The Clinical Value of Radioembolisation in the Treatment of Inoperable Liver Cancer

Laura E Moreno-Luna, James C Andrews, Lewis R Roberts
2008 European Oncology & Haematology  
Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third most common cause of death from cancer worldwide. 1 The incidence of HCC in the US is increasing because of the rise in the prevalence of hepatitis C virus infection. 2,3 HCC-related mortality is high because most cases are diagnosed at an advanced stage, when potentially curative therapies such as liver transplantation, surgical resection and local ablation are not feasible. 4-7 The majority of patients are
more » ... patients are therefore candidates for palliative therapies only. 8 Due to the capacity of liver cells to detoxify and excrete drugs, HCCs are relatively resistant to chemotherapy; in addition, the splenomegaly and cytopenias associated with cirrhosis with portal hypertension render patients prone to systemic chemotherapy-related toxicity. 9 Transarterial chemoembolisation (TACE) is a loco-regional therapy that delivers high doses of chemotherapy to HCCs through the hepatic artery, with limited systemic effect. TACE has been proved to improve survival of patients with unresectable HCC without portal vein thrombosis (PVT). [10] [11] [12] Recently, a number of devices for transarterial radioembolisation (TARE) have been tested for treatment of HCC in early-phase studies. This article will summarise the results thus far, with an emphasis on yttrium-90 ( 90 Y) radioactive glass microspheres, which are the only modality currently approved for use in the US. Theoretical Considerations The liver parenchyma is relatively sensitive to radiation, with a tolerance to external irradiation of approximately 30Gy. 13, 14 In contrast, HCCs are relatively resistant to radiation, requiring doses of 120Gy for tumoricidal effect. The liver is unable to tolerate the radiation doses required to achieve tumoricidal effects by standard external-beam radiation; therefore, whole-liver external-beam radiation therapy is of limited utility in the treatment of unresectable HCC. 15 Several studies have confirmed that focal radiation techniques employing a 3D approach instead of broad axial-plane techniques safely permit higher levels of radiation to targeted regions within the liver. 5,16 HCC tumours are highly vascular and receive almost all of their blood supply (95-100%) from the hepatic artery, in contrast to the normal liver parenchyma, which is primarily supplied by the portal vein (75-85%). 15 Consequently, delivery of therapy through hepatic artery branches preferentially affects HCC tumours and spares the surrounding liver parenchyma. Selective targeting of radionuclides to tumours has been shown to achieve radiation dose ratios (tumour to benign liver) of up to 25-30 to 1. 17 Portal vein occlusion is considered a relative contraindication to TACE. The high-specific-activity radioembolisation microspheres do not occlude a significant portion of the hepatic arterial vascular bed and can therefore be used in patients with portal vein thrombosis. 9 Different transarterial radionuclide therapies have been developed with the objective of achieving selective intraarterial delivery of radiotherapy, including radioactive iodine-131 ( 131 I), rhenium-188 ( 188 Re), 90 Y (resin or glass microspheres) 6,18-21 and others. 22 All of these treatments have been used to treat HCC via a selective transarterial approach as an alternative to TACE. In this article, we will review the devices, toxicities and results with use of the currently available radioembolic devices. Iodine-131-based Devices 131 I was the first radionuclide to have significant use as an intra-arterial therapy for HCC. 23-25 131 I is a γ-emitter with a relatively long half-life of 8.04 days and a maximum energy of 0.364MeV that achieves a mean tissue penetration of 0.4mm. 131 I is most frequently used by exchange with the iodine moiety of lipiodol, a preparation of iodised poppyseed oil (Lipiocis ® ). Arterially administered lipiodol leaks out of vascular spaces and localises in the tumour cell membrane and intracellular compartment. 26 Non-radioactive iodine is administered before treatment to saturate thyroid uptake and prevent the uptake of circulating radioisotope into the thyroid gland. 131 I-lipiodol has been used for treatment of unresectable HCCs, in the adjuvant setting after surgical resection and also prior to surgical resection or liver transplantation. Randomised controlled trials in the adjuvant setting have shown statistically significant decreases in recurrence rate and improvements in overall survival in patients receiving 131 I-lipiodol radioembolisation after surgical resection. 27,28 Presurgical administration has confirmed the ability of 131 I-lipiodol to produce partial and complete tumour necrosis of resected or explanted tumours. 29 Because it does not occlude arterial flow, 131 I-lipiodol radioembolisation has also been used in patients with unresectable HCC and portal vein thrombosis and has demonstrated significantly improved survival compared with best supportive care. 30 Tumour response rates after 131 I-lipiodol therapy range from 17 to 92%. 31 A number of other 131 I complexes have also been used, including radioimmunotherapy with 131 I antiferritin 32 and 131 I-anti-HAb18G/CD147 ( 131 I metuximab/licartin), which targets the human HCC-associated antigen HAb18G/
doi:10.17925/eoh.2008.04.2.66 fatcat:efqx5qdjyzadxmiq7rog3mtr6u