Non-sentinel Node Research Articles

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.

Could Nomograms Used to Identify Non-Sentinel Lymph Node Metastases May Be Valuable in Radiotherapy Planning?

Could Nomograms Used to Identify Non-Sentinel Lymph Node Metastases May Be Valuable in Radiotherapy Planning?

Correlation of clinical factors between non-sentinel lymph nodes and 1, 2 positive patients with sentinel lymph node in breast cancer

Objective To analyze the relationship between non-sentinel lymph node(NSLN)metastases and clinicopathologic features in breast invasive ductal carcinoma patients with 1, 2 positive sentinel lymph node(SLN). Methods A total of one hundred and ninety-eight patients with breast invasive ductal carcinoma from January 2013 to December 2017 were enrolled in this prospective study.Modified radical mastectomy was performed after SLN1-2 positive cases were confirmed by biopsy.Postoperative NSLN was counted and the relationship between NSLN and clinical factors was analyzed. Results The positive rate of NSLN in 198 patients was 40.9% (81/198), of which 80 cases were positive at axillary level I and only 1 case was positive at axillary level I and II.There was no significant correlation between NSLN positive and age (χ2=1.258), lesion grade (χ2=1.327), molecular typing (χ2=1.020), neoadjuvant chemotherapy (χ2=0.923), estrogen receptor (χ2=0.189), progesterone receptor (χ2=0.109), Ki67 (χ2=1.755) (P>0.05). The positive rate of NSLN in HER-2 positive patients was 56.9% (29/51), which was significantly higher than 35.4% (52/147) in HER-2 negative patients (χ2=6.136, P=0.034). Logistic regression analysis showed that HER-2 positive was an independent risk factor for NSLN (OR=0.031, 95%CI 0.012-0.615, P=0.022). Conclusion The risk of NSLN positive in breast cancer patients such as SLN1-2 positive patients is still high, and the risk of NSLN positive in HER-2 positive patients is higher. Key words: Breast neoplasms; Sentinel lymph node biopsy; Mastectomy; Non-sentinel lymph node

Can Morphological and Molecular Parameters of the Primary Breast Tumor Predict the Positivity of Nonsentinel Lymph Nodes After Positive Sentinel Lymph Node Biopsy?

Background: Sentinel lymph node (SLN) biopsy is the gold standard in the evaluation of the axillary status in patients with breast cancer. In cases meeting the Z0011 criteria, no further surgery is needed, while in the remaining cases axillary dissection is required. The aim of the study was to evaluate which morphological and molecular parameters of primary breast tumor or positive SLN can predict the positivity of nonsentinel lymph nodes (NSLN) in order to avoid unnecessary axillary lymphadenectomy. Methods: We conducted a retrospective study on 170 consecutive invasive breast carcinomas, in which SLN biopsy was performed for staging. Results: 42 (24%) cases presented SLN metastases, of which 11 were micrometastases, 6 cases met the Z0011 criteria, requiring no subsequent surgery. 25 patients underwent subsequent ANLD, but only 7 cases (28%) had positive NSLN. In this series, only the tumor diameter 20 mm can predict positive nonsentinel lymph nodes (p= 0.058; CI: 0.05787 to 0.8224). Other parameters such as patient's age (p=0.280; CI:0.7544 to 7.998), histological type (p=0.231; CI: 0.05374 to 9.271), histological grade (p=0.929; CI: 0.2351 to 3.515), molecular profile of the tumor (p=0.362; CI: 0.2416 to 4.663), number of positive SLN (p=0.378; CI: 0.1083 to 1.570), presence of extracapsular extension (p=0.625; CI: 0.5066 to 13.96) and lymph node ratio (p=0.656; CI: 0.5068 to 5.768) cannot predict the presence of metastasis in the NSLN. Conclusion: In cases in which the patient does not meet the Z0011 criteria and/or these criteria are not used, axillary lymph node dissection is the surgical treatment of choice.

Can Neutrophil to Lymphocyte Ratio Be a Predictor Tool for The Non-Sentinel Lymph Node Metastasis in Breast Cancer?

