Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): A randomised, multicentre, open-label, phase 3 non-inferiority trial

Mila Donker, Geertjan van Tienhoven, Marieke E. Straver, Philip Meijnen, Cornelis J. H. van de Velde, Robert E. Mansel, Luigi Cataliotti, A. Helen Westenberg, Jean H. G. Klinkenbijl, Lorenzo Orzalesi, Willem H. Bouma, Huub C. J. van der Mijle, Grard A. P. Nieuwenhuijzen, Sanne C. Veltkamp, Leen Slaets, Nicole J. Duez, Peter W. de Graaf, Thijs van Dalen, Andreas Marinelli, Herman Rijna & 10 others Marko Snoj, Nigel J. Bundred, Jos W. S. Merkus, Yazid Belkacemi, Patrick Petignat, Dominic A. X. Schinagl, Corneel Coens, Carlo G. M. Messina, Jan Bogaerts, Emiel J. T. Rutgers

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: If treatment of the axilla is indicated in patients with breast cancer who have a positive sentinel node, axillary lymph node dissection is the present standard. Although axillary lymph node dissection provides excellent regional control, it is associated with harmful side-effects. We aimed to assess whether axillary radiotherapy provides comparable regional control with fewer side-effects. Methods: Patients with T1-2 primary breast cancer and no palpable lymphadenopathy were enrolled in the randomised, multicentre, open-label, phase 3 non-inferiority EORTC 10981-22023 AMAROS trial. Patients were randomly assigned (1:1) by a computer-generated allocation schedule to receive either axillary lymph node dissection or axillary radiotherapy in case of a positive sentinel node, stratified by institution. The primary endpoint was non-inferiority of 5-year axillary recurrence, considered to be not more than 4% for the axillary radiotherapy group compared with an expected 2% in the axillary lymph node dissection group. Analyses were by intention to treat and per protocol. The AMAROS trial is registered with ClinicalTrials.gov, number NCT00014612. Findings: Between Feb 19, 2001, and April 29, 2010, 4823 patients were enrolled at 34 centres from nine European countries, of whom 4806 were eligible for randomisation. 2402 patients were randomly assigned to receive axillary lymph node dissection and 2404 to receive axillary radiotherapy. Of the 1425 patients with a positive sentinel node, 744 had been randomly assigned to axillary lymph node dissection and 681 to axillary radiotherapy; these patients constituted the intention-to-treat population. Median follow-up was 6.1 years (IQR 4.1-8.0) for the patients with positive sentinel lymph nodes. In the axillary lymph node dissection group, 220 (33%) of 672 patients who underwent axillary lymph node dissection had additional positive nodes. Axillary recurrence occurred in four of 744 patients in the axillary lymph node dissection group and seven of 681 in the axillary radiotherapy group. 5-year axillary recurrence was 0.43% (95% CI 0.00-0.92) after axillary lymph node dissection versus 1.19% (0.31-2.08) after axillary radiotherapy. The planned non-inferiority test was underpowered because of the low number of events. The one-sided 95% CI for the underpowered non-inferiority test on the hazard ratio was 0.00-5.27, with a non-inferiority margin of 2. Lymphoedema in the ipsilateral arm was noted significantly more often after axillary lymph node dissection than after axillary radiotherapy at 1 year, 3 years, and 5 years. Interpretation: Axillary lymph node dissection and axillary radiotherapy after a positive sentinel node provide excellent and comparable axillary control for patients with T1-2 primary breast cancer and no palpable lymphadenopathy. Axillary radiotherapy results in significantly less morbidity. Funding: EORTC Charitable Trust.
Original languageEnglish
Pages (from-to)1303-1310
JournalThe Lancet Oncology
Volume15
Issue number12
DOIs
Publication statusPublished - 2014
Externally publishedYes

