Comparison of SBRT and SIRT With Combination IO for Locally-advanced, Unresectable HCCs (BIIRTH)

One dose of TACE would be performed as per standardized procedure at 21-35 days preceding SBRT. Celiac and superior mesenteric arterial and porto-venogram would be performed to exclude main portal vein occlusion and to delineate the size(s) and number(s) of tumour nodule(s). Supra-selective cannulation of the supplying tumour artery would follow. The 1:1 lipiodol-cisplatin emulsion prepared by pumping would be slowly injected under fluoroscopic guidance according to the tumour size and arterial blood flow.

Patients are immobilized with customized device and abdominal compression or active breathing control. Four-dimensional computed tomography (4D-CT) was phase-sorted into 10 image-sets. A radiation dose of 27.5-50.0 Gy in five fractions, delivered in alternate days, is allowed. The prescription dose is individualized based on normal tissue constraints. This should be based on delivering a maximal tumoricidal dose while respecting the tolerance dose of neighbouring organs-at-risk. SBRT is delivered by dynamic conformal arc therapy, intensity-modulated RT, or volumetric modulated arc RT.

Patients undergo intrahepatic arterial Y90-radioembolisation (TheraSphere glass microspheres; MDS Nordion, Ottawa, Canada or SIR-Spheres, Sirtex Medical Pty Limited; St. Leonards, NSW, Australia). The administered activity of Y90-glass microspheres was determined by the nuclear medicine physician, medical physicist, radiologist and clinical oncologist using the artery-specific partition model within the limits of radiation safety, taking into account treatment variables including patient's body surface area, tumour-to-normal liver ratio, and liver tumour size. Where possible, personalized dosimetry using the partition model was the default methodology to facilitate selective administration of Y90-radioembolisation avoiding toxicities to the normal liver parenchyma.

Patients will start Atezolizumab-bevacizumab 14days upon completion of SBRT or SIRT. Atezolizumab, if given, is administered via IV infusion at a fixed dose of 1200mg, together with Bevacizumab (start 28days after SBRT/SIRT) via IV infusion at a fixed dose of 15mg/kg, on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator, or after curative surgical intervention is performed with no evidence of residual disease. Patients who transiently or permanently discontinued either atezolizumab or bevacizumab due to an adverse event are allowed to continue with single-agent therapy provided there is ongoing clinical benefit as determined by the investigator.