Background: To investigate the relationship between neutrophil to lymphocyte ratio (NLR) and non-sentinel lymph node (SLN) metastasis in early stages of breast cancer. Methods: Records of patients with clinically early stage (cT1-T3, N0) invasive breast cancer who underwent SLN biopsy in combination with blue dye and lymphoscintigraphy between April 2015 and January 2017 were noted retrospectively. Pre-treatment NLR of the patients with and without non-SLN metastasis were compared. Results: A total of 178 patients with a mean age of 51,65+-10,93 years were included. NLR was statistically significant in the non-SLN positive patients (p=0.011). Lymphovascular invasion and extracapsular extension of SLN were more common in the non-SLN positive group (all p 0.05). The ODDS value was found to be 3,733 (95% CI: 1,05-13,24) and the risk of metastasis in those with lymphovascular invasion was 3.73 fold. The ODDS value was found to be 10,267 (95% CI: 2,63- 40,12) and the risk of metastasis was 10,267 times greater in those with capsule spread. Conclusion: Lymphovascular invasion, extracapsular extension and NLR are the predictive parameters of non-SLN positivity. Pre-surgical NLR is a useful diagnostic tool for predicting non-SLN metastasis.

Predictors of nonsentinel lymph node metastasis in patients with breast cancer with metastasis in the sentinel node.

To predict the factors related to axillary nonsentinel lymph node (NSLN) metastasis in patients with positive sentinel lymph node (SLN) of early breast cancer.The retrospective data are collected from the patients with positive SLN who received further completion axillary lymph node dissection (cALND) in Peking Union Medical Hospital between March 2016 and December 2017. Univariate analysis was conducted on data with various clinicopathologic factors at first. Those factors with statistic significance (P < .05) in univariate analysis were then used to implement multivariate analysis and logistic regression.There were total of 734 patients who received SLN biopsy , among whom 153 cases were included in our study. About 39.22% (60/153) of 153 paitents with positive SLN had no NSLN metastasisted to SLN. Univariate analysis showed that 3 variables were significantly correlated with NSLN involvement: tumor size (X2 = 10.384, P = .001), SLN metastasis ratio (number of positive SLNs/number of SLNs removed × 100%) (X2 = 10.365, P = .001) and the number of negative sentinel nodes (X2 = 10.384, P = .006). In multivariate analysis and logistic regression, tumor size (odds ratio [OR] = 3.392, 95% confidence interval [CI]: 1.409–8.166, P = .006) and SLN metastasis ratio (OR = 3.514, 95% CI: 1.416–8.72, P = .007) were the independent risk factors. While the number of negative sentinel nodes (OR = 0.211, 95% CI: 0.063–0.709, P = .014) was the independent protective factor. The calculated risk resulted in an area under the curve of 0.746 (95% CI: 0.644–0.848), suggesting stable discriminative capability in Chinese population.For those patients with positive SLN, larger tumor burden and SLN metastasis ratio are independent risk factors for NSLN metastasis. However, the more of the detected negative SLN, the less possibility with NSLN involvement.

Sentinel Lymph Node Ultra-staging as a Supplement for Endometrial Cancer Intraoperative Frozen Section Deficiencies

For endometrial cancer (EC), most surgeons rely on intraoperative frozen section (IFS) to determine the risk of nodal metastasis and necessity of lymphadenectomy. IFS remains a weak link in this practice due to its susceptibility to diagnostic errors. As a less invasive alternative, sentinel lymph node (SLN) mapping and ultra-staging have gradually gained acceptance for EC. We aimed to establish the SLN success rate, negative predictive value, and whether SLNs provide useful information for cases misdiagnosed on IFS. From 2013 to 2017, 100 patients (63 low-risk and 37 high-risk EC) underwent hysterectomy, bilateral salpingo-oophorectomy, and SLN. Among them, 56 had additional pelvic lymphadenectomy. A total of 337 SLNs were obtained in 86 cases: 55 bilaterally and 31 unilaterally. The remaining 14 cases failed because of patient obesity or leiomyoma. Pathology ultra-staging detected 2 positive SLNs from 2 patients (1 with isolated tumor cells, 1 with micrometastases). One of 773 nonsentinel pelvic nodes was positive on the contralateral hemi-pelvis in a patient who was mapped unilaterally, resulting in negative predictive value of 100%. During IFS, tumor grade and/or depth of myometrial invasion was misdiagnosed in 22 cases (22%). These errors would have resulted in under-staging in 10 high-risk patients or over-staging in 4 low-risk patients. SLNs were mapped in these misestimated patients, with one revealing metastases. SLN provides invaluable information on nodal status while detecting occult metastases in cases misdiagnosed on IFS. Our findings justify the incorporation of SLN in initial surgery for EC as an offset to IFS diagnostic errors, minimizing their negative impact on patient care.

