Non-sentinel Node Involvement Research Articles

Omission of Completion Axillary Lymph Node Dissection for Patients with Breast Cancer Treated by Upfront Mastectomy and Sentinel Node Isolated Tumor Cells or Micrometastases.

Omission of completion axillary lymph node dissection (cALND) in patients undergoing mastectomy with sentinel node (SN) isolated tumor cells (ITC) or micrometastases is debated due to potential under-treatment, with non-sentinel node (NSN) involvement detected in 7% to 18% of patients. This study evaluated the survival impact of cALND omission in a cohort of breast cancer (BC) patients treated by mastectomy with SN ITC or micrometastases. Among 554 early BC patients (391 pN1mi, 163 ITC), the NSN involvement rate was 13.2% (49/371). With a median follow-up of 66.46 months, multivariate analysis revealed significant associations between cALND omission and overall survival (OS, HR: 2.583, p = 0.043), disease-free survival (DFS, HR: 2.538, p = 0.008), and metastasis-free survival (MFS, HR: 2.756, p = 0.014). For Her2-positive or triple-negative patients, DFS was significantly affected by cALND omission (HR: 38.451, p = 0.030). In ER-positive Her2-negative BC, DFS, OS, recurrence-free survival (RFS), and MFS were significantly associated with cALND omission (DFS HR: 2.358, p = 0.043; OS HR: 3.317; RFS HR: 2.538; MFS HR: 2.756). For 161 patients aged ≤50 years with ER-positive/Her2-negative cancer, OS and breast cancer-specific survival (BCSS) were notably impacted by cALND omission (OS HR: 103.47, p = 0.004; BCSS HR: 50.874, p = 0.035). These findings suggest a potential negative prognostic impact of cALND omission in patients with SN micrometastases or ITC. Further randomized trials are needed.

New Zealand patients have a higher melanoma burden in sentinel nodes and completion lymphadenectomy than patients in MSLT-II

New Zealand has the highest rate of melanoma-related mortality in the world. Access to immunotherapy and radiology is limited and surgical treatment of regional disease remains important. A recent pilot study of a single health district observed a higher nodal melanoma burden than was reported in the second Multicentre Selective Lymphadenectomy Trial (MSLT-II). In this study, a series of regional censuses were undertaken covering the 10 years immediately prior to the publication of MSLT-II. The study population was seven District Health Boards covering 62.2% of the population of New Zealand across a 10-year period preceding MSLT-II. The primary outcomes measured were the size of sentinel lymph node metastases and non-sentinel node (NSN) positivity on completion lymph node dissection (CLND) for patients with a positive sentinel lymph node biopsy (SLNB). In the 2323 SLNB identified, the mean sentinel lymph node metastatic deposit size was larger compared to MSLT-II (2.55 vs. 1.07/1.11mm). A greater proportion of New Zealand patients (44.2%) had metastatic deposits larger than 1mm compared to MSLT-II (33.2/34.5%) and the rate of non-sentinel node involvement on CLND was also higher (22.2% vs. 11.5%). These findings indicate that New Zealand is a high-risk population for nodal melanoma metastases. Due to these differences, the conclusions of MSLT-II may not be able to be applied to melanoma patients in the 7 regions studied in New Zealand.

Estudio del ganglio centinela en el cáncer de mama por el método OSNA (One-Step Nucleic Acid Amplification) tras neoadyuvancia en el Hospital Universitario de Navarra

BackgroundSelective sentinel node (SN) biopsy is the standard technique for axillary staging in breast cancer (BC). There is no consensus on the use of OSNA (One-Step Acid Nucleic Amplification) method for SN in patients undergoing neoadjuvant treatment (NAT). We have studied the results obtained in our centre to justify the advantages of its implementation. Material and methods42 cases were selected from the group of 163 patients with BC treated with NAT, who underwent OSNA of the SN, obtaining a mean of 2.1 nodes per patient. We also analyzed cytokeratin 19 (CK19) expression, tumour grade, molecular phenotype and the degree of response to NAT in these patients. The SN were studied using the OSNA technique and non-sentinel nodes using the traditional method. ResultsTumour grade was 2-3 in 97.6% of cases, phenotype luminal A (17%), luminal B (38%), triple-negative (26.1%) and HER2 (19%). The response to NAT was complete in 59.5% of patients and CK19 expression was unchanged. The nodes studied were positive in 9 patients (21.4%) in whom lymphadenectomy was performed and only one case had a non-sentinel node involvement (2.3%). ConclusionsThe OSNA method for the study of SN after NAT is far superior to the traditional method as it: It allows intraoperative detection of isolated cell group and micrometastases not detectable with traditional methods, avoiding second interventions. It avoids false negatives when the whole SN is analyzed. It shows that CK19 expression is not altered by NAT.

