Abstract OT3-01-01: Feasibility of carbon tattooing for targeted lymph node biopsy in breast cancer patients treated by primary systemic therapy (TATTOO trial)
Authors: Hartmann Steffi , Stachs Angrit , Kühn Thorsten , Winckelmann Antje , de Boniface Jana , Gerber Bernd , Reimer Toralf 
Published: March 2020

Abstract
Background: Selective removal of initially suspicious axillary lymph nodes in breast cancer patients downstaged by primary systemic therapy (PST) improves the accuracy of surgical staging and provides the opportunity for less extensive axillary surgery. Different techniques for this targeted lymph node biopsy (TLNB) have been evaluated. These are either prohibited for radiation safety reasons (radioactive seeds) in some countries, or revealed low identification rates for the target lymph node (TLN) in prospective feasibility trials (wire localization of clip-marked TLN). Therefore, an alternative TLN marking procedure avoiding radiation exposure, specialized intraoperative equipment, high costs and preoperative localization procedures is urgently needed. Tattooing TLNs with highly purified carbon suspension prior to PST and identifying the TLN intraoperatively by visual examination, is a method combining low costs with high patient comfort. Because of the data scarcity on the feasibility of TLNB by carbon tattooing, the TATTOO trial was initiated.
Trial design: The Tattoo trial is a single-arm, multicentric, prospective feasibility trial. Before initiation of PST, ultrasound-guided fine needle aspiration or core needle biopsy of the most suspicious ipsilateral axillary lymph node (TLN) is performed and a highly purified carbon suspension then injected into the cortex of the sampled lymph node and the adjacent soft tissue. After completion of PST, TLNB and axillary lymph node dissection Level I/II is performed in all patients. In those with clinical and sonographical axillary down-staging, sentinel lymph node (SLN) biopsy is additionally performed.
Eligibility criteria: Prior to tattooing, written informed consent is obtained. Female patients aged at least 18 years, with histologically confirmed invasive uni- or bilateral breast cancer with clinically or sonographically suspicious axillary lymph nodes and planned PST without signs of distant metastases are eligible.
Specific aims: The primary outcome of the trial is the intraoperative identification rate (IR) of the carbon-labeled TLN after PST. Secondary outcomes are the concordance rate (CR) of sentinel lymph nodes (SLN) and TLN, the false negative rate (FNR) of targeted axillary dissection (TAD, i.e. SLNB biopsy + TLNB) and complications associated with the procedure.
Statistical methods: IR is defined as the proportion of patients with intraoperatively visually detectable TLNs of all patients. CR is expressed as the proportion of patients in whom TLNB and SLN biopsy reveal the same lymph nodes. The proportion of patients with negative TLN and/or SLN but with metastatic axillary lymph nodes on ALND out of all patients with positive lymph nodes will be reported as FNR. Complications associated with tattooing (i.e. bleeding, pain, adverse tattoo effects) are reported. Statistical analyses will be carried out using IBM SPSS statistics version 25.
Present and target accrual: Patient accrual was initiated in November 2017. Until now, 84 patients have been included by three sites in Germany and Sweden. The target enrollment of 100 patients is estimated to be reached by August 2019 and the final trial report is planned for 2020.
Contact information
Steffi Hartmann, MD (steffi.hartmann@kliniksued-rostock.de)
Citation Format: Steffi Hartmann, Angrit Stachs, Thorsten Kühn, Antje Winckelmann, Jana de Boniface, Bernd Gerber, Toralf Reimer. Feasibility of carbon tattooing for targeted lymph node biopsy in breast cancer patients treated by primary systemic therapy (TATTOO trial) [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 OT3-01-01.