Subungual Melanoma of the Hand.

The diagnosis of subungual melanoma (SUM) can be challenging and SUMs generally have a worse prognosis than melanomas arising elsewhere. Due to their rarity, the evidence to guide management is limited. This study sought to identify clinicopathological features predictive of outcome and to provide guidelines for management. From a large, single-institution database, 103 patients with in situ (n = 9) or invasive (n = 94) SUMs of the hand treated between 1953 and 2014 were identified and their features analyzed. The most common site of handSUMs was the thumb (53%). Median tumor thickness was 3.1mm, and SUMs were commonly of the acral subtype (57%), ulcerated (58%), amelanotic (32%), and had mitoses (73%). Twenty-one patients reported prior trauma to the tumor site. Twenty-two patients were stage III at diagnosis; 7 underwent therapeutic lymph node dissection and 22 underwent elective lymph node dissection (5 positive), while 36 had sentinel node biopsy (SNB), 28% of which were positive. Forty percent of SNB-positive patients had involved non-sentinel nodes (SNs) in their completion lymph node dissection. Five-year melanoma-specific survival (MSS) and disease-free survival (DFS) rates were 70% and 52%, respectively. On multivariate analysis, regional node metastasis and right-hand tumor location were significant predictors of shorter DFS and MSS, whereas mitoses negatively impacted DFS only and increasing Breslow thickness impacted MSS only. This study confirms that SUMs on the hand usually present at an advanced stage. Distal amputation appearssafe for invasive SUMs, and SNB should be considered as these patients have a high risk of both SN and non-SN metastasis.

Intraoperative Frozen Section Assessment of Sentinel Lymph Node Biopsy in Breast Carcinoma to Determine the Axillary Lymph Node Status

BACKGROUND: Breast cancer is commonest malignancy of females all over the world. Modified radical mastectomy is still considered as a standard for treating breast cancers. Axillary lymphadenectomy is achieved at the cost of significant morbidity, with a high acute complication rate and a high chronic lymphedema rate. Sentinel lymph node biopsy is associated with better arm function, better quality of life, a shorter hospital stay, and faster recommencement of daily activities than standard axillary lymph node dissection. There are inconsistencies and controversies regarding the pathological work-up of sentinel lymph nodes and no generally applied guidelines exist. METHODS: In total, 60 breast carcinoma cases were studied over a period of 2 years. The axillary lymph node status was determined intra-operatively in carcinoma breast by frozen section assessment of sentinel lymph node. RESULTS: Intraoperative frozen section had sensitivity of 90.3%, specificity of 100%, positive predictive value of 100%, negative predictive value of 90.6% and diagnostic accuracy of 95%. The sentinel lymph node biopsy had a false negative rate of 13.3%. 16.1% cases showed only sentinel lymph node positivity with non-sentinel lymph nodes free from metastasis. The positivity of sentinel lymph node for metastasis was dependent upon certain characteristics of patients such as tumour size, tumour location and grade of tumour and was independent of patient’s age. CONCLUSION: Intraoperative frozen section evaluation of sentinel lymph node (SLN) to predict the status of non-SLN can be recommended only in selected patients in early stage of disease.

