Section outline

    • Required Reading File
    • Forum Discussion

      A 61-year-old man with metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis presents with worsening fatigue and right upper quadrant abdominal fullness. He maintains an ECOG performance status of 1.

      Imaging demonstrates an 8.8 cm infiltrative mass in the right hepatic lobe. The tumor invades the right portal vein branch (Vp3 thrombosis). Chest CT identifies four bilateral subcentimeter pulmonary nodules.

      Laboratory parameters:

      • Child-Pugh score: A5 (Bilirubin 1.0 mg/dL, Albumin 3.9 g/dL, INR 1.1)

      • Platelet count: 68,000/µL

      • Alpha-fetoprotein: 5,400 ng/mL

      • Serum creatinine: 0.9 mg/dL

      Upper endoscopy reveals large esophageal varices with red wale markings. The patient has not received endoscopic band ligation. His medical history includes moderate plaque psoriasis controlled with topical betamethasone.

      Discussion Questions

      1. Efficacy by Disease Etiology (IMbrave150 vs HIMALAYA)

        Exploratory analyses across major trial datasets indicate potential variation in immune checkpoint inhibitor efficacy based on viral versus non-viral disease etiology. How does his MASH-driven liver disease impact your confidence in dual immunotherapy or PD-L1/VEGF blockade compared to tyrosine kinase inhibitors?

      2. Managing Bleeding Hazard Against Tumor Progression

        The IMbrave150 protocol required endoscopic intervention for high-risk varices prior to starting atezolizumab plus bevacizumab. With Vp3 portal vein invasion present, delaying systemic therapy for two to four weeks following variceal ligation risks rapid liver failure from vessel occlusion. Do you proceed with endoscopic banding first, or do you pivot to a non-bevacizumab regimen like STRIDE to avoid treatment delay?

      3. Autoimmune Toxicity Risks with Checkpoint Blockade

        The STRIDE regimen from the HIMALAYA trial avoids anti-VEGF bleeding risks through single-dose tremelimumab and regular durvalumab. Considering his history of psoriasis, how do you weigh the risk of an autoimmune skin or systemic flare between dual CTLA-4/PD-L1 inhibition and single-agent PD-1 blockade based on CheckMate 459 data?

      4. Selecting Tyrosine Kinase Inhibitors in Extensive Vascular Disease

        If bleeding concerns disqualify bevacizumab and psoriasis excludes immunotherapy, you must select a TKI. The REFLECT trial established lenvatinib as non-inferior to sorafenib in overall survival while demonstrating higher objective response rates. Given that REFLECT excluded main trunk portal vein invasion (Vp4) but allowed Vp1-Vp3 disease, would you choose lenvatinib or sorafenib? What primary toxicities require monitoring during the first month of lenvatinib dosing?

      5. Second-Line Strategy Following First-Line TKI Failure

        If this patient receives first-line lenvatinib due to acute variceal risk, what specific trial evidence guides your selection for second-line therapy upon disease progression?