Unresectable Hepatocellular Carcinom
Conditions
Keywords
Hepatocellular Carcinoma, Conversion Therapy, Radiological Complete Response, Systemic Therapy, Surgical Resection
Brief summary
This is a prospective cohort study designed to evaluate the effectiveness and safety of two post-conversion treatment strategies for patients with initially unresectable hepatocellular carcinoma (uHCC). Participants first receive conversion therapy with transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with anti-angiogenic agents and immune checkpoint inhibitors (ICIs). After this therapy, patients who achieve complete radiological response (rCR) or meet resectability criteria will either undergo surgical resection or continue systemic therapy. The study aims to compare outcomes between these two strategies to help guide treatment decisions for advanced liver cancer.
Interventions
None listed
Sponsors
Shanghai Zhongshan Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Signed written informed consent. 2. Age 18-75 years. 3. Hepatocellular carcinoma (HCC) confirmed by histology/cytology or diagnosed according to the AASLD criteria. 4. Initially unresectable HCC (uHCC), defined according to the Chinese Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2024 edition) and the Chinese Expert Consensus on Conversion and Perioperative Therapy for Primary Liver Cancer (2024 edition): HCC considered unsafe for curative resection due to inability to ensure both oncological completeness (R0 resection) and functional hepatic reserve (adequate future liver remnant with good vascular supply and biliary drainage to maintain postoperative liver function and minimize morbidity and mortality). Mainly includes CNLC stage Ib-IIIa or potentially resectable cases. Some stage Ia patients may also be considered uHCC if the tumor is adjacent to major intrahepatic vessels or involves the first/second hepatic hilum making R0 resection infeasible, or if severe cirrhosis increases risk of postoperative liver failure and complications; these can be considered after successful conversion and supportive treatment. 5. No prior systemic therapy before conversion treatment. 6. Conversion therapy regimen must include TACE or HAIC plus anti-angiogenic agents and immune checkpoint inhibitors (ICIs). 7. Anti-angiogenic agents may include lenvatinib, sorafenib, apatinib, donafenib, anlotinib, bevacizumab. 8. ICIs may include pembrolizumab, atezolizumab, nivolumab, sintilimab, tislelizumab, toripalimab, penpulimab, cadonilimab, KN-046. 9. After conversion therapy, hepatic lesions achieve radiological complete response (rCR) by mRECIST criteria on contrast-enhanced CT or MRI, or are assessed to have reached resectability criteria (eligible for curative hepatectomy or downstaging enabling safe surgery). 10. After achieving rCR or resectability, patients must have received either liver resection or continued systemic therapy with scheduled follow-up. 11. Child-Pugh class A or B liver function. 12. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1.
Exclusion criteria
1. Presence of another primary malignancy in other organs. 2. History of other malignancies. 3. Recurrent HCC occurring \<2 years after previous curative surgery or adjuvant therapy. 4. Received treatments other than TACE or HAIC plus anti-angiogenic agents and ICIs during the conversion phase. 5. Received treatments during postoperative or maintenance systemic therapy that differ from the initial conversion regimen. 6. Severe organ dysfunction. 7. Incomplete radiological assessment data after treatment. 8. Child-Pugh class C liver function. 9. Pregnant or breastfeeding women. 10. Patients undergoing only functional future liver remnant (FLR) hypertrophy procedures (e.g., ALPPS or PVE) for insufficient FLR without other criteria for uHCC conversion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-Free Survival (EFS) | From initiation of post-conversion therapy to the first documented event (recurrence, progression, or death), up to 36 months | Defined as the time from the date of achieving rCR or resectability criteria to the time of becoming inoperable, recurrence, progression, or death from any cause for uHCC patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 2-Year Event-Free Survival (EFS) Rate | 2 years after initiation of post-conversion therapy | Defined as the rate of no events (recurrence, progression, or death from any cause) occurring in rCR patients over 2 years. |
| Overall Survival (OS) | Up to 36 months after initiation of post-conversion therapy | Defined as the survival time from the day of achieving rCR to death from any cause。 |
| Treatment Safety | From initiation of post-conversion therapy through 30 days after last treatment or surgery, up to 36 months follow-up | : The incidence of adverse events in the surgery group and the systemic therapy group. Adverse events recorded on the CRF will be mapped to preferred terms using the Medical Dictionary for Regulatory Activities (MedDRA). Severity, seriousness/grade, and the relationship with the study treatment will be assessed by the investigators. The seriousness/grade will be defined according to the National Cancer Institute (NCI) CTCAE v5.0. |
| Cost-Effectiveness of Post-Conversion Treatment Strategies | Up to 36 months after initiation of post-conversion therapy | The cost-effectiveness ratio (C/E) is defined as the ratio of time to an event (EFS) or overall survival (death) from rCR to all direct costs (medical expenses, including outpatient and inpatient), and will be compared between the two groups. |
Contacts
Primary ContactAo Huang, PhD
Outcome results
None listed