Lymph Node Radiation Therapy in Patients With Stage I, Stage II, or Stage III Breast Cancer That Has Been Surgically Removed

PHASE III RANDOMISED TRIAL INVESTIGATING THE ROLE OF INTERNAL MAMMARY AND MEDIAL SUPRACLAVICULAR (IM-MS) LYMPH NODE CHAIN IRRADIATION IN STAGE I-III BREAST CANCER

RATIONALE: Radiation therapy may kill any tumor cells remaining after surgery.

PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared to no further therapy in treating women with stage I, stage II, or stage III breast cancer that has been surgically removed.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Procedure: adjuvant therapy; Radiation: low-LET electron therapy; Radiation: low-LET photon therapy

Detailed Description

OBJECTIVES:

• Compare the effect of irradiation of the homolateral internal mammary and medial supraclavicular lymph node chains vs no further therapy on survival, disease-free survival, metastasis-free survival, and cause of death in women with resected stage I/II/III breast cancer.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by participating institution, tumor location, type of prior breast surgery, pathologic T and N stage, menopausal status, and time sequence of radiotherapy and adjuvant chemotherapy. Patients are randomized to 1 of 2 arms.

• Arm I: Patients receive no nodal irradiation.
• Arm II: Patients receive irradiation of the internal mammary and medial supraclavicular lymph node chains delivered at 1 fraction per day, 5 sessions per week, for a total of 25 fractions over 5 weeks. Radiotherapy must begin no later than 8 weeks after surgery. If adjuvant chemotherapy is given, radiotherapy begins within 6 weeks after the last course of chemotherapy and within 8 months after surgery.

Patients are followed at least yearly after randomization for up to 20 years.

PROJECTED ACCRUAL: A total of 4,000 patients will be accrued for this study within 4 years.

• Study Type: Interventional
• Enrollment (Anticipated): 4000
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium, 2020
    • Ziekenhuis Network Antwerpen Middelheim
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-luc
  • Haine Saint Paul, Belgium, 7100
    • Hopital de Jolimont
  • Kortrijk, Belgium, B-8500
    • Cazk Groeninghe - Campus Maria's Voorzienigheid
  • Leuven, Belgium, B-3000
    • U.Z. Gasthuisberg
  • Wilrijk, Belgium, 2610
    • Algemeen Ziekenhuis Sint-Augustinus
• Bosnia and Herzegovina
  • Sarajevo, Bosnia and Herzegovina, 71000
    • Institute of Oncology - Clinical Center University of Sarajevo
• Chile
  • Santiago, Chile, 10
    • Instituto de Radiomedicina
  • Santiago, Chile, 5951
    • Clinica Alemana
• France
  • Besancon, France, 25030
    • CHR de Besancon - Hopital Jean Minjoz
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Dijon, France, 21079
    • Centre de Lutte Contre le Cancer Georges-Francois Leclerc
  • Grenoble, France, 38043
    • CHU de Grenoble - Hopital de la Tronche
  • Marseille, France, 13009
    • Service Cancerologie Polyclinique Clairval
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Rennes, France, 35042
    • Centre Eugene Marquis
  • Strasbourg, France, 67085
    • Centre Paul Strauss
  • Strasbourg, France, 67085
    • Centre Hospitalier Universitaire Henri Mondor
  • Strasbourg, France, 67085
    • Centre Léon Bérard
  • Strasbourg, France, 67085
    • Institut Gustave Roussy
• Germany
  • Berlin, Germany, D-10117
    • Charité - Campus Charité Mitte
  • Berlin, Germany, D-13122
    • Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch
  • Cologne, Germany, D-50924
    • Klinik I fuer Innere Medizin
  • Erlangen, Germany, DOH-91054
    • University of Erlangen-Nuremberg
  • Essen, Germany, D-45122
    • Universitaetsklinikum Essen
  • Goettingen, Germany, D-37075
    • Universitaetsklinikum Goettingen
  • Tuebingen, Germany, D-72076
    • Universitaetsklinikum Tuebingen
• Israel
  • Haifa, Israel, 31096
    • Rambam Medical Center
  • Ramat-Gan, Israel, 52621
    • Chaim Sheba Medical Center
• Italy
  • Como, Italy, 22100
    • Ospedale Sant Anna
  • Genoa (Genova), Italy, 16132
    • Istituto Nazionale per la Ricerca sul Cancro
• Netherlands
  • 's-Gravenhage (Den Haag, the Hague), Netherlands, 2501 CK
    • Medisch Centrum Haaglanden
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum
  • Blaricum, Netherlands, 1261 AN
    • Streekziekenhuis Gooi-Noord
  • Deventer, Netherlands, 7400 AC
    • Radiotherapeutisch Instituut-(Riso)
  • Enschede, Netherlands, 7500 KA
    • Medisch Spectrum Twente
  • Groningen, Netherlands, 9713 GZ
    • Academisch Ziekenhuis Groningen
  • Maastricht, Netherlands, NL-6229 ET
    • Radiotherapeutisch Instituut Limburg-Maastricht
  • Tilburg, Netherlands, 5042 SB
    • Dr. Bernard Verbeeten Instituut
  • Utrecht, Netherlands, 3584 CX
    • Academisch Ziekenhuis Utrecht
• Poland
  • Gdansk, Poland, 80-211
    • Medical University of Gdansk
• Portugal
  • Porto, Portugal, 4200-072
    • Instituto Portugues de Oncologia Centro do Porto, SA
• Spain
  • Barcelona, Spain, 08907
    • Institut Catala d'Oncologia
• Switzerland
  • Geneva, Switzerland, CH-1211
    • Hôpital Cantonal Universitaire de Genève
  • Lausanne, Switzerland, CH-1011
    • Centre Hospitalier Universitaire Vaudois
  • Zurich, Switzerland, CH-8091
    • UniversitaetsSpital
• Turkey
  • Istanbul, Turkey, 34390
    • Istanbul University-Institute of Oncology
• United Kingdom
  • England
    • Nottingham, England, United Kingdom, NG5 1PB
      • Nottingham City Hospital NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed unilateral adenocarcinoma of the breast

