Cancer Treatment Today

SIRT — a therapy that consists of millions of microscopic, radioactive glass microspheres (20-30 microns diameter) — is infused into the arteries that feed inoperable liver tumors or metastatic cancer to the liver, bathing the malignancy in high levels of extremely localized radiation. In some studies of highly selected patients the response rates and stabilization rates ranged between 20-40 percent. Selective internal radiation therapy (SIRT) is used to treat non-resectable hepatic metastases secondary to colorectal cancer, usually in combination with hepatic arterial chemotherapy. The standard method of treatment for patients with liver metastases from colorectal cancer is surgical resection, but fewer than 10% of patients are suitable for operation. For patients with non-resectable hepatic metastases, treatment options include systematic chemotherapy, radiotherapy, cryotherapy, alcohol injection and laser photocoagulation. Radioactive spheres are injected using a syringe into the hepatic artery via a trans-femoral catheter or a permanently implanted port with a catheter to the hepatic artery. Currently 2 commercial forms of yttrium-90 microspheres are available: TheraSpheres® (Theragenics;Atlanta, GA) and SIR-Spheres® (Sirtex Medical Limited; Lake Forest, IL). Non-commercial forms are used mostly outside the United States. Note also that the U.S. Food and Drug Administration (FDA) granted a premarket approval of SIR-Spheres®, for use in combination with 5-floxuridine (5-FUDR) chemotherapyby HAI, to treat unresectable hepatic metastases from colorectal cancer. SIRT using SIR-Spheres microspheres is approved for use in Australia, New Zealand, the United States of America. Microspheres are taken up by the microvasculature within the liver.

The most recent evidence comes from the the SIRFLOX study. The addition of selective internal radiation therapy (SIRT), using Y-90 resin microspheres, to FOLFOX-based first-line chemotherapy in patients with metastatic colorectal cancer (mCRC) and liver-dominant metastases did not improve overall progression-free survival (PFS). It achieved a 7,9 month improvement in median PFS in the liver, representing a 31% reduction in risk of disease progression in the liver with no negative impact on duration of systemic therapy. The toxicities were acceptable and as predicted. The results from the SIRFLOX study were presented at the 2015 ASCO Annual Meeting.

The NCCN Guidelines (Version 3.2015) on Colon Cancer states: “Some institutions
use arterially directed embolization using yttrium-90 microspheres in select patients
with chemotherapy resistant/refractory disease, (not first line) without obvious systemic disease, and with predominant hepatic metastases (category 3)”. Category 3 is based on any
level of evidence, there is major NCCN disagreement that the intervention is
appropriate).

Gibbs P, Heinemann V, Sharma N, et al. SIRFLOX: Randomized phase III trial comparing first-line mFOLFOX6 ± bevacizumab (bev) versus mFOLFOX6 + selective internal radiation therapy (SIRT) ± bev in patients (pts) with metastatic colorectal cancer (mCRC). Presented at 2015 ASCO Annual Meeting; J Clin Oncol 2015; 33 (Suppl): Abs 3502.

Michl M, Haug AR, Jakobs TF, Paprottka P, Hoffmann RT, Bartenstein P, Boeck S, Haas M, Laubender RP, Heinemann V. Radioembolization with Yttrium-90 microspheres (SIRT) in pancreatic cancer patients with liver metastases: efficacy, safety and prognostic factors. Oncology. 2014;86(1):24-32.

Gary W. Nace et al, Yttrium-90 Radioembolization for Colorectal Cancer Liver Metastases: A Single Institution Experience International Journal of Surgical Oncology Volume 2011 (2011), Article ID 571261

D. L. Bartlett, J. Berlin, G. Y. Lauwers, W. A. Messersmith, N. J. Petrelli, and A. P. Venook
Chemotherapy and Regional Therapy of Hepatic Colorectal Metastases: Expert Consensus Statement
Ann. Surg. Oncol., October 1, 2006; 13(10): 1284 – 1292.