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Protocol for the T-REX-trial : Tailored regional external beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases - An open, multicentre, randomised non-inferiority phase 3 trial

Alkner, Sara LU ; De Boniface, Jana ; Lundstedt, Dan ; Mjaaland, Ingvil ; Ryden, Lisa LU orcid ; Vikstrom, Johan ; Bendahl, Pär Ola LU ; Holmberg, Erik ; Sackey, Helena and Wieslander, Elinore , et al. (2023) In BMJ Open 13(9).
Abstract

Introduction Modern systemic treatment has reduced incidence of regional recurrences and improved survival in breast cancer (BC). It is thus questionable whether regional radiotherapy (RT) is still beneficial in patients with sentinel lymph node (SLN) macrometastasis. Postoperative regional RT is associated with an increased risk of arm morbidity, pneumonitis, cardiac disease and secondary cancer. Therefore, there is a need to individualise regional RT in relation to the risk of recurrence. Methods and analysis In this multicentre, prospective randomised trial, clinically node-negative patients with oestrogen receptor-positive, HER2-negative BC and 1-2 SLN macrometastases are eligible. Participants are randomly assigned to receive... (More)

Introduction Modern systemic treatment has reduced incidence of regional recurrences and improved survival in breast cancer (BC). It is thus questionable whether regional radiotherapy (RT) is still beneficial in patients with sentinel lymph node (SLN) macrometastasis. Postoperative regional RT is associated with an increased risk of arm morbidity, pneumonitis, cardiac disease and secondary cancer. Therefore, there is a need to individualise regional RT in relation to the risk of recurrence. Methods and analysis In this multicentre, prospective randomised trial, clinically node-negative patients with oestrogen receptor-positive, HER2-negative BC and 1-2 SLN macrometastases are eligible. Participants are randomly assigned to receive regional RT (standard arm) or not (intervention arm). Regional RT includes the axilla level I-III, the supraclavicular fossa and in selected patients the internal mammary nodes. Both groups receive RT to the remaining breast. Chest-wall RT after mastectomy is given in the standard arm, but in the intervention arm only in cases of widespread multifocality according to national guidelines. RT quality assurance is an integral part of the trial. The trial aims to include 1350 patients between March 2023 and December 2028 in Sweden and Norway. Primary outcome is recurrence-free survival (RFS) at 5 years. Non-inferiority will be declared if outcome in the de-escalation arm is not >4.5 percentage units below that with regional RT, corresponding to an HR of 1.41 assuming 88% 5-year RFS with standard treatment. Secondary outcomes include locoregional recurrence, overall survival, patient-reported arm morbidity and health-related quality of life. Gene expression analysis and tumour tissue-based studies to identify prognostic and predictive markers for benefit of regional RT are included. Ethics and dissemination The trial protocol is approved by the Swedish Ethics Authority (Dnr-2022-02178-01, 2022-05093-02, 2023-00826-02, 2023-03035-02). Results will be presented at scientific conferences and in peer-reviewed journals. Trial registration number NCT05634889.

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Contribution to journal
publication status
published
subject
keywords
Adult radiotherapy, Breast tumours, RADIOTHERAPY
in
BMJ Open
volume
13
issue
9
article number
e075543
publisher
BMJ Publishing Group
external identifiers
  • scopus:85174068049
  • pmid:37751948
ISSN
2044-6055
DOI
10.1136/bmjopen-2023-075543
language
English
LU publication?
yes
id
a7991865-bcf4-4714-ad88-9e5fd39a9038
date added to LUP
2023-12-15 12:12:21
date last changed
2024-12-23 09:46:21
@article{a7991865-bcf4-4714-ad88-9e5fd39a9038,
  abstract     = {{<p>Introduction Modern systemic treatment has reduced incidence of regional recurrences and improved survival in breast cancer (BC). It is thus questionable whether regional radiotherapy (RT) is still beneficial in patients with sentinel lymph node (SLN) macrometastasis. Postoperative regional RT is associated with an increased risk of arm morbidity, pneumonitis, cardiac disease and secondary cancer. Therefore, there is a need to individualise regional RT in relation to the risk of recurrence. Methods and analysis In this multicentre, prospective randomised trial, clinically node-negative patients with oestrogen receptor-positive, HER2-negative BC and 1-2 SLN macrometastases are eligible. Participants are randomly assigned to receive regional RT (standard arm) or not (intervention arm). Regional RT includes the axilla level I-III, the supraclavicular fossa and in selected patients the internal mammary nodes. Both groups receive RT to the remaining breast. Chest-wall RT after mastectomy is given in the standard arm, but in the intervention arm only in cases of widespread multifocality according to national guidelines. RT quality assurance is an integral part of the trial. The trial aims to include 1350 patients between March 2023 and December 2028 in Sweden and Norway. Primary outcome is recurrence-free survival (RFS) at 5 years. Non-inferiority will be declared if outcome in the de-escalation arm is not &gt;4.5 percentage units below that with regional RT, corresponding to an HR of 1.41 assuming 88% 5-year RFS with standard treatment. Secondary outcomes include locoregional recurrence, overall survival, patient-reported arm morbidity and health-related quality of life. Gene expression analysis and tumour tissue-based studies to identify prognostic and predictive markers for benefit of regional RT are included. Ethics and dissemination The trial protocol is approved by the Swedish Ethics Authority (Dnr-2022-02178-01, 2022-05093-02, 2023-00826-02, 2023-03035-02). Results will be presented at scientific conferences and in peer-reviewed journals. Trial registration number NCT05634889.</p>}},
  author       = {{Alkner, Sara and De Boniface, Jana and Lundstedt, Dan and Mjaaland, Ingvil and Ryden, Lisa and Vikstrom, Johan and Bendahl, Pär Ola and Holmberg, Erik and Sackey, Helena and Wieslander, Elinore and Karlsson, Per}},
  issn         = {{2044-6055}},
  keywords     = {{Adult radiotherapy; Breast tumours; RADIOTHERAPY}},
  language     = {{eng}},
  number       = {{9}},
  publisher    = {{BMJ Publishing Group}},
  series       = {{BMJ Open}},
  title        = {{Protocol for the T-REX-trial : Tailored regional external beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases - An open, multicentre, randomised non-inferiority phase 3 trial}},
  url          = {{http://dx.doi.org/10.1136/bmjopen-2023-075543}},
  doi          = {{10.1136/bmjopen-2023-075543}},
  volume       = {{13}},
  year         = {{2023}},
}