Radioactive Microsphere Therapy: Expanding the continuum of care for patients with colorectal cancer

When a patient presents with metastatic liver tumors, our options as their treating physician are limited. Less than 10 percent of liver tumors can be surgically resected and tumors may recur after resection. Metastatic liver cancer is frequently fatal, and is the most common cause of death in patients with colorectal cancer.
Chemotherapy is the current standard of care and many new effective agents are now available. However, many patients have already undergone chemotherapy and their tumors are resistant, or have quit responding, to chemotherapy. Radiation therapy involving the liver has proven especially challenging because of the liver's low tolerance to radiation compared to tumor cells.
A recent significant advance in technology has enabled us to perform radiation therapy in the liver in a clever way. At Stanford University Medical Center, radioactive microsphere therapy is emerging as an effective treatment option for patients with unresectable colorectal liver metastases.
We are involved in ongoing treatment and research involving a procedure called Selective Internal Radiation Therapy (SIRT) or Radioembolization, which targets high doses of radiation to non-resectable liver tumors using radioactive microspheres.
The microscopic resin microspheres contain the radioactive substance yttrium 90, which emits beta radiation. The yttrium 90 microspheres we use are called SIR-Spheres® microspheres, made by Sirtex Medical in Australia. SIR-Spheres were FDA-approved in 2002 for the treatment of metastatic colorectal cancer in combination with hepatic arterial FUdR chemotherapy, although they are routinely used without the additional chemotherapy. A Canadian company is also producing a similar product, called Theraspheres(R).
The treatment is performed as an outpatient procedure in the Catheterization laboratory and requires the insertion of a catheter into the groin, similar to a heart catheterization. Under X-ray guidance, a very thin microcatheter is positioned in the hepatic artery, the blood vessel supplying blood to the liver tumors.
Taking advantage of the fact that most of the normal liver is supplied by a different blood vessel system, millions of yttrium 90 microspheres are released into the hepatic artery and the radioactive microspheres are selectively trapped by the bloodthirsty tumors. The microspheres emit beta radiation for several weeks, affecting only the areas immediately surrounding each sphere. The targeted nature of microsphere therapy enables us to deliver up to 40 times more radiation to the liver tumors than would be possible using conventional radiotherapy.
Patients typically go home three to six hours after the procedure, and the reported side effects are few; most patients experience fatigue and poor appetite for a period of one to two weeks. Depending on when the radioembolization is performed, median survival of patients can be as long as 29 months.1 Some patients can benefit from repeat treatments.
In the ongoing discussion regarding chemotherapy and radioembolization, many physicians assume it is an "either-or" approach. However in most cases, patients can resume chemotherapy two to four weeks after the procedure, and in special cases, can receive chemotherapy concurrently with the SIRT procedure. Several clinical trials are currently underway or planned, evaluating the optimal timing of radioembolization in combination with newer chemotherapy and molecular agents such as Avastin and Erbitux.
Stanford University Medical Center began using microsphere radiation therapy for metastatic colorectal cancer in June 2004, and has expanded the scope of cancers treated to include hepatoma, neuroendocrine, renal cell, cholangiocarcinoma and sarcoma.2 Theoretically, liver tumors metastasized from any primary tumor including lung, breast, pancreas, stomach, ovary or cervix can be treated, and we are investigating this "off-label" use of microspheres in liver tumors spread from cancers other than colon cancer.
As the cancer continuum evolves to include an even greater variety of treatment modalities, it is important for the medical team to work together to develop the best treatment plan for each patient. In most cases, it will take a combination and succession of therapies to manage tumors of the liver. Although a complete cure is exceedingly rare, by tailoring treatment for each individual patient, and offering state-of-the-art care, we are able to extend both the length and quality of people's lives.
Editor's Note: Mills-Peninsula Health Services in Burlingame, CA began offering microsphere therapy in late 2006 to patients in the Bay Area.
1Randomised Phase 2 Trial of SIR-Spheres plus Fluorouracil/Leucovorin Chemotherapy Versus Florouracil/Leucovorin Chemotherapy Alone in Advanced Colorectal Cancer, Van Hazel G, Blackwell A, Anderson J, Price D, Moroz P, Bower G, Cardaci G, and Gray B, Journal of Surgical Oncology 2004, vol. 88, pp. 78-85.
2Sirtex Medical Inc.'s SIR-Spheres(R) microspheres are indicated for the treatment of non-resectable metastatic colorectal cancer in combination with intra-arterial FUdR chemotherapy. Information regarding other disease states or agents in combination with this device that is presented in this article is different from the approved USA labeling for SIR-Spheres microspheres.

--By Daniel Sze, M.D. Ph.D., Associate Professor of Interventional Radiology, Stanford University Medical Center