Heterogeneity of Treatment Effects of Adding Locoregional Therapies to Atezolizumab Plus Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma (ISMIO-026)

Inclusion Criteria:

• Age ≥18 years on the index date.
• Receipt of at least one dose each of atezolizumab and bevacizumab as part of the same first-line combination regimen, with an interval of ≤28 days between the first administrations of the two drugs.
• At least one intrahepatic lesion amenable to a protocol-specified LRT on the index date, with no absolute contraindication to Atezo+Bev or to all feasible LRTs.
• A clinical, radiologic, or pathologic diagnosis of uHCC on or before the index date; baseline EHS is permitted.
• Survival status or the date last known alive after the index date can be ascertained.
• No systemic therapy for HCC before the regimen initiation date.
• No LRT within 60 days before the index date or between baseline imaging and the index date; earlier prior LRTs are permitted provided that an untreated, measurable intrahepatic lesion remains.
• A technically adequate baseline contrast-enhanced CT/MRI examination and at least one untreated intrahepatic lesion that can be delineated and evaluated.
• Baseline ECOG performance status of 0-2.

Exclusion Criteria:

• Another primary malignancy requiring active systemic treatment on the index date, except for a malignancy that has been cured and has a low risk of recurrence.
• Participation on the index date in an interventional study that could affect treatment allocation or outcome assessment.
• Suitability for immediate curative resection or liver transplantation following multidisciplinary assessment.
• An absolute contraindication to Atezo+Bev or to all feasible LRTs.
• Active autoimmune disease or immunodeficiency requiring systemic immunosuppression or constituting a contraindication to atezolizumab.

Inadequately controlled high-risk esophageal/gastric varices, recent variceal bleeding, an uncorrected bleeding tendency, or clinically significant coagulopathy.

• Inability to determine the index date, primary treatment strategy, OS outcome/censoring date, or absence of a technically adequate baseline contrast-enhanced CT/MRI examination.