Melanoma sentinel lymph node biopsy and completion lymph node dissection: A regional hospital experience

Completion lymph node dissection (CLND) following positive sentinel lymph node biopsy (SLNB) for cutaneous melanoma is a topic of controversy. The second Multicenter Selective Lymphadenectomy Trial (MSLT-II) suggested no survival benefit with CLND over observation amongst patients with a positive SLNB. The findings of the MSLT-II may have limited applicability to our high-risk population where nodal ultrasound and non-surgical melanoma treatment is rationed. In this regional, retrospective study, we reviewed primary melanoma, SLNB and CLND histopathological reports in the Bay of Plenty District Health Board (BOPDHB) across a 10-year period. The primary outcomes measured were size of sentinel lymph node metastases and non-sentinel node (NSN) positivity on CLND for patients with a positive SLNB. In the 157 SLNB identified, the mean sentinel lymph node metastatic deposit size was larger in BOPDHB compared with MSLT-II (3.53 vs 1.07/1.11mm). A greater proportion of BOPDHB patients (54.8%) had metastatic deposits larger than 1mm compared with MSLT-II (33.2/34.5%) and the rate of NSN involvement on CLND was also higher (23.8% vs 11.5%). These findings indicate that the BOPDHB is a high-risk population for nodal melanoma metastases. Forgoing CLND in the context of a positive SLNB may place these patients at risk.

Deep learning radiomics of ultrasonography: Identifying the risk of axillary non-sentinel lymph node involvement in primary breast cancer.

BackgroundCompletion axillary lymph node dissection is overtreatment for patients with sentinel lymph node (SLN) metastasis in whom the metastatic risk of residual non-SLN (NSLN) is low. However, the National Comprehensive Cancer Network panel posits that none of the previous studies has successfully identified such subset patients. Here, we develop a multicentre deep learning radiomics of ultrasonography model (DLRU) to predict the risk of SLN and NSLN metastasis.MethodsIn total, 937 eligible breast cancer patients with ultrasound images were enrolled from two hospitals as the training set (n = 542) and independent test set (n = 395) respectively. Using the images, we developed and validated a prediction model combined with deep learning radiomics and axillary ultrasound to sequentially identify the metastatic risk of SLN and NSLN, thereby, classifying patients to relevant axillary management groups.FindingsIn the test set, the DLRU yields the best performance in identifying patients with metastatic disease in SLNs (sensitivity=98.4%, 95% CI 96.6–100) and NSLNs (sensitivity=98.4%, 95% CI 95.6–99.9). The DLRU also accurately stratifies patients without metastasis in SLN or NSLN into the corresponding low-risk (LR)-SLN and high-risk (HR)-SLN&LR-NSLN category with the negative predictive value of 97% (95% CI 94.2–100) and 91.7% (95% CI 88.8–97.9), respectively. Moreover, compared with the current clinical management, DLRU appropriately assigned 51% (39.6%/77.4%) of overtreated patients in the entire study cohort into the LR group, perhaps avoiding overtreatment.InterpretationThe performance of the DLRU indicates that it may offer a simple preoperative tool to promote personalized axillary management of breast cancer.FundingThe National Nature Science Foundation of China; The National Outstanding Youth Science Fund Project of National Natural Science Foundation of China; The Scientific research project of Heilongjiang Health Committee; The Postgraduate Research &Practice Innovation Program of Harbin Medical University.

One-step nucleic acid amplification CK19 copy number for sentinel node biopsy in breast cancer: Identification of new cutoffs to predict nonsentinel axillary node involvement.

We evaluated novel sentinel node values in breast cancer for one-step nucleic acid amplification (OSNA) to predict further nodal involvement using various methods in clinically node-negative disease with a positive OSNA result and subsequent axillary node dissection. 239 patients (118 macrometastatic) were assessed revealing cutoffs of total tumor load (TTL) 44500copies/µL (AUROC 0.793); average copy number (ACN) 9450 (AUROC 0.790); and highest copy number (HCN) 46,000. For macrometastatic patients only: TTL 221 400copies/µL (AUROC 0.685); ACN 64,000 (AUROC 0.671); HCN 59 500 (AUROC 0.529). Our data favor TTL and represent one of the largest OSNA macrometastatic predictive series.

