2 The procedure
2.1.2 Treatment of hepatic metastases depends on their extent and location. Treatment options include surgical resection, thermal ablation, chemotherapy, different types of arterial embolisation and external beam radiotherapy.
2.2.1 SIRT is used for patients with limited or no extrahepatic disease for the treatment of colorectal cancer liver metastases that are unsuitable for resection or ablation. It may be used alone or in combination with chemotherapy. It aims to deliver radiation directly into the metastases, minimising the risk of radiation damage to healthy surrounding tissues.
2.2.2 With the patient under local anaesthesia, radioactive microspheres that are designed to embolise into small vessels around the metastases are injected into branches of the hepatic artery, usually via a percutaneous femoral approach.
2.2.3 A nuclear medicine liver-to-lung shunt study is usually carried out before the procedure to assess the risk of radioactive microspheres causing lung damage. Radiographic imaging and selective coil embolisation of arteries to the stomach and duodenum are also commonly carried out.
2.2.4 SIRT may be repeated, depending on the response achieved.
Sections 2.3 and 2.4 describe efficacy and safety outcomes from the published literature that the Committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the overview.
2.3.1 In a randomised controlled trial (RCT) of 70 patients with non-resectable colorectal liver metastases, mean survival after treatment by SIRT plus hepatic artery chemotherapy or hepatic artery chemotherapy alone was 23.5 and 18.4 months respectively (p = 0.18). An RCT of 44 patients treated by SIRT plus systemic chemotherapy or systemic chemotherapy alone reported median overall survival of 10.0 and 7.3 months respectively (p = 0.80). Ten out of 23 patients in the control arm crossed over to SIRT at progression and this is likely to have confounded survival data. An RCT of 21 patients treated by SIRT plus systemic chemotherapy or systemic chemotherapy alone reported median survival of 29.4 months and 12.8 months respectively (hazard ratio 0.33, 95% confidence interval [CI] 0.12 to 0.91; p = 0.025).
2.3.2 The RCT of 70 patients reported better tumour response following SIRT plus hepatic artery chemotherapy than hepatic artery chemotherapy alone at minimum 3.5-year follow-up (p = 0.01). The RCT of 44 patients treated by SIRT plus systemic chemotherapy or systemic chemotherapy alone reported median 'time to liver progression' of 5.5 months and 2.1 months respectively (hazard ratio 0.38, 95% CI 0.20 to 0.72; p = 0.003).
2.3.3 Downstaging, which enabled potentially curative surgical resection, was reported in 2 of 50 (4%) patients treated by SIRT in a case series.
2.3.4 In the case series of 50 patients treated by SIRT mean anxiety levels were significantly reduced (compared with pre-treatment levels) in 14 patients who were questioned 6 weeks after treatment (p < 0.01).
2.3.5 The Specialist Advisers listed key efficacy outcomes as tumour response rates, survival and downstaging to allow surgery, or chemoresponsiveness.
2.4.1 In a case series of 100 patients, 1 patient died from radiation hepatitis 9 weeks after SIRT, and another patient died from acute pancreatitis with peptic ulceration.
2.4.2 The RCT of 44 patients treated by SIRT plus systemic chemotherapy or systemic chemotherapy alone reported grade 3 toxicity in 5% (1/21) and 27% (6/22) of patients respectively (p = 0.10). The RCT of 70 patients reported that there was no significant difference between the groups (SIRT plus hepatic artery chemotherapy or hepatic artery chemotherapy alone) in the total number of grade 3 or 4 toxicity adverse events.
2.4.3 Liver abscess requiring drainage was reported in 9% (1/11) of patients (timing not stated) in the systemic chemotherapy plus SIRT arm of the RCT of 21 patients.
2.4.4 A case series of 140 patients treated by SIRT reported that radiation-induced liver dysfunction occurred in 2% (3/140) of patients (median follow-up 9 months).
2.4.5 The Specialist Advisers listed adverse events as pain, vomiting, anorexia, fatigue, portal hypertension, and impaired delivery of radioembolic material after antiangiogenic agent use. They considered theoretical adverse events to include pneumonitis, gastrointestinal haemorrhage or ulceration, cholecystitis, biliary strictures, pancreatitis, radiation dermatitis and radiation hepatitis.
2.5.1 The Committee noted that observational studies report large numbers of patients previously treated by chemotherapy who have received SIRT, but that the number of these patients reported in comparative trials was very small. The Committee considered quality of life after any kind of treatment to be of great importance for these patients. These considerations formed the basis of the recommendations for further research.
2.5.2 The Committee considered that SIRT may be a potential option for patients with limited extra-hepatic disease for whom chemotherapy has failed.
2.5.3 The Committee noted that there have been a small number of reports of SIRT downstaging colorectal metastases to the extent that treatment by resection or ablation became possible. However, it considered that there was insufficient evidence to comment on the potential use of the procedure with this intent.
2.5.4 The Committee also considered a number of patient commentary questionnaires from patients who described benefits from SIRT.