The EORTC 22922/10925 trial investigating regional nodal irradiation in stage I-III breast cancer: Outcomes according to locoregional and systemic therapies

• Published in: Radiotherapy and oncology Vol. 201; p. 110563
• Main Authors: Kaidar-Person, Orit, Boersma, Liesbeth J., De Brouwer, Peter, Weltens, Caroline, Kirkove, Carine, Peignaux-Casasnovas, Karine, Budach, Volker, van der Leij, Femke, Peters, Max, Weidner, Nicola, Rivera, Sofia, van Tienhoven, Geertjan, Fourquet, Alain, Noel, Georges, Valli, Mariacarla, Guckenberger, Matthias, Koiter, Eveline, Racadot, Severine, Abdah-Bortnyak, Roxolyana, Bartelink, Harry, Struikmans, Henk, Fortpied, Catherine, Poortmans, Philip M.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.12.2024
• Subjects: Axilla; Breast cancer; EORTC; Internal mammary; Radiation; Radiotherapy; Internal mammary; Axilla; Breast cancer; Radiotherapy; EORTC; Radiation
• ISSN: 0167-8140; 1879-0887; 1879-0887
• DOI: 10.1016/j.radonc.2024.110563

•The EORTC 22922/10925 trial aimed to investigate the impact of elective internal mammary and medial supraclavicular (IM-MS) radiation therapy (RT) in breast cancer stage I–III, allowing for different locoregional and systematic therapies according to physician’s preference.•Different components of therapy influenced the site of the first breast cancer event.•More “intensive” local therapy: RT boost, mastectomy – reduced the risk for local and/or regional recurrence as first event – but these patients had more distant metastases as first event because of higher risk factors and less competing events.•IM-MS RT reduced regional recurrence as first event, with a borderline effect in reducing distant metastases as first event.•Breast cancer stage is a major driver of outcome regardless of the extent of therapy. The EORTC 22922/10925 trial aimed to investigate the impact on overall survival (OS) of elective internal mammary and medial supraclavicular (IM-MS) radiation therapy (RT) in breast cancer stage I–III. Surgery for the primary tumour and axillary lymph nodes, chest wall RT, boost RT after whole breast RT in breast conserving therapy (BCT), RT to operated axilla, and systemic therapy were per physician’s preference. The aim of the current analysis is to assess breast cancer outcomes according to different locoregional and systemic therapy used in the trial. Data with a median follow-up of 15.7 years were extracted from the trial’s case report forms. Kaplan-Meier curves of disease-free and OS and cumulative incidence curves of breast cancer events were produced. An exploratory analysis of the effect of the type of locoregional and systemic therapy on breast cancer outcomes was conducted using the Cox model or the Fine & Gray model accounting for competing risks, both models being adjusted for baseline patient and disease characteristics and treatment. The significance level was set at 5 %, 2-sided. Of the 4,004 patients included, 625 (16%) did not receive any postoperative systemic therapy, 1,185 (30%) received endocrine therapy only, 994 (25%) chemotherapy only, and 1,200 (30%) both chemotherapy and endocrine therapy, without differences between the randomisation arms. Administration and type of therapy was associated with age, menopausal status, clinical T- and N-stage and ER status (p < 0.0001). Local control was better with mastectomy (with/without postmastectomy RT) as compared to BCT, but mastectomy was associated with more distant metastasis (DM) as first event. Similarly, DM as first event occurred more in the BCT group that received a boost as compared to no boost and in those who received RT to the lower axillary level. IM-MS RT reduced significantly regional recurrences and improved disease-free survival in a sensitivity stratified analysis. OS was worse with mastectomy as compared to BCT and with irradiation of the axilla but better with sentinel node dissection and adjuvant combined chemo and hormonal therapy. Different components of therapy influenced the site of first event. IM-MS RT improved outcomes in different breast cancer outcomes were most probably related that the group were balanced due to the trial arms and stratification methods.