Research progress of sentinel lymph node biopsy after neoadjuvant chemotherapy for breast cancer / 国际外科学杂志

The feasibility and safety of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) for breast cancer are still controversial in clinical practice. SLNB after NAC is feasible and safe for patients with clinically node-negative (cN0) breast cancer, while those with clinically node-positive (cN+ ) should be carefully considered. In addition to methylene blue and 99mTc-sulfur colloid tracing, some other tracing methods have been proposed in clinical studies, such as carbon nanoparticles and indocyanine green fluorescence tracing. The axillary lymph node (ALN) state of SLNB patients after NAC was associated with molecular subtyping, response to chemotherapy, residual breast tumor size, etc. Therefore, a number of factors should be considered to determine whether ALN dissection is needed. The false negative rate of SLNB after NAC can be reduced by some measures such as placing clips prior to surgery and preoperative tattooing with sterile black carbon suspension. Besides ALN, internal mammary lymph nodes is another route for breast cancer metastasis. As a low-invasive diagnostic technique, internal mammary sentinel lymph node biopsy can complete lymph node staging and pathological staging to guide treatment. This review attempts to introduce the research progress of SLNB after NAC from multiple aspects such as feasibility and safety, tracer methods, assessment of ALN status and methods to reduce false negative rate.

Research progress of sentinel lymph node biopsy after neoadjuvant chemotherapy for breast cancer / 国际外科学杂志

The feasibility and safety of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) for breast cancer are still controversial in clinical practice.SLNB after NAC is feasible and safe for patients with clinically node-negative (cN0) breast cancer,while those with clinically node-positive (cN +) should be carefully considered.In addition to methylene blue and 99mTc-sulfur colloid tracing,some other tracing methods have been proposed in clinical studies,such as carbon nanoparticles and indocyanine green fluorescence tracing.The axillary lymph node (ALN) state of SLNB patients after NAC was associated with molecular subtyping,response to chemotherapy,residual breast tumor size,etc.Therefore,a number of factors should be considered to determine whether ALN dissection is needed.The false negative rate of SLNB after NAC can be reduced by some measures such as placing clips prior to surgery and preoperative tattooing with sterile black carbon suspension.Besides ALN,internal mammary lymph nodes is another route for breast cancer metastasis.As a low-invasive diagnostic technique,internal mammary sentinel lymph node biopsy can complete lymph node staging and pathological staging to guide treatment.This review attempts to introduce the research progress of SLNB after NAC from multiple aspects such as feasibility and safety,tracer methods,assessment of ALN status and methods to reduce false negative rate.

[Discussion on the indications of internal mammary sentinel lymph node biopsy in breast cancer in the era of precision medicine].

Objective: To determine the clinical benefits of internal mammary sentinel lymph node biopsy (IM-SLNB) acquired by breast cancer patients with clinically positive axillary lymph node (ALN), and further optimize the IM-SLNB indications. Methods: All primary breast cancer patients with clinically positive ALN from February 2014 to September 2017 were prospectively recruited in this study. IM-SLNB was performed under the guidance of the modified injection technique. The success rate and visualization rate of IM-SLNB, metastatic rate of internal mammary sentinel lymph node (IMSLN) and its related factors were analyzed, and the clinical benefits were accessed according to the current guidelines. Results: Among 126 patients, all of 94 patients (74.6%) who showed internal mammary drainage successfully underwent IM-SLNB. The incidence of internal mammary artery bleeding and pleural lesion were 4.3%(4/94) and 9.6%(9/94), respectively. The metastatic rate of IMSLN was 38.3% (36/94), which was significantly associated with the number of positive ALN (P<0.001) and tumor size (P=0.024). The lymph node staging of 94 patients who underwent IM-SLNB was more accurate. Among them, 36 cases with positive IMSLN underwent internal mammary radiotherapy (IMRT), while the other 58 cases with negative IMSLN avoided radiotherapy. Conclusions: IM-SLNB should be routinely performed in patients with positive ALN. IM-SLNB can provide more accurate staging and guide tailored IMRT to benefit more breast cancer patients.

The Lymphatic Drainage Pattern of Internal Mammary Sentinel Lymph Node Identified by Small Particle Radiotracer (99mTc-Dextran 40) in Breast.

