Imaging bolsters accuracy of microsphere therapy

Multimodality tour de force enables various specialists to safely administer radiation directly into liver tumors

Most patients with colorectal, breast, lung, hepatocellular, and pancreatic cancers are at risk for recurrence from metastatic disease in the liver after potentially curative treatment. When the liver harbors metastatic or primary cancer, treatment options are reduced and patient survival rates rapidly decline. This response can be partly attributed to the remarkable ability of the liver to grow larger, as well as its susceptibility to damage caused by chemotherapy, radiation therapy, and local surgical procedures.

Uncontrolled liver disease is the most common final pathway for nearly half of all patients with colorectal cancer and for the majority of patients diagnosed with hepatocellular carcinoma. It is a worldwide health issue and a leading cause of premature death.

New hope in the push to eradicate cancer from the liver has arrived through use of cutting-edge imaging technology to assist in the delivery of microscopic radioactive spheres. These tiny spheres go directly to the tumor site, attacking cancerous cells while sparing healthy tissue. A multimodality tour de force uses the skills and expertise of several specialties-including diagnostic radiology, interventional radiology, radiation oncology, and nuclear medicine-to safely administer the radiation directly into the liver tumors.

There are currently two forms of microspheres: SIR-Spheres and TheraSpheres. The polymer-based SIR-Spheres microspheres manufactured by Sirtex are currently the only ones approved by the FDA for treatment of metastatic liver cancer. TheraSpheres microspheres, manufactured by Nordion, are made of glass beads that are irradiated. Though they are not FDA-approved, TheraSpheres microspheres have received humanitarian device use approval in the U.S for hepatocellular carcinoma. Because of this difference in FDA approval status, the data included in this article refer solely to SIR-Spheres microspheres.

Physicians are encouraged by the early impressive results of microspheres therapy, and patients cite the minimal side effects and ease of treatment, especially the fact that this therapy is an outpatient procedure. At a clinical symposium on microspheres therapy held in Scottsdale, AZ, earlier this year, new research was presented supporting the expanded use of microspheres therapy for metastatic colorectal cancer, breast cancer, HCC, and carcinoid tumors. Interventional radiologists from across the country attended the meeting to discuss the latest research and uses for microspheres, as well as best practices for infusion techniques.

None of this research or treatment application would be possible without incorporating the latest in imaging technology to localize tumors, evaluate extent of disease, assess the safety of future microsphere treatment, and confirm treatment success. In addition to PET/CT imaging, hepatic angiography, macro-aggregated albumin scans, and thin-section liver CT scans are essential in proper case selection, treatment delivery, and follow-up assessment of treatment response. The critical importance of imaging in successfully treating a patient with microspheres means that the entire process from prequalification to post-treatment follow-up requires a team approach.

Each SIR-Spheres microsphere is composed of resin and yttrium-90, a pure beta emitter that penetrates tissues only up to a quarter of an inch. The radioactive source Y-90 does not come off of the microspheres, so confining the spheres to the tumor means the radiation also is localized exclusively to that area. Therefore, when microspheres are in the tumor-where they remain permanently-they destroy only cancerous cells and spare the surrounding normal liver tissue.

The infusion of microspheres is performed in the angio suite primarily by an interventional radiologist who has experience with chemoembolization. A key feature guiding delivery of microspheres to the tumor is the fact that 80% to 100% of the blood supply to metastases in the liver comes from the hepatic artery.

The latest microcatheters and diagnostic interventional radiology C-arm technology allow for precise placement of radiation into small peripheral vessels. An interventional radiologist uses x-ray guidance to position the catheter into the liver to allow for targeted infusion of the microspheres to the liver tumors.

ROLE OF IMAGING

Since this treatment must be precise, the role imaging plays is crucial. The amount of radiation delivered can be significant, but because the microspheres are about 32 microns in diameter, they enter the tumor from the hepatic artery supply and preferentially collect in the periphery of tumor nodules. The capillary beds allow passage only of particles smaller than 10 microns, thereby trapping the microspheres within the tumor.