• Stage I/II/III (Tx, T0-3, N0-2) disease in one of the following categories or multifocal tumors if one of the foci is in agreement with the following:

  • Centrally or medially located with any lymph node status

    • Central location defined as underlying the areola
    • Medial location defined as at least partial involvement of upper or lower medial quadrant of breast
  • Externally located with axillary node involvement

• Prior mastectomy or breast-conserving surgery and axillary dissection required

  • Sentinel node procedure as axillary intervention without further axillary surgery is allowed
  • No prior internal mammary chain dissection

  • No upper inner lesion treated with breast-conserving surgery that precludes sparing of internal mammary lymph node chain from radiotherapy volume

    • Decision at radiation oncologist's discretion

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age:

• 75 and under

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• No prior cardiac disease

Other:

• No prior malignancy except adequately treated nonmelanomatous skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• See Disease Characteristics

Other:

• Concurrent enrollment in other randomized trials allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

Collaborators and Investigators

• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Investigators: Walter F. Van den Bogaert, MD, PhD, University Hospital, Gasthuisberg; H. Struikmans, MD, PhD, Medisch Centrum Haaglanden Westeinde; Alain Fourquet, MD, Institut Curie; Harry Bartelink, MD, PhD, The Netherlands Cancer Institute

Publications and helpful links

General Publications

• Matzinger O, Heimsoth I, Poortmans P, Collette L, Struikmans H, Van Den Bogaert W, Fourquet A, Bartelink H, Ataman F, Gulyban A, Pierart M, Van Tienhoven G; EORTC Radiation Oncology & Breast Cancer Groups. Toxicity at three years with and without irradiation of the internal mammary and medial supraclavicular lymph node chain in stage I to III breast cancer (EORTC trial 22922/10925). Acta Oncol. 2010;49(1):24-34. doi: 10.3109/02841860903352959.
• Musat E, Poortmans P, Van den Bogaert W, Struikmans H, Fourquet A, Bartelink H, Kirkove C, Budach V, Pierart M, Collette L. Quality assurance in breast cancer: EORTC experiences in the phase III trial on irradiation of the internal mammary nodes. Eur J Cancer. 2007 Mar;43(4):718-24. doi: 10.1016/j.ejca.2006.11.015. Epub 2007 Jan 19.
• Poortmans P, Kouloulias V, van Tienhoven G, Collette L, Struikmans H, Venselaar JL, Van den Bogaert W, Davis JB, Lambin P; EORTC Radiation Oncology and Breast Cancer Groups. Quality assurance in the EORTC randomized trial 22922/10925 investigating the role of irradiation of the internal mammary and medial supraclavicular lymph node chain works. Strahlenther Onkol. 2006 Oct;182(10):576-82. doi: 10.1007/s00066-006-1629-2.
• Poortmans P, Kouloulias VE, Venselaar JL, Struikmans H, Davis JB, Huyskens D, van Tienhoven G, Hurkmans C, Mijnheer B, Van den Bogaert W. Quality assurance of EORTC trial 22922/10925 investigating the role of internal mammary--medial supraclavicular irradiation in stage I-III breast cancer: the individual case review. Eur J Cancer. 2003 Sep;39(14):2035-42. doi: 10.1016/s0959-8049(03)00455-6.
