Abstract OT2-3-01: The LORIS trial: A multicentre, randomized phase III trial of standard surgery versus active monitoring in women with newly diagnosed low risk ductal carcinoma in situ
Authors: Francis A , Bartlett JMS , Billingham LJ , Bowden SJ , Brookes CL , Dodwell DJ , Evans AZ , Fallowfield LJ , Gaunt CH , Hanby AM , Jenkins VA , Pinder S , Reed MW , Roberts T , Thomas JS , Wallis MG , Wilcox MH , Rea DW 
Published: August 2014

Abstract
Background: The independent review of the UK National Health Service Breast Screening Programme reported recently on the benefits and harms of breast screening (The Lancet, Volume 380, Issue 9855, Pages 1778 - 1786, 17 November 2012). This concluded that breast screening saves lives but acknowledged the existence of overtreatment. Consequently, randomized trials were recommended to elucidate the appropriate treatment of screen-detected ductal carcinoma in situ (DCIS) and to gain a better understanding of its natural history. The LORIS trial will address these issues in low and low/intermediate grade screen detected (low risk) DCIS.
Trial Design: LORIS is a phase III, multicentre, 2 arm study, with a built in 2 year feasibility phase, in women confirmed by central pathology review to have low risk DCIS. Comprehensive site training will be complimented by a patient friendly DVD designed to ensure consistent and appropriate use of terminology. Patients will be randomised between standard surgery and active monitoring with annual mammography. Follow-up will be for a minimum of 10 years.
Eligibility Criteria:
1) Female, age ≥ 46 years
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
5) No previous breast cancer or DCIS diagnosis
6) Written informed consent
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) and whether those patients who 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 and assessment of predictive biomarkers.
A digital image data repository and tissue bank will provide a prospective resource for both translational and 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: 20 UK sites have been identified to contribute to the feasibility phase of the trial. Enrolment of the first patient is expected in late 2013/early 2014. A further 40 sites will be recruited upon successful completion of the feasibility phase.
For further information, please contact the LORIS Trial Office LORIS@trials.bham.ac.uk.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT2-3-01.