Selective internal radiation therapy with 90yttrium microspheres for extensive colorectal liver metastases

Increasing attention has been given to treatments for colorectal liver metastases ever since hepatic resection was established as being worthwhile. Given the high proportion of patients who die of colorectal cancer with liver-only disease, it seems appropriate to be developing and investigating methods of local liver tumor ablation. Selective internal radiation therapy (SIRT) is a relatively new, not widely used, modality suitable for use even in patients with extensive liver involvement. Fifty patients with advanced, nonresectable, colorectal liver metastases were treated with SIRT between February 1997 and June 1999. Estimated liver involvement was less than 25% in 30 patients, 25% to 50% in 13, and greater than 50% in seven. A single dose of between 2.0 and 3.0 GBq of 90yttrium microspheres was injected into the hepatic artery via a subcutaneous port and followed at 4-week intervals by regional chemotherapy with 5-fluorouracil. SIRT was well tolerated with no treatment-related mortality, although some treatment-related morbidity did occur including a 12% incidence of duodenal ulceration. Responses to SIRT were assessed by serial carcinoembryonic antigen (CEA) measurements and CT scans. Median CEA values 1 and 2 months after SIRT (expressed as percentage of initial CEA) were 19 and 13, respectively. Patients were assigned to one of two groups based on whether or not extrahepatic disease (EHD) developed within 6 months of SIRT. Median survival from SIRT for group 1 (EHD) (n = 26) was 6.9 months (range 1.3 to 18.8 months) and estimated survival +/- standard error at 6, 12, and 18 months was 57.7 +/- 3.8%, 23.1 +/- 4.8%, and 0%, respectively. For group 2 (no EHD) (n = 24), median survival was 17.5 months (range 1.0 to 30.3 months) with estimated survival at 6, 12, 18, 24, and 30 months of 79.2 +/- 2.9%, 66.7 +/- 3.6%, 55.9 +/- 3.3%, 25.2 +/- 4.4%, and 16.8 +/- 5.0%, respectively. This difference is statistically significant by log-rank test (P < 0.010). SIRT is a highly effective and well-tolerated regional treatment for extensive colorectal liver metastases. Tumor marker data suggest that substantial destruction of liver tumors can be achieved in more than 90% of patients by a single treatment. Survival times, particularly for those who do not develop extrahepatic metastases for some time, appear to be extended. SIRT warrants further use and investigation in patients with advanced colorectal liver metastases.