Supplementary Material for: Case Report: No more Detours: Hepatopulmonary Shunt Reduction in a Patient with Hepatocellular Carcinoma After Treatment with Bevacizumab

Introduction: Treatment options for intermediate stage hepatocellular carcinoma (HCC) include transarterial radioembolization (TARE) and systemic treatment. Currently, in the absence of contraindications, first-line systemic therapies include combinations of immune checkpoint inhibitors (ICIs) with anti-angiogenic agents or different checkpoint inhibitors. Combinations of TARE and systemic treatment are being investigated for synergistic effects due to a boosting of the immune response. However, a high hepatopulmonary shunt (HPS) fraction - abnormal passage of blood from the hepatic vasculature to the pulmonary circulation resulting from the formation of abnormal vasculature within the tumor - precludes some patients from receiving TARE due to the risk of non-target lung radiation. Here, we present a case in which treatment of a patient with atezolizumab and bevacizumab led to a significant reduction in HPS, enabling locoregional treatment of the tumor while the tumor did not respond to systemic treatment alone according to the mRECIST criteria. Case Presentation: Here, we report the case of a patient with intermediate stage HCC who received systemic treatment with atezolizumab and bevacizumab due to a high hepatopulmonary shunt fraction of 42% precluding him from treatment with radioembolization. Despite eventually showing tumor progression to systemic treatment based on clinical and radiological evaluation, the lung shunt fraction was markedly reduced by the systemic treatment to only 3.4%, enabling successful treatment of the tumor with radioembolization. Conclusion: The anti-angiogenic effects of bevacizumab may reduce HPS in patients with intermediate-stage HCC, thereby extending the utility of TARE. In patients who do not respond to systemic treatment and who are amenable to treatment with TARE due to tumor stage, repeated measurements of HPSF might be considered after treatment with bevacizumab.