PURPOSE: The purpose of this study was to detect the lymphatic drainage pattern of internal mammary area and verify the concept of internal mammary sentinel lymph node (IM-SLN) in breast. MATERIALS AND METHODS: A small particle radiotracer (99mTc-Dextran 40) was prepared and tested. 99mTc-Dextran 40 was injected into intraparenchyma at the sound breast by a modified radiotracer injection technique. Subsequently, dynamic single-photon emission computed tomography (SPECT), computed tomography (CT), and SPECT/CT combination images were performed to identify the radioactive lymph vessels and internal mammary lymph nodes (IMLNs). The direction of lymph drainage and the location of the IMLNs were identified in the SPECT/CT imaging. RESULTS: The radiochemical purity of 99mTc-Dextran 40 was > 95%. 99mTc-Dextran 40 could drainage into first, second, and third lymph node and the radioactive lymph node could be detected by the γ detector in the animal experiment. After 99mTc-Dextran 40 injecting into intraparenchyma, 50.0% cases (15/30) were identified the drainage lymphatic vessels and radioactive IMLNs by SPECT. The drainage lymphatic vessel was found from injection point to the first IMLN (IM-SLN) after 10.5±0.35 minutes radiotracer injection, and then 99mTc-Dextran 40 was accumulated into the IM-SLN. The combination imaging of SPECT/CT showed the second IMLN received the lymph drainage from the IM-SLN. The lymphatic drainage was step by step in the internal mammary area. CONCLUSION: The lymph was identified to drain from different regions of the breast to IM-SLN, and then outward from IM-SLN to other IMLN consecutively. It demonstrated the concept of the IM-SLN and provided more evidences for the application of internal mammary sentinel lymph node biopsy.

Definition of Internal Mammary Node Target Volume Based on the Position of the Internal Mammary Sentinel Lymph Nodes Presented on SPECT/CT Fusion Images.

Purpose: Mapping the distribution of internal mammary sentinel lymph nodes (IM-SLNs) presented on single photon emission computed tomography in conjunction with computed tomography (SPECT/CT) images to explore the value of IM-SLN to guide tailored clinical target volume (CTV) delineation of postoperative prophylactic IMNI. Materials and methods: Ninety-seven patients who underwent preoperative lymphoscintigraphy by SPECT/CT and had imaging of IM-SLN were selected in this study. The imaging IM-SLNs on SPECT/CT of eligible patients were projected onto corresponding anatomical positions of a representative axial CT image. The IMN CTVs were delineated on the representative axial CT images according to the Radiation Therapy Oncology Group (RTOG) and Danish Breast Cancer Cooperative Group (DBCG) guideline, and defined as CTVRTOG and CTVDBCG. The location of the IM-SLNs was compared with the RTOG and DBCG guidelines of IMN target volume delineations, respectively. The intercostal space distribution of IM-SLNs was recorded. The distances from the CTVRTOG and CTVDBCG to the IM-SLNs were measured, respectively. Results: The total number of imaging IM-SLNs was 136. IM-SLNs were mostly found in the first intercostal space (40.4%), with 30.2, 24.3, 4.4, and 0.7% of IM-SLNs in the second, third, fourth, and fifth intercostal space, respectively. The average distance from the edge of the CTVRTOG and the edge of CTVDBCG to the central points of the IM-SLNs was 4.10 mm (SD, 3.3 mm) and 1.60 mm (SD, 2.6 mm), respectively (t = 16.640, P = 0.000). The average distance from the edge of CTVRTOG and the edge of CTVDBCG to the lateral border IM-SLN was 6.40 mm (SD, 3.5 mm) and 3.34 mm (SD, 3.3 mm), respectively (t = 19.815, P = 0.000). Only 18.4% of IM-SLN central points were included in the CTVRTOG, and 60.3% of IM-SLN central points were included in the CTVDBCG. When covering 90 and 100% of the IM-SLN center points, the CTVRTOG needs to expand 8 and 15 mm, respectively, and the CTVDBCG needs to expand 5 and 13 mm, respectively. Conclusion: Neither the RTOG nor DBCG consensus guideline about the delineation of IMN CTV was sufficient to cover 90% of IM-SLNs. For 90% coverage of IM-SLN central points, CTVRTOG needed to be expanded by 8 mm, and CTVDBCG needed to be expanded by 5 mm.

Target definition for internal mammary lymph node irradiation based on distribution of internal mammary sentinel lymph node developed on SPECT/CT fusion imaging / 中华放射医学与防护杂志

