Study Evaluates Novel Breast Cancer Radiation Treatment Approach

Single-dose intraoperative radiation therapy (IORT) in conjunction with breast conservation surgery offers a novel approach to treating early-stage breast cancer in that the technique selectively treats only the lumpectomy cavity and 1 cm of tissue around it, sparing the remainder of healthy breast tissue.

Little is currently known about the use of IORT in North America to treat breast cancer, however. The technique began in Europe and continues to emerge as a treatment. Results of the largest trial to date, TARGIT-A, were published in 2010. Participants included a small number of centers performing this technique in the United States.

U.S. medical centers have taken part in some additional IORT studies, including the Targeted Intraoperative Radiotherapy United States (TARGIT-US) registry, in which Cleveland Clinic is currently enrolling patients. TARGIT-US represents the leading prospective IORT registry currently underway in the U.S.

Cleveland Clinic surgeons are the principal investigators of the TARGIT-R (retrospective) trial. This trial is intended to provide an interim picture of North American IORT usage and outcomes prior to 2013.

“This trial includes data from 19 centers across North America that have treated patients with IORT beginning in 2007,” says study investigator and Cleveland Clinic breast surgeon Stephanie Valente, DO. Dr. Valente gave a presentation on the TARGIT-R study results at the Society of Surgical Oncology meeting in March 2015 in Houston, Texas. The results are expected to be published later this summer.

One-time treatment appealing to patients

IORT’s concentrated dose allows a patient to receive a one-time treatment in the operating room, which is appealing compared with the typical six weeks of daily whole-breast radiation therapy.

Fifteen to 30 percent of patients don’t complete the entire prescribed course of whole-breast radiation treatment for various reasons, Dr. Valente says. “Unfortunately, not all women who desire to have a lumpectomy can commit to receiving whole-breast radiation,” she explains. ”Some patients say they can’t drive to the treatment center in snow during winter. Others say they can’t miss that much work, that the treatments cause fatigue, or that the nearest hospital is too far away to get there every day.”

In addition to reducing treatment time, IORT enables a personalized treatment approach in appropriately selected patients. “We are starting to identify a subset of patients with early-stage breast cancers who may be able to have a lesser treatment than the standard,” Dr. Valente says. “Older women with a small, estrogen-positive breast cancer and no evidence of spread to the lymph nodes are likely to not receive chemotherapy. These women also probably do not need standard whole-breast radiation. We do know they need radiation to prevent a recurrence, and that is where IORT fits. This individualized approach is how we need to treat patients, rather than ‘one size fits all.’ ”

Study examines North American IORT impact

The TARGIT-R study’s objective is to define the frequency of IORT use in North America, establish patient selection parameters, and follow outcomes. Investigators invited institutions that performed IORT to participate by entering data on patients treated prior to 2013 into the registry.

Nineteen institutions participated, including those with academic and community practices. A total of 822 women who received IORT following lumpectomy between 2007 and July 2013 were entered into the study.

“In our database, the number of cases performed increased significantly over time, with six patients receiving IORT in 2007 and an estimated 500 in 2013,” Dr. Valente says. Most women had estrogen receptor-positive, invasive ductal carcinoma, with tumors less than 2 cm in size, and were lymph node-negative.

Reported complications were low. Patients had a median follow-up time of 23.3 months; actual follow-up time ranged from six months to slightly more than five years. Crude local in-breast recurrence occurred in 2.3 percent of the women.

Short-term results favorable

“This is the first study to broadly evaluate IORT for treatment of breast cancer in North America,” Dr. Valente says. “Short-term safety and results are favorable, but continued follow-up of this unique data set over time is necessary to confirm the efficacy and safety of this novel treatment approach.”

The risk of performing IORT at the time of breast conservation surgery is that the tumor margin status is not immediately known. If the patient requires additional surgery for close or positive surgical margins, she must then be treated with whole-breast radiation, since she cannot undergo IORT again. “In our study, additional whole breast radiation was recommended 17 percent of the time,” Dr. Valente says.

At present, in the appropriately selected patient, the procedure appears to be as effective as whole breast radiation. The long-term local control to prevent a recurrence of cancer in the breast with IORT compared with whole-breast radiation continues to be established. Studies such as TARGIT-A, TARGIT-R and TARGIT-US aim to follow women treated with IORT over time to evaluate long-term results.

Dr. Stephanie Valente is a breast surgeon at Cleveland Clinic’s Comprehensive Breast Cancer Program. Her special interests include oncoplastic breast surgery, nipple sparing mastectomy, and intraoperative radiation therapy (IORT).