RFA: A Talented Treatment Partner Researchers at the Dana-Farber/Harvard Cancer Center NCI-funded SPORE, working in animal models, have had good success combining RFA with antivascular/antiangiogenesis agents to treat renal cell carcinoma. The approach involves pretreating patients with the agents, reducing blood flow in the tumor and, as a result, heat dissipation. More focused heat means better tumor-cooking ability. Dr. Wood is involved in a clinical trial that uses an RFA device to deliver a heat-activated drug inside a capsule called a liposome into tumors. The heat generated during ablation causes the intravenous liposome to crack open and deliver its payload: the chemotherapy drug doxorubicin.

"Those that the knife does not cure are cured by fire," Hippocrates once wrote. This sentiment could also be considered the unofficial mantra of a small cadre of clinicians who have championed a minimally invasive procedure to eradicate small tumors while sparing patients the physical trauma of major surgery.

The technique is radiofrequency ablation (RFA), an outpatient treatment that involves inserting a thin needle, guided by imaging techniques such as ultrasound or computed tomography, through the skin (or, in some cases, through a laparoscopic incision) and into the core of a tumor. At this point, exactly how the tumors are ablated, or "cooked," depends on the device being used. Generally speaking, radiofrequency waves are delivered down the needle shaft to generate just enough heat - slightly over 100° F for 10 to 15 minutes - to destroy the tumor and, hopefully, any cancer cells in the tissue immediately surrounding the tumor, often called the margin.

As a cancer treatment, RFA is moving beyond clinical trials at academic medical centers, with approximately 60,000 procedures performed worldwide last year. Its most extensive use has been to eradicate small liver tumors in patients who aren't candidates for surgery, says Dr. Brad Wood, an interventional radiologist in the Imaging Sciences Program at the NIH Clinical Center. Impressive results with RFA have also been seen in kidney tumors; several other cancers are now feeling RFA's heat.

"Even with surgery and the advances in chemotherapy over the past few years, we still have patients with no other effective options who could be candidates for RF ablation," says Dr. Wood, who also has an appointment in the NCI Surgery Branch.

Lung cancer is a therapeutic area for which RFA is under intense study, as these patients commonly have few - if any - treatment options.

"We see a lot of patients who have early-stage lung cancer who can't have surgery because of emphysema, heart disease, or advanced age," says Dr. Damian Dupuy, a professor of diagnostic imaging at Brown Medical School, who is leading several trials using RFA to treat early-stage lung cancer patients. In data he presented last December on RFA use in 126 inoperable lung cancer patients, more than 50 percent were still alive at 5 years.

Dr. Dupuy and his colleagues also have had promising results in smaller trials combining RFA with radiation, including brachytherapy. Because both RFA and brachytherapy are localized outpatient procedures, the 14-patient trial "was basically a 1-day cancer treatment."

Dr. Dupuy believes that, at least for patients with smaller tumors, RFA eventually could replace surgery in certain situations.

"I think it's the natural progression, especially as technology gets better at detecting cancer early with technologies like proteomics and imaging," he says. "If we can noninvasively stage cancer more accurately, then we can be confident that we're treating a localized disease with a small, localized procedure."

RFA also lends itself nicely to combination treatments. Researchers at the University of Arkansas for Medical Sciences, for example, are testing RFA to support breast lumpectomy, using it to create cancer-free or "negative" margins around the removal site. The approach, explains Dr. V. Suzanne Klimberg, the study's lead investigator, attempts to address a significant problem: As many as 40 percent of the estimated 150,000 women who undergo lumpectomies must have the procedure repeated because the tumor returns, most often at the lumpectomy site.

The available data indicate that clean or negative lumpectomy margins not only have an impact on these local recurrences, she adds, but may also improve survival.

"Margin positivity is really the only prognostic factor that surgeons can affect," Dr. Klimberg says. "Everything else is up to the patient: Is it ER-positive? How big is it? We can't affect that, but we can affect the surgery that we do."

Soon-to-be published data using this RFA-assisted lumpectomy approach in 25 patients report no local recurrences at a median follow-up of 18 months, Dr. Klimberg said. The approach may also eliminate the need for post-lumpectomy radiation therapy, which many women forego because of fear of side effects.

RFA's role in cancer is not strictly curative, Drs. Dupuy and Wood stress. Both are involved in clinical trials using RFA to treat debilitating pain caused by bone metastases.

"I treated a patient yesterday with bone metastases who was in intractable pain and on massive doses of opiates," Dr. Wood recounts. "He … couldn't use his arm and just couldn't function daily. And the morning after the procedure he had no pain, zero."

By Carmen Phillips