Selective Internal Radiation Therapy Biology Essay

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The SIR-Spheres® are delivered through a catheter placed in the femoral artery of the upper thigh and threaded through the hepatic artery (the major blood vessel of the liver) to the tumor site. The spheres are trapped in the tumor's small blood vessels, where they destroy the tumor from inside.

Selective Internal Radiation Therapy (SIRT) is a revolutionary treatment for advanced liver cancer that utilizes new technologies to deliver radiation directly to the site of tumors.

Conventional radiotherapy can only be applied to limited areas of the body, and it adversely affects nearby tissues. SIRT, on the other hand, involves the delivery of millions of microscopic radioactive spheres, called SIR-Spheres®, directly to the site of the liver tumors, where they selectively irradiate the tumors. The targeted nature of SIRT enables doctors to deliver up to 40 times more radiation to the liver tumors than would be possible using conventional radiotherapy.

The anti-cancer effect is concentrated in the liver and there is little effect on cancer at other sites such as the lungs or bones.

SIRT Process

Using millions of microscopic radioactive spheres, called SIR-Spheres®, the SIRT process enables the specific targeting and destruction of tumors within the liver that would otherwise be inaccessible. Unlike current, conventional treatments, the highly specific nature of the SIRT process increases the effectiveness in killing the cancer while minimizing harmful side effects to surrounding healthy tissue.

SIR-Spheres® are delivered through a catheter placed in the femoral artery of the upper thigh and threaded through the hepatic artery (the major blood vessel of the liver) to the site of the tumor. The microscopic spheres, each approximately 35 microns (one-third the diameter of a strand of hair), are bonded to yttrium-90 (Y-90), a pure beta emitter with a physical half-life of about two-and-a-half days. The microspheres are trapped in the tumor's vascular bed, where they destroy the tumor by reducing its bloodsupply (embolic effect) and through local radiation damage to the cancer cells' DNA. The radiation is wholly contained within the patient's body, and is continually delivered over approximately two weeks, at which point the microspheres are no longer radioactive.

Treatment with SIR-Spheres®exploits a normal physiological process to target the cancerous tissue. Healthy liver tissue receives most of its blood supply via the portal vein, while liver tumors receive the overwhelming majority of their blood supply from the hepatic artery. As a result, catheterization of the hepatic artery permits the targeting of therapeutic material to liver cancer.

Unlike chemotherapy, which is administered in repetitive cycles, SIRT is typically administered to the patient in two separate treatments. One treatment is given to the right lobe of the liver and one to the left lobe, with the treatments occurring at least one month apart. The treatment is considered outpatient, and patients normally go home within 24 hours.

Patient Outcomes

Treatment with SIR-Spheres® is generally not regarded as a cure, but has been shown to shrink the cancer when combined with chemotherapy more than chemotherapy alone. This can increase life expectancy and improve quality of life. On occasion, patients treated with SIR-Spheres® have had such marked shrinkage of the liver cancer that the cancer can be surgically removed at a later date. This has resulted in a long-term cure for some patients.

Clinical trials of SIR-Spheres® have been conducted within the framework of rigorous scientific protocols in major teaching hospitals and cancer centers. Phase I, II and III trials have been completed. In Australia and New Zealand, most patients had secondary (metastatic) liver cancer, while in Hong Kong primary liver cancer was predominant.

Generally, patients with secondary liver cancer were treated by combining SIR-Spheres® with hepatic artery chemotherapy (outside of clinical trials, the majority of patients are treated using systemic chemotherapy). The results for both groups of patients showed response rates higher than other forms of treatment. In both the Asian and Australian trials, the conditions of some patients with very advanced liver cancer were down-staged to the point where their tumors were surgically removed for potential cure after treatment with SIR-Spheres®.

In the U.S., the Food and Drug Administration granted pre-market approval (PMA) to SIR-Spheres® in March 2002 for the treatment of unresectable colorectal hepatic metastases.

Patients suitable for treatment with SIR-Spheres® generally:

Have inoperable secondary (from colorectal primary) liver cancer

Have the liver as the major site of the disease

Have sufficient remaining healthy liver still functioning satisfactorily

Are well enough to tolerate the implant

Meet the pre-selection criteria, as determined by their doctors' pre-treatment testing

SIR-Spheres® are contraindicated in patients who have:

Had previous external beam radiation therapy to the liver

Ascites, or are in clinical liver failure

Markedly abnormal synthetic and excretory liver function tests

Tumors amenable to surgical resection for cure

Greater than 20 percent lung shunting (determined by the nuclear medicine breakthrough scan)

Pre-assessment angiograms and MAA nuclear scans that demonstrate significant reflux of hepatic arterial blood to the stomach, pancreas or bowel

Widely disseminated or extra-hepatic disease

Been treated with capecitabine within the previous two months, or who will be treated with capecitabine at any time following treatment with SIR-Spheres®

When the contraindications and precautions are observed, serious side effects, such as gastritis and peptic ulceration may develop in the weeks after treatment. To prevent that, patients are often placed on medication for the first month. Many patients feel lethargic and may develop nausea with a poor appetite for several days, but this subsides with time and medication. Some patients may develop a low-grade fever that may last for up to one week. Others may develop pain in the abdomen for a few hours after the administration of SIR-Spheres®, but this is easily treated with medication.