Objective To explore the target definition for internal mammary lymph nodes ( IMLNs) irradiation based on the distribution of internal mammary sentinel lymph nodes ( IM-SLNs ) developing on SPECT/CT fusion imaging. Methods A total of 709 breast cancer patients who underwent preoperative SPECT/CT fusion imaging examination in IM-SLN from 2014 to 2018 were selected. All of the selected patients were first diagnosed and did not receive neoadjuvant treatment before SPECT/CT examination. Finally, totally 97 patients with 136 positive imaging IM-SLNs were included in this study. The clinical target volumes ( CTVs) were delineated according to the consensus guidelines from RTOG and DBCG and defined as CTVRTOG and CTVDBCG , respectively. The positional relationship of CTVRTOG , CTVDBCG and IM-SLNs were determined. Results The number of IM-SLNs from the first to fifth intercostal spaces were 55, 40, 33, 6 and 1, respectively. And the number of IM-SLNs in the first three intercostal spaces accounted for 94. 85％ of the total. The average distance from the edge of CTVRTOG to the centre points and the edges of IM-SLNs were 4. 10 mm ( 95％CI 3. 54-4. 65 mm) and 6. 40 mm ( 95％CI 5. 81-6. 98 mm), respectively (t=-30. 486,P<0. 05). For the CTVDBCG, the average distance was 1. 60 mm ( 95％CI 1. 16-2. 05 mm) and 3. 34 mm ( 95％CI 2. 78-3. 89 mm) , respectively ( t=-16. 364,P<0. 05) . The average distances from the edge of CTV to the centre points and the edge of IM-SLNs for CTVRTOG were all significantly greater than those for CTVDBCG(t=16. 640, 19. 815, P<0. 05). The rate of covering IM-SLN center points for CTVRTOG and CTVDBCG were 18. 4％ and 60. 3％, respectively. In order to cover 90％or 100％ of the IM-SLN center points, the edge of CTVRTOG should be expanded by 8 or 15 mm, respectively, and the edge of CTVDBCG should be expanded by 5 or 13 mm, respectively. If the diameter of IM-SLN was assumed as 5 mm, the edge of CTVRTOG needed an expansion of 11 or 17 mm to contain 90％or 100％ of IM-SLNs, respectively, while the edge of CTVDBCG needed 7 or 16 mm to cover 90％ or 100％of IM-SLNs, respectively. Conclusions It is reasonable to include the first three intercostal spaces IMLNs for prophylactic irradiation based on the distribution of IM-SLNs. However, CTVs based on the two guidelines are both insufficient to cover 90％ of IM-SLNs.

The Lymphatic Drainage Pattern of Internal Mammary Sentinel Lymph Node Identified by Small Particle Radiotracer ((99m)Tc-Dextran 40) in Breast / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to detect the lymphatic drainage pattern of internal mammary area and verify the concept of internal mammary sentinel lymph node (IM-SLN) in breast. MATERIALS AND METHODS: A small particle radiotracer ((99m)Tc-Dextran 40) was prepared and tested. (99m)Tc-Dextran 40 was injected into intraparenchyma at the sound breast by a modified radiotracer injection technique. Subsequently, dynamic single-photon emission computed tomography (SPECT), computed tomography (CT), and SPECT/CT combination images were performed to identify the radioactive lymph vessels and internal mammary lymph nodes (IMLNs). The direction of lymph drainage and the location of the IMLNs were identified in the SPECT/CT imaging. RESULTS: The radiochemical purity of (99m)Tc-Dextran 40 was > 95%. (99m)Tc-Dextran 40 could drainage into first, second, and third lymph node and the radioactive lymph node could be detected by the γ detector in the animal experiment. After (99m)Tc-Dextran 40 injecting into intraparenchyma, 50.0% cases (15/30) were identified the drainage lymphatic vessels and radioactive IMLNs by SPECT. The drainage lymphatic vessel was found from injection point to the first IMLN (IM-SLN) after 10.5±0.35 minutes radiotracer injection, and then (99m)Tc-Dextran 40 was accumulated into the IM-SLN. The combination imaging of SPECT/CT showed the second IMLN received the lymph drainage from the IM-SLN. The lymphatic drainage was step by step in the internal mammary area. CONCLUSION: The lymph was identified to drain from different regions of the breast to IM-SLN, and then outward from IM-SLN to other IMLN consecutively. It demonstrated the concept of the IM-SLN and provided more evidences for the application of internal mammary sentinel lymph node biopsy.

Discussion on the indications of internal mammary sentinel lymph node biopsy in breast cancer in the era of precision medicine / 中华肿瘤杂志

