In a patient with unresectable, transplant‑ineligible hepatocellular carcinoma, preserved liver function (Child‑Pugh A or early B), limited tumor burden (up to three lesions ≤5 cm each or a single lesion ≤8 cm) and no main portal vein thrombosis, what are the eligibility criteria, required baseline work‑up (contrast‑enhanced MRI or multiphase CT, technetium‑99m macro‑aggregated albumin scan, liver function panel, ECOG performance status), procedural steps, post‑procedure monitoring, and contraindications for trans‑arterial radio‑embolization (TARE)?

Trans-Arterial Radioembolization (TARE) for Hepatocellular Carcinoma

TARE should be considered for your patient with unresectable, transplant-ineligible HCC when specific clinical scenarios exist: large solitary tumors (>6 cm), portal vein thrombosis (segmental or subsegmental), or after TACE failure (2-3 unsuccessful sessions), provided liver function remains Child-Pugh A or favorable B7 and ECOG performance status is 0-1. 1, 2, 3

Eligibility Criteria

Ideal Candidates

• Liver function: Child-Pugh class A is optimal; Child-Pugh B7 without ascites may be considered in highly selected cases 1, 3
• Tumor burden: Up to three lesions ≤5 cm each or single lesion ≤8 cm, though TARE shows particular advantage for larger tumors (>6 cm) compared to TACE 2, 3
• Performance status: ECOG 0-1 required 1, 3
• Portal vein status: No main portal vein thrombosis is acceptable; segmental or subsegmental portal vein thrombosis is actually an indication favoring TARE over TACE 1, 2, 3
• Hepatic reserve: Future liver remnant volume ≥40% of total liver volume receiving ≤30 Gy radiation dose 3

Specific Clinical Scenarios Favoring TARE Over TACE

• Large tumors: Single lesions >6 cm benefit more from TARE due to superior radiation penetration 2, 3
• Portal vein thrombosis: TARE is safer than TACE when segmental or subsegmental portal vein thrombosis exists 2, 3, 4
• TACE failure: After 2-3 unsuccessful TACE sessions showing no radiological response 2, 4
• Multifocal disease: Confined to liver with adequate hepatic reserve 2, 3

Absolute Contraindications

Do not proceed with TARE if any of the following exist: 1, 2, 3

• Decompensated cirrhosis (Child-Pugh C or decompensated Child-Pugh B8-9)
• Complete main portal vein occlusion
• ECOG performance status ≥2
• Small liver volume (<1.5 L) with inadequate functional hepatic reserve
• Bilirubin >2-3 mg/dL (unless segmental treatment possible)
• Extrahepatic disease with large-volume metastases
• Recent systemic therapy within 2 months
• Tumor involvement >50% of liver volume

Required Baseline Work-Up

Imaging Studies

• Contrast-enhanced multiphasic CT or MRI: Essential for tumor characterization, vascular anatomy assessment, and volumetric analysis 1, 2, 4
• Technetium-99m macro-aggregated albumin (MAA) scan: Mandatory to calculate lung shunt fraction and assess extrahepatic deposition risk 3
  • Lung shunt fraction must be <20% to proceed safely
  • Identifies aberrant arterial anatomy and potential non-target embolization

Laboratory Assessment

• Liver function panel: Total bilirubin, albumin, INR, AST, ALT to calculate Child-Pugh score and ALBI grade 1, 3
• Complete blood count: Assess for cytopenias suggesting portal hypertension
• Renal function: Creatinine clearance (contrast nephrotoxicity risk) 1
• Alpha-fetoprotein (AFP): Baseline tumor marker 1

Functional Assessment

• ECOG performance status: Must document 0-1 1, 3
• ALBI grade: Critical predictor of post-procedure hepatic decompensation and survival 3
• Volumetric analysis: Calculate total liver volume, tumor volume, and future liver remnant volume 3

Additional Evaluations

• Upper GI endoscopy: Within 6 months if portal hypertension present; treat varices before TARE 1
• Multidisciplinary tumor board review: Confirm unresectability and transplant ineligibility 1, 5

Procedural Steps

Pre-Procedure Planning (1-2 Weeks Before)

• Perform diagnostic angiography with MAA scan to map hepatic arterial anatomy 3
• Calculate personalized radiation dosimetry based on tumor volume, liver volume, and lung shunt fraction 3
• Prophylactic embolization of gastroduodenal and right gastric arteries if needed to prevent non-target embolization 3

