• First Posted (Actual): November 3, 2026

Study Record Updates

• Last Update Posted (Actual): November 3, 2026
• Last Update Submitted That Met QC Criteria: October 28, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: HX (2433); 82622057 (Other Grant/Funding Number: National Natural Science Foundation of China)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No