In the National Cancer Institute of Canada Clinical Trials Group MA.20 trial, regional irradiation to the lymph nodes (RNI) added to whole brain irradiation (WBI) improved disease-free survival (DFS), with a trend toward improved overall survival (OS), reported Timothy Whelan, MD, of McMaster University and the Juravinski Cancer Centre in Hamilton, Ontario.
Locoregional recurrences were reduced by 42% and distant recurrences by 36%. “Results from MA.20 suggest that all women with node-positive disease be offered regional node irradiation provided they are made aware of the associated toxicities,” Dr Whelan said.
Specialty guidelines recommend lo - coregional radiation after mastec tomy for women with tumors >5 cm or those who have >3 positive axillary lymph nodes. The benefit in women with 1 to 3 positive nodes has been unclear.
WBI may involve radiation to the lower axillae and some of the internal mammary nodes; RNI to the internal mammary, supraclavicular, and high axillary lymph nodes may provide added benefits to WBI, but it can be more toxic.
The MA.20 trial, therefore, evaluated the benefit of RNI added to WBI after breast-conserving surgery for women with node-positive or highrisk node-negative early breast cancer. The study randomized 1832 patients to WBI or to WBI plus RNI.
At a median follow-up of 62 months, the addition of RNI to WBI significantly improved DFS—preventing locoregional recurrences and, more surprisingly, recurrences elsewhere in the body. A nonsignificant trend toward improved OS was also seen.
DFS at 5 years, defined as any recurrence, contralateral breast cancer, or breast cancer death, was 84.0% in the WBI arm and 89.7% in the WBI/RNI arm, a significant 33% reduction in events. Locoregional DFS was 94.5% with WBI and 96.8% with WBI/RNI, a 42% reduction in risk.
The protection against distant recurrences was an unexpected benefit of the approach, Dr Whelan said. Distant DFS was 87.0% with WBI and 92.4% with WBI/RNI, representing a 36% risk reduction. At 5 years, 90.7% of the patients in the WBI group were alive compared with 92.3% in the WBI/RNI group, a 23% reduction in mortality.
The trade-off for a clinical improvement was an increased toxicity with the combined radiotherapy approach. Compared with WBI alone, the combination of WBI/RNI was associated with more episodes of radiation dermatitis (50% vs 40%, respectively; P <.001), pneumonitis (1.3% vs 0.2%; P = .01), and lymphedema (7% vs 4%; P = .004).
Although cosmetic outcomes were similar at 3 years, more of the RNI group considered the outcome “fair or poor” at 5 years (36% vs 29%, respectively).
Findings Are Practice-Changing
Thomas Buchholz, MD, of the University of Texas M.D. Anderson Cancer Center, Houston, commented that the findings “add to the conclusive evidence that radiation eradication of local-regional microscopic disease reduces subsequent distant metastases and can improve survival.” He said that the benefits of adding regional irradiation “now clearly outweigh the risks.”
“I agree with the investigators’ conclusions,” Dr Buchholz said. “We should offer RNI for higher-risk patients with 1 to 3 positive lymph nodes, but we should await additional data for low-risk patients with 1 to 3 nodes.”