Abstract PD4-01: Preservation of axillary lymph nodes compared to complete dissection in T1-T2 breast cancer patients presenting 1-2 metastatic sentinel lymph nodes : A multicenter randomized clinical trial. Sinodar One.
Authors: Tinterri Corrado , Marrazzo Emilia , Anghelone Chiara , Barbieri Erika , Sagona Andrea , Bottini Alberto , Rubino Arianna , Gentile Damiano , Gatzemeier Wolfgang , Errico Valentina , Testori Alberto , Canavese Giuseppe 
Published: February 2021

Abstract
Introduction: Sentinel lymph node (SLN) staging is currently used to avoid complete axillary lymph node dissection (ALND) in breast cancer (BC) patients. The SLN is the only site of axillary metastasis (MTS) in ≤60% of cases. Recently, a randomized controlled trial (Z0011) comparing SLN biopsy (SLNB) alone with SLNB followed by ALND in patients with 1-2 SLNs+ demonstrated no significant statistical difference in relapse and overall survival rates among the two different groups. However, this study had some limitations: small tumor size (≤2cm in 70% of cases), frequent presence of only microMTS in SLN (40%), prevalent use of “whole breast” adjuvant radiotherapy (&gt;90%). Given these considerations, the SINODAR-ONE study started in April 2015.Objectives: The aims are to assess whether ALND omission in BC patients with 1-2 SLNs+ is associated with worse survival and/or increased rate of regional/distant relapse. Thus evaluating whether SLNB is or is not inferior to ALND. Primary endpoint is overall survival (OS). Secondary endpoints are disease-free survival (DFS) referring to distant MTS and loco-regional recurrence. Methods: Patients receive either mastectomy or conservative surgery plus radiotherapy. They all undergo SLNB and are randomly divided into two arms of treatment: standard (SLNB plus ALND) or experimental treatment (only SLNB). According to multidisciplinary evaluation, patients may undergo additional adjuvant radiotherapy, chemo- and/or hormonal therapy , or no further therapy. Eligibility criteria: age 40-75 years; primary invasive T1-T2 tumor; axillary nodes clinically N0; no more than 2 macro-metastatic SLNs; no distant MTS; no neo-adjuvant therapy; no previous invasive BC; signed informed consent. Exclusion criteria: in situ, inflammatory, contralateral BC; micro-metastic SLNs; pregnancy or breast feeding; comorbidity impeding adjuvant therapy. All analyses are performed both on all patients according to the Intention-To-Treat principle and excluding those patients who did not receive the axillary treatment randomly assigned. Statistical analysis: OS and DFS are calculated using the Kaplan-Meier Product Limit Estimator and differences between arms are assessed with the log-rank test. Results: The enrollment of patients ended in April 2020 with a total of 889 cases (443: standard arm; 446: experimental arm). In June 2020, we conducted an ad interim analysis on 889 patients. We found the two groups homogeneous for epidemiologic characteristics (age and menopausal status), tumor characteristics (tumor size, pTNM, immunohistochemistry, histology, grading, vascular and lymphatic invasion), adjuvant therapies and surgery on T. In particular we have performed a 23,1% of mastectomies in the standard arm and 20,1% in the experimental arm. We found a median of 2 sentinel lymph nodes removed in both arms and 1 non-sentinel positive lymph node in the experimental arm, and only 3 micro-metastases (1 in the standard arm and 2 in the experimental arm). Conclusion: In sum, with a median follow-up of 30 months, there have been no axillary recurrence in both arms. In the standard arm we found 8 total events (2 deaths and 6 distant relapses) and in in the experimental arm 6 events (1 death and 5 distant relapses), with a projected 5-years cumulative incidence of 6,5% in standard arm and 4,85% in the experimental arm.
Citation Format: Corrado Tinterri, Emilia Marrazzo, Chiara Anghelone, Erika Barbieri, Andrea Sagona, Alberto Bottini, Arianna Rubino, Damiano Gentile, Wolfgang Gatzemeier, Valentina Errico, Alberto Testori, Giuseppe Canavese. Preservation of axillary lymph nodes compared to complete dissection in T1-T2 breast cancer patients presenting 1-2 metastatic sentinel lymph nodes : A multicenter randomized clinical trial. Sinodar One. [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD4-01.