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The Role of Transarterial Radioembolization (TARE) in the Management of Hepatocelllar Carcinoma

Raj Ayyagari M.D.Assistant Professor of RadiologySection of Interventional RadiologyYale University School of Medicineraj.ayyagari@yale.edu

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Disclosures

• I do not have any financial interest or other relationship with the manufacturers of any products or providers of services I intend to discuss.

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Overview

• TARE Treatment Rationale

• Patient selection

• Technique

• Dosimetry

• Side Effects, Complications

• Clinical OutcomesWang EA, Broadwell SR, Bellavia RJ, Stein JP. J Gastrointest Oncol. 2017;8(2):266-278.

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TARE Treatment Rationale

• Transarterial radioembolization (TARE) is the hepatic intra-arterial injection of the radioisotope Yttrium-90to treat unresectable HCC.

• Yttrium-90 , a β-emitter with a ½-life of 64.2h and tissue penetration of 2.5-11 mm, is incorporated into glass (TheraSphere) or resin (SIR-Spheres) microspheres 20-60µm in diameter.

• By delivering an internal radiation source, TARE is a form of brachytherapy. Allows safe administration of therapeutically high radiation doses (up to 150 Gy) with lower risk of radiation-induced liver damage than external beam radiation (at 35-40 Gy).

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TARE Treatment Rationale

• High tumoricidal doses achieved by preferential deposit of particles in tumor due to differential perfusion.

• Treatments can be…– Whole liver (higher risk)– Lobar– Segmental (“Radiation

Segmentectomy”)– Sequential– Repeated?

SIRTex, Incorporated

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Patient Selection for TARE• Multifactoral assessment involving disease burden,

biochemical profile, and performance status.

• Unresectable, with large majority of tumor burden (if not all of it) in the liver, with <70% of the liver involved.

• Adequate functional liver reserve needed: total bilirubin <2 mg/dL, albumin >3 g/dL, and a normal INR.

• ECOG performance status score of 0-1, maybe 2.

• Extreme caution when treating patients with ampulla of Vater manipulations due to increased risk of liver abscess.

• Portal vein patency not required, and in fact tumoralportal thrombus cannot be treated any other way.

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TARE Technique

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TARE Technique

• Outpatient procedure involving an initial mapping mesenteric angiogram combined with a liver-lung shunt scan, followed by dose planning and a subsequent angiographic treatment procedure.

• If radioactive particles embolize anywhere but the targeted liver (via shunts, collaterals, reflux)…– Lungs: Radiation pneumonitis– Stomach/Bowel: Ulcers,

bleeding, perforation– Can be DEVASTATING.

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TARE Technique

• Mapping mesenteric angiogram goals:

– embolize collaterals (GDA, right gastric artery)…hepatic arterial variants are common!

– evaluate arterial anatomy to plan catheter placement

– obtain liver lobar/segmental/tumoral volumes…needed for dosimetry.

– inject ~4 mCi technetium-99m MAA test dose…arteriovenous shunting can be extensive!

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TARE Technique

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TARE Technique

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TARE Dosimetry

• Lobar or segmental liver volumes are calculated using diagnostic MRI/CT, axial SPECT-CT, or even better, cone-beam CTA images.

• Liver tumor volumes are calculated using a diagnostic MRI/CT.

• BSA is calculated using patient height and weight.• Lung shunt fraction is calculated by a nuclear medicine

scan that measures the amount of 99mTc-MAA that gets to the lungs.

• Treatment Dose calculation method differs based on whether glass TheraSpheres (2500 Bq/sphere) or resin SIR-Spheres (50 Bq/sphere) are being used.

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TARE Dosimetry

• TheraSpheres:

Activity = Absorbed Dose (Gy) x Mass of Liver50 x (1-%LSF/100) x (1-%R/100)

Target delivered activity is typically 80-150 Gy

• SIR-Spheres:

Activity = BSA – 0.2 + %Tumor Involvement100

LSF <10% = no dose reduction; LSF 10-15% = 20% reduction; LSF 15-20% = 40% reduction

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TARE Side Effects, Complications

SIDE EFFECTS:• Fatigue – 50-60% patients in first 1-2 weeks after.• Low grade abdominal pain, nausea/vomiting – 20%.

COMPLICATIONS:• Radiation-induced GI ulcers often refractory to

conservative management.• Biliary complications (10%): dyskinesia, cholecystitis

(2.7%), stricture (2.4%), necrosis (3.9%), biloma (1%).• Radiation-induced liver disease – sinusoidal congestion,

venous occlusion, hepatic fibrosis; 4-8 weeks after; 4-7%, but in a series including liver metastatic lesions previously treated with chemotherapy; no predictive model for RILD.

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TARE Clinical Outcomes

• 1-year survival rates of untreated HCC patients are ~50% among intermediate stage (BCLC-B) patients and ~25% among advanced stage (BCLC-C) patients.

• Salem et al reported TARE results in 291 intermediate and advanced stage patients. Response rates were 42% (WHO) and 57% (EASL). TTP was 7.9 mo. CP-A patients had median survival of 17.2 mo, CP-B 7.7 mo, and CP-B with PVT 5.6 mo.

• Hilgard et al validated these results in 108 patients, and showed outcomes equivalent to cTACE and DEB-TACE.

• A 325 patient study by Sangro et al showed TARE patients to have median survival of 24.4 mo (BCLC-A), 16.9 mo (BCLC-B), and 10.0 mo (BCLC-C).

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TARE Clinical Outcomes

• As yet, no RCT comparing TARE and TACE in HCC.

• Salem et al’s “comparative effectiveness report” of a 245 patient cohort (123 TARE, 122 cTACE) described adverse events, toxicities, repsonse rates, and TTP to be improved in TARE, with no difference in overall survival.

• TARE has also been shown to superior favorable rate of down-staging HCC patients to transplantation.

• TARE also seems to cause less hepatotoxicity than TACE in patients with a TIPS in place, likely due to the minimal embolic effect of TARE.

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THANK YOU!

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Raj.Ayyagari@yale.eduCell: 206-853-0197