title: Feasibility of a prospective, randomised, open-label, international multicentre, phase III, non-inferiority trial to assess the safety of active surveillance for low risk ductal carcinoma in situ - The LORD study.
abstract: BACKGROUND
  The current debate on overdiagnosis and overtreatment of screen-detected ductal carcinoma in situ (DCIS) urges the need for prospective studies to address this issue. A substantial number of DCIS lesions will never form a health hazard, particularly if it concerns non- to slow-growing low-grade DCIS. The LORD study aims to evaluate the safety of active surveillance in women with low-risk DCIS.
  
  
  METHODS
  This is a randomised, international multicentre, open-label, phase III non-inferiority trial, led by the Dutch Breast Cancer Research Group (BOOG 2014-04) and the European Organization for Research and Treatment of Cancer (EORTC-BCG 1401). Standard treatment will be compared to active surveillance in 1240 women aged ⩾ 45 years with asymptomatic, screen-detected, pure low-grade DCIS based on vacuum-assisted biopsies of microcalcifications only. Both study arms will be monitored with annual digital mammography for a period of 10 years. The primary end-point is 10-year ipsilateral invasive breast cancer free percentage. Secondary end-points include patient reported outcomes, diagnostic biopsy rate during follow-up, ipsilateral mastectomy rate and translational research.
  
  
  RESULTS
  To explore interest in and feasibility of the LORD study we conducted a survey among EORTC and BOOG centres. A vast majority of EORTC and BOOG responding centres expressed interest in participation in the LORD study. The proposed study design is endorsed by nearly all centres.
authors.affiliation: Department of Surgery, Netherlands Cancer Institute/Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; Department of Molecular Pathology, Netherlands Cancer Institute/Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; Department of Epidemiology, Netherlands Cancer Institute/Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Electronic address: l.elshof@nki.nl.
authors.forename: Lotte E
authors.initials: LE
authors.lastname: Elshof
authors.affiliation: Medical Department, European Organisation for Research and Treatment of Cancer, Avenue E. Mounier 83/11, 1200 Brussels, Belgium. Electronic address: konstantinos.tryfonidis@eortc.be.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Tryfonidis
authors.affiliation: Department of Statistics, European Organisation for Research and Treatment of Cancer, Avenue E. Mounier 83/11, 1200 Brussels, Belgium. Electronic address: leen.slaets@eortc.be.
authors.forename: Leen
authors.initials: L
authors.lastname: Slaets
authors.affiliation: BOOG Study Center, PP Box 9236, 1006 AE Amsterdam, The Netherlands. Electronic address: e.vanleeuwen@boogstudycenter.nl.
authors.forename: A Elise
authors.initials: AE
authors.lastname: van Leeuwen-Stok
authors.affiliation: Department of Surgery, Netherlands Cancer Institute/Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Electronic address: v.skinner@nki.nl.
authors.forename: Victoria P
authors.initials: VP
authors.lastname: Skinner
authors.affiliation: Department of Clinical Operations, European Organisation for Research and Treatment of Cancer, Avenue E. Mounier 83/11, 1200 Brussels, Belgium. Electronic address: nicolas.dif@eortc.be.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dif
authors.affiliation: Department of Radiology, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands. Electronic address: r.m.pijnappel@umcutrecht.nl.
authors.forename: Ruud M
authors.initials: RM
authors.lastname: Pijnappel
authors.affiliation: Department of Radiotherapy, Academic Medical Center, PO Box 227700, 1100 DE Amsterdam, The Netherlands. Electronic address: n.bijker@amc.uva.nl.
authors.forename: Nina
authors.initials: N
authors.lastname: Bijker
authors.affiliation: Department of Surgery, Netherlands Cancer Institute/Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Electronic address: e.rutgers@nki.nl.
authors.forename: Emiel J Th
authors.initials: EJ
authors.lastname: Rutgers
authors.affiliation: Department of Molecular Pathology, Netherlands Cancer Institute/Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; Department of Pathology, Netherlands Cancer Institute/Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Electronic address: j.wesseling@nki.nl.
authors.forename: Jelle
authors.initials: J
authors.lastname: Wesseling
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis; D011446:Prospective Studies; D057832:Watchful Waiting
keywords: Active surveillance; Ductal carcinoma in situ; Hormonal therapy; Low-grade; Overdiagnosis; Overtreatment; Radiotherapy; Surgery