Thomas, JS, Hanby, AM orcid.org/0000-0001-7966-1570, Russell, N et al. (10 more authors) (2017) The BIG 2.04 MRC/EORTC SUPREMO Trial: pathology quality assurance of a large phase 3 randomised international clinical trial of postmastectomy radiotherapy in intermediate-risk breast cancer. Breast Cancer Research and Treatment, 163 (1). pp. 63-69. ISSN 0167-6806
Abstract
Introduction SUPREMO is a phase 3 randomised trial evaluating radiotherapy post-mastectomy for intermediate-risk breast cancer. 1688 patients were enrolled from 16 countries between 2006 and 2013. We report the results of central pathology review carried out for quality assurance. Patients and methods A single recut haematoxylin and eosin (H&E) tumour section was assessed by one of two reviewing pathologists, blinded to the originally reported pathology and patient data. Tumour type, grade and lymphovascular invasion were reviewed to assess if they met the inclusion criteria. Slides from potentially ineligible patients on central review were scanned and reviewed online together by the two pathologists and a consensus reached. A subset of 25 of these cases was double-reported independently by the pathologists prior to the online assessment. Results The major contributors to the trial were the UK (75%) and the Netherlands (10%). There is a striking difference in lymphovascular invasion (LVi) rates (41.6 vs. 15.1% (UK); p = <0.0001) and proportions of grade 3 carcinomas (54.0 vs. 42.0% (UK); p = <0.0001) on comparing local reporting with central review. There was no difference in the locally reported frequency of LVi rates in node-positive (N+) and node-negative (N−) subgroups (40.3 vs. 38.0%; p = 0.40) but a significant difference in the reviewed frequency (16.9 vs. 9.9%; p = 0.004). Of the N− cases, 104 (25.1%) would have been ineligible by initial central review by virtue of grade and/or lymphovascular invasion status. Following online consensus review, this fell to 70 cases (16.3% of N− cases, 4.1% of all cases). Conclusions These data have important implications for the design, powering and interpretation of outcomes from this and future clinical trials. If critical pathology criteria are determinants for trial entry, serious consideration should be given to up-front central pathology review.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
Keywords: | Breast cancer; Radiation therapy; Clinical trial; Pathology; Quality assurance |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Pathology & Tumour Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 03 Mar 2017 11:24 |
Last Modified: | 05 Oct 2017 16:27 |
Status: | Published |
Publisher: | Springer Verlag |
Identification Number: | 10.1007/s10549-017-4145-4 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:113142 |