NCIC MA.20 Trial: Addition of Regional Nodal Irradiation in Early Breast Cancer Improves Disease-Free but Not Overall Survival
In a phase III trial (National Cancer Institute of Canada [NCIC] Clinical Trials Group MA.20) reported in The New England Journal of Medicine, Whelan et al found that the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival in women with node-positive or high-risk node-negative breast cancer treated with breast-conserving surgery and adjuvant systemic therapy.
Study Details
In the study, 1,832 women were randomly assigned between March 2000 and February 2007 to undergo whole-breast irradiation with (n = 916) or without (n = 916) regional nodal irradiation, including internal mammary, supraclavicular, and axillary lymph nodes. All patients received adjuvant chemotherapy, endocrine therapy, or both. The primary outcome was overall survival.
The nodal-irradiation and control groups were generally balanced for age (median, 54 and 53 years), initial sentinel node biopsy (39% in both), axillary nodes removed (≥ 10 in 68% and 67%), number of positive axillary nodes (one in 50% and 49%, two in 23% and 25%), tumor size (≤ 2 cm 50% and 55%), estrogen receptor status (positive in 75% in both), progesterone receptor status (positive in 60% in both), adjuvant chemotherapy (anthracycline without taxane in 61% and 59%, anthracycline with taxane in 25% and 27%), adjuvant endocrine therapy (aromatase inhibitor in 57% and 58%, tamoxifen in 19% and 18%), and boost irradiation (32% and 35%).
Survival Results
Median follow-up was 9.5 years. At the 10-year follow-up, rates of overall survival were 82.8% in the nodal-irradiation group vs 81.8% in the control group (hazard ratio [HR] = 0.91, P = .38). Ten-year rates were 82.0% vs 77.0% for disease-free survival (HR = 0.76, P = 0.01), 95.2% vs 92.2% for isolated locoregional disease-free survival (HR = 0.59, P = .009), and 86.3% vs 82.4% for distant disease-free survival (HR = 0.76, P = .03).
Adverse Events
Among acute adverse events, rates of grade ≥ 2 pneumonitis (1.2% vs 0.2%, P =.01) and radiation dermatitis (49% vs 40%, P < .001) were higher in the nodal-irradiation group. Among delayed events, rates of grade ≥ 2 lymphedema (8.4% vs 4.5%, P = .001), skin telangiectasia (6.9% vs 4.3%, P = .02), and subcutaneous fibrosis (4.1% vs 2.0%, P = .01) were higher in the nodal-irradiation group. There was no difference between groups in rates of second cancers (11.0% vs 10.0%).
The investigators concluded: “Among women with node-positive or high-risk node-negative breast cancer, the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence.”
Timothy J. Whelan, BM, BCh, MSc, of McMaster University, Ontario, is the corresponding author for the New England Journal of Medicine article.
The study was funded by the Canadian Cancer Society Research Institute and others. For full disclosures of the study authors, visit www.nejm.org.
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