Associated Features with Non-Sentinel Lymph Node Involvement in Early Stage Breast Cancer Patients who Have Positive Macrometastatic Sentinel Lymph Node.

The main goal of this study is to determine the clinico-pathological factors that correlate non-sentinel lymph nodes (LNs) involvement in clinically node negative breast cancer (BC) patients with positive macrometastatic sentinel lymph node (SLN) in order to derive future evidence to define a subgroup where completion axillary lymph node dissection (cALND) might not be recommended. Total 289 SLN biopsies were performed in clinically node negative BC patients between March 2014 and April 2017. Seventy patients who performed cALND due to positive macrometastatic SLN were retrospectively selected and classified into two groups, according to non-SLN involvement (NSLNI). Clinico-pathological features of patients were examined computerized and documentary archives. Extracapsular extension (ECE) of SLN, number of harvested SLNs, metastatic rate of SLNs, absence of ductal carcinoma in situ (DCIS) and presence of multilocalization were significantly associated with the likelihood of non-SLN involvement after univariate analysis (p<0,05). Absence of DCIS and presence of multilocalization were found to be significant after multivariate analysis. Careful examination of clinico-pathological features can help to decide avoiding cALND if enough LNs are removed and the rate of SLN metastases is low, particularly in case DCIS accompanying invasive cancer in patients without multi localized tumour.

Sentinel Node Biopsy in Early Breast Cancer Patients with Palpable Axillary Node.

Background:Sentinel lymph node biopsy is a reliable method for evaluation of the axillary lymph node status in early stage breast cancer patients with non-palpable lymph nodes. The present study evaluated the status of sentinel and non-sentinel lymph nodes in T1T2 patients with palpable axillary lymph nodes. Materials and Methods:One hundred and two women with early breast cancer were investigated in this study. Patients were selected for axillary sentinel lymph node biopsy and then surgery .Then the rates of false negative and true positive, and diagnostic accuracy of sentinel lymph nodes biopsy were evaluated. In addition, the hormone receptors status of the tumor was determined through IHC and data was analyzed in SPSS21. Results:In this study, the mean age of the patients was 49 years, 85% had invasive ductal carcinoma in their pathology reports, 77% were ER/PR positive, 30% HER2 positive and 9.8% triple negative and 69% had KI67<14%. In frozen pathology, 15.7 and 84.3% were sentinel positive and negative, respectively, and in the final pathology, 41 and 58.8% were sentinel positive and negative, respectively. This difference arises from the false negative rate of the frozen pathology, which was about 31.3%. The sensitivity, specificity, and diagnostic accuracy of the frozen section were 24, 90 and 43%, respectively. Lymphovascular invasion is an important effective factor in the involvement of sentinel and non-sentinel lymph nodes. Statistical analysis showed that the probability of sentinel and non-sentinel lymph nodes involvement was higher in receptor positive patients and those with KI67>14% (p<0.002) whereas the rate of involvement was lower in triple negative patients. Conclusion:Sentinel node biopsy can be used in a significant percentage of breast cancer patients with palpable and reactive axillary lymph nodes.

The ratio and size of positive sentinel lymph nodes predicts the involvement of non-sentinel lymph nodes following completion axillary lymph node dissection

Background: The role of completion axillary lymph node dissection (CALND) following positive sentinel lymph node biopsy (SLNB) is being actively debated. The involvement of our unit in the POSNOC trial (which has a no-treatment arm), has prompted a review of our unit’s CALND results, in order to examine predictors of involvement of non-sentinel lymph nodes (n-SLN). Methods: We retrospectively analyzed our experience of SLNB between July 2008 to 2013. A total of 1,152 breast cancer patients underwent SLNB based on lymphoscintigraphy, intraoperative gamma probe detection, and blue dye mapping using 99mTc-nanocolloid and Patent Blue V injected peri-areola. Results: Out of 1,152 SLNB performed, 224 were positive for metastatic disease; 203 patients were anesthetically capable of progressing to CALND. On univariate analysis, involved n-SLN on CALND could not be predicted by age, size of tumor, procedure performed, lymph vascular invasion, number of positive SLN, receptor status; ER, PR, HER2 or triple negative. There was a trend toward higher incidence of positive n-SLN with increasing grade, and extracapsular spread, but these did not reach statistical significance. Positive n-SLN on CALND was however predicted by macrometastases in SLN and ratio of positive nodes on SLNB. Conclusions: In our series of more than 200 SLNB, a ratio of >0.5 positive SLN yield and presence of macrometastases in positive SLN, were associated with positive n-SLN on CALND.

