New techniques expand arsenal of tumor therapies

Surgery and chemotherapy may form the frontline of cancer treatment, but a growing array of image-guided therapies can play supporting roles, providing palliative treatment or working in tandem to debulk or chemically alter tumors. Intensity-modulated radiation therapy (IMRT) may be the best known example of harnessing imaging techniques to improve treatment precision, but multiple modalities are also used to guide ablation needles, target focused ultrasound beams to destroy cells, and pinpoint placement of drug-laden beads and bubbles.

Ablation techniques run both hot and cold. Cryoablation has picked up supporters for its success in the breast and prostate, and some investigators have pursued chemical ablation via ethanol or acetic acid injection. Thermal ablation, however, remains the most popular. Radio-frequency ablation distributes a high alternating current of 460 to 480 kHz that heats tissue to more than 50¼C. Microwave ablation uses high-frequency electromagnetic waves to oscillate water molecules and create frictional heating and steam.

RFA has been used successfully in patients with primary or metastatic tumors in the lung and liver; kidney, adrenal, breast, and head and neck masses; osteoid osteomas and bone metastases; and other targets. RFA is primarily a palliative technique for patients who are not surgical candidates, but it can be used for masses that are unresponsive to therapy or as a debulking technique prior to other therapies, according to Brown University radiologist Dr. Damian Dupuy.

"At this point most insurers don't cover the procedure, and it tends to be a last resort for most cancer teams," Dupuy said at the 2004 RSNA meeting.

The technique is not without its challenges, including creating clear margins of treatment and avoiding damage to sensitive structures nearby. Ultrasound and CT are used most often to guide probe placement, and tools under development could allow interventional radiologists to fuse a previously acquired CT volume with live ultrasound images for more accurate needle placement. For cryoablation, MR guidance can monitor the margins of iceballs and overall temperature within the treated region.

Treatment area remains a persistent issue for ablation techniques. Single-probe applications can treat an area of up to 3 to 5 cm in diameter, and multiple probes can expand that area significantly, but operators must exercise caution not to leave untreated margins. Particularly in lung masses, ablation techniques show promise as an adjunct to other therapies. If borne out in trials, a hybrid approach could potentially challenge standard lobectomy for stage IA tumors.

"There is a synergy between radiation and hyperthermia, so we can reduce tumor volume with RFA, then sterilize the tumor bed with radiation therapy," Dupuy said. "Heat changes the cell biology and makes the tumor easier to treat."

Other experimental techniques include RFA followed by brachytherapy with iridium-192 seeds, reducing tumor blood flow prior to ablation to lessen the heat-sink effect of vascularity, and localized chemotherapy.

Other image-guided techniques take advantage of tumor vascularity to delivery localized treatment. Irradiated intra-arterial microspheres with a half-life of 64 hours can be injected into hepatomas or colorectal metastases in the liver, where they deliver beta radiation to a 2.5-mm radius. The challenge, according to University of Pennsylvania radiologist Dr. Michael Soulen, is getting them to the tumor only. A variation on the technique would be to use iron-based beads and direct them to the tumor using a strong external magnet.

"There's little proof these techniques are actually better than standard therapy so far," Soulen said.

Intra-arterial gene therapy and drug-eluting beads, also on the horizon, show promise in animal trials. Imaging can help guide and monitor the treatments, which might eventually offer an alternative to systemic chemotherapy.

FOCUSED ULTRASOUND

Rather than using imaging modalities to guide delivery of external therapy, several research centers have had promising results letting the modality itself be the treatment. At Brigham and Women's Hospital, MR-guided focused ultrasound (FUS) is used to destroy small volumes of tissue by concentrating the focal point of ultrasound waves to transfer energy to cells, heating and destroying them.

The "sonications" are small, cigar-shaped regions of destroyed tissue. Plotted out in a grid with MR guidance, they can be deployed in one or several layers of depth, according to Dr. Clare Tempany, director of clinical MR. Using ExAblate 2000 (InSightec) phased-array transducers, the average treatment time for uterine fibroids is about three hours. Multiple or faster transducers could make the process more efficient.

Anatomic barriers present some limitations: The sound waves cannot safely or effectively be passed through bone, bowel tissue, the sacrum, or scars, and blood vessels can get in the way. In addition, the sound waves tend to bounce off calcified fibroids.

While fibroids have been the most frequent target, the appropriateness of the liver, brain, and prostate for sonification is undergoing preclinical investigation. The technique could eventually be used to open the blood-brain barrier or to perform targeted therapy delivery by bursting drug-laden microbubbles.

"The technique is still in its infancy, but it's totally noninvasive, and the MR guidance and monitoring is excellent," Tempany said. "It's expensive to spend three hours in the MR scanner, but versus the costs and long recovery time for a hysterectomy, it might be worthwhile."