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

BackgroundThree 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 (ClinicalTrials.gov, number NCT01717131) 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.MethodsSERC 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.ResultsOf 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.ConclusionThe 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.Trial registrationThis study is registered with ClinicalTrials.gov, number NCT01717131 October 19, 2012.

Validation of a Nomogram for Non-sentinel Node Positivity in Melanoma Patients, and Its Clinical Implications: A Brazilian-Dutch Study.

Non-sentinel node (NSN) positivity impacts the prognosis of melanoma patients; however, the benefits of completion lymph node dissection in patients with positive sentinel nodes (SNs) are limited. We aimed to present a predictive nomogram for NSN positivity in melanoma patients with a positive SN biopsy. This retrospective analysis from patients who underwent SN biopsy in a Brazilian institution from 2000 to 2015 was used for the construction and internal validation of the nomogram. This nomogram was then externally validated in a cohort of Dutch patients. The Brazilian cohort comprised 1213 patients, with a mean follow-up of 5.11years. Breslow thickness (odds ratio [OR] 1.170, 95% confidence interval [CI] 1.043-1.314]; p = 0.008), number of positive SNs (OR 1.092, 95% CI 1.034-1.153; p = 0.001), and largest diameter of the metastatic deposit (OR 3.217, 95% CI 1.551-6.674; p = 0.002) were statistically significant for NSN positivity. Internal validation was performed using a bootstrapping technique. A good performance was observed (Brier score 0.097) and an excellent power of discrimination was achieved (area under the curve [AUC] 0.822). The nomogram was then applied to the Dutch cohort, and its overall performance (Brier score 0.085), calibration (Hosmer-Lemeshow goodness-of-fit test; p = 0.198), and discriminatory power (AUC 0.752, 95% CI 0.615-0.890) were all adequate. We presented a nomogram for assessing NSN probability that should not only be used for surgical considerations but also for risk stratification and clinical decisions. Internal validation has shown that this is an adequate model, while external validation increases the model's reliability and suggests that it can be globally incorporated.

Validation of a Nomogram Predicting Non-Sentinel Lymph Node Metastases among Patients with Breast Cancer after Primary Systemic Therapy - a transSENTINA Substudy

Background: Prediction of non-sentinel lymph node (SLN) status after primary systemic therapy (PST) may allow tailored axillary staging. The aim of this analysis was to compare established nomograms from i) the primary operative (n = 6) and ii) the neoadjuvant (n = 1) setting with an optimized nomogram to predict non-SLN status in patients after PST. Methods: 181 patients converting from cN1 prior to PST to ycN0 but found to have a histologically positive SLN in the SENTINA trial were analyzed. Established models were applied. An optimized model was compiled using univariate and subsequent multivariable logistic regression (backward selection, likelihood ratio test). Results: Area-under-the-curve (AUC) values from the primary operative models showed sufficient performance (0.82-0.71). For the neoadjuvant model, the AUC was found to be inferior to prior analyses (0.66) but within published confidence intervals. The SENTINA nomogram comprised the diameter of the largest lymph node (p = 0.006, odds ratio (OR) = 1.19), tumor size prior to PST (p = 0.085, OR = 1.31), and number of all positive SLN (p = 0.083, OR = 2.04). This model was validated using a separate cohort of arm C (n = 168, AUC 0.79, 95% confidence interval 0.74-0.85). Conclusion: We validated 7 models of prediction of non-SLN among patients showing axillary conversion through PST. Our own ‘SENTINA nomogram' yielded AUC values comparable to previous nomograms.

Positive non-sentinel axillary lymph nodes in breast cancer with 1-2 sentinel lymph node metastases.

