Preliminary Application Of Fluorescence Imaging Combined With Ultrasound In Axillary Sentinel Lymph Node Biopsy Of Breast Cancers Treated With Neoadjuvant Therapy

Objective: Neoadjuvant therapy(NAT)has become an important part of the treatment in breast cancers,which can reduce the clinical staging and operative difficulty,increase the chance of breast-conserving and axillaryconserving surgery,and obtain information of body's response to drugs.However,it is still difficult and controversial to determine the status of axillary sentinel lymph node(SLN)after NAT and whether sentinel lymph node biopsy(SLNB)can replace the traditional axillary lymph node dissection(ALND).The study aims to investigate the accuracy of indocyanine green(ICG)fluorescence imaging combined with ultrasound in locating abnormal lymph nodes in sentinel area before NAT,investigate the feasibility of replacing axillary lymph node dissection(ALND)with sentinel lymph node biopsy(SLNB)after NAT,analyze the relationship between ki-67 expression and the changings in axillary lymph node(ALN)after NAT and discuss the shift of tissue markers under ultrasound-guidance.Methods: A total of 61 breast cancers scheduled to undergo NAT were selected from September 2016 to June 2019 at the Breast Center of the Fourth Hospital of Hebei Medical University.Before NAT,ICG fluorescence imaging combined with ultrasound was used to confirm the lymphatic vessel distribution and the location of abnormal lymph nodes in axillary region,and ultrasound-guided core needle biopsy(CNB)was performed on the lowest abnormal lymph nodes.(near the tail of Spence).The marker was ultrasound-guided placed in the center of the lymph node confirmed metastasis after CNB and the patient was tattooed on the skin to observe the marked lymph node easily.According to the pathological molecular typing and preoperative staging,the patients were undergone 6 to 8 cycles of standardized NAT,and the conditions of ALNs and marker were recorded during NAT.After NAT,intraoperative SLNB with methylene blue was performed,the numbers and the locations of SLNs and the condition of marked-SLN were recorded,then ALND was performed.Results:1.Accuracy of SLN localization by ICG fluorescence imaging combined with ultrasoundSLNs were detected by ICG fluorescence imaging combined with ultrasound before NAT and the detection rate was 100%(61/61).The detection rate of intraoperative SLNB with methylene blue was 75.4%(46/61).The numbers of SLNs had a significant correlation between preoperative and intraoperative detections,the correlation coefficient was 0.94(P <0.05).2.Feasibility of SLNB replacing ALND after NATA total of 13 patients' ALNs achieved pathological complete response(p CR)confirmed by postoperative paraffin pathology,which meant the positive SLNs and ALNs all turning to negative after NAT.And 53.8%(7/13)of those patients were HER-2 positive.There were 9 patients with positive SLNs and negative the other ALNs,meanwhile there were 4 patients with negative SLNs and positive the other ALNs.And the left 35 patients' SLNs and other ALNs were still all positive.In group there were 20 HER-2 positive patients with 35%(7/20)ALN-p CR rate and 41 HER-2 negative ones with 14.6%(6/41)ALN-p CR rate,and the difference of the two group was significant(P < 0.05).Even though the pathological correlation between SLNs and ALNs after NAT was general(correlation coefficient 0.52),there was still statistical significance(P<0.05).And the HER-2 positive patients had higher ALN-p CR rate after NAT.The results showed that in some patients the status of SLN could reflect the ALN status after NAT,which laying the foundation of SLNB replacing ALND after NAT.3.Relationship between Ki-67 expression and the reaction of ALNs afterNATIn group there were 43 Ki-67 positive patients,in which 22 patients with negative SLNs or negative other ALNs after NAT.The obvious reaction rate after NAT was 51.2% and the p CR rate was 30.2%.While the left 18 Ki-67 negative patients,in which 4 patients with negative SLNs or negative other ALNs pathology.The obvious reaction rate was 22.2%,the p CR rate was 0%.Analyzed by paired chi-square test,it showed that the Ki-67 positive patients had better ALNs' reaction rate and higher p CR rate after NAT(P = 0.037).4.The shift of tissue marker after NATA total of 56 marked lymph nodes were detected in the sentinel region during intraoperative SLNB with methylene-blue tracer,in which 48 marked lymph nodes were labeled as the first SLN and the other were labeled as non-first SLN.Only 5 markers were not found in the sentinel region,including 2 markers found in the non-SLN of the first level of ALN after ALND,2 markers found in the soft tissues of the axilla,and the last marker found at the tail of spence by mammography.Conclusions:1.ICG fluorescence imaging combined with ultrasound-guided SLN localization before NAT could accurately determine and locate SLN,which had a high quantitative consistency with intraoperative SLNB traced by methylene blue.2.After NAT,the status of SLN could reflect the ALN status in some patients,especially in those HER-2 positive ones with high ALN-p CR rate,which laying the foundation of SLNB replacing ALND after NAT.3.Ki-67 positive patients had better reaction rate of ALN after NAT and higher ALN-p CR rate.4.The shift rate of marker in the lymph node was low after NAT.The shift of marker was related to the skill of ultrasound-guided displacement,the changes of the size and structure of SLN after NAT and the changes of the lymphatic vessels,which may decrease the detection rate of the first SLN.