The importance of the extracapsular extension of the sentinel node metastasis in the surgical treatment of breast cancer

Introduction: The introduction of sentinel node biopsy (SNB) has led to a significant decrease of axillary lymph node dissections (ALND). The importance of the extracapsular extension (ECE) in the sentinel lymph node (SN) remains unclear. Method: The data of 635 patients with T1-T2N0M0 invasive breast cancer who underwent SNB between 2014 and 2018 were retrospectively analysed. 25% of the SNB patients (158) had metastasis in the SNs. These patients were grouped based on the presence or absence of ECE. The main objective of our study was to analyse the occurrence of massive (>3) node metastasis in the case of ECE negative and ECE positive patients, where ALND was performed. Results: There were 91/158 patients (58%) in the ECE negative group and 67/158 patients (42%) in the ECE positive group. ALND was performed in 42% of the ECE negative and in 69% of the ECE positive patients. There were no significant differences in the mean age of the patients; size, histological type and grade of the tumours, presence of lymphovascular invasion and proportion of hormone and HER2 receptor positivities. In the ECE negative ALND group, pN1 involvement was 82%, pN2+pN3 involvement represented 18% of cases. In the ECE positive ALND group, pN1 involvement was 60%, pN2+pN3 involvement was found in 40% of cases. The presence of ECE was associated with greater axillary disease burden. These results show a significant difference (p = 0.038). Conclusions: ECE of the SN is an important predictor for non-sentinel lymph node involvement. These data suggest, when ECE is confirmed, it is a further factor to be considered in deciding about ALND.

Imaging Predictors for Nonsentinel Lymph Node Metastases in Breast Cancer Patients

Background: The relationship between imaging features and nonsentinel lymph node (NSLN) metastasis is not clear. Objectives: To determine whether imaging features could predict NSLN metastasis in sentinel lymph node (SLN)-positive breast cancer patients and to provide new clues for avoiding unnecessary axillary lymph node dissection. Method: 171 patients with clinically negative axillary lymph nodes and a pathologically positive SLN were recruited between January 2007 and January 2014. According to the Breast Imaging Reporting and Data System (BI-RADS), the effects of clinicopathological factors, especially imaging features, on NSLN metastases were assessed by univariate and multivariate statistical analyses. Results: The average number of dissected SLNs was 2.11 (range, 1–6); 56 of the 171 (32.75%) patients exhibited NSLN metastases. In univariate analysis, tumor size, number of positive SLNs, ratio of positive SLNs, mammographic mass margins, ultrasonographic mass margins, and ultrasonographic vascularity were significantly correlated with NSLN involvement. Furthermore, through multivariate analysis, tumor size, number of positive SLNs, mammographic mass margins, and ultrasonographic vascularity were still independent predictors of NSLN involvement. Additionally, in SLN-positive patients, number of positive SLNs and ultrasonographic vascularity could also predict the tumor burden in NSLN. Conclusions: In addition to tumor size and the number of positive SLNs, mammographic mass margins and ultrasonographic vascularity were also independent predictors of NSLN metastases in SLN-positive patients of breast cancer. The number of positive SLNs and ultrasonographic vascularity could also predict the tumor burden in NSLN.

A Prospective Validation Cohort Study of a Prediction Model on Non-sentinel Lymph Node Involvement in Early Breast Cancer.

