|Does Medifocus have the answer for increased shrinkage in large breast cancer tumors?|
|By Staff and Wire Reports|
|Thursday, 28 July 2011 05:41|
On July 19, 2011 Medifocus, Inc. announced that it had initiated its first two clinical sites to begin a randomized Phase III study for the treatment of large breast cancer tumors with focused microwave thermotherapy (heat treatment). The two initial clinical sites are at the University of Oklahoma Breast Institute in Oklahoma City (William C. Dooley, MD, Principal Investigator) and at the Comprehensive Breast Center in Coral Springs, Florida (Mary Beth Tomaselli, MD, Investigator).
The randomized Phase III clinical trial has regulatory approvals from both the Food and Drug Administration (FDA) and Health Canada, and the trial will enroll 238 patients at clinical sites in the United States and Canada. This clinical trial is designed to assess the safety and improvement in efficacy, as measured by increased tumor shrinkage, using wide-field focused microwave heat energy in combination with pre-operative chemotherapy compared to pre-operative chemotherapy alone on large breast cancer tumors. Due to large tumor size at enrollment, patients will be candidates for mastectomy (complete breast removal), but they can be converted to a lumpectomy (breast conservation treatment) if sufficient tumor shrinkage is achieved. Increased tumor shrinkage and increased rate of conversion to breast conservation are some of the goals of the study.
Depending on the size of the breast cancer tumor, standard of care patient treatments can involve surgery, radiation therapy, chemotherapy and hormonal therapy; however, each of these treatments has limitations and side effects. Breast cancer is a diffuse disease which means that besides the primary visible tumor, there will be microscopic cancer cells spread locally in the surrounding ductal system and in other breast tissues. Based on this diffuse distribution of cancer cells, when the surgeon removes the primary breast tumor, an additional 1 to 2 cm margin of healthy tissue surrounding the tumor is often removed to attempt to eliminate all of the tumor cells. Thus, even for a small 1 cm diameter tumor, the surgeon will remove 3 to 5 cm of tissue. After surgery, tumor cells that remain at the surgical edge are referred to as a positive margin, which can lead to an increased probability for the cancer to recur; hence, additional treatment modalities are desired to avoid positive margins. Radiation therapy administered after breast surgery attempts to eliminate any remaining tumor cells. Chemotherapy is often administered for breast tumors greater than 1 cm. For large breast cancer tumors, chemotherapy is sometimes administered before surgery (referred to as preoperative or neoadjuvant treatment) in an effort to shrink the tumor so that the patient can receive breast conserving surgery instead of mastectomy. The success rate for converting patients from mastectomy to lumpectomy by means of pre-operative chemotherapy varies widely, in the range of about 30 to 70 percent, and to improve conversion rates additional treatment approaches are desired.
It is well known that heat alone can kill cancer cells and a number of ablation technologies such as radiofrequency (RF), laser, and focused ultrasound have been investigated for treating small breast cancers on the order of 1 to 2 cm or less. Heat treatment (referred to as thermotherapy or hyperthermia) can also be used in combination with radiation therapy and chemotherapy to kill cancer cells; however, the challenge has been to deliver the heat to the cancer without burning the surrounding healthy tissues and skin.
In the focused microwave heat treatment for breast cancer, noninvasive (external) wide-field applicators are used to treat small and large tumors including cancer cells in the tumor margins. Any high-water high-ion content cancer cells within the wide microwave field will be heated more rapidly than the lower water content healthy breast tissue. To focus the microwaves and monitor the tumor temperature during treatment, a minimally invasive catheter with a combination microwave sensor and temperature sensor is placed within the tumor. Temperature sensors are placed on the skin to monitor the skin to avoid skin burns. The wide-field microwave applicators are positioned on opposite sides of the breast with the breast gently compressed in a mammography fashion. The focused microwave treatment system used in clinical trials (Medifocus, Inc. APA 1000 Breast Thermotherapy System) also applies air cooling to the skin for added safety. The patient lies prone during the focused microwave heat treatment which lasts about 30 to 45 minutes. Patients are fully awake during treatment which is given in a doctor’s office, and they can go home with a single small band aid after the thermotherapy treatment. Clinical results achieved in four small studies with focused microwave thermotherapy for patients with early-stage and large breast cancer tumors are summarized in a review article published last year (W.C. Dooley, Annals of Surgical Oncology, April 2010). Approximately 100 patients have received the focused microwave thermotherapy treatment in these earlier clinical studies.
In a small randomized study, early-stage invasive breast cancer tumors were treated with heat-alone focused microwave treatment prior to surgery or with surgery alone. The targeted heat-alone tumor temperature was approximately 48 degrees Celsius or about 118 degrees Fahrenheit. In the focused microwave thermotherapy arm, after surgery 0 of 34 (0%) patients had positive margins compared to 4 of 41 (9.8%) patients in the surgery-alone arm (W.C. Dooley, Cancer Therapy, 2008). A future study with a larger number of patients will be needed to demonstrate statistical significance and confirm this improvement in positive margins. The clinical benefit to patients would be a reduced recurrence of breast cancer.
In another randomized study, large invasive breast cancer tumors treated with a combination of chemotherapy and two focused microwave heat treatments (approximately 45 degrees Celsius or about 113 degrees Fahrenheit) shrunk nearly 50 percent more (on a relative basis) than tumors treated with chemotherapy alone (88.4% versus 58.8%). This increase in median tumor shrinkage was statistically significant with a P value equal to 0.048 (H.I. Vargas, Cancer Therapy, 2007). A larger clinical study is required to confirm this result, which will be addressed in the new 238-patient Phase III study. The potential clinical benefit to patients in this study would be an increased use of breast conservation.
The focused microwave thermotherapy technology for breast cancer treatment was developed at Massachusetts Institute of Technology (MIT), and is under exclusive license to Medifocus, Inc. The focused microwave treatment is based on adaptive phased array microwave radar technology originally developed at MIT in the late 1980s as part of the Strategic Defense Initiative for missile detection. In the case of an adaptive phased array microwave radar, the radar focuses it energy on a missile while nullifying enemy jamming. In the case of cancer treatment, the adaptive phased array microwave technology focuses its energy on the cancerous tumor while nullifying energy that might overheat and burn surrounding healthy tissues and skin.
About the Author:
Alan J. Fenn, PhD, Fellow IEEE, is a researcher at Massachusetts Institute of Technology, and is the inventor of the adaptive phased array focused microwave thermotherapy heat treatment for cancer. He is the author of two related books, Breast Cancer Treatment by Focused Microwave Thermotherapy (Jones and Bartlett, 2007) and Adaptive Phased Array Thermotherapy for Cancer (Artech 2009).