Selective internal radiation therapy
Selective internal radiation therapy (SIRT) is a form of radiation therapy used in interventional radiology to treat cancer. It is generally for selected patients with unresectable cancers, those that cannot be treated surgically, especially hepatic cell carcinoma or metastasis to the liver. The treatment involves injecting tiny microspheres of radioactive material into the arteries that supply the tumor. Because this treatment combines radiotherapy with embolization, it is also called radioembolization. The chemotherapeutic analogue (combining chemotherapy with embolization) is called chemoembolization, of which transcatheter arterial chemoembolization is the usual form.
Radiation therapy is used to kill cancer cells; however, normal cells are also damaged in the process. Currently, therapeutic doses of radiation can be targeted to tumors with great accuracy using linear accelerators (see radiation oncology); however, the normal liver tissue is very sensitive to external beam radiotherapy. Fortunately, malignancies (including primary and metastatic liver cancers) are often hypervascular; tumor blood supplies are often increased compared to those of normal tissue. Furthermore, the liver has a dual blood supply, receiving blood from both the hepatic artery and the portal vein. Hepatic malignancies derive most of their blood supply from the hepatic artery; whereas the normal liver derives most of its blood supply from the portal vein. Therefore, delivery of radioembolic particles through the branch of the hepatic artery supplying a tumor will preferentially lead to deposition of the particles in the tumor, while sparing normal liver from harmful side effects.
Patients who are candidates for radioembolization include those with:
- 1) unresectable primary liver cancer or metastatic cancer (colorectal cancer, neuroendocrine tumor )
- 2) liver-dominant tumor burden
- 3) life expectancy of at least 3 months
A phase III trial (SIRT versus sorafenib) is in progress.
Y-90 microsphere treatment requires patient-individualized planning with cross-sectional imaging and arteriograms. Contrast computed tomography and/or contrast-enhanced magnetic resonance imaging of the liver is required to assess tumor and normal liver volumes, portal vein status, and extrahepatic tumor burden. Hepatic and renal function tests should be performed; patients with irreversibly elevated serum bilirubin are excluded, and iodinated contrast use should be avoided or minimized in patients with renal insufficiency. Tumor marker levels are also evaluated. Hepatic artery technetium (99mTc) albumin aggregated (MAA) scan is performed to evaluate hepatopulmonary shunting (resulting from hepatopulmonary syndrome). Increased pulmonary shunt fraction (>20%) indicates an increased likelihood of the radioactive particles traveling to the lung during therapy, leading to the adverse side effect of radiation pneumonitis.
The initial angiographic evaluation can include an abdominal aortogram, Superior mesenteric and Celiac arteriograms, and selective right and left hepatic arteriograms. These studies allow for documentation of the gastrointestinal vascular anatomy and flow characteristics. Extrahepatic vessels found on angiographic evaluation are often embolized in order to prevent nontarget deposition of microspheres, that can lead to gastrointestinal ulceration. Once the branch of the hepatic artery supplying the tumor is identified and the tip of the catheter is selectively placed within the artery, the 90Y microspheres are infused.
After treatment, Bremsstrahlung scanning may be performed within 24 hours after radioembolization to evaluate the distribution of the Y-90 microspheres. Weeks after treatment, computed tomography or MRI can performed to evaluate anatomic changes, and positron emission tomography may also be performed to evaluate changes in metabolic activity.
The microspheres themselves are made of glass or resin. Inside the microspheres is the isotope yttrium-90, which has beta-emission with a half-life of 2.6 days. Currently there are 2 types of microspheres: TheraSphere and SIR-Spheres, which differ in their radioactivity per sphere and embolic effect.
|Manufacturer and location||Sirtex Medical, Lane Cove, Australia||MDS Nordion, Kanata, Canada|
|Diameter||20-60 µm||20-30 µm|
|Specific gravity||1.6 g/dL||3.6 g/dL|
|Activity per particle||50 Bq||2500 Bq|
|Number of microspheres per 3 GBq vial||40-80 million||1.2 million|
|Material||resin with bound yttrium||glass with yttrium in matrix|
Complications include postradioembolization syndrome (PRS), hepatic complications, biliary complications, portal hypertension, radiation pneumonitis, gastrointestinal ulcers, vascular injury, and lymphopenia.
Postradioembolization syndrome (PRS) includes fatigue, nausea, vomiting, anorexia, fever, abdominal discomfort, and cachexia, occurring in 20-55% of patients. Steroids and antiemetic agents may decrease the incidence of PRS.
Hepatic complications include hepatic fibrosis leading to portal hypertension, radiation-induced liver disease (RILD), transient elevations in liver enzymes, and fulminant liver failure.
Investigations using yttrium-90 (90Y, Y-90) and other radioisotopes for cancer treatment began in the 1960s. Reports of the initial use of resin particles of Y-90 in humans were published in the late 1970s. In the 1980s, the safety and feasibility of Y-90 microsphere therapy for liver cancer were validated in a canine model. Clinical trials of Y-90 applied to the liver continued throughout the late 1980s to the 1990s, establishing the safety of the therapy. More recently, larger trials and RCTs have demonstrated safety and efficacy of Y-90 therapy for the treatment of both primary and metastatic liver malignancies.
- Atassi, B; Gates VL; Lewandowski RJ; et al. (2007). "Radioembolization with Yttrium-90 microspheres: review of an emerging treatment for liver tumors". Future Oncology. 3 (1): 73–81. doi:10.2217/14796622.214.171.124.
- Kennedy, A; Nag S; Salem R; et al. (2007). "Recommendations for radioembolization of hepatic malignancies using yttrium-90 microsphere brachytherapy: a consensus panel report from the radioembolization brachytherapy oncology consortium". Int J Radiat Oncol Biol Phys. 68 (1).
- Salem, R; Lewandowski RJ; Mulcahy MF; et al. (2010). "Radioembolization for Hepatocellular Carcinoma Using Yttrium-90 Microspheres: A Comprehensive Report of Long-term Outcomes". Gastroenterology. 138 (1): 52–64. doi:10.1053/j.gastro.2009.09.006. PMID 19766639.
- Nicolay, NH; Berry DP; Sharma RA (2009). "Liver metastases from colorectal cancer: radioembolization with systemic therapy". Nat Rev Clin Oncol. 6 (12): 687–697. doi:10.1038/nrclinonc.2009.165.
- Rhee, TK; Lewandowski RJ; Liu DM; et al. (2008). "90Y Radioembolization for metastatic neuroendocrine liver tumors: preliminary results from a multi-institutional experience". Ann Surg. 247 (6): 1029–1035. doi:10.1097/sla.0b013e3181728a45.
- Study to Compare Selective Internal Radiation Therapy (SIRT) Versus Sorafenib in Locally Advanced Hepatocellular Carcinoma (HCC)
- Riaz, A; Lewandowski RJ; Kulik LM; et al. (2009). "Complications Following Radioembolization with Yttrium-90 Microspheres: A Comprehensive Literature Review". Journal of Vascular and Interventional Radiology. 20 (9): 1121–1130. doi:10.1016/j.jvir.2009.05.030.