Fifteen-year results of the randomised EORTC trial 22922/10925 investigating internal mammary and medial supraclavicular (IM-MS) lymph node irradiation in stage I-III breast cancer.

Abstract

504 Background: EORTC trial 22922-10925 investigates whether internal mammary and medial supraclavicular (IM-MS) lymph nodes (LN) irradiation improves outcome for stage I-III breast cancer patients (Clinicaltrials.gov NCT00002851). The 10 years analysis showed an improvement of 3.0% in metastases free survival (p = 0.02) and of 1.6% in overall survival (p = 0.056). Toxicity was limited and no increased lethal side effects were seen. This is the second of 3 scheduled analyses, at 15-year follow-up. Methods: Eligible patients had involved axillary nodes and/or a medially located primary tumour. Randomisation was to irradiate or not the IM-MS. The final trial design aimed at detecting a 4% increase in 10-year overall survival (OS) (from 75 to 79%, HR = 0.82) with 2-sided unadjusted Log-rank test at the 5% significance level. Secondary endpoints are disease-free survival (DFS), metastases-free survival (MFS) and cause of death. Two long-term analyses were planned, at respectively 15 and 20 years of follow-up. Results: Between 1996 and 2004, 4004 patients were randomized in 43 centres. Median age was 54 years; 59.0% were postmenopausal; 55.6% had involved axillary LN; 33.8%, 52.0% and 14.2% had stage I, II and III, respectively. Nearly all LN-positive (99.0%) and 66.3% of LN-negative patients received adjuvant systemic treatment. At a median follow-up of 15.7 years, 1117 patients died. At 15 years, overall survival was 73.2% in the nodal-irradiation group and 70.8% in the control group (HR IM-MS RT vs. control = 0.95; 95%CI, 0.84-1.06;P = 0.358).). Regional recurrences in IM-MS LN occurred in 1.8% vs. 3.1% of patients. Distant disease-free survival rate was 70.1% vs. 68.1% (HR = 0.92; 95%CI, 0.83-1.04; P = 0.178), breast-cancer mortality was 15.8% vs. 19.7% (HR = 0.81; 95%CI, 0.69-0.94; P = 0.005). Probability of breast cancer recurrence was 24.5% vs. 27.1% (HR = 0.87; 95%CI, 0.77-0.98; P = 0.024. No difference was observed in the incidence of second malignancies, contralateral breast cancer or cardiovascular deaths. Conclusions: The 15-years results show a significant reduction of breast cancer mortality and breast cancer recurrence by internal mammary and medial supraclavicular lymph node irradiation in stage I-III breast cancer. However, this is not converted in improved overall survival without a clear explanation for this. Subgroup analyses and continued follow-up will be performed to better define patients that may benefit from this treatment and define the causes of death. Clinical trial information: NCT00002851.