Abstract OT1-3-02: Will chest wall and regional nodal radiotherapy post mastectomy or the addition of regional nodal radiotherapy to breast radiotherapy post lumpectomy reduce the rate of invasive cancer events in patients with positive axillary nodes who convert to ypN0 af
Authors: Mamounas Eleftherios P , Bandos Hanna , White Julia R , Julian Thomas B , Khan Atif J , Shaitelman Simona F , Torres Mylin A , McCloskey Susan A , Vicini Frank A , Ganz Patricia A , Paik Soonmyung , Gupta Nilendu , Costantino Joseph P , Curran Walter J , Wolmark Norman 
Published: May 2015

Abstract
Background
This phase III randomized post-neoadjuvant chemotherapy trial will evaluate if chest wall and regional nodal XRT (CWRNRT) after mastectomy or whole breast irradiation (WBI) with RNRT after breast-conserving surgery significantly reduces the rate of events for invasive breast cancer recurrence-free interval (IBCR-FI) in patients who present with histologically positive axillary nodes but become histologically negative axillary nodes after neoadjuvant chemotherapy. Secondary aims are OS, LRR-FI, DRFI, DFS-DCIS, and second primary cancer. HYPOTHESIS: Can We Use Tumor and Nodal Response to Neoadjuvant Chemotherapy in Order to Individualize the Use of L-R XRT?
Correlative science will examine the effect of RT by tumor subtype, molecular predictors of outcome for patients with residual disease, and the development of predictors of degree of reduction in loco-regional recurrence.
Methods
Eligible patients with clinical T1-3, N1 breast cancer with pathologic axillary nodal involvement (positive FNA or core needle biopsy) must complete ≥12 weeks of neoadjuvant chemotherapy (anthracycline and/or taxane-based regimen). HER2-positive patients must receive neoadjuvant trastuzumab or other anti-HER2 therapy. After neoadjuvant chemotherapy either breast-conserving surgery or mastectomy will be performed. At the time of surgery, all removed axillary nodes must be histologically free from cancer. 3 or more histologically negative sentinel nodes are acceptable to determine axillary nodal involvement. ER/PR and HER-2 neu status before neoadjuvant chemotherapy is required. All patients will receive additional required systemic therapy.
Site radiation credentialing with a facility questionnaire and case benchmarking is required. Randomization for mastectomy patients will be to no CWRNRT or CWRNRT and for breast-conserving surgery patients to WBI or WBI RNRT.
Statistical Considerations
1636 patients will be enrolled over 5 years with definitive analysis at 7.5 years. The study is powered at 80% to test the main hypothesis that RT reduces the annual hazard rate of events for IBCR-FI by 35% for an absolute risk reduction in the 5-year cumulative rate of 4.6%. Analysis will be on intent-to-treat with 3 formal interim analyses at 43, 86, and 129 events, with a 4th/final analysis at 172 events. Current accrual is 37. (as of 6-10-14)
736 enrolled patients will be evaluated with targeted patient-reported outcome instruments focusing on the effect of RT. Patient assessments will be prior to randomization and then at 3, 6, 12, and 24 months.
Contact Information
Study protocol information can be found under the protocol-specific web page on the CTSU member web site https://www.ctsu.org. For protocol-specific questions contact – NRG Oncology Pittsburgh Clinical Coordinating Department. Phone: 1-800-477-7227. Email: ccd@nsabp.org. All investigators will enroll patients by accessing OPEN at https://open.ctsu.org or from the OPEN tab on the CTSU members’ side of the web site.
Support: NCI PHS U10-CA-12027, -69651, -37377, -69974, and -2166.
Citation Format: Eleftherios P Mamounas, Hanna Bandos, Julia R White, Thomas B Julian, Atif J Khan, Simona F Shaitelman, Mylin A Torres, Susan A McCloskey, Frank A Vicini, Patricia A Ganz, Soonmyung Paik, Nilendu Gupta, Joseph P Costantino, Walter J Curran Jr, Norman Wolmark. Will chest wall and regional nodal radiotherapy post mastectomy or the addition of regional nodal radiotherapy to breast radiotherapy post lumpectomy reduce the rate of invasive cancer events in patients with positive axillary nodes who convert to ypN0 af [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT1-3-02.