FROM THE SIR RESIDENTS AND FELLOWS SECTION (RFS)
Teaching Topic: Yttrium-90 Radioembolization as Salvage Treatment following Chemoembolization for Hepatocellular Carcinoma
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A recent article in JVIR retrospectively evaluated the safety and efficacy of Yttrium-90 (90Y) transarterial radioembolization in patients who have undergone TACE for HCC at a single institution. 40 patients with multifocal disease were identified that had undergone a Tc-99m mapping study. The patients had a median age of 61 years, with various tumor stages and classes, with a median tumor diameter of 4.2 cm (range 1-11.6 cm). There were 28 (70%) Child-Pugh class A patients and 12 (30%) class B. 106 prior TACE procedures were performed on this group of patients, using drug eluting embolic agents and oiled based agents; 29 underwent TARE, with 11 excluded after their mapping study indicated that Y90 would be contraindicated. Follow up imaging was done 1 month and 3 months there-after, with tumor response assessed by tumor size. Most common grade ≥ 3 toxicities were fatigue and biochemical alterations. Of 27 patients treated with TARE with follow-up, 60% had partial or complete response and only 33% had progression of disease. Median progression-free survival and overall survival were 90 days and 257 days. Median follow-up was 266 days. The authors conclude that TARE may be considered for salvage therapy in patients after TACE with a median overall survival comparable to other large series using TARE for HCC.
What were some limiting factors and important timelines to mention regarding this study?
Salvage therapy via TACE may be limited by tumor progression, portal vein invasion, and technical inability to deliver a chemoembolic agent secondary to arterial changes resulting from prior chemoembolization, poor patient tolerance, or progression of underlying liver disease. In the event of exhaustion of chemoembolization options, TARE could be considered as a salvage treatment.
After TACE, hepatic arterial recanalization is known to occur overtime, although variable due to which chemoembolic agent was used during TACE. This study suggests that patients who were mapped less than 90 days and over 365 days from the most recent TACE were more feasible for TARE than those who fell in the time between.
Other limitations included a small sample of patients not having adequate hepatic arterial blood flow due to attenuation in patency, as a result >4 TACE procedures in the past. These patients did not undergo TARE. (Please see below Figure A)
A recent article in JVIR retrospectively evaluated the safety and efficacy of Yttrium-90 (90Y) transarterial radioembolization in patients who have undergone TACE for HCC at a single institution. 40 patients with multifocal disease were identified that had undergone a Tc-99m mapping study. The patients had a median age of 61 years, with various tumor stages and classes, with a median tumor diameter of 4.2 cm (range 1-11.6 cm). There were 28 (70%) Child-Pugh class A patients and 12 (30%) class B. 106 prior TACE procedures were performed on this group of patients, using drug eluting embolic agents and oiled based agents; 29 underwent TARE, with 11 excluded after their mapping study indicated that Y90 would be contraindicated. Follow up imaging was done 1 month and 3 months there-after, with tumor response assessed by tumor size. Most common grade ≥ 3 toxicities were fatigue and biochemical alterations. Of 27 patients treated with TARE with follow-up, 60% had partial or complete response and only 33% had progression of disease. Median progression-free survival and overall survival were 90 days and 257 days. Median follow-up was 266 days. The authors conclude that TARE may be considered for salvage therapy in patients after TACE with a median overall survival comparable to other large series using TARE for HCC.
Clinical Pearls
What were some limiting factors and important timelines to mention regarding this study?
Salvage therapy via TACE may be limited by tumor progression, portal vein invasion, and technical inability to deliver a chemoembolic agent secondary to arterial changes resulting from prior chemoembolization, poor patient tolerance, or progression of underlying liver disease. In the event of exhaustion of chemoembolization options, TARE could be considered as a salvage treatment.
After TACE, hepatic arterial recanalization is known to occur overtime, although variable due to which chemoembolic agent was used during TACE. This study suggests that patients who were mapped less than 90 days and over 365 days from the most recent TACE were more feasible for TARE than those who fell in the time between.
Other limitations included a small sample of patients not having adequate hepatic arterial blood flow due to attenuation in patency, as a result >4 TACE procedures in the past. These patients did not undergo TARE. (Please see below Figure A)
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| Figure A: Mapping hepatic arteriogram in a 61-year-old man with HCC and a history of multiple hepatic chemoembolization procedures. Vague tumor hypervascularity (arrow) is seen in the superior aspect of the right lobe. There is marked attenuation of the distal hepatic arteries. The patient was deemed not to be a candidate for radioembolization because of the condition of the hepatic |
Further, retrospective investigation on its own is a limitation that may be clinically significant. The TARE procedure technique was consistent, however, the differences in TACE technique may mount to changes in the results, given their effects on arterial vasculature in some patients. This heterogeneity remains a major obstacle in all chemoembolization studies. Also, after mapping, the decision to proceed to TARE was left up to the Interventional Radiologist.
Questions to Consider
Besides post TACE salvage therapy for HCC with 90Y, what has TARE commonly been used to treat?Palliative treatment of non-resectable metastatic disease to the liver, usually colorectal has become popular using 90Y-labeled glass or resin microspheres (TheraSphere and SIR-Sphere) in the last several years. The benefits of this technique include more precise targeting of tumor volumes, decreases side effects and morbidity, and decreased radiation of normal tissues. Microsphere sizes vary from 20 to 60 microns in diameter and is delivered via an angiographic catheter into the hepatic artery. Treatment activity localizes in the capillary bed of the hypervascular tumor and, to a lesser extent, in the normal parenchyma. Radiation dose diameter is about 2.4mm, with a typical activity of about 40-70mCi.
What are patient assessment measures to be taken prior and following to 90Y treatment?
Patient assessment includes issues related to tumor resectibility, disease extent, extrahepatic involvement, hepatic vascular anatomy, AV shunting, liver and kidney function and the general health of the patient.
Imaging workup begins with angiographic evaluation of abdominal aorta, celiac access, SMA and hepatic arteriograms to identify anatomy, followed by embolization of the Gastroduodenal artery and sometimes, the Right Gastric Artery.
Before 90Y microsphere delivery, during the mapping portion of the procedure, catheter directed 99mTc macroaggregated albumin infusion into the hepatic artery followed by nuclear medicine imaging is performed to rule out hepatopulmonary shunting (>20%), which could cause radiation pneumonitis. Other possible shunts include those to the stomach, gallbladder and the duodenum.
Patients may head back home after the procedures without any special instructions for linens and clothing, but a small amount of activity could be present in the urine. As a result, for the first immediate 24 hours, a toilet should be used and flushed twice. Patient should have short term follow up imaging (usually 3 months) after treatment.
Additional reading:
Gaba RC. Plannng arteriography for yttrium-90 microsphere radioembolization. Semin Intervent Radiol 2015; 32: 428-438.
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Lewandowski RJ, Salem R. Yttrium-90 radioembolization of hepatocellular carcinoma and metastatic disease of the liver. Semin Intervent Radiol 2006; 23: 64-72.
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Post author:
Ali Alikhani, MD
Diagnostic Radiology Resident, PGY-4
University of Tennessee Methodist Healthcare
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