The role of imaging in microsphere therapy of liver mets

Radioactive microsphere therapy is gaining in popularity among specialists who deal with both primary and metastatic solid tumors in the liver (see images on page 1 and "On the cover" box below). During the past 2 years, sessions dedicated to this therapeutic approach have been held in meetings of all major related specialties: interventional radiology, radiology, radiation oncology, surgical oncology, hepatobiliary surgery, nuclear medicine, and medical oncology.

More than 6,000 patients

With more than 6,000 patients treated in the United States alone in the past 3 years, a significant body of peer-reviewed literature has been published to aid in understanding how and in which patient population to use this treatment.

Key issues in 2007 have been refinement of patient selection and expansion of treatment to a variety of histologic tumor types. Major successes have been achieved in breast cancer metastases, cholangiocarcinoma, neuroendocrine metastases, and ocular melanoma. Several multi-institutional clinical trials and dedicated quality of life studies have either started or are expected to be completed soon in neuroendocrine, colorectal, and hepatocellular cancers.

None of this research or treatment application would be possible without a multidisciplinary approach that incorporates the latest in imaging technology to localize tumors, evaluate extent of disease, assess the safety of future microsphere treatment, and confirm treatment success (Figure 1). This pictorial shows how imaging is used in microsphere therapy.

Gauging response

PET imaging greatly assists in treatment planning and assessment of response in a large number of different tumor types affecting the liver in patients receiving radioembolization. Researchers at the Third Annual Symposium on Liver-Directed Microsphere Therapy presented compelling pretreatment and post-treatment PET scans of patients who received internal radiotherapy for unresectable and chemorefractory tumors from melanoma and from breast, colon, bile duct, pancreatic, esophageal, and neuroendocrine (see image) cancers. The general conclusion was that PET was more reliable than CT in gauging tumor response.

Carcinoid tumor

Carcinoid tumor in the liver treated with microspheres has shown excellent response and reversal of clinical symptoms. The effects of internal radiotherapy are apparent (see Figure 2), with overall liver healing accompanied by a change in contour and volume of segments. This is due to a combination of parenchymal retraction during fibrotic healing and hypertrophy of unirradiated healthy liver immediately adjacent to the tumor deposits. This patient experienced 70% reduction in his serum tumor marker value and significant reduction in carcinoid symptoms after a single microsphere treatment. He ultimately died of distant metastatic disease but did not experience liver dysfunction over his 2.5-year survival after radiation. He had been treated with chemotherapy and octreotide (Sandostatin) prior to radiotherapy (Kennedy et al: Manuscript in press, presented at the North American Neuroendocrine Society Annual Meeting, Sept. 26, 2007).

Ocular melanoma

Ocular melanoma is unique in that it almost always metastasizes only to the liver, which, in turn, is the most common reason for patient death, as so few treatment options are available for patients.

Chemotherapy is ineffective, and the disease is typically spread throughout the liver, thus excluding surgical removal or treatment with external-beam radiation therapy.

Internal radiotherapy with yttrium-90 microspheres has demonstrated consistent and useful tumor reductions (see Figure 3) (Kennedy, Nutting, and Dezarn: Manuscript in press).

This patient presented with right uveal cancer (see Figure 3A) and synchronous liver metastases (see Figure 3B). The patient had a complete response within 6 months of microsphere treatment in the liver (see Figure 3C), which contained persistent cancer despite 13 prior transcatheter arterial chemoembolization procedures. The ocular tumor was treated surgically.

Overall toxicity

In the largest report to date on microspheres, 515 patients receiving 680 treatments were studied for toxicity, with 2% of patients developing significant liver scarring or damage.

Most patients received multiagent chemotherapy and liver-directed non-radiation therapies, which have a cumulative effect on liver tolerance (Kennedy et al: International Congress on Anti Cancer Treatment [ICACT], Paris, France, 2007).