Partial-breast irradiation is an effective strategy to prevent breast cancer recurrence after breast-conserving surgery. However, brachytherapy, the most-studied method of delivery, is invasive and not widely available; and accelerated partial-breast external-beam radiation therapy has had unacceptable levels of toxicity in some studies. In search of a less invasive and less toxic but still rapid adjuvant radiation therapy technique, researchers at The University of Texas MD Anderson Cancer Center are conducting a clinical trial of hypofractionated partial-breast external-beam irradiation for early-stage breast cancer patients.
Hypofractionated dosing, in which external-beam radiation is delivered at higher doses in fewer fractions than in standard fractionated dosing, has been proven safe and effective for whole-breast irradiation following lumpectomy and is more convenient and less expensive for patients. In fact, hypofractionated whole-breast irradiation is now standard practice at MD Anderson for patients who have undergone lumpectomy for early-stage breast cancer.
“Our trial of hypofractionated partial-breast irradiation is the next natural step: taking some of the advantages of partial-breast irradiation and some of the advantages of hypofractionated whole-breast irradiation and making those two concepts meet in the middle,” said Benjamin Smith, M.D., an associate professor in the Department of Radiation Oncology.
“We want to find the most convenient and least toxic way to deliver partial-breast irradiation,” added Elizabeth Bloom, M.D., a professor in the Department of Radiation Oncology.
Benefits and limitations of standard partial-breast irradiation
Compared with whole-breast irradiation, partial-breast irradiation has a smaller radiation field, which translates into fewer radiation-related toxic effects. For example, whole-breast irradiation sometimes causes cosmetic alterations or scar tissue in the breast or underlying muscles. Such damage could potentially be avoided with partial-breast irradiation because a smaller volume of tissue is treated.
Partial-breast irradiation using brachytherapy is safe and effective, but it has some drawbacks. First, the catheters used to deliver the radioactive beads can be uncomfortable for patients and must remain in place for the duration of treatment. Second, the catheters carry a risk of infection. Finally, because placement of the catheters requires specialized training, the treatment is not widely available. “Brachytherapy works very well,” Dr. Bloom said, “but a limited number of people in the country know how to do it well.”
In contrast to brachytherapy, external-beam radiation therapy is widely available but is not commonly used for partial-breast irradiation owing to its reputation for having undesirable side effects. “Several studies have shown that partial-breast external-beam irradiation has higher risks of breast tissue scarring and poor cosmetic outcomes than expected with brachytherapy,” Dr. Smith said. However, he added that those studies treated patients twice a day for 5 days because such an accelerated dosing schedule had worked for brachytherapy.
“External-beam radiation given in twice-daily fractions doesn’t provide enough time between treatments for the normal breast tissue to repair itself,” Dr. Smith said. And standard fractionation (i.e., given over 6 weeks) for partial-breast external-beam irradiation would have the same disadvantages of inconvenience and expense that it has for whole-breast irradiation.
Drs. Smith and Bloom and their co-investigators hypothesized that once-daily hypofractionated dosing could avoid the side effects seen in the previous studies of partial-breast external-beam irradiation. In March, they began enrolling patients in a clinical trial of hypofractionated partial-breast external-beam irradiation at MD Anderson clinics in the Texas Medical Center, The Woodlands, Sugar Land, the Bay Area, and Katy—all of which are in the Houston area.
The phase II trial, called OPAL (No. 2016-1035), is currently enrolling women 50 years and older who have ductal carcinoma in situ or early-stage (T1 or T2, N0, M0) invasive breast cancer. Invasive tumors must be smaller than 3 cm and estrogen receptor–positive.
After undergoing breast-conserving surgery and, if desired, immediate oncoplastic reconstruction, patients receive hypofractionated partial-breast external-beam radiation therapy. A total dose of 35 Gy is delivered in once-daily fractions on 10 consecutive treatment days (excluding weekends and holidays). Patients whose tumors had resection margins narrower than 2 mm receive an additional 9-Gy boost in three fractions. The regimen was evaluated by radiobiologist Howard Thames, Jr., Ph.D., a professor in the Department of Biostatistics, to ensure that the dose was equivalent to the standard regimen used for whole-breast irradiation.
The trial’s primary outcome measure is the rate of grade 2 or higher toxic effects from the start of radiation therapy through the 6-month follow-up visit. “Our goal is for this rate to be lower than the lowest rate from our most recent study of hypofractionated whole-breast irradiation,” Dr. Smith said, “because the patients in our current trial, like almost any patient who’s had a lumpectomy, would also be candidates for that treatment.”
The secondary outcome measure is patient-reported cosmetic results. Patients complete questionnaires about how their breast looks and feels at baseline, at the 6-month follow-up visit, and at five yearly follow-up visits afterward. These results will be compared with data from the recent study of hypofractionated whole-breast irradiation.
If the outcomes of the OPAL trial are satisfactory, Drs. Smith and Bloom and their co-investigators may propose a randomized trial to directly compare outcomes from hypofractionated partial-breast irradiation and hypofractionated whole-breast irradiation. Dr. Bloom said, “Why treat more healthy tissue if you don’t have to?”
For more information, contact Dr. Elizabeth Bloom at 281-646-2244 or firstname.lastname@example.org or Dr. Benjamin Smith at 713-563-2380 or email@example.com. For more information about the OPAL trial, visit www.clinicaltrials.org and select study No. 2016-1035.