Twenty‐year results of the randomized European Organization for Research and Treatment of Cancer trial 22922/10925 evaluating internal mammary chain and medial supraclavicular lymph node irradiation in stage I–III breast cancer

O Orit Kaidar‐Person (Oncology Institute Sheba Medical Center Ramat Gan Israel) C Caroline G. Weltens (Department of Radiation Oncology University Hospitals Leuven Leuven Belgium) C Catherine Fortpied (European Organization for Research and Treatment of Cancer Brussels Belgium) L Luc J. E. E. Scheijmans (Department of Radiation Oncology Institute Verbeeten Tilburg Netherlands) C Carine Y. Kirkove (Department of Radiation Oncology University Hospital Saint Luc Université Catholique de Louvain Brussels Belgium) V Volker Budach (Department of Radiation Oncology Comprehensive Cancer Center Charite–University Medicine Berlin Corporate Member of Free University of Berlin and Humboldt University of Berlin BE Berlin Germany) K Karine Peignaux‐Casasnovas (Department of Radiation Oncology Centre Georges François Leclerc Dijon France) M Mariacarla Valli (Department of Radiation Oncology Sant Anna Hospital Como Italy) M Max Peters (Department of Radiation Oncology Radiotherapiegroep Deventer/Arnhem Netherlands) F Femke van der Leij (Department of Radiation Oncology University Medical Centre Utrecht Utrecht Netherlands) S Sofia Rivera (Department of Radiation Oncology Gustave Roussy Cancer Centre Villejuif France) N Nicola Weidner (Department of Radiation Oncology University Hospital Tübingen Germany) D Desirée H. J. G. van den Bongard (Department of Radiation Oncology Cancer Center Amsterdam Amsterdam University Medical Center University of Amsterdam Amsterdam Netherlands) C Claudia Linsenmeier (Department of Radiation Oncology University Hospital Zürich University of Zürich Zürich Switzerland) R Roxolyana Abdah‐Bortnyak (Department of Radiation Oncology The Joseph Fishman Oncology Center Rambam Health Care Campus Haifa Israel) S Shaymaa Hosni (Nottingham University Hospitals National Health Service Trust Nottingham UK) E Eveline Koiter (Department of Radiation Oncology Medisch Spectrum Twente Enschede Netherlands) A Antoine M. Engelen (Department of Radiation Oncology Institute Verbeeten Tilburg Netherlands) A Adinda Baten (Department of Radiation Oncology University Hospitals Leuven Leuven Belgium) L Lydia Champezou (European Organization for Research and Treatment of Cancer Brussels Belgium) A Alain Fourquet (Department of Radiation Oncology Institut Curie Paris France) H Harry G. M. M. Bartelink (Department of Radiation Oncology Netherlands Cancer Institute Amsterdam Netherlands) H Henk Struikmans (Department of Radiation Oncology Haaglanden Medical Center the Hague Leidschendam Netherlands) P Philip M. P. Poortmans (Department of Radiation Oncology Iridium Netwerk Wilrijk‐Antwerp Belgium)

Abstract

Abstract European Organization for Research and Treatment of Cancer trial EORTC 22922/10925 evaluated internal mammary and medial supraclavicular (IM‐MS) lymph node irradiation (IM‐MS‐RT) in patients with stage I–III breast cancer. Eligible patients had involved axillary nodes and/or centrally/medially located tumors regardless of nodal involvement. The primary end point was overall survival, secondary end points were disease‐free survival, distant metastases‐free survival, breast cancer mortality, and any breast recurrence. Between 1996 and 2004, 4004 patients were randomized. The median patient age was 54 years. At a median follow‐up of 22.2 years, 1550 (38.7%) patients died, of whom 796 (51.4%) died from breast cancer. At 20 years, the overall survival rate was 61.8% in the control group versus 61.0% in the IM‐MS‐RT group (hazard ratio [HR], 1.00; p  = .967); the disease‐free survival rate was 49.0% versus 48.2%, respectively (HR, 0.97; p  = .515); and the distant metastases‐free survival rate was 59.8% versus 58.9%, respectively (HR, 0.97; p  = .578). The breast cancer mortality rate was 22.4% in the control group and 18.6% in the IM‐MS‐RT group (HR, 0.82; p  = .006), whereas the rate of deaths not from breast cancer or from unknown causes was 15.8% versus 20.4%, respectively (HR, 1.26; p  = .002). Lung fibrosis, cardiac fibrosis, and cardiac diseases were more frequent after IM‐MS‐RT versus no IM‐MS‐RT (6.3% vs. 3.2%, 2.7% vs. 1.7%. and 15.2% vs. 11.7%, respectively); and the rates of severe cardiac and lung morbidities (scores of 3 or 4) were 1.9% versus 1.7% and 0.3% versus 0.0%, respectively. Breast cancer mortality at 20 years was statistically significantly lower after IM‐MS‐RT, but deaths not from breast cancer increased after 15 years, resulting in no long‐term benefit of IM‐MS‐RT on overall survival. Therefore, the authors strongly call for very long‐term follow‐up of treatments for prognostically favorable cancers such as breast cancer.