Day of Procedure

• Selective or superselective catheterization of tumor-feeding arteries 2, 4
• Delivery of Yttrium-90 microspheres (resin or glass) via microcatheter 6
• Confirm adequate tumor coverage with post-delivery imaging 4

Technical Considerations

• Superselective approach preferred: Minimizes radiation to non-tumorous liver parenchyma 1, 4
• Lobar vs. segmental treatment: Depends on tumor distribution and hepatic reserve 3
• Avoid bilateral whole-liver treatment: Significantly increases risk of radiation-induced liver disease (REILD) 3

Post-Procedure Monitoring

Immediate Post-Procedure (0-48 Hours)

• Monitor for post-embolization syndrome: fever, abdominal pain, nausea (occurs in 20-55% of patients) 6
• Assess liver function tests: transient transaminase elevation expected 7
• Manage symptoms: antiemetics, analgesics, antipyretics 6

Early Follow-Up (4-8 Weeks)

• First imaging assessment: Contrast-enhanced CT or MRI at 4-6 weeks using mRECIST criteria 2, 4
• Monitor for REILD: Typically occurs 4-8 weeks post-procedure; presents with ascites, jaundice, elevated bilirubin without biliary obstruction 3
• Liver function panel: Assess Child-Pugh score and ALBI grade changes 3
• AFP level: Trend tumor marker response 1

Long-Term Monitoring

• Imaging every 2-3 months: Assess tumor response and detect new lesions 2, 4
• Late hepatotoxicity: Can occur up to 6 months post-TARE in some patients 3
• Time to progression: Median TTP approximately 5.5-14.4 months depending on tumor characteristics 6, 8

Criteria to Stop or Modify Treatment

• Progression to Child-Pugh B8 or higher: Indicates inadequate hepatic reserve for additional therapy 2, 4
• ECOG performance status decline to ≥2: No survival benefit from continued locoregional therapy 2
• Development of extrahepatic metastases: Transition to systemic therapy 1, 2

Expected Outcomes

Survival Data

• Intermediate-stage HCC (BCLC-B): 1-year OS 63%, 3-year OS 27% 6
• Advanced HCC with portal vein thrombosis (Child-Pugh A-B7): 1-year OS 37%, 3-year OS 13% 6
• Combination TARE followed by TACE: Median OS 36.8 months vs. 10.6 months for TARE alone in select patients 8

Tumor Response

• Mean tumor shrinkage: Approximately 24.5% in large tumors 9
• Complete necrosis: Achievable in select patients with personalized dosimetry 3
• Bridging to transplant: Effective for maintaining patients within Milan criteria 2, 9

Critical Pitfalls to Avoid

Technical Errors

• Inadequate MAA scan assessment: Failure to identify lung shunt >20% risks fatal radiation pneumonitis 3
• Non-selective catheterization: Increases radiation to non-tumorous liver and risk of REILD 1, 4
• Bilateral whole-liver treatment in single session: Dramatically increases hepatic decompensation risk 2, 3

Patient Selection Errors

• Treating Child-Pugh B8-9 or C patients: High risk of fatal hepatic decompensation 1, 3
• Ignoring ECOG status: Patients with ECOG ≥2 derive no survival benefit and experience worse quality of life 1, 2
• Proceeding with complete main portal vein occlusion: Absolute contraindication due to inadequate hepatic perfusion 1, 2

Post-Procedure Management Errors

• Delayed recognition of REILD: Monitor closely at 4-8 weeks; presents with ascites, jaundice, elevated bilirubin 3
• Continuing treatment despite progression: After 2-3 unsuccessful sessions, transition to systemic therapy rather than repeating TARE 2, 4
• Inadequate variceal screening: Patients with portal hypertension require endoscopy within 6 months and variceal treatment before TARE 1

Alternative Considerations

When TARE is not suitable, consider: 1

• TACE: Standard for intermediate-stage HCC without portal vein thrombosis, tumor burden <7 cm or <4 nodules
• Thermal ablation: For tumors <3 cm when technically feasible
• Stereotactic radiotherapy: When both TARE and TACE contraindicated
• Systemic therapy (atezolizumab + bevacizumab): First-line for advanced HCC with adequate liver function and no contraindications to immunotherapy or anti-VEGF therapy