As reported in The Lancet Oncology by Kaidar-Person et al, an unplanned subset analysis at 20 years in the phase III EORTC trial 22922/10925 showed that internal mammary and medial supraclavicular (IM-MS) nodal irradiation was associated with a significantly lower rate of breast cancer mortality—but no benefit in non–breast cancer mortality—compared with no IM-MS in patients with node-negative stage I to III breast cancer.
Study Details
In the trial, 4,004 women with stage I to III disease were randomly assigned to receive postsurgery IM-MS irradiation at 50 Gy in 25 fractions (IM-MS irradiation group) or no IM-MS irradiation (control group). The current analysis was confined to the subgroup of 890 patients (44.5%) in the IM-MS irradiation group and 888 patients (44.4%) in the control group with pN0 disease. Patients had a median age of 55 years. The primary outcome measure was overall survival.
Key Findings
At a median follow-up of 22.2 years (interquartile range = 20.1–24.5 years), 276 (31.1%) of 888 patients in the IM-MS irradiation group and 277 (31.1%) of 890 patients in the control group had died due to any cause; 87 (31.5%) of 276 deaths and 122 (44.0%) of 277 deaths were due to breast cancer.
At 20 years, the overall survival rate was 69.0% (95% confidence interval [CI] = 65.4%–72.3%) in the IM-MS irradiation group and 68.4% (95% CI = 64.8%–71.6%) in the control group (hazard ratio [HR] = 0.98, 95% CI = 0.83–1.15, P = .77). At 20 years, the breast cancer mortality rate was 10.0% (95% CI = 8.0%–12.3%) in the IM-MS irradiation group and 14.2% (95% CI = 11.9%–16.8%) in the control group (HR = 0.70, 95% CI = 0.53–0.92, P = .010). However, the cumulative mortality of unknown cause or non–breast cancer cause was higher in the IM-MS irradiation group after 15 years and reached 20.9% (95% CI = 17.9%–24.1%) at 20 years, compared with 17.4% (95% CI = 14.7%–20.3%) in the control group (HR = 1.24, 95% CI = 1.00–1.53, P = .048).
Among patients with left-sided breast cancer, late cardiac fibrosis occurred in 15 (3.4%) of 445 patients in the IM-MS irradiation group and 12 (2.8%) of 436 patients in the control group. Among all patients, lung fibrosis of any grade occurred in 6.4% and 2.1% of patients.
The investigators concluded: “Breast cancer mortality at 20 years was significantly lower in the IM-MS irradiation group, whereas non–breast cancer mortality was numerically higher in the IM-MS irradiation group after 15 years, resulting in no long-term benefit of IM-MS irradiation on overall survival. Our results emphasize the importance of very long–term follow-up and advanced irradiation techniques to reduce the dose to organs of interest.”
Philip Poortmans, PhD, of Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk-Antwerp, Belgium, is the corresponding author for The Lancet Oncology article.
DISCLOSURE: The study was funded by the Ligue Nationale contre le Cancer, KWF Kankerbestrijding, and EORTC Cancer Research Fund. For full disclosures of the study authors, visit thelancet.com.
