May 2010

Cryotherapy — Researchers Look to Ice Breast Cancer
Radiology Today

Vol. 11 No. 5 P. 26
Editor’s Note: This article is based on research presented at scientific press conferences at the Society of Interventional Radiology’s (SIR) 35th Annual Scientific Meeting in Tampa, Fla. All abstracts can be viewed at www.sirmeeting.org.
Interventional radiologists are exploring ways to use cryotherapy to destroy breast cancer tumors without open surgery. Results from the first reported study investigating this possibility and recently presented at SIR’s Annual Scientific Meeting show investigators successfully froze breast cancer tumors in patients who refused surgery. The interventional radiologists involved with the study reported that the women did not have to undergo surgery after treatment to ensure the tumors had been eliminated.

“Minimally invasive cryotherapy opens the door for a potential new treatment for breast cancer and needs to be further tested,” said Peter J. Littrup, MD, director of imaging research and image-guided therapy at the Barbara Ann Karmanos Cancer Institute in Detroit. “When used for local control and/or potential cure of breast cancer, it provided safe and effective breast conservation with minimal discomfort for a group of women who refused invasive surgery or had a local recurrence and needed additional management. This is the first reported study of successfully freezing breast cancer without having to undergo surgery afterward to prove that it was completely treated.”

In the 13-patient study, no localized treatment recurrences were seen for up to five years, no significant complications were noted, and women were pleased with the cosmetic outcomes, according to Littrup, who is also a professor of radiology, urology, and radiation oncology at Wayne State University in Detroit.

Cryotherapy was applied using well-established freezing principles. Biopsies at the margins of the cryotherapy site immediately after the procedure and at the cryotherapy site in follow-up checks were all negative and showed no cancer, said Littrup. In the United States, women have about a 13% lifetime risk of developing breast cancer, with those aged 50 and older accounting for approximately 80% of cases.

Alternative to Surgery
Breast cancer treatments can be highly effective but often require invasive treatment options such as surgery and chemotherapy, with surgery offering the best chance for a cure. Treatments such as cryotherapy, thermal ablation, and laser therapy are reserved for women who are not surgical candidates or have refused to undergo surgery until long-term data are available on the procedures’ safety and efficacy. 

In this study’s cryotherapy treatment, researchers inserted several needlelike cryoprobes through the skin to deliver extremely cold gas directly to the tumor to freeze it. The technique has been used for many years by surgeons in the operating room, but during the past few years, the needles have become small enough to be inserted through a small nick in the skin without open surgery. The so-called ice ball created around the needle grows in size and destroys the tumor cells.
Surgeons and radiation oncologists have long tried to provide at least a 1-cm treatment margin surrounding all aspects of a localized breast cancer, and it was important to ensure that cryotherapy offered a similar surgical margin of lethal temperatures beyond all tumor edges.

“The well-visualized ice margin by ultrasound CT or MR is actually only the 0˚ Celsius line, or isotherm, which is not sufficiently lethal to cancer cells but has unfortunately been confused with the actual treatment margin,” Littrup said. “We made sure that the lethal isotherm of approximately -30˚ Celsius extended beyond all tumor margins.”

After breast MRI and thorough consultation, patient consent was obtained for institutional review board-approved breast cryotherapy. In 13 cryotherapy sessions, 25 breast cancer foci were treated in 13 patients in stages 1 through 4 using multiple 2.4-mm cryoprobes. Using only local anesthesia with mild sedation, ultrasound guidance alone was used in six patients; seven patients required both CT and ultrasound to better define ice margins. MR and/or clinical follow-up were available for up to 65 months after cryotherapy. Pretreatment breast tumor diameter was 1.7 + 1.2 cm (range, 0.5 to 5.8 cm) and an average of 3.3 cryoprobes produced ice diameters of 5.2 + 2.2 cm (range, 2 to10 cm).

“With recent developments of powerful new cryotechnology, multiple directions for breast cryotherapy can be pursued, including translating the current, somewhat challenging procedure done with ultrasound and/or CT guidance to a more consistent and reproducible MR-guided approach,” said Littrup.

Littrup said the major advantages of cryotherapy are excellent visualization of the ice treatment zone during the procedure, its low pain profile in an outpatient setting, and its excellent healing with minimal scarring.

Breast MRI improvements provide excellent treatment planning images to determine tumor size and its extent within the breast and for postoperative assessment of tissue destroyed by cryotherapy.

Littrup pointed out that larger studies in multiple centers are needed to confirm these basic cryobiology principles of sufficient lethal temperatures generated by multiple cryoprobes spaced evenly throughout a breast cancer region.

