Checkpoint Inhibitor, Hepatocellular Carcinoma, mRNA Vaccination
Conditions
Keywords
hepatocellular carcinoma, mRNA vaccination, response, immune checkpoint inhibitor
Brief summary
A multicenter retrospective cohort analysis in Austria Primary Objective: To assess whether receiving an mRNA COVID-19 vaccine within 3 months before starting ICI (Immune checkpoint inhibitors) therapy improves best overall response (mRECIST) in HCC (hepatocellular carcinoma). Secondary Objectives: Evaluate whether vaccination within 1 or 3 months affects OS (overall survival) , PFS (Progression free survival)), or TTP (Time to progression); compare outcomes by vaccination status, vaccine type, and prior infection; explore modification by cirrhosis severity and tumor characteristics; and assess safety (irAEs, steroid use, toxicity-related discontinuation).
Detailed description
Immune checkpoint inhibitors (ICIs) have become a cornerstone of systemic therapy for advanced hepatocellular carcinoma (HCC). Their efficacy, however, varies substantially between patients, and factors that modulate immunotherapy response remain incompletely understood . Recent mechanistic and clinical data have raised the hypothesis that SARS-CoV-2 mRNA vaccines might augment responsiveness to ICIs. A landmark study by Grippin et al. demonstrated that mRNA vaccines induce a systemic surge of type-I interferons, activate antigen-presenting cells, increase PD-L1 expression on tumor cells, and ultimately sensitize tumors to ICIs across various malignancies including NSCLC (non-small cell lung cancer) and melanoma. In their retrospective cohorts, receiving a COVID-19 mRNA vaccine within 100 days before starting ICI was associated with significantly improved overall survival and progression-free survival While these findings suggest that COVID-19 mRNA vaccines may act as potent immune modulators in the context of immunotherapy, no data exist for HCC, a tumor entity that is characterized by an immunosuppressive, 'immune-cold' microenvironment that limits effective anti-tumor immune responses. Given the widespread implementation of COVID-19 vaccination programs in Austria since 2021, and the large number of HCC patients receiving ICI-based therapies at tertiary centers, a rigorous retrospective analysis is now feasible.
Interventions
None listed
Sponsors
Klinikum Wels-Grieskirchen
University Hospital St. Polten
Ordensklinikum Linz GmbH Krankenhaus Barmherzige Schwestern
Krankenhaus der Barmherzigen Brüder St. Veit/Glan
Medical University of Graz
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Radiologically or histologically confirmed hepatocellular carcinoma * Treatment with immune checkpoint inhibitor-based therapy (mono- or combination therapy; e.g., atezolizumab/bevacizumab, durvalumab/tremelimumab, nivolumab, pembrolizumab) * Complete electronic medical records available * At least one imaging-based response assessment using mRECIST
Exclusion criteria
* Missing key clinical data required for main analyses (e.g. survival status, date of progression, Child-Pugh class, BCLC stage)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best overall response | up to 4 years | according to mRECIST criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | up to 4 years | death yes/no |
| Progression free survival | up to 4 years | Progression according to RECIST yes/no |
| Time to progression | up to 4 years | Time until progression occurs according to RECIST |
Countries
Austria
Contacts
Primary ContactFlorian Rainer, MD
Backup ContactVanessa Stadlbauer, Univ. Prof. MD
Outcome results
None listed