On November 18, 2020 EORTC reported that Results of the 15-year update of the EORTC 22922/10925 phase III trial on internal mammary and medial supraclavicular (IM-MS) lymph node irradiation in stage I–III breast cancer were published in The Lancet Oncology journal this month1 (Press release, EORTC, NOV 18, 2020, https://www.eortc.org/blog/2020/11/18/15-year-follow-up-of-eortc-22922-10925-phase-iii-trial-shows-reduction-in-breast-cancer-mortality-and-recurrence-but-does-not-confirm-improved-overall-survival/ [SID1234571309]).

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This trial assessed the impact on overall survival of elective IM-MS irradiation. Breast cancer can spread to the regional lymph nodes, through the axillary and internal mammary nodes to the medial supraclavicular nodes. Traditionally, non-metastasised breast cancer is treated by surgical resection of the primary tumour with surgical axillary staging and, in case of involved axillary lymph nodes, elective nodal irradiation of the non-dissected axillary, the internal mammary and medial supraclavicular lymph nodes. While studies have shown a favourable effect of locoregional postoperative irradiation, an increased risk of non-breast cancer-related mortality was also seen, which is assumed to be due to radiation on the heart, resulting in some centres continuing to use locoregional nodal treatment while others restricting their treatments.

This trial was conducted across 46 radiation oncology departments from 13 countries. A total of 4004 patients, up to the age of 75, with unilateral stage I–III adenocarcinoma of the breast, with axillary nodal involvement and/or a primary tumour located centrally or in the medial quadrants of the breast, were randomised to IM-MS irradiation or no IM-MS irradiation. Surgery consisted of mastectomy or breast-conserving surgery and axillary lymph node dissection or sentinel lymph node biopsy.

Results showed that 27·7% patients in the IM-MS irradiation group and 28·4% patients in the control group had died. Overall survival rate at 15 years was 73·1% in the IM-MS irradiation group and 70·9% in the control group. Breast cancer recurrence and breast cancer mortality rates at 15 years were lower in the IM-MS irradiation group (24.5% and 16·0% respectively) than in the control group (27.1% and 19·8%, respectively). No significant differences were seen in the IM-MS irradiation group versus the control group for disease-free survival, or distant metastasis-free survival. Causes of death between groups were similar.

After a follow-up of 10.9 years, the study showed that regional nodal irradiation improved overall disease-free survival, distant disease-free survival, and breast cancer mortality. At 15·7 years of follow-up, the trial confirmed a significant reduction of breast cancer-related mortality and any recurrence after medial supraclavicular and internal mammary lymph node irradiation in stage I–III breast cancer. However, this is not translated into improved overall survival. Remarkably, toxicity after IM-MS irradiation was very limited, without an increased non-breast cancer related mortality.

Philip PoortmansProfessor Philip Poortmans, Principal Investigator of the study, from Iridium Kankernetwerk and Faculty of Medicine and Health Sciences, University of Antwerp, Belgium commented: "The 15-year results of the EORTC trial hoped to shed light in the uncertainties surrounding selecting the right breast cancer patients for more extensive regional lymph node treatment. Unfortunately, it is not clear yet. For the time being, supported by the low level of side effects, we advise elective nodal irradiation for patients at high risk for recurrence, especially in case of a long-life expectancy and providing that modern volume-based treatment techniques are used. We continue follow-up up to 20 years and contribute to the ongoing EBCTCG meta-analysis, both helping to sort out the remaining questions."