Whole- or partial-breast radiation therapy can reduce a patient’s chance of breast cancer recurrence after lumpectomy, but this benefit must be weighed against the risk of damage to healthy tissue.
A new partial-breast irradiation regimen employing protons shows promise as an effective adjuvant treatment that minimizes the radiation dose to healthy tissue.
Whole-breast irradiation, the standard of care, has a proven track record but may damage healthy breast tissue or, rarely, nearby organs such as the heart or lung. The currently used modalities for accelerated partial-breast irradiation target the region adjacent to the initial tumor and typically deliver treatment over a 1-week period. These modalities reduce but do not eliminate the radiation dose to healthy tissue.
The most common partial-breast irradiation modalities are three-dimensional (3D) conformal external-beam radiation and brachytherapy. “With 3D conformal therapy, about half of the breast receives half the dose,” said Eric A. Strom, M.D., a professor in the Department of Radiation Oncology at The University of Texas MD Anderson Cancer Center. With brachytherapy, Dr. Strom added, the radiation sources, which are inserted near the tumor site via a needle or catheter and emit radiation in all directions, also affect healthy tissue as well as the tumor bed.
In contrast, proton therapy has virtually no scatter (radiation to tissue outside the treatment field) but presents a different problem. Protons release a relatively small radiation dose when they enter the body and move through tissue until they start to run out of energy. At the end of their energy range, protons suddenly release their remaining dose of ionizing radiation—the Bragg peak—with no scatter. “The problem is that to treat a tumor bed, you have to stack a lot of these Bragg peaks on top of one another at various depths,” Dr. Strom said. When the tumor bed is near the skin surface, as many breast tumors are, the same area of skin receives multiple small doses, which add up to a large cumulative entrance dose.
This high entrance dose caused minor burns and skin irritation in breast cancer patients in the early proton therapy studies, which were not done at MD Anderson. Because skin sparing is a benefit of both 3D conformal radiation therapy and brachytherapy, proton therapy has not been commonly used for breast cancer patients—until recently. A phase II clinical trial now under way at MD Anderson is testing the effect of multiple proton beams aimed at the tumor bed from different directions. “By spreading the skin dose over several adjacent areas, no one point gets a high dose,” said Dr. Strom, the study’s principal investigator.
Participants in the study are women who have undergone lumpectomy for ductal carcinoma in situ or stage I or II invasive adenocarcinoma of the breast. The inclusion and exclusion criteria for the trial are similar to the selection criteria used for other partial-breast irradiation techniques: tumors must be no larger than 3 cm and excised with clean margins. In addition, patients with multifocal tumors or lymph node involvement are not eligible for the trial, nor are those who have undergone neoadjuvant chemotherapy. Starting within 8 weeks of surgery, each patient receives 10 fractions of proton therapy (2 fractions per day over 5 or 6 days).
The goal of the study is to assess the toxicity and cosmesis of proton therapy in breast cancer patients. The preliminary results, which are scheduled to be presented at an upcoming conference, are encouraging, according to Dr. Strom. “In our first 25 patients, we’ve seen only mild skin redness and no grade 3 skin reactions of any kind,” he said.
Another potential advantage is that—unlike proton therapy for some cancers—partial-breast irradiation with protons costs about the same as the standard radiation options. In fact, 10 fractions of partial-breast irradiation with protons cost less than the 10 fractions of brachytherapy used for partial-breast irradiation or the 30 fractions of intensity-modulated radiation therapy used in some centers to deliver whole-breast irradiation.
“Proton partial-breast irradiation has the potential to provide better cost-effectiveness and more exact matching of the radiation to the tumor bed while avoiding adjacent tissues than other types of partial-breast irradiation,” Dr. Strom said.