Cite this

Donker, Mila ; van Tienhoven, Geertjan ; Straver, Marieke E. ; Meijnen, Philip ; van de Velde, Cornelis J. H. ; Mansel, Robert E. ; Cataliotti, Luigi ; Westenberg, A. Helen ; Klinkenbijl, Jean H. G. ; Orzalesi, Lorenzo ; Bouma, Willem H. ; van der Mijle, Huub C. J. ; Nieuwenhuijzen, Grard A. P. ; Veltkamp, Sanne C. ; Slaets, Leen ; Duez, Nicole J. ; de Graaf, Peter W. ; van Dalen, Thijs ; Marinelli, Andreas ; Rijna, Herman ; Snoj, Marko ; Bundred, Nigel J. ; Merkus, Jos W. S. ; Belkacemi, Yazid ; Petignat, Patrick ; Schinagl, Dominic A. X. ; Coens, Corneel ; Messina, Carlo G. M. ; Bogaerts, Jan ; Rutgers, Emiel J. T. / Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): A randomised, multicentre, open-label, phase 3 non-inferiority trial. In: The Lancet Oncology. 2014 ; Vol. 15, No. 12. pp. 1303-1310.
@article{9f7b8fe40a7b46b384dc31c68d9ceb2f,
title = "Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): A randomised, multicentre, open-label, phase 3 non-inferiority trial",
abstract = "Background: If treatment of the axilla is indicated in patients with breast cancer who have a positive sentinel node, axillary lymph node dissection is the present standard. Although axillary lymph node dissection provides excellent regional control, it is associated with harmful side-effects. We aimed to assess whether axillary radiotherapy provides comparable regional control with fewer side-effects. Methods: Patients with T1-2 primary breast cancer and no palpable lymphadenopathy were enrolled in the randomised, multicentre, open-label, phase 3 non-inferiority EORTC 10981-22023 AMAROS trial. Patients were randomly assigned (1:1) by a computer-generated allocation schedule to receive either axillary lymph node dissection or axillary radiotherapy in case of a positive sentinel node, stratified by institution. The primary endpoint was non-inferiority of 5-year axillary recurrence, considered to be not more than 4{\%} for the axillary radiotherapy group compared with an expected 2{\%} in the axillary lymph node dissection group. Analyses were by intention to treat and per protocol. The AMAROS trial is registered with ClinicalTrials.gov, number NCT00014612. Findings: Between Feb 19, 2001, and April 29, 2010, 4823 patients were enrolled at 34 centres from nine European countries, of whom 4806 were eligible for randomisation. 2402 patients were randomly assigned to receive axillary lymph node dissection and 2404 to receive axillary radiotherapy. Of the 1425 patients with a positive sentinel node, 744 had been randomly assigned to axillary lymph node dissection and 681 to axillary radiotherapy; these patients constituted the intention-to-treat population. Median follow-up was 6.1 years (IQR 4.1-8.0) for the patients with positive sentinel lymph nodes. In the axillary lymph node dissection group, 220 (33{\%}) of 672 patients who underwent axillary lymph node dissection had additional positive nodes. Axillary recurrence occurred in four of 744 patients in the axillary lymph node dissection group and seven of 681 in the axillary radiotherapy group. 5-year axillary recurrence was 0.43{\%} (95{\%} CI 0.00-0.92) after axillary lymph node dissection versus 1.19{\%} (0.31-2.08) after axillary radiotherapy. The planned non-inferiority test was underpowered because of the low number of events. The one-sided 95{\%} CI for the underpowered non-inferiority test on the hazard ratio was 0.00-5.27, with a non-inferiority margin of 2. Lymphoedema in the ipsilateral arm was noted significantly more often after axillary lymph node dissection than after axillary radiotherapy at 1 year, 3 years, and 5 years. Interpretation: Axillary lymph node dissection and axillary radiotherapy after a positive sentinel node provide excellent and comparable axillary control for patients with T1-2 primary breast cancer and no palpable lymphadenopathy. Axillary radiotherapy results in significantly less morbidity. Funding: EORTC Charitable Trust.",
author = "Mila Donker and {van Tienhoven}, Geertjan and Straver, {Marieke E.} and Philip Meijnen and {van de Velde}, {Cornelis J. H.} and Mansel, {Robert E.} and Luigi Cataliotti and Westenberg, {A. Helen} and Klinkenbijl, {Jean H. G.} and Lorenzo Orzalesi and Bouma, {Willem H.} and {van der Mijle}, {Huub C. J.} and Nieuwenhuijzen, {Grard A. P.} and Veltkamp, {Sanne C.} and Leen Slaets and Duez, {Nicole J.} and {de Graaf}, {Peter W.} and {van Dalen}, Thijs and Andreas Marinelli and Herman Rijna and Marko Snoj and Bundred, {Nigel J.} and Merkus, {Jos W. S.} and Yazid Belkacemi and Patrick Petignat and Schinagl, {Dominic A. X.} and Corneel Coens and Messina, {Carlo G. M.} and Jan Bogaerts and Rutgers, {Emiel J. T.}",
year = "2014",
doi = "10.1016/S1470-2045(14)70460-7",
language = "English",
volume = "15",
pages = "1303--1310",
journal = "Lancet Oncology",
issn = "1470-2045",
publisher = "Lancet Publishing Group",
number = "12",

