A multicenter retrospective cohort analysis in AustriaPrimary 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 byvaccination status, vaccine type, and prior infection; explore modification by cirrhosisseverity and tumor characteristics; and assess safety (irAEs, steroid use,toxicity-related discontinuation).
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.
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)
Medical University of Graz
Graz, Austria
Ordensklinikum Linz
Linz, Austria
University Hospital St. Pölten
Sankt Pölten, Austria
Krankenhaus der Barmherzigen Brüder St Veit an der Glan
Sankt Veit an der Glan, Austria
Klinikum Wels-Grieskirchen
Wels, Austria
Florian Rainer, MD
+43 316 385 - 30164
florian.rainer@medunigraz.at
Vanessa Stadlbauer, Univ. Prof. MD
+43 316 385 - 82282
vanessa.stadlbauer@medunigraz.at