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
(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.
(Less)
- author
- organization
- publishing date
- 2023-09
- type
- 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 >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}}, }