}

Donker, M, van Tienhoven, G, Straver, ME, Meijnen, P, van de Velde, CJH, Mansel, RE, Cataliotti, L, Westenberg, AH, Klinkenbijl, JHG, Orzalesi, L, Bouma, WH, van der Mijle, HCJ, Nieuwenhuijzen, GAP, Veltkamp, SC, Slaets, L, Duez, NJ, de Graaf, PW, van Dalen, T, Marinelli, A, Rijna, H, Snoj, M, Bundred, NJ, Merkus, JWS, Belkacemi, Y, Petignat, P, Schinagl, DAX, Coens, C, Messina, CGM, Bogaerts, J & Rutgers, EJT 2014, 'Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): A randomised, multicentre, open-label, phase 3 non-inferiority trial' The Lancet Oncology, vol. 15, no. 12, pp. 1303-1310. https://doi.org/10.1016/S1470-2045(14)70460-7

Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): A randomised, multicentre, open-label, phase 3 non-inferiority trial. / Donker, Mila; van Tienhoven, Geertjan; Straver, Marieke E.; Meijnen, Philip; van de Velde, Cornelis J. H.; Mansel, Robert E.; Cataliotti, Luigi; Westenberg, A. Helen; Klinkenbijl, Jean H. G.; Orzalesi, Lorenzo; Bouma, Willem H.; van der Mijle, Huub C. J.; Nieuwenhuijzen, Grard A. P.; Veltkamp, Sanne C.; Slaets, Leen; Duez, Nicole J.; de Graaf, Peter W.; van Dalen, Thijs; Marinelli, Andreas; Rijna, Herman; Snoj, Marko; Bundred, Nigel J.; Merkus, Jos W. S.; Belkacemi, Yazid; Petignat, Patrick; Schinagl, Dominic A. X.; Coens, Corneel; Messina, Carlo G. M.; Bogaerts, Jan; Rutgers, Emiel J. T.

In: The Lancet Oncology, Vol. 15, No. 12, 2014, p. 1303-1310.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): A randomised, multicentre, open-label, phase 3 non-inferiority trial

AU - Donker, Mila

AU - van Tienhoven, Geertjan

AU - Straver, Marieke E.

AU - Meijnen, Philip

AU - van de Velde, Cornelis J. H.

AU - Mansel, Robert E.

AU - Cataliotti, Luigi

AU - Westenberg, A. Helen

AU - Klinkenbijl, Jean H. G.

AU - Orzalesi, Lorenzo

AU - Bouma, Willem H.

AU - van der Mijle, Huub C. J.

AU - Nieuwenhuijzen, Grard A. P.

AU - Veltkamp, Sanne C.

AU - Slaets, Leen

AU - Duez, Nicole J.

AU - de Graaf, Peter W.

AU - van Dalen, Thijs

AU - Marinelli, Andreas

AU - Rijna, Herman

AU - Snoj, Marko

AU - Bundred, Nigel J.

AU - Merkus, Jos W. S.

AU - Belkacemi, Yazid

AU - Petignat, Patrick

AU - Schinagl, Dominic A. X.

AU - Coens, Corneel

AU - Messina, Carlo G. M.

AU - Bogaerts, Jan

AU - Rutgers, Emiel J. T.