Recent clinical trials have shown that sentinel lymph node biopsy (SLNB) alone without axillary lymph node dissection (ALND) can offer excellent regional control if there is sentinel lymph nodes (SLN) metastases to 1-2 nodes. This study aimed to explore the predictive factors for non-sentinel lymph node (NSLN) metastasis in breast cancer patients with 1-2 positive SLNs.Patients with breast cancer and 1-2 positive SLN admitted between March 2009 and March 2017 and who underwent ALND after SLN biopsy (SLNB) at Beijing Chaoyang Hospital were analyzed retrospectively. Factors influencing the status of NSLN were studied by univariate and multivariate analysis.Of 1125 patients, 147 patients had SLN metastasis (13.1%) and 119 patients (81.0%) had 1-2 positive SLNs. Among them, 42 patients (35.3%) had NSLN metastasis. The invasive tumor size (P <.001), histological grade (P =.011), lymphovascular invasion (LVI) (P =.006), and over-expression of HER2 (P =.025) significantly correlated with non-SLN metastasis by univariate analysis. LVI (LVI) (P =.007; OR: 4.130; 95% confidence interval [CI]: 1.465–11.641), invasive tumor size (P <.001; OR: 7.176; 95% CI: 2.710–19.002), and HER2 over-expression (P =.006; OR: 5.489; 95% CI: 1.635–18.428) were independently associated with NSLN metastasis by the Logistic regression model. The ROC analysis identified a cut-off point of 26 mm of tumor size (area under the receiver operating characteristic [ROC] curve [AUC] 0.712, CI: 0.614–0.811) was useful for dividing patients with positive SLN (1-2 nodes) into non-SLN-positive and non-SLN-negative groups.For 1-2 positive SLNs of breast cancer, LVI, large invasive tumor size, and HER2 over-expression are independent factors affecting NSLN metastases.

Sentinel node for malignant melanoma: An observational study of a consecutive single centre experience

IntroductionSentinel node biopsy (SNB) for melanoma gives prognostic information, however the success is dependent on several factors. The aim of this study was to describe outcome data after the introduction of the technique at our centre, including analysis of false negative rate (FNR), predictive factors for positive sentinel node (SN) and non-sentinel node (NSN), as well as prognostic factors for melanoma-specific survival (MSS). Materials and methodsThis is a retrospective observational study of a prospectively kept database at Sahlgrenska University Hospital. Between March 2000 and December 2013, 769 consecutive patients with cutaneous malignant melanoma undergoing SNB were included. The median follow-up time was 55 months (2–179 months). Tumour load in the SN was categorized according to the largest tumour deposit, low when ≤1 mm and high when >1 mm. ResultsThe FNR was 20% and the SN positivity rate was 14% with a decrease in both FNR and SN positivity rate during the study period. In multivariate analysis the only predictive factor for a positive SN was Breslow thickness. The 5-year melanoma specific survival (MSS) was 81% and in multivariate analysis the prognostic factors were SN-status (low metastatic load HR = 2.6, p = 0.001; high metastatic load HR = 2.7, p = 0.004) followed by Breslow thickness and ulceration. ConclusionsIn this study Breslow thickness was the only independent predictive factor for a positive SN, no predictive factors were identified for NSN. Independent prognostic factors for MSS were SN status, Breslow thickness and ulceration. Interestingly, there was no survival difference depending on SN tumour burden when using 1 mm as cut-off.

Axillary metastasis in clinically node-negative breast cancer

Aim of workThis study investigates the factors related to metastasis detection in a sentinel lymph node biopsy (SLN) in patients without clinical axillary involvement. Patients and methodsThe medical records of patients who underwent an SLN biopsy after diagnosis with early-stage breast cancer were evaluated retrospectively. The study sample included 64 patients divided into two groups according to the histopathological examination of the SLN biopsy: Group I (positive for axillary metastasis) and Group II (negative for axillary metastasis). ResultsThe frequency of lymphovascular invasion was significantly higher in Group I (57%) than in Group II (13%) (p = 0.003). The progesterone receptor status (p = 0.036), tumor T-stage(p = 0,047), and Ki-67 index differed significantly (p = 0.045) between the two groups. While in univariate analysis, lymphovascular invasion, T-stage and KI-67 index were significant, in multivariate analysis only lymphovascular invasion was found to be significant. No significant differences were found in terms of estrogen receptor and HER2 considering tumor invasion type, histologic grade, vascular invasion, neural invasion, multifocality or bilaterality, hormone receptor status, menopause status, total number of lymph nodes, presence of non-sentinel lymph nodes and the number of SLNs in the groups (p > 0.05). ConclusionsThe results of this study indicate that lymphovascular invasion is associated with axillary metastasis, based on an SLN biopsy.

