Contrast-enhanced Ultrasound Using Intradermal Microbubble Sulfur Hexafluoride for Identification of Sentinel Lymph Nodes During Breast Cancer Surgery: A Clinical Trial

Abstract

Background/Aim: Sentinel lymph node (SLN) procedures have gained popularity in early breast cancer thanks to the reduction of surgical side-effects. The standard SLN mapping procedure uses 99m Tc-nanocolloid human serum albumin with/without blue dye; limitations include logistical challenges and adverse reactions. Recently, contrast-enhanced ultrasound (CEUS) using sulfur hexafluoride has emerged as a promising technique for SLN mapping. Our study aimed to compare the CEUS technique with the standard isotope method. Materials and Methods: AX-CES, a prospective, monocentric, single-arm phase-3 study was designed (EudraCT: 2020-000393-20). Inclusion criteria were histologically diagnosed early breast cancer eligible for upfront surgery and SLN resection, bodyweight 40-85 kg, and no prior history of ipsilateral surgery or radiotherapy. All patients underwent CEUS prior to surgery and blue dye injection was performed in areas with contrast accumulation. After the experimental procedure, all patients underwent the standard mapping procedure and SLN frozen section assessment was performed. Data on the success rate, systemic reactions, mean procedure time, CEUS appearance, SLN number, and concordance with standard mapping procedure were collected. Results: Among 16 cases, a median of two SLNs were identified during CEUS. In all cases, at least one SLN was identified by CEUS (100%). In six cases, SLNs were classified during CEUS as abnormal, which was confirmed by definitive staining in four cases. After the standard mapping technique, in 15 out of the 16 cases (87.50%), at least one SLN from the standard mapping procedure was marked with blue dye in the CEUS procedure. In our series, sensitivity and specificity of SLN detection by CEUS were 75% and 100%, respectively. Conclusion: CEUS is a safe and manageable intraoperative procedure. When compared with standard techniques, US appearance during CEUS may provide additional information when associated with histological assessment.Breast cancer (BC) represents the leading oncological diagnosis among the female population (1). Despite the global burden, in the past 30 years, a multidisciplinary approach has led to a steady reduction in mortality (2, 3). Additionally, BC screening programs have allowed a higher rate of early-stage diagnosis, enabling de-escalation in medical and surgical treatment (4, 5). However, despite a deeper knowledge of etiopathogenesis and development of biological markers for BC, axillary involvement is still the leading prognostic factor affecting clinical decisions after surgery (6-9).Among axillary treatments, sentinel lymph node (SLN) procedures, introduced by Krag et al. (10) and Giuliano et al. (11) in 1993 and 1994, respectively, gained popularity in 557

Role of Nuclear Sentinel Lymph Node Mapping Compared to New Alternative Imaging Methods

“…Contrast-enhanced ultrasound (CEUS), like other diagnostic methods, also uses a contrast agent in order to identify the first lymph node that accumulates it in real time [ 23 ]. The contrast agents used are divided according to the rigidity of the outer envelope, which contains an inert gas, usually sulfur hexafluoride, inside it [ 24 ]. The outer shells can be made of polymers, proteins or lipids that affect their performance [ 23 ].…”