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Targeted therapies address hard-to-treat liver tumors

Targeted therapies address hard-to-treat liver tumors

ABSTRACT: Radioactive microspheres treat lesions, but spare healthy surrounding tissue, improving patients’ odds against a deadly disease.

Not long ago, our approach to treating difficult metastatic tumors was to “spray and pray.” We knew that chemotherapy and other traditional treatment approaches could cause great damage and had a limited chance of successfully destroying the entire tumor. At the time, a proven safer and more effective option did not exist, and patients were desperately in need of treatment. Fortunately, as our knowledge of the complexities of advanced liver tumors has grown, so has our ability to develop treatments that target and treat tumors while avoiding harmful side effects to normal tissue.

Treatment challenges
Over the past 10 years, we have noticed a shift toward targeted therapies in numerous types of cancer, including breast, lung, lymphomas, and colorectal. Some of the most significant treatment advances have been realized with the development of targeted and innovative therapies to treat liver tumors. Historically these types of tumors are difficult to treat, making liver cancers some of the deadliest forms of cancer. Colorectal liver metastases present one of the greatest challenges. Each year, more than 150,000 Americans will be diagnosed with colorectal cancer, and at least 80% will see their cancer spread to the liver.

Unfortunately for those diagnosed, options for treating metastatic liver tumors are few. The liver’s unique anatomy presents numerous challenges when evaluating conventional treatments. Since fewer than 20% of liver tumors can be surgically resected, metastatic liver cancer is often fatal, with up to 90% of patients dying from liver failure. 

Chemotherapy is considered the gold standard of care, but it is often not optimal given the fact that over a long period of time the cancerous tumors become unresponsive and grow despite more chemotherapy. In the past, radiation therapy for liver tumors has proven especially challenging due to limitations on our ability to deliver a lethal dose without killing healthy liver tissue.

The sheer paucity of treatment options forced physicians to look for alternatives that offered efficacy without the damaging side effects. This didn’t happen overnight. Targeted treatments are a natural progression from decades of research that saw less specific anticancer agents destroy tumors—but at the cost of normal tissue.

Advances in the technology of radiation therapy, medical oncology, radiology, and surgery have greatly reduced collateral damage to normal tissue and thus enabled improved outcomes. By reducing the threat to normal tissue, these advances also allow us to deliver higher doses of drugs and radiation to tumors.

Microsphere development
Research into the use of yttrium-90 microspheres for the treatment of liver cancer actually began in the 1960s. However, it wasn’t until much later that researchers became able to embed radioactive elements into a consistently manufactured microsphere of the correct diameter that could travel easily in the bloodstream to the capillary bed of the liver tumor. Today’s microspheres are microscopic radioactive spheres that can be delivered by the millions directly to the site of a cancer, where they selectively irradiate the tumors.

During the procedure, called selective internal radiation therapy (SIRT) or radioembolization, a targeted high dose of radiation is delivered to liver tumors. The treatment is performed as an outpatient procedure in radiology and requires the placement of a transfemoral microcatheter that is positioned in the hepatic artery. Using the liver’s unique vascular supply, millions of tiny microspheres charged with yttrium-90 are released into the hepatic artery in a carefully chosen location unique to that patient. The radioactive microspheres become implanted in the microvascular supply of the tumor, where they become permanently trapped. The microspheres emit beta radiation over a period of two weeks.


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