June 7, 2010
A 10-year, international multicenter clinical trial found single-dose intraoperative radiotherapy was both safe and effective, with results comparable to conventional external beam radiation therapy delivered daily over the course of weeks.
The findings could have significant implications in both time and expense for patients – particularly those with early forms of breast cancer – as well as the healthcare system because the patient receives all required radiation before awakening from surgery, said the trial leaders.
UCSF, which enrolled nearly 100 patients in the trial, was the lead cancer center in the U.S. Altogether the randomized controlled trial involved 2,232 breast cancer patients with invasive ductal carcinoma who were treated at 28 centers in nine countries throughout Europe, North America and Asia.
Preliminary results were presented today during the 46th annual meeting of the American Society of Clinical Oncology in Chicago. The June 4-8 meeting is expected to draw some 30,000 cancer specialists from around the world.
Long term follow up of the clinical trial will be continuing.
Study results are published in the June 5 online edition of The Lancet (http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60837-9/fulltext).
“Radiation therapy for women who have had a lumpectomy typically lasts three to six weeks, Monday through Friday,’’ said UCSF Principal Investigator Michael D. Alvarado, MD, a breast cancer surgeon at the Carol Franc Buck Breast Care Center at the UCSF Helen Diller Family Comprehensive Cancer Center. “This can be a significant burden for women across all socioeconomic levels. It can be especially difficult for women who need to travel a significant distance on a daily basis. By giving radiation as a one-time dose during the lumpectomy, the woman does not need to come back for radiation treatments.
“What is exciting and new is that the radiation is actually delivered during surgery. The radiation given in the operation room treats the area more precisely and the fact that it is immediate may also be beneficial,’’ said Alvarado who serves on the international writing committee of the project.
“The benefits are not only convenience; we believe it will be less dangerous than irradiating the whole breast because there is less ‘scatter’ to the lungs and heart, and fewer problems with the breast becoming hard after radiation.’’
During the last half-century, treatment of breast cancer has shifted from classical radical mastectomy to local treatment that preserves the breast and axillary lymph nodes along with adjuvant systemic therapy. Breast conserving surgery followed by postoperative whole breast external beam radiotherapy has become the standard of care for many patients with early breast cancer. While radiotherapy is safe and effective and the risk of side effects is low, the duration of daily treatments can be inconvenient or untenable.
The international clinical trial, called TARGIT-A (Targeted Intra-operative radiation therapy), was designed to determine whether single dose intraoperative radiotherapy is equivalent to standard external beam radiotherapy, which uses linear accelerators to irradiate the entire breast externally during a period that typically extends from three to six weeks.
In the trial, the one-time dose was administered in the operating room immediately after the tumor was removed. A miniature electron beam-driven device, INTRABEAM, manufactured by Carl Zeiss Meditec, was surgically positioned in the tumor bed and radiation was switched on for 20-35 minutes to target tissues at highest risk of local recurrence.
The median age of UCSF patients who underwent the treatment was 58.
“We are now trying to get a U.S.-based trial off the ground with major academic institutions across the country,’’ said Alvarado. “We are very excited about moving forward with this new technology.’’
Co-author Laura Esserman, MD, MBA, of UCSF and a member of the international steering committee for the trial, said “The target device is truly an innovation in radiation oncology and helps change our thinking about how to achieve breast conservation. For many women, the radiation therapy can be completed in one visit, instead of visits over a few weeks.’’
“This device truly revolutionizes patient management and the patient experience,’’ said Esserman, director of the UCSF Carol Franc Buck Breast Care Center and co-leader of the breast oncology program. “For patients this is amazing. We have identified a subset of patients for whom it is safe, and we should ensure that all such patients can access this technology. We will continue to study this device in higher risk patients to see if its role can be expanded.’’
Presenting the results during the ASCO meeting was lead author and co-principal investigator Michael Baum, MD, professor emeritus of surgery and visiting professor of medical humanities at University College London. He pioneered the targeted approach along with Jayant S. Vaidya, MD, PhD, consultant surgeon at the Whittington, Royal Free and University College London Hospitals; and Jeffrey S. Tobias, MD, PhD, of the Department of Radiation Oncology, University College London.
The trial “is the longest-running breast cancer study of its kind and it is also the first randomized partial breast irradiation study to be reported,’’ said Baum. “These study results, representing a decade of interdisciplinary clinical experience by leading surgeons, radiation-oncologists, scientists and physicists, has the potential of changing the way we think about the primary management of early breast cancer as well as financial considerations that impact the health care system.’’
Alvarado and Esserman said the single-dose therapy will be offered in the future in conjunction with the ATHENA Breast Health Network, a University of California statewide collaboration for breast cancer patients that designs and tests new approaches to research, technology and health care delivery. Under ATHENA, which launched in 2009, some 150,000 women throughout California are being screened for breast cancer and followed for decades through the five UC medical centers.
The TARGIT study was sponsored by the Comprehensive Biomedical Research Centre of University College London Hospitals and University College London.
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