Philip M Poortmans1, Caroline Weltens2, Catherine Fortpied3, Carine Kirkove4, Karine Peignaux-Casasnovas5, Volker Budach6, Femke van der Leij7, Ernest Vonk8, Nicola Weidner9, Sofia Rivera10, Geertjan van Tienhoven11, Alain Fourquet12, Georges Noel13, Mariacarla Valli14, Matthias Guckenberger15, Eveline Koiter16, Severine Racadot17, Roxolyana Abdah-Bortnyak18, Erik F Van Limbergen2, Antoine Engelen19, Peter De Brouwer19, Henk Struikmans20, Harry Bartelink21. 1. Department of Radiation Oncology, Iridium Kankernetwerk, Wilrijk-Antwerp, Belgium; Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk-Antwerp, Belgium. Electronic address: philip.poortmans@telenet.be. 2. Department of Radiation Oncology, University Hospital Leuven, Leuven, Belgium; Department of Oncology, Faculty of Medicine, KU Leuven, Leuven, Belgium. 3. European Organisation for Research and Treatment of Cancer, Brussels, Belgium. 4. Department of Radiation Oncology, University Hospital Saint Luc, Université Catholique de Louvain, Brussels, Belgium. 5. Department of Radiation Oncology, Centre Georges François Leclerc, Dijon, France. 6. Department of Radiation Oncology and Radiotherapy, Comprehensive Cancer Center, Charite University Medicine, Berlin, Germany. 7. Department of Radiation Oncology, University Medical Centre Utrecht, Utrecht, Netherlands. 8. Radiotherapiegroep, Deventer, Netherlands. 9. Department of Radiation Oncology, University Hospital, Tübingen, Germany. 10. Department of Radiation Oncology, Gustave Roussy Cancer Centre, Villejuif, France. 11. Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Netherlands. 12. Department of Radiation Oncology, Institut Curie, Paris, France. 13. Department of Radiation Oncology, Institut de Cancérologie Strasbourg-Europe, Strasbourg, France. 14. Department of Radiation Oncology, Sant Anna Hospital, Como, Italy. 15. Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Switzerland. 16. Department of Radiation Oncology, Medisch Spectrum Twente, Enschede, Netherlands. 17. Department of Radiation Oncology, Centre Léon Bérard, Lyon, France. 18. Department of Radiation Oncology, Rambam Health Care Campus, Haifa, Israel. 19. Department of Radiation Oncology, Institute Verbeeten, Tilburg, Netherlands. 20. Department of Radiation Oncology, Leiden University Medical Centre, Leiden, Netherlands. 21. Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands.
Abstract
BACKGROUND: 10-year results from several studies showed improved disease-free survival and distant metastasis-free survival, reduced breast cancer-related mortality, and variable effects on overall survival with the addition of partial or comprehensive regional lymph node irradiation after surgery in patients with breast cancer. We present the scheduled 15-year analysis of the European Organisation for Research and Treatment of Cancer (EORTC) 22922/10925 trial, which aims to investigate the impact on overall survival of elective internal mammary and medial supraclavicular (IM-MS) irradiation. METHODS: EORTC 22922/10925, a randomised, phase 3 trial done across 46 radiation oncology departments from 13 countries, included women up to 75 years of age with unilateral, histologically confirmed, stage I-III breast adenocarcinoma with involved axillary nodes or a central or medially located primary tumour. Surgery consisted of mastectomy or breast-conserving surgery and axillary staging. Patients were randomly assigned (1:1) centrally using minimisation to receive IM-MS irradiation at 50 Gy in 25 fractions (IM-MS irradiation group) or no IM-MS irradiation (control group). Stratification was done for institution, menopausal status, site of the primary tumour within the breast, type of breast and axillary surgery, and pathological T and N stage. Patients and investigators were not masked to treatment allocation. The primary endpoint was overall survival analysed according to the intention-to-treat principle. Secondary endpoints were disease-free survival, distant metastasis-free survival, breast cancer mortality, any breast cancer recurrence, and cause of death. Follow-up is ongoing for 20 years after randomisation. This study is registered with ClinicalTrials.gov, NCT00002851. FINDINGS:Between Aug 5, 1996, and Jan 13, 2004, we enrolled 4004 patients, of whom 2002 were randomly assigned to the IM-MS irradiation group and 2002 to the no IM-MS irradiation group. At a median follow-up of 15·7 years (IQR 14·0-17·6), 554 (27·7%) patients in the IM-MS irradiation group and 569 (28·4%) patients in the control group had died. Overall survival was 73·1% (95% CI 71·0-75·2) in the IM-MS irradiation group and 70·9% (68·6-72·9) in the control group (HR 0·95 [95% CI 0·84-1·06], p=0·36). Any breast cancer recurrence (24·5% [95% CI 22·5-26·6] vs 27·1% [25·1-29·2]; HR 0·87 [95% CI 0·77-0·98], p=0·024) and breast cancer mortality (16·0% [14·3-17·7] vs 19·8% [18·0-21·7]; 0·81 [0·70-0·94], p=0·0055) were lower in the IM-MS irradiation group than in the control group. No significant differences in the IM-MS irradiation group versus the control group were seen for disease-free survival (60·8% [95% CI 58·4-63·2] vs 59·9% [57·5-62·2]; HR 0·93 [95% CI 0·84-1·03], p=0·18), or distant metastasis-free survival (70·0% [67·7-72·2] vs 68·2% [65·9-70·3]; 0·93 [0·83-1·04], p=0·18). Causes of death between groups were similar. INTERPRETATION: The 15-year results show a significant reduction of breast cancer mortality and any breast cancer recurrence by IM-MS irradiation in stage I-III breast cancer. However, this is not converted to improved overall survival. FUNDING: US National Cancer Institute, Ligue Nationale contre le Cancer, and KWF Kankerbestrijding.
