BMC Cancer 2005, 5:132 http://www.biomedcentral.com/1471-2407/5/132 most third most common malignancy in the developed world [2]. Around fifty to sixty percent of these patients will develop liver metastases, and in approximately 20% of cases the liver is the only site of disease at death[3]. Sur- gical resection of all apparent disease is possible in selected patients, however for the majority of patients with metastatic CRC the standard approach remains sys- temic chemotherapy. Selective Internal Radiation (SIR) spheres (Sirtex Medical, Sydney, Australia) are a new radiotherapeutic treatment for liver metastases. These resin microspheres contain yttrium, a high energy beta-emitting isotope, and are embolised into the hepatic artery where they become lodged within the microvasculature of the tumour. The treatment is relatively selective as hepatic tumours derive their blood supply almost exclusively from the hepatic artery whereas normal liver parenchyma is supplied pre- dominantly by the portal circulation. Animal studies sug- gest that SIR spheres allow on average 200–300 Gy to be delivered to liver tumours [4]. In contrast the delivery of standard external beam radiation therapy to the whole liver is limited by the ability of the normal parenchyma to tolerate only 30–35 Gy, an insufficient dose to produce a significant anti-tumour effect [5]. Encouraging results have been reported following previ- ous studies of SIR spheres in metastatic colorectal cancer. In a series of 21 chemonaive patients with colorectal liver metastases who were randomised to receive intravenous 5FU alone or intravenous 5FU plus SIR spheres, the com- bination demonstrated a higher response rate and signifi- cantly improved progression free survival compared to chemotherapy alone [6]. In a larger study of 74 patients combining SIR-spheres with hepatic artery chemotherapy superior response rates and time to progression over treat- ment with chemotherapy alone were seen in patients with colorectal cancer [7]. With the exception of hepatocellular carcinoma[8] results in other tumour types have not been so encouraging [9]. We report here the first prospective series conducted to better define the efficacy and safety of SIR- spheres(Yttrium90) in patients with colorectal cancer and liver metastases that have previously received 5-FU based chemotherapy. No financial support was received from SIRTex for the purposes of this study. Methods Data for consecutive patients with metastatic colorectal cancer treated with Sirtex microspheres were collected prospectively across 3 Australian centres from Jan 2002 and March 2004. During this period of the time both oxaliplatin and irinotecan were not reimbursable in Aus- tralia as part of first-line therapy for patients with meta- static colorectal cancer outside of a clinical trial. These agents were available for patients that had progressed fol- lowing initial 5-FU based treatment. Patients were informed of the available evidence regard- ing SIR-spheres treatment. Patients that elected to proceed with treatment were informed that data would be col- lected prospectively as part of a research project. Toxicities and protocols were outlined in accordance with the man- ufacturer's guidelines and were common across all partic- ipating centres. Patients were considered eligible if they had liver metastases from colorectal cancer with histolog- ical confirmation of their primary tumour. All patients were required to have measurable disease within the liver. Extra-hepatic disease was allowed if the liver was the dom- inant site of disease. Patients with an expected survival of less than 3 months, documented brain metastases, or a poor performance sta- tus (ECOG >2) were excluded. Adequate hepatic, renal and liver function was required including a normal clot- ting profile, an albumin >30 g/L, bilirubin <20 umol/L and no evidence of liver decompensation such as ascites or portal hypertension was permitted. Patients with portal vein thrombosis were also excluded from this study. Previous treatment with chemotherapy was allowed pro- vided this had been more than 2 months prior to planned treatment with SIR-spheres. Patients received bolus 5FU chemotherapy concurrent with the SIR-spheres, as a radi- osensitiser, and subsequently in responding patients at the investigator's discretion. Pre treatment workup and disease evaluation All patients underwent a standard pre-treatment evalua- tion as per manufacturers guidelines. An hepatic angi- ogram was performed to define arterial anatomy prior to treatment and to permit a nuclear medicine scan with radio labeled Tc 99 m-MAA (macro-aggregated albumin) in order to exclude patients at high risk of lung (radiation pneumonitis) or GI toxicity (gastric/duodenal ulceration) due to hepato-systemic shunting or aberrant vasculature. The fraction of extra-hepatic shunting was determined for each patient as a percentage. Patients who had shunting of greater than 20% were excluded from the study. Shunting of between 12 and 20% resulted in a reduction in the dos- age of spheres delivered. The final dose of SIR-spheres administered in units of GBq was calculated according to each patient's body surface area and percentage of tumour involvement of liver (an assessment made by the radiolo- gist after viewing the baseline CT scan). Across the three participating centres, the workup and delivery of SIR spheres was performed by a total of four experienced interventional radiologists with two centres having all Page 2 of 6 (page number not for citation purposes)