Phasing Out Breast Cancer

by Joan Zimmermann/jzimmermann@nttc.edu

A radar anti-jamming technique once directed toward missile detection is now poised to shoot down cancer cells.

By simultaneously nullifying and amplifying electromagnetic waves, phased-array techniques improve many types of radar and communications systems. With a focused heating regimen based on an adaptive phased array (APA) technique, the founder of Celsion Corporation (Columbia, MD) has established Celsion Canada, Ltd., which is now testing a targeted microwave therapy in the fight against breast cancer.

While improvements in technology and awareness have reduced average tumor size at diagnosis, breast cancer remains the third leading cause of death in women in the United States. New classes of drugs and biotherapeutic agents have brought the five-year survival rate to 85 percent, but problems remain with specifically targeting tumors. Mastectomies still must be performed in about half of all U.S. breast cancer diagnoses (the rate was 56 percent in 2004), leaving women with physical and emotional scars, and side effects such as swelling and pain that may persist for years.

In addition to accepted standards, other approaches to tumor destruction have been studied, including focused ultrasound, cryoablation (freezing), and laser photocoagulation. Heat applied in the form of radio waves and microwaves has also been used. A specialized application of microwave heat is now under consideration in an exciting new clinical trial scheduled to take place in 2006, thanks to a technology that MDA funded at Lincoln Laboratory nearly two decades ago. During the latter years of the Cold War, Dr. Alan Fenn of the Massachusetts Institute of Technology developed an adaptive phased-array antenna for nulling and focusing radar under the auspices of the Strategic Defense Initiative Organization (SDIO), for missile detection applications. It soon became apparent that this same technique could be useful in directing heat to deep-seated tumors, while reducing “hot spots” in surrounding healthy tissue.

Dr. Augustine Cheung, founder of the medical device company Celsion Corporation, had long been interested in using heat to treat disease. He acquired an exclusive license to Dr. Fenn’s technology and incorporated it into an early device, the MicroFocus 1000™. Over the years Celsion has gone on to establish a line of related thermotherapy platforms for the treatment of benign prostatic hyperplasia (BPH), and most recently liver cancer, using radio-frequency (RF) waves to provide the heat. However, as Celsion moved more towards the development of RF-based thermal therapy with liposome-encapsulated chemotherapy drugs, the APA technique simmered on the back burner, but on a parallel course. In a series of studies conducted from 1999 to 2004, however, Dr. Fenn and a host of breast cancer specialists continued to test the APA-based Microfocus 1000 device in breast cancer patients as a neoadjuvant treatment prior to breast surgery.

Two advantages of APA focusing are its ability to deliver heat into tumor sites deep in the body, and the fact that micro-wave energy preferentially heats tumor cells, which have a comparatively higher water content than surrounding healthy tissue. In addition, the placement of the antenna is minimally invasive, allowing patients to leave the treatment with “a tiny bandage,” according to Dr. Fenn. Eventually, it is hoped that APA can be applied remotely, without the need to insert any needle into the tumor. Remote application would also be helpful in focusing energy on chest wall tumors—such cancers are more difficult to treat than those that occur on the periphery of the breast.

In two papers published in the Annals of Surgical Oncology (2002 and 2004), researchers were able to demonstrate in a total of 35 breast cancer patients the safety and utility of this method for killing tumors by the use of heat alone. In one study, 10 patients scheduled for mastectomy received the heat-alone APA focusing treatment prior to surgery and 8 of 10 patients had a tumor response. As part of this safety study, all of the patients were required to have a mastectomy regardless of any tumor response. In another study, 25 patients with early-stage breast cancer scheduled for lumpectomy received the heat-alone focusing treatment, and the heat dose for 100 percent tumor kill was established. All of these patients had lumpectomies and only one patient had any residual cancer cells after surgery. Two other studies of the APA focusing treatment in more than 40 additional patients with early-stage and advanced breast cancer have since been explored and the results are awaiting publication. The outcomes of these initial trials in more than 75 patients are encouraging, and clinicians have decided to add a new component to the APA treatment, again prior to surgery in a clinical trial for patients with advanced breast cancer.

To this end, in early 2006, Dr. Augustine Cheung resigned his executive positions at Celsion, while retaining his license to APA technology and related assets, and began to devote his full-time efforts to the development of APA technology as a thermotherapy platform for breast cancer treatment. Currently, he is preparing a round of clinical studies that combine APA-based tumor-heating with intravenous infusion of Adriamycin® (doxorubicin) and other drugs. The idea is that the drugs will be “enhanced” by heating, possibly speeding up reaction times, resulting in a higher response rate at the site of the tumor. Simultaneously, the ordinary systemic action of the drugs will target any circulating tumor cells or potential micrometastases elsewhere in the body. Celsion has already established a track record in clinical trials using RF heating and liposome-encapsulated doxorubicin, with a therapy called ThermoDox™, in the treatment of liver and prostate cancers. Encouraging results from the company’s experience in this area have strengthened the evidence supporting this application, hopefully pointing to better outcomes for breast cancer. The ultimate goal of this effort, of course, is to destroy tumors, prevent recurrence, and help patients avoid mastectomy.