Additional Nodal Disease Research Articles

Residual Nodal Burden After Neoadjuvant Chemotherapy in cN1 Breast Cancer Patients with Positive Nodes at Targeted Axillary Dissection.

Targeted axillary dissection (TAD) facilitates nodal staging in cN1 breast cancer after neoadjuvant chemotherapy (NAC). Completion axillary node dissection (cALND) remains the standard of care for TAD-positive patients. This study investigated factors associated with additional positive nodes at cALND (cALND+) and the impact on the residual cancer burden (RCB). Retrospective review of cN1 breast cancer patients treated with NAC and TAD was conducted from July 2013 to June 2023. The review defined cN1 status by ultrasound (US) and biopsy. Patient, tumor, and treatment characteristics were evaluated. Multivariate analysis was performed to identify factors associated with cALND+, and RCB was calculated. Of 902 patients who underwent TAD, 554 (61.4%) were TAD-positive. 457 underwent cALND, and 124 (27%) were cALND+ (average 4.1 additional +nodes). The cALND+ patients had larger primary tumors at diagnosis (4 vs 3.5 cm; p=0.04), more than three suspicious nodes on initial US (30% vs 13%; p≤0.0001), larger residual primary tumors on pathology (median, 3 vs 2.1 cm; p=0.0004), and more positive TAD nodes (median, 2 vs 1; p≤0.0001). In the multivariate analysis, the factors associated with cALND+ were more than three suspicious nodes on initial US (odds ratio [OR], 2.9; p≤0.0001), more positive TAD nodes (OR, 1.1; p≤0.0001), larger clipped node metastasis (OR, 1.1; p≤0.0001), and larger residual tumor on pathology (OR, 1.1; p=0.006). Of 65 cALND+ patients with RCB class I or II, 29 (45%) had an increase in RCB based on cALND. Of cN1 breast cancer patients treated with NAC who are TAD-positive, approximately 25% will have additional nodal disease on cALND. In these patients, positive cALND is associated with greater disease burden, which has potential implications for RCB status and prognosis.

Prediction of non-sentinel lymph node metastases in T1–2 sentinel lymph node-positive breast cancer patients undergoing mastectomy following neoadjuvant therapy

BackgroundAxillary lymph node dissection (ALND) is the standard axillary management for breast cancer patients with positive sentinel lymph node biopsy (SLNB) after neoadjuvant therapy. Nevertheless, when that happens, the frequency of additional positive nodes is not properly evaluated. We aim to develop a prediction model to assess the frequency of additional nodal disease after a positive sentinel lymph node following neoadjuvant therapy.MethodsWe retrospectively analyzed the ultrasound and clinicopathological characteristics of breast cancer patients with 1–3 positive sentinel lymph nodes (SLN) undergoing mastectomy after neoadjuvant therapy (NAT) at our institution, and performed univariate and multivariate logistic analyses to confirm the factors affecting non-SLN metastasis. These factors were included to establish a nomogram, and the area under receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were utilized to assess the validity of this model.ResultsA total of 126 breast cancer patients were ultimately included in our study, 38 (53.5%) patients were diagnosed with non-SLN metastases of all 71 patients in training set. The results of multifactorial logistic analysis suggested that lymph node metastasis ratio (LNR), short axis of lymph node and progesterone receptor (PR) were strongly associated with non-SLN metastasis. We established a nomogram using the above three variables as predictors, which yielded an area under the curve of 0.795, and validated with a favorable AUC of 0.876.ConclusionThe nomogram we constructed can accurately predict the likelihood of non-SLN metastasis in our patients with 1–3 positive SLN after NAT, which may help guide decision making regarding axillary management.

Sentinel Lymph Node Biopsy Alone is Adequate for Chemotherapy Decisions in Postmenopausal Early-Stage Hormone-Receptor-Positive, HER2-Negative Breast Cancer with One to Three Positive Sentinel Lymph Nodes.