Early breast cancer with one or two sentinel lymph nodes (SLNs) may omit axillary lymph node dissection (ALND) if followed by radiotherapy. However, only less than one-third of the patients have positive non-SLNs and can truly benefit from radiotherapy. Before any regional treatment decision, the risk of non-SLN metastasis must be identified. The authors previously developed a predictive model for non-SLN involvement using CK19 mRNA and contrast-enhanced ultrasound (CEUS) score in a training set. They designed a further study to evaluate the predictive effect using the model prospectively in a validation set of one or two involved SLNs. This study identified early breast cancer patients at Zhejiang Cancer Hospital from July 2017 to June 2018. The CK19 mRNA tested by quantitative real-time polymerase chain reaction and CEUS scores were collected before surgery. Patients with one or two involved SLNs were enrolled and underwent ALND. The estimated percentage of non-SLN involvement was calculated by the authors' model formula and the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram. The false-negative rates, predictive accuracy, and area under curve (AUC) were compared between two predictive models. The study enrolled 235 patients, and 35.36% (83/235) of them had non-SLN involvement. The authors' model had a false-negative rate of 6% and an accuracy of 94.9%. The AUC was 0.952 (95% confidence interval [CI] 0.922-0.982), which was significantly higher than that of the MSKCC model at all three cutoff value levels. The authors' model, using CK19 mRNA and the CEUS score, showed the potential predictive value of non-SLNs before surgery for early breast cancer patients. NCT02992067, NCT03280134.

A prospective validation cohort study of a prediction model on non-sentinel lymph node involvement in early breast cancer.

559 Background: Early breast cancer (cT1-2N0) with one or two sentinel lymph node (SLN) involved may avoid axillary lymph node dissection (ALND) if follow by radiotherapy supported by Z0011 and AMAROS trials. However, only less than one-third of those patients have positive non-sentinel lymph node (nSLN) and can truly benefit from radiotherapy or ALND in those two trials. It is necessary to identify the risk of nSLN metastasis before local treatment decision. We previously developed a predictive model for nSLN involvement using circulating CK19 mRNA level combined with contrast-enhanced ultrasound (CEUS) score (ASCO2017 poster 239, NCT02992067) in a training set. To evaluate the predict effect of this model, we designed a further study using the model prospectively in a validation set (NCT03280134). Methods: We identified early breast cancer cases in Zhejiang Cancer Hospital from July 2017 to June 2018. The level of circulating CK19 mRNA tested by qRT-PCR and CEUS scores were collected before surgery in each case. Patients with 1~2 SLN involved were enrolled and continued for ALND. The estimated percentage of nSLN-involved were calculated both by our model formula and the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram. The predictive accuracy and false negative rates (FNR) were evaluated and the area under curve (AUC) was compared between two predictive models. Results: Totally, 235 patients diagnosed as early breast cancer with 1~2 SLN involved were enrolled and 35.36% of them were nSLN involved after ALND. The total accuracy and FNR by our model for nSLN-involved prediction was 94.89% and 6.02%, respectively. The AUC was 0.952 (95%CI, 0.922~0.982), significantly higher than that in MSKCC model 0.880 (95%CI, 0.833~0.927). Furthermore, only CK19 mRNA level (HR = 40.091, 95%CI, 13.663~117.635) and CEUS score (HR = 2.009, 95%CI 1.158~3.485) are significantly related to nSLN involvement in both univariate and multivariate analysis, adjusted by age, menopause statue, tumor size, histological grade, estrogen receptor, progesterone receptor and human epidermalgrowth factor receptor-2 expression. Conclusions: Our model using CK19 mRNA and CEUS score showed potential predictive value of nSLN before surgery in early breast cancer patients. Further validation in larger multicenter cohort is warranted before changing clinical practice.

Magnetic detection of sentinel lymph node in papillary thyroid carcinoma: The MAGIC-PAT study results

IntroductionDespite the controversy concerning sentinel lymph node biopsy (SLNB) in papillary thyroid carcinoma (PTC), successful detection rates can be achieved by radioguidance and vital dyeing. However, the drawbacks in both techniques are notable. Magnetic-guided SLNB (mSLNB) using superparamagnetic iron oxide (SPIO) nanoparticles is appealing as an alternative procedure. Materials and MethodsmSLNB using the Sentimag-Sienna System®, total thyroidectomy and central compartment dissection (CCD) were performed on all PTC patients. Lymph node involvement was assessed by postoperative pathological examination. ResultsFrom 2014 to 2016, 33 consecutive patients with PTC were enrolled in the study. A total of 20 patients met the eligibility. mSLNB succeeded in 16 patients, with a detection rate of 80%. A median of two SLN per patient were detected. A median of 10.5 non-sentinel lymph nodes (NSLN) from CCD were examined. Among the patients, 56.25% (9/16) had no metastatic nodes, while 12.5% (2/16) had exclusively SLN involvement. No false negative cases were found. The agreement between SLN and NSLN status was 87.5%. The prediction of NSLN involvement by SLN status showed 100% sensitivity, 81.8% specificity, 71.4% PPV and 100% NPV. Subsequently, mSLNB and the final pathological analysis would discriminate 43.75% (7/16) of patients who would certainly benefit from CCD whilst 56.25% of the total would confirm an unnecessary lymphadenectomy and avoid morbidity. ConclusionmSLNB showed satisfactory performance in PTC with clinical-negative nodes. We have shown mSLNB to be a good predictor of central compartment status that can improve the staging and management of PTC patients.

