Sentinel Lymph Node Biopsy Metastases Research Articles

Predictive Factors for Unnecessary Axillary Dissection According to SLN Metastasis in T1, T2 Stage Breast Cancer.

The axillary nodes' status is essential in determining the treatment algorithm according to complete clinical staging. Unnecessary axillary lymph node dissection (ALND) has been prevented after sentinel lymph node biopsy (SLNB) has occurred in current practice. However, approximately half of patients with positive SLNB do not have axillary metastatic lymph nodes. Our study aims to predict unnecessary ALND in patients with SLN metastases by evaluating the patients' clinicopathological data. In total, 221 patients with macrometastasis in SLNB who underwent completion ALND were evaluated retrospectively. Patients were divided into two groups: patients with metastases only in the sentinel lymph node and additional axillary lymph nodes. Univariate and multivariate logistic regression analyses were used to analyze the correlation between SLN metastasis and axillary lymph node metastasis; clinicopathological characteristics, including patient age, menopause status, tumor size and grade, receptor status proliferative marker status, and molecular subtypes of the tumor. In the evaluation of T1-2, cN0 breast cancer patients with SLNB in the form of macrometastasis, only SLNB metastasis was found in 118 (53.4%) patients. In 103 (46.6%) patients, additional axillary node metastasis was observed. The risk of additional nodal spread correlated with patient age older than fertility age (age of 49) (p = 0.015, OR: 1.96, 95% CI: 1.14-3.39) and the number of increased metastatic sentinel nodes (p < 0.001). In line with the data shown by our study, the rate of axillary metastases increases in patients over the age of fertility and as the number of metastatic SLNs increases.

A Predictive Model for Nonsentinel Node Status after Sentinel Lymph Node Biopsy in Sentinel Lymph Node-Positive Chinese Women with Early Breast Cancer.

Background Axial lymph node dissection (ALND) is needed in patients with positive sentinel lymph node (SLN). ALND is easy to cause upper limb edema. Therefore, accurate prediction of nonsentinel lymph nodes (non-SLN) which may not need ALND can avoid excessive dissection and reduce complications. We constructed a new prognostic model to predict the non-SLN metastasis of Chinese breast cancer patients. Methods We enrolled 736 patients who underwent sentinel lymph node biopsy (SLNB); 228 (30.98%) were diagnosed with SLNB metastasis which was determined by intraoperative pathological detection and further accepted ALND. We constructed a prediction model by univariate analysis, multivariate analysis, “R” language, and binary logistic regression in the abovementioned 228 patients and verified this prediction model in 60 patients. Results Based on univariate analysis using α = 0.05 as the significance level for type I error, we found that age (P=0.045), tumor size (P=0.006), multifocality (P=0.011), lymphovascular invasion (P=0.003), positive SLN number (P=0.009), and negative SLN number (P=0.034) were statistically significant. Age was excluded in multivariate analysis, and we constructed a predictive equation to assess the risk of non-SLN metastasis: Logit(P)=Ln(P/1 − P)=0.267∗a+1.443∗b+1.078∗c+0.471∗d − 0.618∗e − 2.541 (where “a” represents tumor size, “b” represents multifocality, “c” represents lymphovascular invasion, “d” represents the number of metastasis of SLN, and “e” represents the number of SLNs without metastasis). AUCs for the training group and validation group were 0.715 and 0.744, respectively. When setting the risk value below 22.3%, as per the prediction equation's low-risk interval, our model predicted that about 4% of patients could avoid ALND. Conclusions This study established a model which demonstrated good prognostic performance in assessing the risk of non-SLN metastasis in Chinese patients with positive SLNs.

Declining Use of Inguinofemoral Lymphadenectomy in the Treatment of Clinically Negative, Pathologic Node Positive Vulvar Cancer: A National Cancer Database Analysis