The RxPONDER trial randomized patients with cT1-3N0 hormone receptor-positive, HER2-negative (HR+HER2-) breast cancer and one to three positive nodes and Recurrence Score (RS) < 26 to endocrine therapy (ET) or chemoendocrine therapy (CET) with equivalent survival in postmenopausal women. In current practice, cN0 patients with one or two positive sentinel lymph nodes (SLN) do not undergo axillary lymph node dissection (ALND), raising concerns about applying these data in patients who may have additional nodal disease. We identified institutional [Dana-Farber Brigham Cancer Center (DF/BCC), 2016-2020] and national [National Cancer Database (NCDB), 2012-2017] cohorts of women aged 50-75 years with cT1-3N0 HR+HER2- breast cancer and RS < 26 treated with upfront surgery with one to three positive SLN. Axillary nodal burden and outcomes were assessed on the basis of the number of positive nodes and CET use. A total of 197 and 13,499 HR+HER2- eligible patients with one to three positive SLN and RS < 26 were identified in the DF/BCC and NCDB databases, respectively, and 12.7% of DF/BCC and 32.4% of NCDB patients had ALND. Of these, only 12.0 and 4.9% had more than three total positive nodes, respectively. Rates of CET were 6.6% in DF/BCC and 20.9% in NCDB patients. In the NCDB, similar adjusted 4-year overall survival was seen between patients treated with CET or ET for any number of positive nodes (98.1-99.9%, all p > 0.05). Postmenopausal women with cT1-3N0 HR+HER2- breast cancer and RS < 26 with one to three positive SLN are unlikely to have more than three total positive nodes. CET decisions should continue to be based on SLN biopsy as ALND is unlikely to change treatment recommendations or outcomes.

Predicting Non-sentinel Lymph Node Metastases in Patients with a Positive Sentinel Lymph Node After Neoadjuvant Chemotherapy.

The standard of care for breast cancer patients treated with neoadjuvant chemotherapy (NAC) who have a positive sentinel lymph node (+SLN) after NAC is completion axillary lymph node dissection (ALND). This study aimed to develop a nomogram to predict additional nodal disease in patients with +SLN after NAC. The study reviewed patients 18years of age or older who had invasive breast cancer treated with NAC followed by SLN surgery with +SLN and ALND between 2006 and 2017 at the authors' institution. Factors predictive of positive non-SLNs were analyzed using uni- and multivariable logistic regression. The study identified 120 patients with +SLN after NAC and ALND. Of these patients, 30.8% were clinically node-negative (cN-), and 69.2% were clinically node-positive (cN+) before NAC. Tumor biology was human epidermal growth factor receptor 2-positive (HER2+) for 20%, hormone receptor-positive (HR+)/HER2- for 66.7%, and triple-negative breast cancer (TNBC) for 13.3% of the patients. Additional nodal disease was found on ALND for 63.3% of the patients. In the univariate analysis, the factors predictive of positive non-SLNs were biologic subtype (TNBC and HR+/HER2- vs HER2+; p < 0.001), higher grade (p = 0.047), higher pT category (p = 0.02), SLN extranodal extension (p = 0.03), larger SLN metastasis size (p < 0.001), and higher number of +SLNs (p = 0.02). The factors significant in the multivariable analysis included number of +SLNs, grade 3 vs grade 1 or 2, HER2+ versus HER2-, cN+ versus cN-, and larger SLN metastasis size. The resulting model showed excellent discrimination (area under the curve, 0.82; 95% confidence interval, 0.74-0.90) and good calibration (p = 0.54, Hosmer-Lemeshow). A clinical prediction model incorporating biologic subtype, grade, clinical node status, size of the largest SLN metastasis, and number of +SLNs can help physicians and patients estimate the likelihood of additional nodal disease and may be useful for guiding decision making regarding axillary management.

Additional Nodal Disease Prediction in Breast Cancer with Sentinel Lymph Node Metastasis Based on Clinicopathological Features.

The standard-of-care in breast cancer (BC) with positive sentinel lymph node (SLN) metastasis includes complete axillary lymph node dissection (ALND); however, almost half of such cases have no further tumor burden. This study aimed to assess the clinicopathological factors that predict non-SLN metastasis to define subgroups of SLN-positive patients in whom the axilla may be staged by SLN biopsy alone, while avoiding unnecessary overtreatment. The records of 191 patients with histologically-proven primary BC who underwent a positive (SLN) biopsy between 2005 and 2017 were reviewed. Patients with at least one tumor-involved SLN who underwent completion ALND were enrolled. Demographic and clinicopathological characteristics, including age, primary tumor size and histological grade, lymphovascular invasion, ratio of positive SLNs to the harvested SLNs, SLN metastasis size, and molecular subtype classification according to immunohistochemical biomarker status [estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)], were evaluated. Data were collected retrospectively and analyzed using the Mann-Whitney and Chi-square tests (statistical significance: p<0.05). The incidence of non-SLN metastasis associated with positive SLN was 48.6% (93/191). The risk of additional nodal spread correlated with high sentinel nodal ratio >0.67 [odds ratio (OR)=2.55, p=0.032], luminal BC subtype (OR=2.67, p=0.06), HER2 overexpression (OR=0.4, p=0.016), and ER+PR-HER2- profile (OR=2.95, p=0.027). There was a tendency (statistically insignificant; p>0.05) toward higher incidence of non SLN metastasis with increasing age and histological grade, which could be attributed to the small sample size. According to this study, sentinel nodal ratio and BC subtypes as per ER, PR, and HER2 status significantly predicted the likelihood of additional lymphatic involvement. Validation of these parameters in prospective studies is indicated, and may help individualize treatment modalities.