Nomogram to predict non-sentinel lymph node status using total tumor load determined by one-step nucleic acid amplification: first report from Thailand.

Axillary staging is a significant prognostic factor often used to determine the treatment course for breast cancer. One-step nucleic acid amplification (OSNA) is now the most accepted method for intra-operative assessment of sentinel lymph nodes (SLN) as it can semi-quantitatively determine the tumor burden in these SLN. Axillary lymph node dissection (ALND) may be omitted in patients with limited disease in the axilla. The objective was to create nomogram for prediction of non-sentinel lymph node (NSLN) status using OSNA to avoid unnecessary ALND. Patients with invasive breast cancer T1-T3 and clinically negative axillary lymph nodes underwent SLN biopsy assessed by OSNA. The patients with positive SLN underwent ALND. Correlations between total tumor load (TTL), clinicopathological parameters, and NSLN status were analyzed by Chi square statistic and logistic regression. Model discrimination was evaluated using receiver-operating characteristic (ROC) analysis. The total number of patients who underwent SLN biopsies was 278. There were 89 patients with positive SLN. NSLNs were positive in 40 patients. Larger tumor size, presence of lymphovascular invasion (LVI) and higher log TTL were independent factors that predicted positive NSLN. TTL can discriminate NSLN status with area under the ROC curve of 0.789 (95% CI 0.686-0.892). Two nomograms using different parameters obtained pre- and post-operatively can predict NSLN involvement with better area under the ROC curve (0.801, 95% CI 0.702-0.900 and 0.849, 95% CI 0.766-0.932, respectively). Nomograms using results obtained via OSNA can predict NSLN status, as well as aid in deciding to omit the use of ALND.

Application of sentinel lymph node biopsy in patients with melanoma

Objective: To investigate the difference between routine hematoxylin-eosin (HE) staining and immunohistochemistry in diagnosing metastatic melanoma in sentinel lymph node (SLN) metastases, and to evaluate the association of SLN tumor burden with the status of non-sentinel lymph nodes (NSLN). Methods: 126 melanoma patients were treated with SLN biopsy and further examined with immunohistochemistry at Fudan University Shanghai Cancer Center between 2010 and 2016, and the status of SLN was respectively estimated by HE stain and immunohistochemistry (S-100 protein, HMB45, Melan A and SOX10). In 39 patients who were treated with complete lymph node dissection, characteristics of SLN tumor burden (maximum diameter of the tumor deposit, tumor penetrative depth and the microanatomic location of the metastasis) and the associations of SLN tumor burden with the involvement of NSLN were all evaluated. Results: Of the total 126 cases, 33 (26.2%) were positive by HE staining and 49 (38.3%) were positive by immunohistochemistry. S-100 protein was positive in 48 out of 49 cases (98.0%). HMB45 was positive in 46 out of 49 cases (93.9%). Melan A was positive in 47 out of 49 cases (96.0%). SOX10 was positive in 8 out of 8 cases. The outcome indicated that the application of immunohistochemistry identified positive SLN missed by HE stain in about 12.1% of cases. Of the 39 patients who were treated with complete lymph node dissection, six showed metastases in NSLN. The frequency of metastases in NSLN was 15.4% (6/39) when SLN was positive. Additionally, the frequency of metastases in NSLN in cases with SLN metastatic deposits ≤2 mm was significantly lower than that in cases with SLN metastatic deposits >2 mm; eight cases with SLN metastatic deposits <0.2 mm had no additional positive NSLN. Conclusions: The findings suggest that immunohistochemistry could effectively improve the detection of positive SLN in melanoma. Cases with SLN metastatic deposits ≤2 mm are less likely to have further metastases in NSLN. There is a need for prospective large-population based studies to identify a subgroup of SLN positive patients who can safely be spared complete lymph node dissection.

A mathematical prediction model incorporating molecular subtype for risk of non-sentinel lymph node metastasis in sentinel lymph node-positive breast cancer patients: a retrospective analysis and nomogram development.