265P - Nomogram to predict non-sentinel lymph node status of breast cancer using total tumor load determined by one-step nucleic acid amplification (OSNA)

265P - Nomogram to predict non-sentinel lymph node status of breast cancer using total tumor load determined by one-step nucleic acid amplification (OSNA)

Sentinel and Non-Sentinel Lymph Node Metastasis Prediction and Validation of the MSKCC Nomograms for Indian Breast Cancer Patients

Background: Sentinel lymph node (SLN) biopsy accurately stages the axilla, but is time consuming and resource intensive. Nomograms and scoring systems have been developed, based on clinical and pathologic data available before surgery, to attempt to predict the likelihood of lymph node metastasis before surgery. As the management of the axilla in patients with low nodal burden changes, it is also important to predict whether there will be further axillary disease in patients with a positive SLN. Aim: To explore the risk factors for SLN and non-SLN metastasis in Indian women with breast cancer, by analysis of clinical and pathologic data. To assess the validity and clinical utility of two MSKCC nomograms that predicts axillary lymph node status for Western patients. Methods: Clinical data, and pathologic data available from core biopsy, for a consecutive series of women having SLNB was analyzed, and was plotted on two MSKCC nomograms. Univariate analysis was done by χ2 and Fischer exact tests and multivariate analysis was done by logistic regression method. A receiver-operating characteristic (ROC) curve was drawn and predictive accuracy was assessed by calculating the area under the ROC curve (AUC). Results: 34% (89 out of 256) of our patients had SLN positivity. When correlated with SLN metastasis by univariate analysis, LVI (χ2 = 80, P ≤ 0.001), PNI (χ2 = 13.36, P ≤ 0.001), ER+ (χ2 = 6.85, P = 0.009), PR+ (χ2 = 7.1, P = 0.008) and age ( P = 0.03) were significant. However, multivariate analysis showed that age (OR=1.04, P = 0.007) and LVI (OR=0.07, P ≤ 0.001) were identified as independent predictors for SLN metastasis. The area under the ROC curve was 0.772 and it fairly correlated with MSKCC nomogram. Patients with MSKCC scores lower than 38% had a frequency of SLN metastasis of 7.7% (5/65) and this cut-off could be used as a guide for not doing frozen section analysis in this subgroup. Further axillary dissection showed 41% (38 out of 92) had non-sentinel nodes positive. When correlated with non-SLN metastasis by univariate analysis, LVI (χ2 = 8.8, P = 0.003), PNI (χ2 = 6.85, P = 0.009), and extracapsular extension (χ2 = 4.18, P = 0.04) were significant. Number of SLN negative ( P = 0.01), SLN ratio (number of SLN positive/total number of SLN removed) ( P = 0.01) and size of SLN metastasis ( P = 0.002) were significant. However, multivariate analysis showed that only size of SLN metastasis (OR=0.845, P = 0.02) was identified as independent predictor for non-SLN metastasis. The area under the ROC curve was 0.66 and it poorly correlated with MSKCC nomogram. Conclusion: The MSKCC nomogram can provide a fairly accurate prediction of the probability of SLN metastasis, but is not for non-SLN metastasis. An institutional nomogram for non-SLN metastasis, including additional factors such as size of SLN metastasis, may improve prediction.

A model for predicting low probability of nonsentinel lymph node positivity in melanoma patients with a single positive sentinel lymph node.

