No Added Benefit of RT Hyperfractionation for LABC Pts

DENVER-In patients with noninflammatory locally advanced breast cancer (LABC), hyperfractionated radiation of the chest wall does not improve clinical outcomes relative to conventional radiation, according to long-term results of a trial presented at the 47th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (abstract 2008).

Investigators at M.D. Anderson Cancer Center undertook the randomized phase III trial to determine if altering the schedule of radiation improves the efficacy of radiation therapy in patients with LABC, lead author Thomas A. Buchholz, MD, told ONI in an interview. In particular, he and his colleagues note, some patients continue to have a risk of locoregional recurrence despite neoadjuvant chemotherapy, mastectomy, and conventional postmastec-tomy radiation therapy.

The patients studied were women with noninflammatory LABC participating in a trial of neoadjuvant chemotherapy (vincristine, doxorubicin, cyclophosphamide, and prednisone). A subset of 108 patients who underwent mastectomy were assigned to receive radiation therapy to the chest wall and internal mammary chain delivered either once-daily (50 Gy in 25 fractions, followed by a chest wall boost of 10 Gy) or twice-daily (60 Gy in 50 fractions, followed by a chest wall boost of 12 Gy). In addition, all patients received 50 Gy to the supraclavicular fossa and axillary apex.

Characteristics of the treatment groups did not differ significantly. In both groups, the majority of patients were 41 to 60 years old and had stage IIIA or IIIB, T3N0-1 tumors with positive or unknown estrogen-receptor status, and pathologic node-positive disease. Pathologic tumor size exceeded 2 cm in about half of patients and was unknown in about one-fifth.

Safety and Efficacy Results

In safety analyses, the incidence of any grade 3 or higher acute toxicity did not differ significantly between the once-daily and twice-daily radiation therapy groups (4% vs 5%, respectively), although the incidence of moderate moist desquamation tended to be lower with once-daily radiation (28% vs 42%).

With a median follow-up of 15 years, the actuarial rate of moderate-to-severe late toxicity did not differ significantly between the once-daily and twice-daily groups (6% vs 11%). The severe late events were rib fractures (2 cases), leukemia (2), soft tissue necrosis (2), severe telangiectasia (1), and severe cellulitis (1).

In efficacy analyses, patients treated with the once-daily and the twice-daily regimens had statistically indistinguishable 15-year actuarial rates of locoregional recurrence (5% vs 11%, respectively). In addition, the groups were similar in terms of rates of distant metastases and rates of overall survival.

No Further Studies Warranted

The results do not support a clinical benefit of hyperfractionated radiation therapy for postmastectomy radiation therapy in patients with LABC, the investigators concluded; moreover, despite the modest sample size, the findings do not warrant additional studies of this strategy. "This attempt of changing the radiation schedule did not work," Dr. Buchholz commented. "We should direct our efforts to exploring other mechanisms for enhancing radiation effects, such as combining radiation with some of the new biological therapies."