Abstract OT1-03-01: The UK LORIS trial: Randomizing patients with low or low intermediate grade ductal carcinoma in situ (DCIS) to surgery or active monitoring
Authors: Francis A , Bartlett J , Billingham L , Bowden S , Brookes C , Dodwell D , Evans A , Fairbrother P , Fallowfield L , Gaunt C , Hanby A , Jenkins V , Matthews L , Pinder S , Pirrie S , Rea D , Reed M , Roberts T , Thomas J , Wallis M , Wilcox M , Young J 
Published: March 2017

Background: The independent review of the UK National Health Service Breast Screening Programme reported (The Lancet, Volume 380, Issue 9855, Page 1778, 17 Nov 2012) on the benefits and harms of breast screening. It concluded that breast screening saves lives and acknowledged the existence of overtreatment. It encouraged randomized trials to elucidate the appropriate treatment of screen-detected DCIS to gain a better understanding of its natural history. The LORIS trial addresses the possible overtreatment of low and low/intermediate grade screen-detected (low risk) DCIS by randomizing patients to standard surgical treatment or active monitoring, each with long term follow up.

Trial Design: LORIS is a phase III, multicentre, 2 arm study, with a built in 2 year Feasibility Phase, in patients confirmed to have low risk DCIS defined by strict criteria and determined by central pathology review. Patients will be randomized between standard surgery and active monitoring with annual mammography. Patients will be followed up 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 ipsilateral 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 that do require surgery can be identified by pathological and radiological means.

Primary endpoint: Ipsilateral invasive breast cancer free survival time

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 ipsilateral invasive breast cancer free survival (iiBCFS) time compared to treatment with surgery. The iiBCFS time 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 at 5 years, utilizing 80% power to exclude a difference of more than 2.5% in the active monitoring arm.

Present Accrual and Target Accrual: 32 UK centres are open for the Feasibility Phase of the trial which is nearing completion. The web-based central pathology review process is functioning efficiently, with a one week maximum turn around. Registrations and sites randomizing patients are on or above target. Randomizations are currently approximately 70% of target. A total of 60 centres will open in the main trial.

Contact Information: For further information, please email the LORIS Trial Office LORIS@trials.bham.ac.uk.

Citation Format: Francis A, Bartlett J, Billingham L, Bowden S, Brookes C, Dodwell D, Evans A, Fairbrother P, Fallowfield L, Gaunt C, Hanby A, Jenkins V, Matthews L, Pinder S, Pirrie S, Rea D, Reed M, Roberts T, Thomas J, Wallis M, Wilcox M, Young J. The UK LORIS trial: Randomizing patients with low or low intermediate grade ductal carcinoma in situ (DCIS) to surgery or active monitoring [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-03-01.