Explorer 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

Introduction SUPREMO is a phase 3 randomised trial evaluating radiotherapy post-mastectomy for intermediaterisk 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 Ncases, 104 (25.1%) would have been ineligible by initial central review Electronic supplementary material The online version of this article (doi:10.1007/s10549-017-4145-4) contains supplementary material, which is available to authorized users. & J. S. Thomas jeremy.thomas@nhslothian.scot.nhs.uk A. M. Hanby a.m.hanby@leeds.ac.uk N. Russell n.russell@nki.nl G. van Tienhoven g.vantienhoven@amc.uva.nl K. Riddle k.riddle@nhs.net N. Anderson n.anderson@ed.ac.uk D. A. Cameron d.cameron@ed.ac.uk J. M. S. Bartlett john.bartlett@oicr.on.ca T. Piper t.piper@igmm.ed.ac.uk C. Cunningham carrie.cunningham@ed.ac.uk P. Canney pg.canney@me.com I. H. Kunkler iankunkler@yahoo.com 1 Department of Pathology, Western General Hospital, Edinburgh EH4 2XU, UK 2 Leeds Institute of Cancer and Pathology, St James’s University Hospital, Leeds LS9 7TF, UK 3 Department of Radiation Oncology, Netherlands Cancer Institute, Postbus 90203, 1006 BE Amsterdam, Netherlands 4 Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands 5 Scottish Clinical Trials Research Unit, NHS National Services Scotland, Edinburgh EH12 9EB, UK 123 Breast Cancer Res Treat DOI 10.1007/s10549-017-4145-4