SIRT and Peri-immunotherapy : a New Concept

Not yet recruiting

• Conditions: Advanced Hepatocellular Carcinoma (HCC), Classified as BCLC Stage B or C, Treated With a Combination of Selective Internal Radiation Therapy

• Registration Number: NCT06971237
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Study Timeline

• Status Verified: 2025-04
• Study First Submitted: 2025-04-25
• Study First Submitted QC: 2025-05-12
• Last Update Submitted: 2025-05-12
• Study First Posted: 2025-05-14
• Last Update Posted: 2025-05-14
• Study Start: 2025-06-01
• Primary Completion: 2026-07-01
• Study Completion: 2026-07-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.

Trial Locations

Locations (1)

Hôpital Paul Brousse - Radiology Department; 🇫🇷 Villejuif, France