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The generalisability of randomised clinical trials : an interim external validity analysis of the ongoing SENOMAC trial in sentinel lymph node-positive breast cancer

de Boniface, Jana ; Ahlgren, Johan ; Andersson, Yvette ; Bergkvist, Leif ; Frisell, Jan ; Lundstedt, Dan ; Olofsson Bagge, Roger ; Rydén, Lisa LU orcid and Sund, Malin (2020) In Breast Cancer Research and Treatment 180(1). p.167-176
Abstract

Purpose: None of the key randomised trials on the omission of axillary lymph node dissection (ALND) in sentinel lymph-positive breast cancer have reported external validity, even though results indicate selection bias. Our aim was to assess the external validity of the ongoing randomised SENOMAC trial by comparing characteristics of Swedish SENOMAC trial participants with non-included eligible patients registered in the Swedish National Breast Cancer Register (NKBC). Methods: In the ongoing non-inferiority European SENOMAC trial, clinically node-negative cT1–T3 breast cancer patients with up to two sentinel lymph node macrometastases are randomised to undergo completion ALND or not. Both breast-conserving surgery and mastectomy are... (More)

Purpose: None of the key randomised trials on the omission of axillary lymph node dissection (ALND) in sentinel lymph-positive breast cancer have reported external validity, even though results indicate selection bias. Our aim was to assess the external validity of the ongoing randomised SENOMAC trial by comparing characteristics of Swedish SENOMAC trial participants with non-included eligible patients registered in the Swedish National Breast Cancer Register (NKBC). Methods: In the ongoing non-inferiority European SENOMAC trial, clinically node-negative cT1–T3 breast cancer patients with up to two sentinel lymph node macrometastases are randomised to undergo completion ALND or not. Both breast-conserving surgery and mastectomy are eligible interventions. Data from NKBC were extracted for the years 2016 and 2017, and patient and tumour characteristics compared with Swedish trial participants from the same years. Results: Overall, 306 NKBC cases from non-participating and 847 NKBC cases from participating sites (excluding SENOMAC participants) were compared with 463 SENOMAC trial participants. Patients belonging to the middle age groups (p = 0.015), with smaller tumours (p = 0.013) treated by breast-conserving therapy (50.3 versus 47.1 versus 65.2%, p < 0.001) and less nodal tumour burden (only 1 macrometastasis in 78.8 versus 79.9 versus 87.3%, p = 0.001) were over-represented in the trial population. Time trends indicated, however, that differences may be mitigated over time. Conclusions: This interim external validity analysis specifically addresses selection mechanisms during an ongoing trial, potentially increasing generalisability by the time full accrual is reached. Similar validity checks should be an integral part of prospective clinical trials. 

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author
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author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Breast cancer, Clinical trial, Omission of axillary dissection, Sentinel lymph node biopsy
in
Breast Cancer Research and Treatment
volume
180
issue
1
pages
10 pages
publisher
Springer
external identifiers
  • pmid:31989379
  • scopus:85078500324
ISSN
0167-6806
DOI
10.1007/s10549-020-05537-1
language
English
LU publication?
yes
id
64149891-ac43-45ce-a347-6ff77e5b3ba5
date added to LUP
2020-02-06 14:15:00
date last changed
2024-03-04 13:04:44
@article{64149891-ac43-45ce-a347-6ff77e5b3ba5,
  abstract     = {{<p>Purpose: None of the key randomised trials on the omission of axillary lymph node dissection (ALND) in sentinel lymph-positive breast cancer have reported external validity, even though results indicate selection bias. Our aim was to assess the external validity of the ongoing randomised SENOMAC trial by comparing characteristics of Swedish SENOMAC trial participants with non-included eligible patients registered in the Swedish National Breast Cancer Register (NKBC). Methods: In the ongoing non-inferiority European SENOMAC trial, clinically node-negative cT1–T3 breast cancer patients with up to two sentinel lymph node macrometastases are randomised to undergo completion ALND or not. Both breast-conserving surgery and mastectomy are eligible interventions. Data from NKBC were extracted for the years 2016 and 2017, and patient and tumour characteristics compared with Swedish trial participants from the same years. Results: Overall, 306 NKBC cases from non-participating and 847 NKBC cases from participating sites (excluding SENOMAC participants) were compared with 463 SENOMAC trial participants. Patients belonging to the middle age groups (p = 0.015), with smaller tumours (p = 0.013) treated by breast-conserving therapy (50.3 versus 47.1 versus 65.2%, p &lt; 0.001) and less nodal tumour burden (only 1 macrometastasis in 78.8 versus 79.9 versus 87.3%, p = 0.001) were over-represented in the trial population. Time trends indicated, however, that differences may be mitigated over time. Conclusions: This interim external validity analysis specifically addresses selection mechanisms during an ongoing trial, potentially increasing generalisability by the time full accrual is reached. Similar validity checks should be an integral part of prospective clinical trials. </p>}},
  author       = {{de Boniface, Jana and Ahlgren, Johan and Andersson, Yvette and Bergkvist, Leif and Frisell, Jan and Lundstedt, Dan and Olofsson Bagge, Roger and Rydén, Lisa and Sund, Malin}},
  issn         = {{0167-6806}},
  keywords     = {{Breast cancer; Clinical trial; Omission of axillary dissection; Sentinel lymph node biopsy}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{167--176}},
  publisher    = {{Springer}},
  series       = {{Breast Cancer Research and Treatment}},
  title        = {{The generalisability of randomised clinical trials : an interim external validity analysis of the ongoing SENOMAC trial in sentinel lymph node-positive breast cancer}},
  url          = {{http://dx.doi.org/10.1007/s10549-020-05537-1}},
  doi          = {{10.1007/s10549-020-05537-1}},
  volume       = {{180}},
  year         = {{2020}},
}