What are peoples thoughts on treating IMNs with the following EORTC study (much like MA.20) Irradiation of the internal mammary and medial supraclavicular lymph nodes in stage I to III breast cancer: 10 years results of the EORTC Radiation Oncology and Breast Cancer Groups phase III trial 22922/10925 P. Poortmans(1), H. Struikmans(2), C. Kirkove(3), V. Budach(4), P. Maingon(5), M.C. Valli(6), S. Collette(7), A. Fourquet(8), H. Bartelink(9), W. Van den Bogaert(10) (1)Institute Verbeeten, Radiation Oncology, Tilburg, Netherlands (2)RCWEST, Radiation Oncology, Den Haag, Netherlands (3)University Hospital St Luc, Radiation Oncology, Brussels, Belgium (4)Charité Universitaetsmedizin, Radiation Oncology, Berlin, Germany (5)Centre G.F.Leclerc, Radiation Oncology, Dijon, France (6)Hospital Sant Anna, Radiation Oncology, Como, Italy (7)EORTC, Headquarters, Brussels, Belgium (8)Institute Curie, Radiation Oncology, Paris, France (9)The Netherlands Cancer Institute, Radiation Oncology, Amsterdam, Netherlands (10)University Hospitals Leuven, Radiation Oncology, Leuven, Belgium Background: Locoregional radiation therapy (RT) improves overall survival in patients with involved lymph nodes (LN). EORTC trial 22922-10925 investigates how much RT to the internal mammary and medial supraclavicular LN (IM-MS) contributes to this effect (Clinicaltrials.gov NCT00002851). Material and methods: Eligible patients had involved axillary LN and/or a medially located primary tumour. Randomisation was to yes or no IM-MS RT to 50 Gy in 25 fractions. 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 Logrank test at the 5% significance level. Secondary endpoints are disease-free survival (DFS), metastases-free survival (MFS) and cause of death. 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. The majority (76.1%) was treated with breast conserving therapy, in 85.1% with a boost to the primary tumour bed. After mastectomy, chest wall irradiation was applied to 73.2% of patients in both arms. Axillary RT was given in 6.8% patients of the no IM-MS group and in 7.8% patients of the IM-MS group. Nearly all LN-positive (99.0%) and 66.3% of LN-negative patients received adjuvant systemic treatment. At a median follow-up of 10.9 years, 811 patients have died. IM-MS RT improved outcome at 10 years: 82.3 vs. 80.7% OS (HR=0.87 (95%CI: 0.76, 1.00), Logrank p=0.056); 72.1 vs. 69.1% DFS (HR=0.89 (95%CI: 0.80, 1.00), Logrank p=0.044); 78.0 vs. 75.0% MFS (HR=0.86 (95%CI: 0.76, 0.98), Logrank p=0.020). The treatment effect on OS was independent from the number of involved LN: HR = 0.79 (95%CI: 0.61, 1.02) for LN-negative; 0.89 (95%CI: 0.73, 1.09) for 1-3; 0.85 (95%CI: 0.61, 1.18) for 4-9 and 1.00 (95%CI: 0.59, 1.71) for 10+ involved axillary LN (p>0.1 for heterogeneity). In the IM-MS group 382 patients died vs. 429 patients in the no IM-MS group. The causes of death were similar except for breast cancer (259 vs. 310). No increase in lethal complications was observed so far. Conclusions: With a median follow-up of 10 years, postoperative RT to the IM-MS LN shows to improve overall, disease free and metastases free survival in patients with stage I-III breast cancer without an increase in non-breast cancer related mortality. Combined with the earlier report of good tolerance and limited toxicity up to 3 years, we advise radiation therapy to the internal mammary and medial supraclavicular lymph nodes for patients with involved axillary LN and/or a medially located primary tumour.