PY - 2014

Y1 - 2014

N2 - Background: If treatment of the axilla is indicated in patients with breast cancer who have a positive sentinel node, axillary lymph node dissection is the present standard. Although axillary lymph node dissection provides excellent regional control, it is associated with harmful side-effects. We aimed to assess whether axillary radiotherapy provides comparable regional control with fewer side-effects. Methods: Patients with T1-2 primary breast cancer and no palpable lymphadenopathy were enrolled in the randomised, multicentre, open-label, phase 3 non-inferiority EORTC 10981-22023 AMAROS trial. Patients were randomly assigned (1:1) by a computer-generated allocation schedule to receive either axillary lymph node dissection or axillary radiotherapy in case of a positive sentinel node, stratified by institution. The primary endpoint was non-inferiority of 5-year axillary recurrence, considered to be not more than 4% for the axillary radiotherapy group compared with an expected 2% in the axillary lymph node dissection group. Analyses were by intention to treat and per protocol. The AMAROS trial is registered with ClinicalTrials.gov, number NCT00014612. Findings: Between Feb 19, 2001, and April 29, 2010, 4823 patients were enrolled at 34 centres from nine European countries, of whom 4806 were eligible for randomisation. 2402 patients were randomly assigned to receive axillary lymph node dissection and 2404 to receive axillary radiotherapy. Of the 1425 patients with a positive sentinel node, 744 had been randomly assigned to axillary lymph node dissection and 681 to axillary radiotherapy; these patients constituted the intention-to-treat population. Median follow-up was 6.1 years (IQR 4.1-8.0) for the patients with positive sentinel lymph nodes. In the axillary lymph node dissection group, 220 (33%) of 672 patients who underwent axillary lymph node dissection had additional positive nodes. Axillary recurrence occurred in four of 744 patients in the axillary lymph node dissection group and seven of 681 in the axillary radiotherapy group. 5-year axillary recurrence was 0.43% (95% CI 0.00-0.92) after axillary lymph node dissection versus 1.19% (0.31-2.08) after axillary radiotherapy. The planned non-inferiority test was underpowered because of the low number of events. The one-sided 95% CI for the underpowered non-inferiority test on the hazard ratio was 0.00-5.27, with a non-inferiority margin of 2. Lymphoedema in the ipsilateral arm was noted significantly more often after axillary lymph node dissection than after axillary radiotherapy at 1 year, 3 years, and 5 years. Interpretation: Axillary lymph node dissection and axillary radiotherapy after a positive sentinel node provide excellent and comparable axillary control for patients with T1-2 primary breast cancer and no palpable lymphadenopathy. Axillary radiotherapy results in significantly less morbidity. Funding: EORTC Charitable Trust.

AB - Background: If treatment of the axilla is indicated in patients with breast cancer who have a positive sentinel node, axillary lymph node dissection is the present standard. Although axillary lymph node dissection provides excellent regional control, it is associated with harmful side-effects. We aimed to assess whether axillary radiotherapy provides comparable regional control with fewer side-effects. Methods: Patients with T1-2 primary breast cancer and no palpable lymphadenopathy were enrolled in the randomised, multicentre, open-label, phase 3 non-inferiority EORTC 10981-22023 AMAROS trial. Patients were randomly assigned (1:1) by a computer-generated allocation schedule to receive either axillary lymph node dissection or axillary radiotherapy in case of a positive sentinel node, stratified by institution. The primary endpoint was non-inferiority of 5-year axillary recurrence, considered to be not more than 4% for the axillary radiotherapy group compared with an expected 2% in the axillary lymph node dissection group. Analyses were by intention to treat and per protocol. The AMAROS trial is registered with ClinicalTrials.gov, number NCT00014612. Findings: Between Feb 19, 2001, and April 29, 2010, 4823 patients were enrolled at 34 centres from nine European countries, of whom 4806 were eligible for randomisation. 2402 patients were randomly assigned to receive axillary lymph node dissection and 2404 to receive axillary radiotherapy. Of the 1425 patients with a positive sentinel node, 744 had been randomly assigned to axillary lymph node dissection and 681 to axillary radiotherapy; these patients constituted the intention-to-treat population. Median follow-up was 6.1 years (IQR 4.1-8.0) for the patients with positive sentinel lymph nodes. In the axillary lymph node dissection group, 220 (33%) of 672 patients who underwent axillary lymph node dissection had additional positive nodes. Axillary recurrence occurred in four of 744 patients in the axillary lymph node dissection group and seven of 681 in the axillary radiotherapy group. 5-year axillary recurrence was 0.43% (95% CI 0.00-0.92) after axillary lymph node dissection versus 1.19% (0.31-2.08) after axillary radiotherapy. The planned non-inferiority test was underpowered because of the low number of events. The one-sided 95% CI for the underpowered non-inferiority test on the hazard ratio was 0.00-5.27, with a non-inferiority margin of 2. Lymphoedema in the ipsilateral arm was noted significantly more often after axillary lymph node dissection than after axillary radiotherapy at 1 year, 3 years, and 5 years. Interpretation: Axillary lymph node dissection and axillary radiotherapy after a positive sentinel node provide excellent and comparable axillary control for patients with T1-2 primary breast cancer and no palpable lymphadenopathy. Axillary radiotherapy results in significantly less morbidity. Funding: EORTC Charitable Trust.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/25439688

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DO - 10.1016/S1470-2045(14)70460-7

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JO - Lancet Oncology

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