Advanced Hepatocellular Carcinoma (HCC), Classified as BCLC Stage B or C, Treated With a Combination of Selective Internal Radiation Therapy
Conditions
Keywords
Hepatocellular Carcinoma, Advanced Liver Cancer
Brief summary
The combination of selective internal radiation therapy (SIRT) with immunotherapy represents an innovative and potentially highly effective therapeutic strategy for the treatment of advanced-stage hepatocellular carcinoma (BCLC stage B or C). Although promising results have been observed in preliminary clinical trials, further research is needed to better understand the underlying mechanisms, optimize treatment protocols, and confirm the long-term efficacy and safety of this combined approach
Detailed description
This retrospective cohort study aims to evaluate the efficacy and safety of a novel combination treatment for advanced hepatocellular carcinoma (HCC), involving Selective Internal Radiation Therapy (SIRT) with Yttrium-90 (Y90) microspheres and peri-immunotherapy (atezolizumab ± bevacizumab) administered in both neoadjuvant and adjuvant settings. The study targets patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC, initially deemed ineligible for curative therapies such as resection, transplantation, or percutaneous ablation. Recent advances in immunotherapy have shown promise for HCC treatment, but overall response rates remain low due to the immunosuppressive tumor microenvironment. SIRT delivers high-dose localized radiation directly to the tumor, inducing immunogenic cell death and potentially priming the immune system for enhanced response to immune checkpoint inhibitors. This study investigates whether this combination can produce synergistic anti-tumor effects, prolong progression-free survival (PFS) and overall survival (OS), and potentially downstage tumors to make curative treatment feasible. Data will be retrospectively collected from electronic health records (Orbis), imaging systems (PACS), and pathology databases at the AP-HP GH Paris-Saclay institutions (Hôpital Paul Brousse and Hôpital Bicêtre). A total of 60 patients treated between 2021 and 2024 will be included. Key clinical variables (e.g., age, sex, comorbidities, AFP), imaging response (based on RECIST 1.1, mRECIST, iRECIST, LI-RADS criteria), treatment parameters (e.g., Y90 dose, immunotherapy schedule), histological findings, and adverse events (CTCAE grading) will be systematically extracted and anonymized. A matched control group of patients treated with immunotherapy alone will be used for comparative analysis. Imaging will be reviewed independently by two senior abdominal imaging radiologists. Statistical analyses will be conducted using R Software (version 3.2.3) in collaboration with the GH Paris-Saclay methodology unit. This study complies with French and European data protection regulations (MR-004) and has obtained ethical approval from the Bicêtre ethics committee (CER POLETHIS). Patients are informed by mail and included upon non-objection within one month. The overarching goal is to determine whether the SIRT + peri-immunotherapy protocol offers improved disease control and survival outcomes compared to standard treatment, while maintaining acceptable safety and tolerability.
Interventions
DRUGAtezolizumab ± Bevacizumab and Yttrium-90 Radioembolization
Atezolizumab ± Bevacizumab: Peri-immunotherapy with , with or without bevacizumab, given before and after SIRT. \- Yttrium-90 Radioembolization: Selective Internal Radiation Therapy (SIRT) via intra-arterial injection of Yttrium-90 microspheres for liver tumor control
DRUGAtezolizumab ± Bevacizumab
Standard systemic immunotherapy administered without SIRT, using atezolizumab with or without bevacizumab.
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Age ≥ 18 years Diagnosis of hepatocellular carcinoma (HCC) confirmed by imaging or biopsy Tumor \> 6 cm Child-Pugh score A to B7 Not eligible for curative treatment (resection, ablation, transplant, TACE) Macrovascular invasion or AFP \> 100 ng/mL Treated with intra-arterial Yttrium-90 SIRT combined with atezolizumab ± bevacizumab
Exclusion criteria
Age \< 18 Non-HCC diagnosis on imaging or pathology Child-Pugh \> B7 Prior immunotherapy or intra-arterial hepatic treatment Under legal guardianship or curatorship
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Tumor Response Rate | At 3, 6, 9 and 12 months post-treatment | Proportion of patients achieving complete or partial response, evaluated by CT or MRI using RECIST 1.1, mRECIST, iRECIST, and LI-RADS therapeutic criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | From treatment to disease progression or death, up to 12 months | Time between start of treatment and first documented progression or death, based on imaging and clinical records |
| Overall Survival (OS) | From treatment to death, up to 12 months | Time from treatment initiation to death from any cause. |
| Treatment-Related Adverse Events | through study completion, an average of 1 year | Assessment of adverse events related to SIRT and/or immunotherapy, graded using CTCAE v5.0. |
Countries
France
Contacts
Primary ContactClara Prud'homme, MD
Backup ContactMaïté Lewin, Professor
Outcome results
None listed