Original PaperA retrospective analysis of selective internal radiation therapy (SIRT) with yttrium-90 microspheres in patients with unresectable hepatic malignancies
Introduction
Selective internal radiation therapy (SIRT) is a form of radio-embolization of the liver. This involves the intra-arterial administration of microspheres implanted with the radioisotope yttrium-90 (Y-90), a beta-emitter. This treatment is used in patients with unresectable liver malignancies, either primary in origin or metastatic.1
SIRT is a relatively new treatment, entering clinical practice in the 1990s in Australasia. The procedure was approved a few years later in the USA. In Europe, the treatment has been licensed for use since 2003. In recent years the procedure has been used more frequently. Now, many centres worldwide are using radio-embolization with Y-90, either alone or alongside other treatments, in treating both primary and metastatic hepatic malignancies.1
In hepatic malignancies, the favoured treatment, where possible, is surgical resection of the tumour.2 This is a potentially curative treatment.3 Unfortunately, only around 10–20% of patients with hepatic malignancy will qualify for resection.4, 5, 6 In those who do undergo surgical resection, a published 5 year survival of 25–40% is reported.3
In most patients, systemic chemotherapy has been the chosen treatment for hepatic metastases, especially in those with advanced disease. A large study using some of the newer chemotherapy regimens, such as FOLFOX (a chemotherapy regimen combining folinic acid, flurouracil, and oxaliplatin), has reported response rates of approximately 45%.7 However, these treatments are not usually curative, and almost all patients eventually develop resistance to the drugs. In patients who have unresectable hepatic lesions and have developed chemotherapy resistance, or in those who can no longer tolerate chemotherapy, radiation of their tumour may be their only remaining hope of further survival.8
External beam radiation has major limitations in the treatment of hepatic metastases, due to the sensitivity of the hepatic parenchyma to radiation. Normal hepatic tissue can only tolerate radiation levels of around 30–35 Gy.9 The tumourcidal dose is around 120 Gy.6 SIRT allows up to 200–300 Gy to be delivered to the tumour, with little of this radiation exposure reaching the normal parenchyma.9
The basis of SIRT is related to the dual hepatic blood supply. The hepatic artery supplies 80–100% of blood to hepatic tumours greater than 3 mm in size. Normal hepatic tissue derives approximately 80% of its blood supply from the portal venous system and only 20% from the hepatic arteries. As a result, the majority of yttrium beads lodge within the tumours, while limiting radiation to normal parenchyma.8, 9
Radiation-induced liver disease (RILD) can produce abnormal liver enzyme activity, as well as neutropenia and coagulation defects. Later fibrosis, pseudocirrhosis, jaundice, and ascites can develop, and the abnormal enzyme activity may become permanent. Less commonly, radiation hepatitis and veno-occlusive disease may also occur.8
Of all metastatic cancers, SIRT is especially effective in treating patients with liver metastases from colorectal cancer. Half of all patients with colorectal cancer will develop hepatic metastases. Colorectal cancer metastases tend to remain confined to the liver, not spreading to other areas of the body, whereas in other primary cancers the metastases tend to be more widespread.10 Therefore, colorectal hepatic metastases respond well to local treatments, such as SIRT, compared with other types of primary carcinoma.11
Potential complications following SIRT are primarily due to radiation exposure to the liver or other organs. This may cause pancreatitis, gastrointestinal ulcers, cholecystitis, radiation pneumonitis, and radiation hepatitis.12 Meticulous pre-treatment angiography and prophylactic coil embolization of all non-hepatic vessels arising from the target arteries is performed during the work-up procedure. Following this, pre-treatment 99mtechnetium macro-aggregated albumin (MAA) scintigraphy is performed. This simulates therapy as the catheter is positioned in the intended therapy position. The MAA particles are very similar in size to the Y-90 microspheres, which enables estimation of extra-hepatic shunting of the microspheres, as well as indicating intra-hepatic distribution of the 99mtechnetium. An estimated lung shunt of greater than 13% indicates that the patient may be at risk of radiation pneumonitis, and SIRT treatment should be reconsidered.9, 13
Published literature comparing SIRT plus chemotherapy to chemotherapy alone has demonstrated improved response rates and survival in the combination group.4, 6, 9, 11, 14, 15, 16, 17, 18, 19, 20 However, as yet, there is very little literature regarding SIRT in the UK. The aim of the present study was to evaluate the safety and efficacy of SIRT in the initial 12 patients treated at a single UK institution.
Section snippets
Materials and methods
The initial 12 patients selected for SIRT therapy on an intention-to-treat basis between September 2005 and May 2008 were retrospectively audited. Five patients were male and seven female. One female patient was rejected for treatment following her diagnostic angiography, due to complex hepatic anatomy, early in our experience. The other 11 patients received 13 SIRT therapies approximately 2 weeks after work-up procedures.
Results
Twelve patients underwent SIRT work-up angiography on an intention-to-treat basis between 21/09/2005 and 07/05/2008. They all had advanced disease and had previously received multiple prior courses of chemotherapy. One patient was unable to receive Y-90 due to complex vascular anatomy. This was our third patient who had a replaced left hepatic artery arising from the left gastric artery as well as complex anastamoses between the superior mesenteric artery and celiac axis. In view of our
Discussion
SIRT is an effective treatment for patients with unresectable hepatic malignancies. The literature appears to demonstrate efficacy and safety, but this is a relatively new and evolving therapy. It is time-consuming and technically demanding from an interventional radiology viewpoint, is relatively expensive, and, due to the high radiation dose delivered, has the potential to produce catastrophic complications.
The present study retrospectively analysed patients treated with SIRT at a single
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Preface
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Cited by (9)
Update on the optimal management of patients with colorectal liver metastases
2012, Critical Reviews in Oncology/HematologyCitation Excerpt :Median survival was 10.5 months for responders compared with only 4.5 months for non-responders. Comparable results have been reported in smaller cohorts that received SIRT as salvage therapy, with median OS ranging from 6.9 months to 11.6 months [44–47]. The feasibility of administering SIRT in conjunction with first-line chemotherapy was evaluated in a phase I trial involving 20 patients with CLM, of whom seven (35%) had liver-only metastases [48].
A descriptive analysis of the characteristics, treatment response and prognosis of hepatic dominant solid tumors undergoing selective internal radiation therapy (SIRT)
2022, Journal of Gastrointestinal OncologyMechanisms of inflammatory responses to radiation and normal tissues toxicity: clinical implications
2018, International Journal of Radiation BiologyNew Developments in Interventional Oncology: Liver Metastases from Colorectal Cancer
2016, Cancer Journal (United States)Effects of Yttrium-90 selective internal radiation therapy on non-conventional liver tumors
2015, World Journal of GastroenterologyRandomized Comparison of Selective Internal Radiotherapy (SIRT) Versus Drug-Eluting Bead Transarterial Chemoembolization (DEB-TACE) for the Treatment of Hepatocellular Carcinoma
2015, CardioVascular and Interventional Radiology