Objective@#To determine the clinical benefits of internal mammary sentinel lymph node biopsy (IM-SLNB) acquired by breast cancer patients with clinically positive axillary lymph node (ALN), and further optimize the IM-SLNB indications.@*Methods@#All primary breast cancer patients with clinically positive ALN from February 2014 to September 2017 were prospectively recruited in this study. IM-SLNB was performed under the guidance of the modified injection technique. The success rate and visualization rate of IM-SLNB, metastatic rate of internal mammary sentinel lymph node (IMSLN) and its related factors were analyzed, and the clinical benefits were accessed according to the current guidelines.@*Results@#Among 126 patients, all of 94 patients (74.6%) who showed internal mammary drainage successfully underwent IM-SLNB. The incidence of internal mammary artery bleeding and pleural lesion were 4.3%(4/94) and 9.6%(9/94), respectively. The metastatic rate of IMSLN was 38.3% (36/94), which was significantly associated with the number of positive ALN (P<0.001) and tumor size (P=0.024). The lymph node staging of 94 patients who underwent IM-SLNB was more accurate. Among them, 36 cases with positive IMSLN underwent internal mammary radiotherapy (IMRT), while the other 58 cases with negative IMSLN avoided radiotherapy.@*Conclusions@#IM-SLNB should be routinely performed in patients with positive ALN. IM-SLNB can provide more accurate staging and guide tailored IMRT to benefit more breast cancer patients.

The progress of internal mammary lymphatic drainage and internal mammary lymph node biopsy in breast cancer / 中华内分泌外科杂志

There are two main lymphatic drainage routes of the breast: a superficial system and a deep system, and only the deep one can drain into the internal mammary lymph node (IMLN) which receive about 25%of the lymph of the breast. As one of the important nodal sites of lymphatic spread of breast, IMLN is important for neoplasm staging and it will guide adjuvant radiotherapy. However, there still lack an effective and feasible minimally invasive diagnosis technology of IMLN, leading to inaccurate staging and over/under-treatment. The“modified injection technique” broke through the bottle-neck of the low internal mammary visualization rate with traditional injection technique, and made the internal mammary sentinel lymph node biopsy possible to be a min-imally invasive assessment for IMLN status, and further guided internal mammary radiotherapy (IM-RT). Patients with IMLN positive should accept IM-RT, with IMLN negative can avoid IM-RT. With the unceasing progress in studies on internal mammary lymph drainage area, patients may obtain the individualized diagnosis and treat-ment. The review summarizes current knowledge on the anatomy and physiology of the lymphatic system of the breast to translate this into implications for clinical practice of IM-SLNB.

A retrospective study of axillary and internal mammary sentinel lymph node biopsy in breast cancer patients after neoadjuvant chemotherapy / 中国癌症杂志

Background and purpose:Whether axillary sentinel lymph node biopsy (ASLNB) could replace axillary lymph node dissection (ALND) in patients who converted after neoadjuvant chemotherapy (NAC) from cN+ to ycN0 is still contentious, and the previous study only evaluated the pathological status of ALN without internal mammary lymph node (IMLN) condition. This study is to evaluate roles of ASLNB and internal mammary sentinel lymph node biopsy (IM-SLNB) in breast cancer patients after NAC.Methods:From Jan. 2012 to Dec. 2014, 60 breast cancer cT1-4N0-3M0patients who were scheduled for neoadjuvant chemotherapy (NAC) and agreed to accept surgery after NAC from our department were enrolled into the retrospective study. Patients with cN0 before NAC and ycN0 after NAC underwent ASLNB (group A). Patients with cN+ received NAC and ycN0 after NAC (group B) were treated with ASLNB and ALND. Only patients whose clinical nodal status remained positive (ycN+) after NAC underwent ALND without ASLNB (group C). All the patients received radiotracer injection and patients in group A and group B received blue dye injection additionally. Meanwhile, IM-SLNB would be performed for all patients with IM-SLN visualization.Results:The number of patients enrolled in group A, group B and group C was 6, 45 and 9 cases respectively. The accuracy rate of ASLNB in group A was 100% (6/6). Only one patient was axillary sentinel lymph node (ASLN) positive performed ALND. With combination of blue dye and radiolabeled colloid, the accuracy rate of ASLNB in group B was 100% (48/48) and the false negative rate (FNR) was 17.9% (5/28). The FNR in patients with 1, 2 and>2 SLNs examined was 27.3% (3/11), 20.0% (2/10) and 0% (0/7). All of the ALNs were positive in group C. The visualization rate of IM-SLN was 63.3% (38/60). The detection rate of IM-SLNB was 97.4% (37/38) and the metastasis rate was 8.1% (3/37). The incidence of complications was 5.3% (2/38).Conclusion:ASLNB can be performed either before or after preoperative chemotherapy for patients with cN0 disease. Among women with cN+ converted to ycN0 who had 3 or more SLNs examined, the FNR could return to be less than 10%. Those patients whose nodes are still ycN+ should perform ALND. IM-SLNB should be performed routinely in all breast cancer patients after NAC, for it might help to make clear of the nodal staging and the pathological status of IM-SLN and provide the accurate indication of radiation to the internal mammary area in case of under-stage and under-/over-treatment, expecting to develop the deifnition of pathological complete response (pCR).