Molecular subtype of breast cancer is associated with sentinel lymph node status. We sought to establish a mathematical prediction model that included breast cancer molecular subtype for risk of positive non-sentinel lymph nodes in breast cancer patients with sentinel lymph node metastasis and further validate the model in a separate validation cohort. We reviewed the clinicopathologic data of breast cancer patients with sentinel lymph node metastasis who underwent axillary lymph node dissection between June 16, 2014 and November 16, 2017at our hospital. Sentinel lymph node biopsy was performed and patients with pathologically proven sentinel lymph node metastasis underwent axillary lymph node dissection. Independent risks for non-sentinel lymph node metastasis were assessed in a training cohort by multivariate analysis and incorporated into a mathematical prediction model. The model was further validated in a separate validation cohort, and a nomogram was developed and evaluated for diagnostic performance in predicting the risk of non-sentinel lymph node metastasis. Moreover, we assessed the performance of five different models in predicting non-sentinel lymph node metastasis in training cohort. Totally, 495 cases were eligible for the study, including 291 patients in the training cohort and 204 in the validation cohort. Non-sentinel lymph node metastasis was observed in 33.3% (97/291) patients in the training cohort. The AUC of MSKCC, Tenon, MDA, Ljubljana, and Louisville models in training cohort were 0.7613, 0.7142, 0.7076, 0.7483, and 0.671, respectively. Multivariate regression analysis indicated that tumor size (OR = 1.439; 95% CI 1.025-2.021; P = 0.036), sentinel lymph node macro-metastasis versus micro-metastasis (OR = 5.063; 95% CI 1.111-23.074; P = 0.036), the number of positive sentinel lymph nodes (OR = 2.583, 95% CI 1.714-3.892; P < 0.001), and the number of negative sentinel lymph nodes (OR = 0.686, 95% CI 0.575-0.817; P < 0.001) were independent statistically significant predictors of non-sentinel lymph node metastasis. Furthermore, luminal B (OR = 3.311, 95% CI 1.593-6.884; P = 0.001) and HER2 overexpression (OR = 4.308, 95% CI 1.097-16.912; P = 0.036) were independent and statistically significant predictor of non-sentinel lymph node metastasis versus luminal A. A regression model based on the results of multivariate analysis was established to predict the risk of non-sentinel lymph node metastasis, which had an AUC of 0.8188. The model was validated in the validation cohort and showed excellent diagnostic performance. The mathematical prediction model that incorporates five variables including breast cancer molecular subtype demonstrates excellent diagnostic performance in assessing the risk of non-sentinel lymph node metastasis in sentinel lymph node-positive patients. The prediction model could be of help surgeons in evaluating the risk of non-sentinel lymph node involvement for breast cancer patients; however, the model requires further validation in prospective studies.

Abstract P3-01-02: Overview of the pathological results and treatment characteristics in the first 1000 patients randomized in the SERC trial: Axillary dissection versus no axillary dissection in patients with involved sentinel node

Abstract Background: Three randomized trials have concluded at non inferiority of omission of complementary axillary lymph node dissection (cALND) for patients with involved sentinel node (SN). However, we can outline strong limitations of these trials to validate this attitude with a high scientific level. We designed the SERC randomized trial to compare outcomes in patients with SN involvement treated with ALND or no further axillary treatment. The aim of this study was to analyze results of the first 1000 patients included. Patients and Methods: SERC trial is a multicenter non-inferiority phase 3 trial. Multivariate logistic regression analysis was used to identify independent factors associated with adjuvant chemotherapy administration and non-sentinel node (NSN) involvement. Results : Of the 963 patients included in the analysis set, 478 were randomized to receive cALND and 485 SLNB alone. All patient demographics and tumor characteristics were balanced between the two arms. SN ITC was present in 6.3% patients (57/903), micro metastases in 33.0% (298), macro metastases in 60.7% (548) and 289 (34.2%) were non eligible to Z0011 trial criteria. Whole breast or chest wall irradiation was delivered in 95.9% (896/934) of patients, adjuvant chemotherapy in 69.5% (644/926), endocrine therapy in 89.6% (673/751) and the proportions were similar in the two arms. The overall rate of positive NSN was 19% (84/442) for patients with cALND. Crude rates of positive NSN according to SN status were 4.5% for ITC (1/22), 9.5% for micro metastases (13/137), 23.9% for macro metastases (61/255) and were respectively 29.36% (64/218), 9.33% (7/75) and 7.94% (10/126) when chemotherapy was administered after cALND, before cALND and for patients without chemotherapy. Conclusion: The main objective of SERC trial is to demonstrate non inferiority of cALND omission. A strong interaction between timing of cALND and chemotherapy with positive NSN rate was observed. Citation Format: Houvenaeghel G, Cohen M, Raro P, De Troyer J, Tunon De Lara C, Guimbergues P, Gauthier T, Faure C, Vaini-Cowen V, Lantheaume S, Regis C, Darai E, Ceccato V, D'Halluin G, Del Piano F, Villet R, Jouve E, Beedassy B, Theret P, Gabelle P, Zinzindohoue C, Opinel P, Marsollier-Ferrer C, Dhainaut-Speyer C, Colombo P-E, Di Beo V, Lambaudie E, Tallet A, Boher J-M. Overview of the pathological results and treatment characteristics in the first 1000 patients randomized in the SERC trial: Axillary dissection versus no axillary dissection in patients with involved sentinel node [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-01-02.