Inguinofemoral lymphadenectomy (IFL) is a morbid procedure, and studies support the use of sentinel lymph node biopsy (SLNB) as an initial staging procedure for women with early stage operable vulvar cancer. However, in the recently presented GROINSS-V II study, for patients with SLNB metastasis > 2 mm, groin radiotherapy with a total dose of 50 Gy was not a safe alternative to IFL due to an increased number of groin recurrences. Therefore, the management of patients with SLNB-positive groin disease remains controversial. We used the National Cancer Database (NCDB) to examine national trends in the use of SLNB, IFL, and adjuvant therapies in clinically node negative, pathologic node positive (cN-/pN+) vulvar cancer.The NCDB was used to identify patients with cN-/pN+ vulvar cancer between 2012 and 2017. Patients with benign histologies, Paget's disease, and melanoma were excluded. Demographic and clinical data were compared with the chi-squared and Wilcoxon rank-sum test. Overall survival (OS) was analyzed with the Kaplan-Meier method and log-rank test. Cox proportional hazards regression modeling was used to determine factors associated with OS.A total of 1,715 patients with cN-/pN+ vulvar cancer were identified. Of this group, sentinel lymph node data was recorded for 1,172 patients. The rate of SLNB with or without IFL increased from 10.2% in 2012 to 24.0% in 2017. The rate of patients who had SLNB alone increased from 3.4% to 15.1% and conversely, the rate of IFL +/- SLNB decreased from 96.6% to 84.9% (P < 0.05). The SLNB-alone cohort (n = 126) did not differ from the IFL +/- SLNB (n = 1046) cohort in terms of race, age, tumor size, margin status, treatment at academic vs. community center, income, insurance, and residence in a metropolitan or non-metropolitan area. Rates of adjuvant treatments were similar with radiation therapy utilized in 63.5% and 64.9% of the SLNB-alone and IFL +/- SLNB cohorts, respectively. Rates of adjuvant chemoradiation were 29.4% and 31.1% of the SLNB-alone and IFL +/- SLNB cohorts, respectively. Median follow-up was 29 months. On multivariate analysis, there was no significant difference in OS between patients who received SLNB-alone vs. those who received IFL +/- SLNB (HR:0.92, 95% CI: 0.7-1.3, P = 0.617).In this large national sample of vulvar cancer patients with cN-/pN+ groin disease, the rate of IFL is decreasing with time as SLNB is becoming more common and a majority receive either adjuvant radiation or chemoradiation. There was no significant difference in OS observed between patients who received SLNB-alone vs. those who received IFL +/- SLNB. Whether the favorable outcomes in the SLNB-alone cohort may be attributed to radiation technique and/or use of chemoradiation warrants further study.M. Mokhtech: None. S. Gao: None. M. Kassick: None. G. Menderes: None. S. Damast: None.

Our sentinel lymph node experience in patients diagnosed with DCIS and microinvasive breast carcinoma

Aim: Along with the increased availability of radiologic imaging methods, early identification of tumor tissue, and patient surveillance programs; ductal carcinoma in situ (DCIS) and microinvasive DCIS became more commonly identified in the tru-cut biopsy specimens and resected samples of patients. Pathological examinations of the excision materials from these patients reveal invasive tumors, microinvasions or DCIS alone. Recently, it has become debatable whether to perform a sentinel lymph node biopsy (SLNB) in patients diagnosed with DCIS or microinvasive DCIS. In this present study, we evaluated the diagnosis made by examining the excision material, any presence of lymph node metastases, and the relationship of hormone profile to the presence of metastases in the patients diagnosed with DCIS or microinvasive DCIS by the examination of tru-cut biopsy specimens. Based on our study results, we discussed the requirement for SLNB in patients with a tru-cut diagnosis of DCIS or microinvasive DCIS.Materials and Methods: The study included 172 patients, who underwent surgical excision and SLNB after receiving a tru-cut biopsy diagnosis of DCIS and microinvasive DCIS in our hospital from the year 2010 to 2018.Results: Tru-cut biopsy diagnoses were DCIS and microinvasive DCIS in 69.8% (120 patients) and 30.2% (52 patients) respectively. SLNB metastases were identified in 35.8% (n=43) of the DCIS positive patients and 44.2% (n=23) in the microinvasive DCIS positive patients. The diagnosis of invasive ductal carcinoma after mastectomy was made at a rate of 90.0% (n=108) among the DCIS positive patients and 92.3% (n=48) among the microinvasive DCIS positive patients. Conclusion: SLNB metastases were found in 35.8% (n=43) and 44.2% (n=23) of the DCIS positive patients and microinvasive DCIS positive patients, respectively. We conclude that SLNB should be favorably proper to perform in the patients with tru-cut diagnoses of DCIS and microinvasive DCIS because a high rate of SLNB metastases was detected in our DCIS and microinvasive DCIS patients and a high rate of invasive ductal carcinoma diagnosis was made after examining the excision material of these patients.

β3 integrin immunohistochemistry as a method to predict sentinel lymph node status in patients with primary cutaneous melanoma.

