Multimodal Ultrasonographic Assessment of Ipsilateral Axillary Lymph Nodes in Patients With Breast Cancer: A STARD Study

BACKGROUND Breast cancer (BrCa) is the most common malignant neoplasm in women worldwide with a continuous rise on both its incidence and cancer-related deaths (1-3). Accurate evaluation of the presence, extent and status of axillary lymph nodes (ALNs) in patients with BrCa has an important prognostic value, and is essential for disease staging and treatment planning (4).

Historically, axillary lymph node dissection (ALND) and histopathology was used for staging BrCa, but with inevitable short- and long-term complications such as lymphedema, nerve injury, seroma and infection (5). Afterwards, sentinel lymph node (SLN) biopsy (SLNB) has gradually replaced ALND despite its invasive nature, unavoidable false negative results and post-operative complication, which are far less than those encountered with ALND (6). According to the American Society of Oncology Guidelines, If the SLNB results are negative, no further dissection is done because there is no survival benefit for performing ALND in this setting. Patients with positive SLNB results traditionally undergo "completion" ALND (6,7)

Grey-scale ultrasound (US) is a non-invasive method that plays an important role in the preoperative evaluation of ALNs and obtaining samples in patients with BrCa (8-11). Nevertheless, US is operator dependent and focuses mainly on the morphological features lymph nodes (LNs). Addition of Color-Doppler Ultrasound (CDU helps in assessing the presence and distribution of vasculature pattern as well as the resistive index (RI) of ALNs (11-13). Despite their promising results, US and CDU, studies showed very wide ranges and variations in sensitivity and specificity (8-13).

Real-time strain ultrasound elastography (UE) is an imaging technique that utilizes the long-established clinical concept that malignant lesions are often stiffer than normal tissues. The stiffness, a characteristic that can't be assessed by US nor CDU (14) and the UE has therefore been utilized to assess pathological changes in many organs, such as liver, breast, thyroid, muscle, Kidney, Prostate, and cervical LNs (Nicely reviewed in 14). Additionally, elastograms obtained by UE are color-coded images indicating differences in stiffness of portions of a target tissue. These color maps or images arise from analysis of the changes in the radiofrequency impulses before and after the rhythmic manual compression directed along the radiation axis. In addition, UE images are produced simultaneously with the conventional gray-scale US to ensure that images of the same node are precisely obtained (14). UE has also been used in assessing ALNs, but with variable and conflicting results (15,16). Two recent meta-analyses concluded that UE can provide additive useful information regarding ALN assessment prior to surgical procedure selection (17,18).

Other imaging modalities such as mammography, magnetic resonance imaging (MRI), multi-detector computed tomography (CT), Positron-emission tomography (PET-CT) were also tried, but their wide use is limited by their moderate sensitivity, low specificity, need for special protocol for ALNs assessment, law availability, high cost and radiation hazard (19-25).