Kyoshi Namba M.D. (Breastopia Namba Hospital, Japan) presented a very comprehensive and optimistic review of the clinical trials investigating breast cancer treatment with MRgFUS. He started by applauding the remarkable progress in breast conserving treatments for breast cancer, and predicted that focused ultrasound would be the ultimate minimally invasive treatment which avoids scarring, a possibility which he, as a breast surgeon, is keen to embrace.
Dr Namba described the importance of ongoing monitoring of disease using MRI during the pre-operative phase during which chemotherapy and radiation are utilized. The great benefit of the MRI modality is that it allows the rapid identification of non-responders and switching to other treatments. (References given: Lehman and Furusawa).
Like MRI, focused ultrasound is seen as a conservative treatment as it does not use ionizing radiation and does not preclude other more aggressive therapy to follow. Since 2002 it has been studied as comparison to lumpectomy in breast cancer, and integrated into the breast healthcare system in his hospital in Japan.
Previously, Radio Frequency (RF) ablation, microwaves, laser ablation and cryoablation have all been investigated as alternatives to surgical resection. In order to translate the benefit of focused ultrasound surgery from uterine fibroid to breast cancer, feasibility studies in breast cancer were completed. The key benefit of this modality is that real time monitoring via distribution by MR images and thermometry through proton resonance shift allows for precise guidance and control.
The sonication pattern in cancer treatment is much tighter than when used in fibroid treatment, and a treatment plan shows the overlap between each sonication spot. Each spot requires 2 minutes to allow for heating and cooling. FUS is described as an excellent “knife” in soft tissue, whilst being non invasive and repeatable. MRI is the ideal partner because of real time monitoring and also because of perfusion measurement – should be easy to identify any untreated area still receiving blood supply. Dr Namba noted that pathologists who have not seen thermal coagulation before may doubt the histological results because samples show only subtle differences even though the cells are no longer viable.
The first pilot study in breast cancer comprised 12 cases of fibroadenomas (benign breast tumors) in 2002. Patients scheduled for lumpectomy received focused ultrasound several days prior to their procedure. The ive here was to look at the lumpectomy pathology specimen to determine the degree of tissue necrosis that could be obtained using focused ultrasound as well as the safety of the procedure. A second pilot study used a similar protocol and treated 25 breast cancer patients prior to their scheduled resection. No contrast medium was used at that time because of possible effect of heat on the contrast medium itself. The pathology results of these studies showed a higher rate of tumor tissue destruction than previous studies, but less than 100% complete. From a safety perspective, much was also learned from these two studies. If the target cancer tissue is too close to the skin, the focusing of the ultrasound waves can cause a surface skin burn. In order to solve these problems, engineers developed a new treatment array that could anatomically fit the targeted region better, reduce heat buildup within the tissue and focus the ultrasound rays better than the flat table design used to treat uterine fibroids. Better inclusion/exclusion criteria were also developed to exclude cancers too close to the skin surface.
A third pilot study was conducted in 2004 and allowed contrast medium (gadolinium) to be used as part of the treatment for 30 patients. Some adjustments were made to the sonication regimen and the contrast medium allowed for more precise targeting. Residual cancer cell rates were very much lower, but still not eliminated – the goal of surgical resection in cancer treatment.
A new international trial is now close to commencement. In this study, in partnership with ACRIN (American College of Radiology Imaging Network), MRgFUS was selected from a number of possible alternatives to lumpectomy. It is expected to start soon and aims to recruit 220 patients in 15 sites. This study will be treating patients scheduled for lumpectomy as in previous studies, but in a larger number of patients.
In summary Dr Namba predicts that once optimized, MRgFUS will have similar efficacy to lumpectomy in breast cancer, but trials will take time because monitoring during a long follow-up period is needed to be conclusive about recurrence rates compared to existing treatments. With the possibility of treatment without scars, the continued evolution of breast cancer treatment looks promising.