• Poortmans PM, Venselaar JL, Struikmans H, Hurkmans CW, Davis JB, Huyskens D, van Tienhoven G, Vlaun V, Lagendijk JJ, Mijnheer BJ, De Winter KA, Van der Hulst MH, Van den Bogaert WF. The potential impact of treatment variations on the results of radiotherapy of the internal mammary lymph node chain: a quality-assurance report on the dummy run of EORTC Phase III randomized trial 22922/10925 in Stage I--III breast cancer(1). Int J Radiat Oncol Biol Phys. 2001 Apr 1;49(5):1399-408. doi: 10.1016/s0360-3016(00)01549-2.
• Poortmans P, Van Den Bogaert W, Venselaar J, et al.: Quality assurance in EORTC trial 22922/10925 concerning internal mammary chain (IMC) irradiation: the dummy run. Radiother Oncol 48(suppl 1): A735, s186, 1998.
• Poortmans P, Van Den Bogaert W, Venselaar J, et al.: EORTC randomized phase III trials 22922/10925 investigating the role of internal mammary chain (IMC) irradiation in stage I-II breast cancer: a quality assurance report on the dummy run. Eur J Cancer 34(suppl 5): A257, s58, 1998.
• Kaidar-Person O, Fortpied C, Hol S, Weltens C, Kirkove C, Budach V, Peignaux-Casasnovas K, van der Leij F, Vonk E, Valli M, Weidner N, Guckenberger M, Koiter E, Fourquet A, Bartelink H, Struikmans H, Poortmans P; EORTC Radiation Oncology and Breast Cancer Groups. The association of internal mammary and medial supraclavicular lymph node radiation technique with clinical outcomes: Results from the EORTC 22922/10925 randomised trial. Radiother Oncol. 2022 Jul;172:99-110. doi: 10.1016/j.radonc.2022.05.006. Epub 2022 May 12.
• Poortmans PM, Struikmans H, De Brouwer P, Weltens C, Fortpied C, Kirkove C, Budach V, Peignaux-Casasnovas K, van der Leij F, Vonk E, Valli M, vanTienhoven G, Weidner N, Noel G, Guckenberger M, Koiter E, vanLimbergen E, Engelen A, Fourquet A, Bartelink H; EORTC Radiation Oncology and Breast Cancer Groups. Side Effects 15 Years After Lymph Node Irradiation in Breast Cancer: Randomized EORTC Trial 22922/10925. J Natl Cancer Inst. 2021 Oct 1;113(10):1360-1368. doi: 10.1093/jnci/djab113.
• Poortmans PM, Weltens C, Fortpied C, Kirkove C, Peignaux-Casasnovas K, Budach V, van der Leij F, Vonk E, Weidner N, Rivera S, van Tienhoven G, Fourquet A, Noel G, Valli M, Guckenberger M, Koiter E, Racadot S, Abdah-Bortnyak R, Van Limbergen EF, Engelen A, De Brouwer P, Struikmans H, Bartelink H; European Organisation for Research and Treatment of Cancer Radiation Oncology and Breast Cancer Groups. Internal mammary and medial supraclavicular lymph node chain irradiation in stage I-III breast cancer (EORTC 22922/10925): 15-year results of a randomised, phase 3 trial. Lancet Oncol. 2020 Dec;21(12):1602-1610. doi: 10.1016/S1470-2045(20)30472-1. Epub 2020 Nov 2. Erratum In: Lancet Oncol. 2021 Jan;22(1):e5.
• Poortmans PM, Collette S, Kirkove C, Van Limbergen E, Budach V, Struikmans H, Collette L, Fourquet A, Maingon P, Valli M, De Winter K, Marnitz S, Barillot I, Scandolaro L, Vonk E, Rodenhuis C, Marsiglia H, Weidner N, van Tienhoven G, Glanzmann C, Kuten A, Arriagada R, Bartelink H, Van den Bogaert W; EORTC Radiation Oncology and Breast Cancer Groups. Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer. N Engl J Med. 2015 Jul 23;373(4):317-27. doi: 10.1056/NEJMoa1415369.

Study record dates

Study Major Dates

• Study Start: July 1, 1996

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): January 29, 2010
• Last Update Submitted That Met QC Criteria: January 28, 2010
• Last Verified: December 1, 2004

More Information

Terms related to this study

• Keywords: stage IIIA breast cancer; stage II breast cancer; stage I breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: CDR0000065094; EORTC-10925; EORTC-22922