Article Details

Volume / Issue Vol. 76, Issue 3
Published May 01, 2026
ISSN 0007-9235
Publisher Wiley

Journal Info

CA: A Cancer Journal for Clinicians

Wiley

ISSN: 0007-9235 Open Access Q1 Medicine

Authors (24)

O

Orit Kaidar‐Person

Oncology Institute Sheba Medical Center Ramat Gan Israel

C

Caroline G. Weltens

Department of Radiation Oncology University Hospitals Leuven Leuven Belgium

C

Catherine Fortpied

European Organization for Research and Treatment of Cancer Brussels Belgium

L

Luc J. E. E. Scheijmans

Department of Radiation Oncology Institute Verbeeten Tilburg Netherlands

C

Carine Y. Kirkove

Department of Radiation Oncology University Hospital Saint Luc Université Catholique de Louvain Brussels Belgium

V

Volker Budach

Department of Radiation Oncology Comprehensive Cancer Center Charite–University Medicine Berlin Corporate Member of Free University of Berlin and Humboldt University of Berlin BE Berlin Germany

K

Karine Peignaux‐Casasnovas

Department of Radiation Oncology Centre Georges François Leclerc Dijon France

M

Mariacarla Valli

Department of Radiation Oncology Sant Anna Hospital Como Italy

M

Max Peters

Department of Radiation Oncology Radiotherapiegroep Deventer/Arnhem Netherlands

F

Femke van der Leij

Department of Radiation Oncology University Medical Centre Utrecht Utrecht Netherlands

S

Sofia Rivera

Department of Radiation Oncology Gustave Roussy Cancer Centre Villejuif France

N

Nicola Weidner

Department of Radiation Oncology University Hospital Tübingen Germany

D

Desirée H. J. G. van den Bongard

Department of Radiation Oncology Cancer Center Amsterdam Amsterdam University Medical Center University of Amsterdam Amsterdam Netherlands

C

Claudia Linsenmeier

Department of Radiation Oncology University Hospital Zürich University of Zürich Zürich Switzerland

R

Roxolyana Abdah‐Bortnyak

Department of Radiation Oncology The Joseph Fishman Oncology Center Rambam Health Care Campus Haifa Israel

S

Shaymaa Hosni

Nottingham University Hospitals National Health Service Trust Nottingham UK

E

Eveline Koiter

Department of Radiation Oncology Medisch Spectrum Twente Enschede Netherlands

A

Antoine M. Engelen

Department of Radiation Oncology Institute Verbeeten Tilburg Netherlands

A

Adinda Baten

Department of Radiation Oncology University Hospitals Leuven Leuven Belgium

L

Lydia Champezou

European Organization for Research and Treatment of Cancer Brussels Belgium

A

Alain Fourquet

Department of Radiation Oncology Institut Curie Paris France

H

Harry G. M. M. Bartelink

Department of Radiation Oncology Netherlands Cancer Institute Amsterdam Netherlands

H

Henk Struikmans

Department of Radiation Oncology Haaglanden Medical Center the Hague Leidschendam Netherlands

P

Philip M. P. Poortmans

Department of Radiation Oncology Iridium Netwerk Wilrijk‐Antwerp Belgium