Feasibility and diagnostic performance of ultrasound assisted carbon nanoparticle suspension versus dual-tracer-guided sentinel lymph node mapping in patients with early breast cancer: A prospective, randomized controlled, phase III clinical trial

Abstract Introduction Our previous research has confirmed that a carbon nanoparticle suspension (CNS) tracer for sentinel lymph node biopsy (SLNB) has a satisfactory identification rate. The aim of this randomized study was to compare the performance of ultrasound-assisted carbon nanoparticle suspension with that of a dual-tracer method using CNS plus indocyanine green (ICG) for sentinel lymph node (SLN) mapping in patients with early breast cancer (BC). Methods This was a prospective, randomized, controlled phase III clinical study. We included patients with primary lymph node-negative (cN0) BC or with initial cN1 BC that downstaged to cN0 after neoadjuvant chemotherapy (NAC). SLNB was performed in all enrolled patients by certified breast surgeons who were well trained in SLNB. The dual method using the CNS and ICG was standardized for SLNB in our study. All patients were randomized 1:1 to receive the CNS assisted by preoperative ultrasound positioning (CNS group) or the CNS plus ICG (CG group) for SLN mapping. The node to which black-stained or fluorescent lymph vessels flowed first was defined as the first sentinel lymph node. If there were other fluorescent or black-stained lymph nodes, they were removed as the second and later SLNs. Resected LNs that contained fluorescent ICG and/or black staining were defined as true sentinel lymph nodes. The remaining palpable and axillary enlarged LNs (not blue stained or without fluorescence) were removed as suspicious SLNs.The primary end point was the SLN identification rate in the CNS group compared with that in the CG group. Secondary end points, including the metastatic SLN rate, SLN counts, metastatic SLN counts, time to the first SLN and adverse events, were compared between the two groups. Results Overall, 340 patients were enrolled and randomized 1:1 to the CNS group and the CNS+ICG group between December 2019 and April 2021. There were 330 evaluable patients, 163 in the CNS group and 167 in the CG group; 10 patients were excluded from the analysis due to incomplete data. Parameters such as average age, tumor stage, and molecular type were comparable between the two groups.The SLN identification rate was 94.5% (154/163) in the CNS group and 95.8% (160/167) in the CG group (P=0.57). The rate of metastatic SLNs in the CNS group was identical to that in the CG group (30.7% vs. 25.1%, P =0.26). No significant differences were observed between the CNS and CG groups in SLN counts (4.6±2.25 vs. 5.07±2.43, P > 0.05), positive metastatic SLN counts (0.53±1.27 vs. 0.43±1.09, P > 0.05), and time to the first SLN (7.75 min±3.08 min vs. 7.60 min±3.29 min, P > 0.05).In the NAC subgroups, the SLN identification rate was 88.9% (32/36) in the CNS group and 90.7% (39/43) in the CG group (P=0.54). The rate of metastatic SLNs in the CNS group was identical to that in the CG group (52.8% vs. 23.3%, P =0.06). No significant differences were observed between the CNS and CG groups in SLN counts (4.67±2.17 vs. 5.62±3.13, P =0.24), positive metastatic SLN counts (0.97±1.38 vs. 0.38±1.09, P > 0.05), and time to the first SLN (7.64 min±3.15 min vs. 7.93 min±4.01 min, P > 0.05). The proportion of patients with cN1 BC was 77.8% (28/36) in the CNS group and 58.1% (25/43) in the CG group. The SLN identification rate was 85.7% (24/28) in the CNS group and 84.0% (21/25) in the CG group for patients with cN1 BC after NAC (P=0.58). The SLN identification rate was 100% in both groups for cN0 patients after NAC.During and after the operation, no complications, including allergic reactions or skin necrosis, occurred in either group. Conclusions The ultrasound-assisted CNS was comparable to the ICG plus CNS technique for SLN mapping in patients with early breast cancer and also has potential application value in SLNB after NAC. Citation Format: Minyi Cheng, Liulu Zhang, Yuanqi Chen, Xiaosheng Zhuang, Ciqiu Yang, Fei Ji, Hongfei Gao, Mei Yang, Teng Zhu, Jieqing Li. Feasibility and diagnostic performance of ultrasound assisted carbon nanoparticle suspension versus dual-tracer-guided sentinel lymph node mapping in patients with early breast cancer: A prospective, randomized controlled, phase III clinical trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-01-03.