Abstract OT2-02-04: The LORIS trial: A multicentre, randomised phase III trial of standard surgery versus active monitoring in women with newly diagnosed low risk ductal carcinoma in situ
Authors: Francis A , Fallowfield L , Bartlett J , Thomas J , Wallis M , Hanby A , Pinder S , Evans A , Billingham L , Brookes C , Dodwell D , Fairbrother P , Gaunt C , Jenkins V , Matthews L , Pirrie S , Reed M , Roberts T , Wilcox M , Young J , Rea D 
Published: May 2016

Background: The independent review of the UK National Health Service Breast Screening Programme reported (The Lancet, Volume 380, Issue 9855, Pages 1778 - 1786, 17 November 2012) on the benefits & harms of breast screening. It concluded that breast screening saves lives & acknowledged overtreatment. It encouraged randomized trials to elucidate the appropriate treatment of screen-detected ductal carcinoma in situ (DCIS) to gain a better understanding of its natural history. The LORIS trial addresses overtreatment of low & low/Intermediate grade screen detected (low risk) DCIS by randomizing patients to standard surgical treatment or active monitoring.

Trial Design: LORIS is a phase III, multicentre, 2 arm study, with a 2 year feasibility phase, in patients confirmed to have low risk DCIS by central pathology review. Patients are randomised to standard surgery or active monitoring with annual mammography. Patients will be followed up for a minimum of 10 years.

Key Eligibility Criteria:

1) Female 46 years or over.

2) Screen-detected or incidental microcalcification (with no mass lesion clinically or on imaging)

3) Low risk DCIS on large volume vacuum-assisted biopsy, confirmed by central pathology review

4) Patient fit to undergo surgery

Specific Aims: The LORIS Trial aims to establish whether patients with newly diagnosed low risk DCIS can safely avoid surgery without detriment to their wellbeing (psychological and physical) & whether those patients that do require surgery can be identified by pathological and radiological means.

Primary endpoint: Ipsilateral invasive breast cancer free survival rate at 5 years

Secondary endpoints: Overall survival; mastectomy rate; time to mastectomy; time to surgery; patient reported outcomes & health resource utilisation.

A digital image data repository and tissue bank provide a prospective resource for both translational & imaging studies.

Statistical Methods: A total of 932 patients will be randomized to a non-inferiority design to test the null hypothesis that active monitoring of women diagnosed with low risk DCIS is not non-inferior in terms of 5 year ipsilateral invasive breast cancer free survival (iiBCFS) rate compared to treatment with surgery. The iiBCFS rate will be compared across the two arms on a per protocol and intent-to-treat basis, using a 1-sided (α=0.05) log-rank test for non-inferiority. The iiBCFS rate is assumed to be 97.5% in the surgery arm giving 80% power to exclude a difference of more than 2.5% in the active monitoring arm at 5 years.

Present Accrual and Target Accrual: 21 UK centres are open & the feasibility phase of the trial is recruiting to target. The web based central pathology review process is functioning well with a one week maximum turn around. A further 40 centres will be opened on completion of the feasibility phase.

Contact: LORIS@trials.bham.ac.uk

This project was funded by the National Institute for Health Research [Health Technology Assessment Programme] (project number 11/36/16)

Department of Health Disclaimer: The views & opinions expressed therein are those of the authors & do not necessarily reflect those of the Health Technology Assessment Programme, NIHR, NHS or the Department of Health.

Citation Format: Francis A, Fallowfield L, Bartlett J, Thomas J, Wallis M, Hanby A, Pinder S, Evans A, Billingham L, Brookes C, Dodwell D, Fairbrother P, Gaunt C, Jenkins V, Matthews L, Pirrie S, Reed M, Roberts T, Wilcox M, Young J, Rea D. The LORIS trial: A multicentre, randomised phase III trial of standard surgery versus active monitoring in women with newly diagnosed low risk ductal carcinoma in situ. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT2-02-04.