RCT Entities:
BACKGROUND: 10-year results from several studies showed improved disease-free survival and distant metastasis-free survival, reduced breast cancer-related mortality, and variable effects on overall survival with the addition of partial or comprehensive regional lymph node irradiation after surgery in patients with breast cancer. We present the scheduled 15-year analysis of the European Organisation for Research and Treatment of Cancer (EORTC) 22922/10925 trial, which aims to investigate the impact on overall survival of elective internal mammary and medial supraclavicular (IM-MS) irradiation. METHODS: EORTC 22922/10925, a randomised, phase 3 trial done across 46 radiation oncology departments from 13 countries, included women up to 75 years of age with unilateral, histologically confirmed, stage I-III breast adenocarcinoma with involved axillary nodes or a central or medially located primary tumour. Surgery consisted of mastectomy or breast-conserving surgery and axillary staging. Patients were randomly assigned (1:1) centrally using minimisation to receive IM-MS irradiation at 50 Gy in 25 fractions (IM-MS irradiation group) or no IM-MS irradiation (control group). Stratification was done for institution, menopausal status, site of the primary tumour within the breast, type of breast and axillary surgery, and pathological T and N stage. Patients and investigators were not masked to treatment allocation. The primary endpoint was overall survival analysed according to the intention-to-treat principle. Secondary endpoints were disease-free survival, distant metastasis-free survival, breast cancer mortality, any breast cancer recurrence, and cause of death. Follow-up is ongoing for 20 years after randomisation. This study is registered with ClinicalTrials.gov, NCT00002851. FINDINGS: Between Aug 5, 1996, and Jan 13, 2004, we enrolled 4004 patients, of whom 2002 were randomly assigned to the IM-MS irradiation group and 2002 to the no IM-MS irradiation group. At a median follow-up of 15·7 years (IQR 14·0-17·6), 554 (27·7%) patients in the IM-MS irradiation group and 569 (28·4%) patients in the control group had died. Overall survival was 73·1% (95% CI 71·0-75·2) in the IM-MS irradiation group and 70·9% (68·6-72·9) in the control group (HR 0·95 [95% CI 0·84-1·06], p=0·36). Any breast cancer recurrence (24·5% [95% CI 22·5-26·6] vs 27·1% [25·1-29·2]; HR 0·87 [95% CI 0·77-0·98], p=0·024) and breast cancer mortality (16·0% [14·3-17·7] vs 19·8% [18·0-21·7]; 0·81 [0·70-0·94], p=0·0055) were lower in the IM-MS irradiation group than in the control group. No significant differences in the IM-MS irradiation group versus the control group were seen for disease-free survival (60·8% [95% CI 58·4-63·2] vs 59·9% [57·5-62·2]; HR 0·93 [95% CI 0·84-1·03], p=0·18), or distant metastasis-free survival (70·0% [67·7-72·2] vs 68·2% [65·9-70·3]; 0·93 [0·83-1·04], p=0·18). Causes of death between groups were similar. INTERPRETATION: The 15-year results show a significant reduction of breast cancer mortality and any breast cancer recurrence by IM-MS irradiation in stage I-III breast cancer. However, this is not converted to improved overall survival. FUNDING: US National Cancer Institute, Ligue Nationale contre le Cancer, and KWF Kankerbestrijding.
Authors: Raymond B Mailhot Vega; Shu Wang; Eric D Brooks; Oluwadamilola T Oladeru; Natalie A Lockney; Lisa E Spiguel; Shannon M MacDonald; Eleftherios P Mamounas; Nancy P Mendenhall; Paul G Okunieff; Ji-Hyun Lee; Julie A Bradley Journal: Int J Radiat Oncol Biol Phys Date: 2022-03-29 Impact factor: 8.013