Abstract OT1-09-01: A randomized study comparing surgical excision versus NeOadjuvant Radiotherapy followed by delayed surgical excision of Ductal carcinoma In Situ (NORDIS)
Authors: Wapnir Irene , Marquez Carol , Stone Kimberly , Allison Kimberly , DeMartini Wendy , Salem Catherine , Tsai Jacqueline , West Robert , McMillan Alex , Telli Melinda , Horst Kathleen 
Published: March 2022

Abstract
Lumpectomy and breast radiotherapy (RT) achieve good longterm control of disease in patients diagnosed with ductal carcinoma in situ (DCIS). In the combined analysis of NSABP B-17/B-24 DCIS trials, these treatments were shown to reduce invasive ipsilateral breast tumor recurrences by 52% compared to lumpectomy alone. RT has been consistently used as an adjuvant to surgery and therefore, little is known of its activity on intact/untreated DCIS. Elucidating the effectiveness of radiation therapy may help optimize the treatment of DCIS and avoid over-treatment.Trial Design The objective of the ongoing phase 2 pilot trial is to evaluate the ablative and treatment effects of neoadjuvant RT (neoRT) on DCIS. Patients diagnosed with DCIS on core needle biopsy are randomized to upfront lumpectomy (Arm 1) followed by partial breast irradiation (PBI) or neoRT PBI followed by delayed surgical excision (Arm 2). Arm 1 serves as a reference group for pathological-radiological correlations as well as to ascertain the rate of upstaging to invasive cancer. The neoRT regimen consists of 6 Gy daily x 5 (consecutive or non-consecutive days) to the intact tumor with a 0.5 cm margin. Surgical excision is delayed 12-16 weeks, allowing for the ablative effects of neoRT to occur. Specific Aims •To determine if neoRT can completely ablate 30% of DCIS cases•To determine if DCIS subtypes exhibit differential sensitivity to neoRT•To evaluate microscopic treatment effects; wound complication rates; post-RT breast imaging changes; and invasive carcinoma rate.Eligibility Women 18 years of age or older diagnosed with DCIS by core needle biopsy and intending to receive breast conserving surgery are eligible. Tumors must be ≤4 cm, discovered as mammographic microcalcifications and/or MRI non-mass enhancement measuring with evidence of residual imaging abnormality after diagnostic needle biopsy. Statistics A total of 50 patients will be recruited. Upstaging to invasive cancer is anticipated to be approximately 10%. 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 neoadjuvant PBI. Accrual 10 (open 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, Carol Marquez, Kimberly Stone, Kimberly Allison, Wendy DeMartini, Catherine Salem, Jacqueline Tsai, Robert West, Alex McMillan, Melinda Telli, Kathleen Horst. A randomized study comparing surgical excision versus NeOadjuvant Radiotherapy followed by delayed surgical excision of Ductal carcinoma In Situ (NORDIS) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-09-01.