Abstract OT3-09-04: A randomized phase II study comparing surgical excision versus NeOadjuvant Radiotherapy followed by delayed surgical excision of Ductal carcinoma In Situ (NORDIS)
Authors: Wapnir Irene , DeMartini Wendy , Allison Kimberly , Stone Kimberly , Dirbas Frederick , Marquez Carol , Ikeda Debra , Pal Sunita , Tsai Jacqueline , Yang Rachel , West Robert , McMillan Alex , Telli Melinda , Horst Kathleen 
Published: March 2020

Abstract
A randomized phase II study comparing surgical excision versus NeOadjuvant Radiotherapy followed by delayed surgical excision of Ductal carcinoma In Situ (NORDIS)
Breast radiotherapy (RT) for DCIS has been studied only in the adjuvant setting, following lumpectomy surgery. Adjuvant RT reduced invasive recurrences by 52% in the combined analysis of the two largest DCIS trials NSABP B-17/B-24, and reduced recurrences even for low or intermediate grade DCIS in the RTOG 9804 trial (recurrence 0.9% with RT versus 6.7% without RT). The mechanism of action is hypothesized to be elimination of occult disease and/or inhibition of neoplastic transformation in normal breast tissue.
Trial Design To understand the ablative effects of RT on pure DCIS, we are conducting a prospective randomized trial comparing histopathological findings of surgical excision (Arm 1) to neoadjuvant partial breast irradiation (neoRT) followed by delayed surgical excision (Arm 2) for patients with core needle biopsy proven DCIS. Arm 1 will provide a reference group for upstaging to invasive cancer, molecular markers and pathological-radiological correlations. Arm 2 participants will receive 6 Gy daily x 5 to the intact tumor with a 0.5 cm margin of normal tissue. Surgical excision will be delayed 12-16 weeks to allow for the radioablative effects to occur and radiation-induced inflammation to subside.
Specific Aims To determine if neoRT can completely ablate at least 30% of pure DCISTo determine if DCIS subtypes exhibit differential sensitivity to neoRTTo determine the radiation-induced treatment effects; wound complication rates; radiological
Eligibility Women 18 years of age or older with DCIS diagnosed on vacuum assisted core needle biopsy who intend to receive breast conserving surgery are eligible, excluding those with a prior history of ipsilateral breast cancer. The imaging abnormality must be mammographic microcalcifications and/or MRI non-mass enhancement measuring &lt;3 cm and not completely removed by core needle biopsy.
Statistics A total of 50 patients will be recruited. Upstaging to invasive cancer is anticipated to be approximately 10% in the reference group. With 25 subjects in each arm, we will have 80% power to detect a 30% or higher improvement in the DCIS complete response rate following neoRT.
Accrual Opened to accrual June 1, 2019
Contact wapnir@stanford.edu
Wapnir IL, Dignam JJ, Fisher B, et al. Long-term outcomes of invasive ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and B-24 randomized clinical trials for DCIS. J Natl Cancer Inst. 2011;103(6):478-488. doi:10.1093/jnci/djr027.
McCormick B, Winter K, Hudis C, et al. RTOG 9804: a prospective randomized trial for good-risk ductal carcinoma in situ comparing radiotherapy with observation. J Clin Oncol. 2015;33(7):709-715. doi:10.1200/JCO.2014.57.9029.
Citation Format: Irene Wapnir, Wendy DeMartini, Kimberly Allison, Kimberly Stone, Frederick Dirbas, Carol Marquez, Debra Ikeda, Sunita Pal, Jacqueline Tsai, Rachel Yang, Robert West, Alex McMillan, Melinda Telli, Kathleen Horst. A randomized phase II study comparing surgical excision versus NeOadjuvant Radiotherapy followed by delayed surgical excision of Ductal carcinoma In Situ (NORDIS) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-09-04.