If an arteriovenous fistula or other abnormally large passageway between the arterial and venous vascular systems is present, these radioactive spheres will pass into the next capillary bed: the pulmonary system. Lungs are very sensitive to radiation, and great damage can occur if a significant amount of microspheres escapes the liver.

Imaging is critical in all phases of internal radiation therapy. The treatment process starts with establishing the location, size, and volume of tumors in the liver. At the same time, a search for any extrahepatic tumor deposits occurs. PET/CT provides complementary information in 3D on the location and cellular activity of tumor deposits. High-resolution three-phase liver imaging is obtained with CT, followed by hepatic arterial system mapping obtained internally with angiography.

Next, the hepatic vasculature and potential release point of the microspheres are tested with a macro-aggregated albumin scan (technetium-99m MAA), which uses the ubiquitous human serum protein albumin processed into the same size as the radioactive microspheres but bound to a gamma-emitting isotope for imaging instead of the beta source used for therapy, which cannot be easily imaged. The albumin particles lodge in the tumor just as the microspheres will do, thus detecting deposition of particles in the stomach, small bowel, or lungs instead of the intended target-the liver tumors-in a simulation of the treatment.

Corrective measures can then be taken to make microsphere delivery safer by avoiding extrahepatic spread. Finally, after microsphere delivery, a gamma camera is used to perform a postimplant scan, which detects the small amount of characteristic gamma x-rays released by Y-90 during beta decay to stable zirconium-90.

A SPECT scan performed post-SIR-Spheres infusion ensures that the microspheres have been successfully delivered to the liver only. Once in place, the microspheres deliver radiation to the tumors during a 14-day period. Follow-up CT and/or PET scans are performed every three months to measure effectiveness. In approximately 90% of cases, microspheres have either reduced or eliminated secondary tumors in just one treatment. By contrast, patients treated with traditional chemotherapy are expected to survive less than a year after treatment.

PRICE OF PRECISION

The delivery of radiation to liver tumors is a step forward for physicians and patients, made possible by precise imaging. The entire care team must embrace the procedure and its intricate imaging demands, however, to create a successful microspheres program. When implemented properly, microspheres therapy is a rewarding offering for the entire team. Its multiple imaging demands give it the potential to become a revenue source for practitioners and medical centers.

An even greater potential, however, is the ability to offer patients-many of them told they had only months to live-an effective treatment option that extends survival time and maintains quality of life. This treatment is relatively new to the U.S. With the growing body of research on the use of microspheres for liver cancer, we may one day be able to tell patients that metastatic liver cancer is a treatable and even beatable disease.

Dr. Kennedy is a radiation oncologist and co-medical director of Wake Radiology Oncology in Cary, NC.

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CASE STUDY ILLUSTRATES POWER OF TECHNIQUE

A 45-year-old woman who underwent surgery and postoperative chemotherapy for sigmoid colon adenocarcinoma was also diagnosed with unresectable synchronous liver metastases. State-of-the-art chemotherapy was delivered, but her liver tumors were largely unaffected, and some even grew during treatment. Because of the extent and location of the lesions, surgery and other locally ablative approaches (e.g., radiofrequency ablation, cryotherapy, and laser ablation) were not recommended. Rather than ordering salvage chemotherapy, her doctors chose to first use liver brachytherapy via Y-90 microspheres and chemotherapy together, then proceed with systemic chemotherapy.

Physicians treated the whole liver with Y-90 microspheres, 5-fluoruoracil, and leucovorin chemotherapy intravenously. The patient tolerated the therapy well, and she was discharged the same day as treatment, returning to work full time in a few days. Her side effects were typical for this type of treatment: mild nausea and epigastric pain, with fatigue for several days. (Some patients have these symptoms longer.) A PET scan showed complete regression of the liver tumors by 12 weeks post-treatment. A CT scan showed the tumors to be stable but "hollowed out," consistent with scar formation.