Integrins are heterodimeric proteins composed of noncovalently linked ɑ and β subunits which are essential for a wide range of normal physiology and also play prominent roles in cancer. Here we tested whether integrin expression in diagnostic skin biopsies is associated with sentinel lymph node (SLN) metastasis. We utilized a cohort of 854 consecutive patients with primary cutaneous melanoma to quantify the expression of β integrin subunits by reverse transcriptase quantitative PCR (RT-qPCR). In addition, we quantified the expression of β3 integrin by immunohistochemistry (IHC) in a subset of 271 patients by H score. Outcome of interest was SLN biopsy metastasis within 90days of melanoma diagnosis. Logistic regression analyses were used to develop models for the likelihood of SLN metastasis from molecular, clinical, and histologic variables. β3 integrin expression quantified by IHC or RT-qPCR was associated with SLN metastasis. β1, β5, β6, and β8 integrin expression was not associated with SLN metastasis. The incremental gain in performance of a predictive model which included β3 integrin expression as quantified by IHC in combination with established clinicopathologic variables (Breslow depth and patient age) was limited. β3 integrin is the principal integrin subunit associated with sentinel lymph node biopsy (SLNb) metastasis in primary cutaneous melanoma. However, β3 integrin H score does not significantly improve models for the likelihood of SLN metastasis over Breslow depth and patient age.

Model Combining Tumor Molecular and Clinicopathologic Risk Factors Predicts Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma.

PURPOSEMore than 80% of patients who undergo sentinel lymph node (SLN) biopsy have no nodal metastasis. Here, we describe a model that combines clinicopathologic and molecular variables to identify patients with thin- and intermediate-thickness melanomas who may forgo the SLN biopsy procedure because of their low risk of nodal metastasis.PATIENTS AND METHODSGenes with functional roles in melanoma metastasis were discovered by analysis of next-generation sequencing data and case-control studies. We then used polymerase chain reaction to quantify gene expression in diagnostic biopsy tissue across a prospectively designed archival cohort of 754 consecutive thin- and intermediate-thickness primary cutaneous melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. A penalized maximum likelihood estimation algorithm was used to train logistic regression models in a repeated cross-validation scheme to predict the presence of SLN metastasis from molecular, clinical, and histologic variables.RESULTSExpression of genes with roles in epithelial-to-mesenchymal transition (glia-derived nexin, growth differentiation factor 15, integrin-β3, interleukin 8, lysyl oxidase homolog 4, transforming growth factor-β receptor type 1, and tissue-type plasminogen activator) and melanosome function (melanoma antigen recognized by T cells 1) were associated with SLN metastasis. The predictive ability of a model that only considered clinicopathologic or gene expression variables was outperformed by a model that included molecular variables in combination with the clinicopathologic predictors Breslow thickness and patient age (area under the receiver operating characteristic curve, 0.82; 95% CI, 0.78 to 0.86; SLN biopsy reduction rate, 42%; negative predictive value, 96%).CONCLUSIONA combined model that included clinicopathologic and gene expression variables improved the identification of patients with melanoma who may forgo the SLN biopsy procedure because of their low risk of nodal metastasis.

Tumor Cell Adhesion As a Risk Factor for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma.

Less than 20% of patients with melanoma who undergo sentinel lymph node (SLN) biopsy based on American Society of Clinical Oncology/Society of Surgical Oncology recommendations are SLN positive. We present a multi-institutional study to discover new molecular risk factors associated with SLN positivity in thin and intermediate-thickness melanoma. Gene clusters with functional roles in melanoma metastasis were discovered by next-generation sequencing and validated by quantitative polymerase chain reaction using a discovery set of 73 benign nevi, 76 primary cutaneous melanoma, and 11 in-transit melanoma metastases. We then used polymerase chain reaction to quantify gene expression in a model development cohort of 360 consecutive thin and intermediate-thickness melanomas and a validation cohort of 146 melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. Logic and logistic regression analyses were used to develop a model for the likelihood of SLN metastasis from molecular, clinical, and histologic variables. ITGB3, LAMB1, PLAT, and TP53 expression were associated with SLN metastasis. The predictive ability of a model that included these molecular variables in combination with clinicopathologic variables (patient age, Breslow depth, and tumor ulceration) was significantly greater than a model that only considered clinicopathologic variables and also performed well in the validation cohort (area under the curve, 0.93; 95% CI, 0.87 to 0.97; false-positive and false-negative rates of 22% and 0%, respectively, using a 10% cutoff for predicted SLN metastasis risk). The addition of cell adhesion-linked gene expression variables to clinicopathologic variables improves the identification of patients with SLN metastases within 90 days of melanoma diagnosis.