Larger Treatment Area
One major difference between this study and prior breast cryotherapy research is its use of multiple probes to treat larger tumors by producing sufficient deadly temperatures in a larger area. Littrup noted that prior breast cryotherapy studies had used only a single cryoprobe and suggested that tumors larger than 1.5 cm could not be adequately treated.

“This is incongruent with more than 10 years of treating an entire prostate, which is approximately 5 cm, with more than six probes in order to generate well-defined sufficient deadly temperatures throughout the whole gland,” Littrup said. “We simply translated this concept to breast cancer in order to ensure deadly temperatures well beyond all apparent tumor margins in order to generate successful use of cryotherapy in women…”

Littrup said the work illustrates the valuable role interventional radiologists using image-guided therapies can play in delivering a sufficient treatment dose rather than relying on subspecialists’ organ-specific expertise. “An interventional radiologist can better focus on the image-guidance similarities of nearly any treatment technology and thereby help lead the effort of improved cancer treatments for many organ sites,” he said.

— Source: Abstract 158: “Cryotherapy for a Spectrum of Breast Cancer: US and CT-Guidance”

MRgFUS — Ablating Fibroids With Heat Shows Promise in Study

A study of more than 100 women found that MR-guided focused ultrasound (MRgFUS) could provide lasting relief from uterine fibroid-related symptoms with myomectomy or hysterectomy, according to research presented at the SIR annual meeting.

“Our 119-patient study shows that magnetic resonance-guided focused ultrasound is highly effective and can provide lasting relief from uterine fibroid-related symptoms,” said Gina Hesley, MD, of the Mayo Clinic in Rochester, Minn. In the 12 months following MRgFUS treatment, 97% of the women in the study reported improvement of their symptoms, with 90% rating their improvement considerable or excellent.
MRgFUS is a minimally invasive treatment that uses high-energy ultrasound waves to generate heat targeted on uterine fibroid tissue to destroy it and ultimately relieve fibroid symptoms. It’s performed as an outpatient procedure and uses high-intensity focused ultrasound waves that can pass through skin, muscle, fat, and other soft tissues to destroy fibroid tissue. During treatment, the physician uses MRI to see inside the body to deliver the treatment directly to the fibroid. MRI scans identify the tissue to be treated and are used to plan each patient’s procedure. MRI provides a 3D view of the targeted tissue, allowing for precise focusing and delivery of the ultrasound energy. MRI also enables the physician to monitor tissue temperature in real time to ensure adequate but safe heating of the target. Immediate imaging of the treated area following MRgFUS helps the physician determine the success of the treatment.

The MRgFUS procedure was approved by the FDA for treating uterine fibroids in October 2004; however, it is still considered new, it is not widely available, and not all insurance carriers cover it.
“MRgFUS is newer than another interventional radiology fibroid treatment—uterine fibroid embolization, or UFE—a widely available treatment that blocks blood flow to fibroid tumors. Our results with effectiveness of MRgFUS technology are promising and comparable with that of UFE, but its longer-term effectiveness needs continued study,” said Hesley. “Today, women have interventional radiology options that do not involve the use of a scalpel incision. Women should ask for a consult with an interventional radiologist who can determine from MR imaging whether they are candidates for either procedure.”

Uterine fibroids are very common noncancerous growths that develop in the muscular wall of the uterus. They can cause prolonged, heavy menstrual bleeding that can be severe enough to cause anemia or require transfusion and create disabling pelvic pain and pressure, urinary frequency, pain during intercourse, miscarriage, interference with fertility, and an abnormally large uterus resembling pregnancy. Twenty percent to 40% of women aged 35 and older have uterine fibroids of a significant size. Black women are at a higher risk for fibroids, with as many as 50% having fibroids of a significant size.

Results
In the nearly three-year study, 119 women completed MRgFUS treatment at the Mayo Clinic and were followed for 12 months using phone interviews to assess fibroid-related symptoms and symptomatic relief.
Of the 89 patients who were available for phone interviews at 12 months, 69 indicated they experienced the following level of symptom relief: excellent (74%), considerable (16%), moderate (9%), or insignificant (1%). The rate of additional treatments needed post-MRgFUS was 8%, which is within values reported for myomectomy and UFE, said Hesley.

The Mayo researchers will continue to study two- and three-year results of symptom relief. They will also compare their current results with those reported for myomectomy and uterine artery embolization and investigate the efficacy of MRgFUS in treating other uterine conditions, such as adenomyosis, a condition in which tissue that normally lines the uterus also grows within the muscular walls of the uterus, said Hesley.
— Source: Abstract 56: “Magnetic Resonance-Guided Focused Ultrasound of Uterine Fibroids: Patient Follow-Up 12 Months After Treatment”