Near-infrared fluorescence axillary reverse mapping (ARM) procedure in invasive breast cancer: relationship between fluorescence signal in ARM lymph nodes and clinical outcomes

Abstract Introduction: Near-infrared (NIR) fluorescence axillary reverse mapping (ARM) procedure is a promising tool to identify and preserve arm lymphatic drainage during axillary lymph node dissection (ALND). The ARMONIC clinical trial was conducted to validate the technique on a large cohort of patients and to analyse predictive clinical factors for ARM lymph node metastasis. For the first time, the fluorescence signal intensity from the ARM lymph nodes was measured and correlated with clinical findings. Materials and methods: 109 patients with invasive breast cancer with an indication of mastectomy and ALND underwent the NIR fluorescence ARM procedure. Indocyanine green was administered by intradermal injection followed by the intraoperative identification and resection of ARM lymph nodes with NIR fluorescence camera guidance. Fluorescence signal intensity and signal distribution were then measured ex vivo and compared with clinical outcomes.Results: ARM lymph nodes were successfully identified by fluorescence in 94.5% of cases. The mean normalised fluorescence signal intensity value was 0.47 with no significant signal difference between metastatic and non-metastatic ARM lymph nodes (p=0.3728). At the microscopic level, fluorescence signal distribution was focally intense in lymphoid tissue areas. Only preoperative diagnosis of metastasis in the axillary nodes of patients was significantly associated with higher ARM node fluorescence signal intensity (p=0.0253) but not the pathological nodal (pN) status (p=0.8081). Based on an optimal cut-off fluorescence value, the final sensitivity and specificity of NIR fluorescence ARM procedure for ARM lymph node metastatic involvement was 64.7% and 47.3%, respectively.Conclusion: Although our preliminary results did not show fluorescence signal intensity is a reliable diagnostic tool, NIR fluorescence ARM procedure may be useful for ARM lymph node identification. Clinical trial registration: NCT02994225