P341 Use of fibrin glue in the prevention of seroma formation after axillary lymphadenectomy

Goals: The ACOSOG Z0011 trial showed that an axillary lymph node dissection (ALND) may be safely omitted in selected patients with a positive sentinel lymph node biopsy (SNB). One of these eligible criteria has non palpable lymphadenopathy. However, the eligibility for patients with a suspicious Ultrasonography (US) is controversial. The purpose of this study was to evaluate the validity of the SNB for patients with suspicious lymph node (sN+) compared to clinical node negative patients (cN0). Methods: Patients with suspicious axillary lymph node positive breast cancer by preoperative assessed US or CT were performed fine needle aspiration (FNA) cytology between 2004 and 2014. Patients with a negative axillary US (cN0 group) or negative FNAC (sN+ group) result underwent SNB. All SNB positive patients underwent completion ALND. The number of positive nodes after ALND was compared cN0 group with sLN group. Results: 530/2683 patients (19.7%) had positive SNB. Ultrasoundaxilla was 49% sensitive and 84% specific in predicting SNB metastases. The positive (PPV) and negative predictive value (NPV) was 53% and 81% respectively. For suspicious group, this was 68.4% sensitive and 99.7% specific in detecting SNB metastases. PPV and NPV were 99.6% and 74.2% respectively. The number of metastasis lymph nodes is 1 (48%), 2 (19%), 3 (9%), more than 4 (54%) and N1mic (17%) in the cN0 group, and 1 (37%), 2 (14%), 3 (7%), more than 4 (10%) and N1mic (28%) in the cN1 suspicious group. Conclusion: These results suggest that patients with suspicious axillary metastases on ultrasound-guided biopsy have less involved nodes than SNB-positive patients with clinical negative node. Therefore, we conclude that SNB can be safely performed in patients with clinically suspicious lymph node on ultrasonography. Disclosure of Interest: No significant relationships.

Risk of node metastasis of sentinel lymph nodes detected in level II/III of the axilla by single-photon emission computed tomography/computed tomography.

In breast cancer, single-photon emission computed tomography/computed tomography (SPECT/CT) shows the exact anatomical location of sentinel nodes (SN). SPECT/CT mainly exposes axilla and partly exposes atypical sites of extra-axillary lymphatic drainage. The mechanism of how the atypical hot nodes are involved in lymphatic metastasis was retrospectively investigated in the present study, particularly at the level II/III region. SPECT/CT was performed in 92 clinical stage 0-IIA breast cancer patients. Sentinel lymph nodes are depicted as hot nodes in SPECT/CT. Patients were divided into two groups: With or without hot node in level II/III on SPECT/CT. The existence of metastasis in level II/III was investigated and the risk factors were identified. A total of 12 patients were sentinel lymph node biopsy metastasis positive and axillary lymph node dissection (ALND) was performed. These patients were divided into two groups: With and without SN in level II/III, and nodes in level II/III were pathologically proven. In 11 of the 92 patients, hot nodes were detected in level II/III. There was a significant difference in node metastasis depending on whether there were hot nodes in level II/III (P=0.0319). Multivariate analysis indicated that the hot nodes in level II/III and lymphatic invasion were independent factors associated with node metastasis. There were 12 SN-positive patients followed by ALND. In four of the 12 patients, hot nodes were observed in level II/III. Two of the four patients with hot nodes depicted by SPECT/CT and metastatic nodes were pathologically evident in the same lesion. Therefore, the present study indicated that the hot node in level II/III as depicted by SPECT/CT may be a risk of SN metastasis, including deeper nodes.

Which Patients Need an Axillary Clearance after Sentinel Node Biopsy?

Sentinel lymph node biopsy (SLNB) is a safe and accurate minimally invasive method for detecting axillary lymph node (ALN) involvement in the clinically negative axilla thereby reducing morbidity in patients who avoid unnecessary axillary lymph node dissection (ALND). Although current guidelines recommend completion ALND when macro- and micrometastatic diseases are identified by SLNB, the benefit of this surgical intervention is under debate. Additionally, the management of the axilla in the presence of isolated tumour cells (ITCs) in SLNB is questioned. Particularly controversial is the prognostic significance of minimal SLNB metastasis in relation to local recurrence and overall survival. Preliminary results of the recently published Z0011 trial suggest similar outcomes after SNB or ALND when the SN is positive, but this finding has to be interpreted with caution.