EORTC Trial Shows Marginal Overall Survival and Significant Disease-Free Survival Benefit of Adding Regional Nodal Irradiation in Early Breast Cancer
In a phase III trial conducted by the European Organisation for Research and Treatment of Cancer (EORTC) Radiation Oncology and Breast Cancer Groups, the addition of regional nodal irradiation to whole-breast or thoracic-wall irradiation after surgery produced a marginal overall survival benefit and a significant disease-free survival benefit in women with early-stage breast cancer. The study was reported by Poortmans and colleagues in The New England Journal of Medicine.
Study Details
In the study, 4,004 women with a centrally or medially located primary tumor, irrespective of axillary involvement, or an externally located tumor with axillary involvement were randomly assigned between 1996 and 2004 to undergo whole-breast or thoracic-wall irradiation with (n = 2,002) or without (n = 2,002) regional nodal irradiation (internal mammary and medial supraclavicular nodes) after surgery. The primary endpoint was overall survival.
The nodal-irradiation and control groups were balanced for age (median, 54 years in both), surgery (mastectomy in 24% in both, breast-conserving in 76% in both), tumor size (≤ 2 cm in 60% in both), number of involved axillary nodes (0 in 44% in both, 1–3 in 43% in both), and adjuvant treatment (none in 16% and 15%, chemotherapy in 25% in both, hormonal therapy in 29% and 30%, both in 30% in both). Among patients undergoing mastectomy, 73% of the patients in both groups underwent chest-wall irradiation. Adjuvant systemic treatment was received by 99% of patients with node-positive disease and 66% of patients with node-negative disease.
Survival Results
Median follow-up was 10.9 years. Rates of overall survival at 10 years were 82.3% in the nodal-irradiation group vs 80.7% in the control group (hazard ratio [HR] = 0.87, P = .06). Ten-year rates were 72.1% vs 69.1% for disease-free survival (HR = 0.89, P = .04), 78.0% vs 75.0% for distant disease-free survival (HR = 0.86, P = .02), and 12.5% vs 14.4% for breast cancer mortality (HR = 0.82, P = .02). A greater overall survival benefit appeared to be associated with nodal irradiation among patient who received both adjuvant chemotherapy and hormonal therapy (HR = 0.72, 95% confidence interval = 0.55–0.94).
Adverse Events
Acute side effects of regional nodal irradiation were reported to be modest. Among long-term effects, pulmonary fibrosis occurred in 4.4% of the nodal irradiation group vs 1.7% of the control group (P < .001), cardiac fibrosis occurred in 1.2% vs 0.6% (P = .06), and cardiac disease occurred in 6.5% vs 5.6% (P = .25). Second cancers were observed in 9.5% vs 11.1%.
The investigators concluded: “In patients with early-stage breast cancer, irradiation of the regional nodes had a marginal effect on overall survival. Disease-free survival and distant disease-free survival were improved, and breast-cancer mortality was reduced.”
Philip Poortmans, PhD, of Radboud University, the Netherlands, is the corresponding author for the New England Journal of Medicine article.
The study was funded by Fonds Cancer. For full disclosures of the study authors, visit www.nejm.org.
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