Validation of Breast Cancer Models for Predicting the Nonsentinel Lymph Node Metastasis After a Positive Sentinel Lymph Node Biopsy in a Chinese Population.

Objectives:Over the years, completion axillary lymph node dissection is recommended for the patients with breast cancer if sentinel lymph node metastasis is found. However, not all of these patients had nonsentinel lymph node metastasis on final histology. Some predicting models have been developed for calculating the risk of nonsentinel lymph node metastasis. The aim of our study was to validate some of the predicting models in a Chinese population.Method:Two hundred thirty-six patients with positive sentinel lymph node and complete axillary lymph node dissection were included. Patients were applied to 6 models for evaluation of the risk of nonsentinel lymph node involvement. The receiver–operating characteristic curves were shown in our study. The calculation of area under the curves and false negative rate was done for each model to assess the discriminative power of the models.Results:There are 105 (44.5%) patients who had metastatic nonsentinel lymph node(s) in our population. Primary tumor size, the number of metastatic sentinel lymph node, and the proportion of metastatic sentinel lymph nodes/total sentinel lymph nodes were identified as the independent predictors of nonsentinel lymph node metastasis. The Seoul National University Hospital and Louisville scoring system outperformed the others, with area under the curves of 0.706 and 0.702, respectively. The area under the curve values were 0.677, 0.673, 0.432, and 0.674 for the Memorial Sloan-Kettering Cancer Center, Tenon, Stanford, and Shanghai Cancer Hospital models, respectively. With adjusted cutoff points, the Louisville scoring system outperformed the others by classifying 26.51% of patients with breast cancer to the low-risk group.Conclusion:The Louisville and Seoul National University Hospital scoring system were found to be more predictive among the 6 models when applied to the Chinese patients with breast cancer in our database. Models developed at other institutions should be used cautiously for decision-making regarding complete axillary lymph node dissection after a positive biopsy in sentinel lymph node.

Is extracapsular nodal extension in sentinel nodes a predictor for nonsentinel metastasis and is there an impact on survival parameters?-A retrospective single center cohort study with 324 patients

The Z0011 trial has fundamentally changed axillary management in breast cancer patients. However, some important questions remain, like the role of extracapsular nodal extension (ENE) in positive sentinel nodes and the need for further axillary treatment. In this retrospective cohort study, we reviewed and analyzed data from 342 clinically node negative (cN0) breast cancer patients with a positive sentinel node and subsequent axillary lymph node dissection (ALND) from the BRENDA data base. The 104 (30.4%) ENE positive patients had a significantly higher proportion of ≥3 positive axillary lymph nodes (65.0%) compared to ENE negative patients with a positive sentinel node (21.4%). Likewise, ENE positive patients had significantly more often lymph node metastasis size >2mm (96.2%) than ENE negative patients (72.7%). T1 status was observed significantly more often in ENE negative patients (53.2%) than in ENE positive patients (24.0%). While ENE was linked to worse overall survival in univariate analysis, this effect disappeared when adjusting for nodal status, age, and comorbidities in multivariate analysis. ENE of the sentinel node is an important predictor for nonsentinel lymph node involvement. We suggest that ENE influences survival only via a higher number of positive nodes - one of the most predictive parameters for survival outcome in breast cancer.