Identifying factors associated with nonsentinel lymph node (NSN) metastases in melanoma patients with a single positive sentinel lymph node (SLN) could aid decision making regarding adjuvant therapy. We describe a model for identifying patients with a single positive SLN at low risk for NSN metastasis. Factors associated with NSN metastasis in patients with a primary cutaneous melanoma and a single positive SLN who underwent completion lymph node dissection (CLND) were identified. These factors were used to construct a model for predicting the NSN status. The model was validated using a separate data set from another tertiary referral cancer center. In the training data set, 111 patients had a single positive SLN. Of these, 27 had positive NSN. SLN tumor deposit diameter ≥0.75 mm (OR, 3.43; P = 0.047), age ≥40 (OR, 12.14; P = 0.024), and multifocal SLN tumor deposit location (OR, 4.16; P = 0.0096) were independently associated with NSN positivity. Patients with 0 to 1 of these risk factors had a low risk of NSN metastasis in both the training (7.5%) and validation (4.6%) data sets. A combination of patient and SLN tumor burden characteristics can help to identify patients with a single positive SLN who are at a low risk of NSN metastasis.

Risk factors of sentinel and non-sentinel lymph node metastases in patients with ductal carcinoma in situ of the breast: A nationwide study

ObjectivesUnexplained axillary metastases have been detected in some patients with ductal carcinoma in situ (DCIS), possibly because of occult invasion or iatrogenic tumor cell displacement. The significance of these metastases is unknown and brings into questions the need for upstaging and axillary surgery. What are the risk factors for sentinel lymph node (SN) and non-SN metastases, including the risk of iatrogenic displacement of tumor cells in relation to an excisional biopsy, in patients diagnosed with DCIS? MethodsNationwide data on 1787 women diagnosed with DCIS between 2001 and 2015 were retrieved from the Danish Breast Cancer Group database. The association of clinicopathological variables with a positive SN (isolated tumor cells (ITCs), micro- or macrometastases) was evaluated using univariate and multivariate analyses. ResultsOf the 1787 patients, 71 (4.0%) had a positive SN: 15 (0.8%) had macrometastases, 42 (2.4%) had micrometastases, and 14 (0.8%) had ITCs. Five patients with a positive SN also had a positive non-SN. In adjusted analysis, a positive SN was associated with younger age (P = 0.036), increased size (P = 0.002), palpability (P = 0.0004) and surgical excisional biopsy (P < 0.001). ConclusionsThe overall risk of a positive SN in patients with DCIS on final pathology is low and less than 9% of these patients had positive non-SNs. This argues against using axillary lymph node dissection in this group. The odds of positive SN after surgical excisional biopsies showed more than a four-fold increase, indicating iatrogenic tumor cell displacement. It is questioned whether these patients should be upstaged and classified as having invasive carcinoma.

Intraoperative Nomograms, Based on One-Step Nucleic Acid Amplification, for Prediction of Non-sentinel Node Metastasis and Four or More Axillary Node Metastases in Breast Cancer Patients with Sentinel Node Metastasis

BackgroundOne-step nucleic acid amplification (OSNA) for cytokeratin 19 messenger RNA is an intraoperative diagnostic procedure for the detection of lymph node metastasis.ObjectiveThis study aimed to construct intraoperative nomograms using OSNA for the prediction of non-sentinel lymph node (NSLN) metastasis and four or more axillary lymph node (ALN) metastases.MethodsOf the 4736 breast cancer patients (T1-3, N0) who underwent sentinel lymph node (SLN) biopsy and had SLNs examined intraoperatively with OSNA, 623 with SLN metastasis treated with completion ALN dissection (cALND) were retrospectively analyzed, and were randomly divided into training (n = 312) and validation (n = 311) sets.ResultsOf the clinicopathological parameters available preoperatively and intraoperatively, the multivariate analysis of the training set revealed that clinical tumor size and total tumor load (TTL) determined by OSNA were significantly associated with NSLN metastasis, and that clinical tumor size, number of macrometastatic SLNs, and TTL were significantly associated with four or more ALN metastases. Nomograms for NSLN metastasis and four or more ALN metastases were constructed using these parameters, and their area under the receiver operating characteristic curve (AUC) of the validation set were both 0.70, with a diagnostic accuracy similar to that of previously reported postoperative nomograms.ConclusionsWe constructed intraoperative nomograms using OSNA for the prediction of NSLN metastasis and four or more ALN metastases. These nomograms are as accurate as the conventional postoperative nomograms and might be helpful for decision making regarding the indication for cALND or the choice of adjuvant chemotherapeutic regimens and radiation field.