Axillary nodal metastases in Italian early breast cancer patients with positive sentinel lymph node: can axillary node dissection be avoided by using predictive nomograms?

Clinical guidelines recommend axillary lymph node dissection (ALND) in cases of metastatic sentinel lymph node (SNL) in patients with clinically node-negative early breast cancer. However, a relevant number of ALND could be avoided in a subset of patients in whom the risk of non-SNL metastases is low. In order to define this population, several authors have proposed mathematical models, which have been validated in many studies. These studies reached different conclusions regarding which model demonstrated the best statistical discrimination power, mainly due to differences in clinical and pathologic variables used, and particularly differences in the number of dissected SLNs. We retrospectively reviewed clinically node-negative patients who underwent ALND in our surgical ward after the diagnosis of breast cancer metastases on SLN biopsy from January 2000 to December 2012. The predictive accuracy of the widely used nomograms to predict the risk of additional nodal disease in our patients with SLN breast cancer metastases was measured by receiver operating characteristic curve. We then attempted to develop a new nomogram by analyzing the dataset. A total of 105 patients were included in this study, with ratio of metastatic lymph node/removed lymph node of about 0.89; we found axillary nodal metastases on ALND in only 31 patients (29.5%). Applied to our dataset, Mayo nomogram showed the best area under the receiving operator characteristic curve (0.74) followed by our model (0.71). Instead, the Memorial Sloan-Kettering model showed poor discrimination, as did Tenon (0.56). Based on our data, we cannot recommend the clinical use of validated predictive nomograms in order to avoid ALND. We suggest setting up a multicenter Italian study to build a model specific to our setting and based on larger series.

Desmoplastic Melanoma: Is There a Role for Sentinel Lymph Node Biopsy?

The utility of sentinel lymph node biopsy (SLNB) for desmoplastic melanoma (DM) is debated. We describe a large single-institution experience with SLNB for DM to determine clinicopathologic factors predictive of SLN metastasis. Retrospective review identified 205 patients with DM who underwent SLNB from 1992 to 2010. Clinicopathologic characteristics were correlated with SLN status and outcome. Median age was 66 years, and 69 % of patients were male. Median Breslow thickness was 3.7 mm. In 128 cases (62 %), histologic subtype data was available; 61 cases (47.7 %) were mixed and 67 cases (52.3 %) were pure DM. A positive SLN was found in 28 cases (13.7 %); 24.6 % of mixed and 9 % of pure DM had SLN metastases. Multivariable analysis demonstrated that after controlling for age, histologic subtype correlated with SLN status [odds ratio: 3.0 for mixed vs pure, 95 % confidence interval: 1.1-8.7; p < .05]. Completion lymph node dissection was performed in 24 of 28 positive SLN patients with 16.7 % of cases having additional nodal disease. After a median follow-up of 6.3 years, 38 patients developed recurrence and 61 patients died. Positive SLN patients had a significantly higher risk of melanoma-related death compared with negative SLN patients (p = .01). The overall risk for SLN metastasis for DM is 13.7 % and is significantly higher for mixed (24.6 %) compared with pure (9.0 %) DM. We believe that these rates are sufficient to justify consideration of SLNB for both histologic variants, especially since detection of SLN disease appears to predict a higher risk for melanoma-related death.

P3-07-09: Prediction of Additional Nodal Metastasis in Breast Cancer Patients with a Positive Sentinel Node Biopsy: A New Nomogram Including HER2 Status.

Abstract Background The Memorial Sloan Kettering Cancer Center-Breast Cancer Nomogram (MSKCC-BCN) predicts additional nodal metastasis in patients with positive sentinel lymph node (SLN). This statistical tool does not include HER2 status. It has been shown that the interaction covariate between estrogen receptor (ER) and HER2 status was a determinant of SLN positivity. The purpose of our study was to determine if the accuracy of MSKCC BCN could be enhanced with new variables. Patients and methods: Our dataset consisted of 2769 consecutive patients treated for operable breast cancer with SLN biopsies between 2006 and 2009. We selected all the patients (n = 588) with a positive SLN who underwent a completion axillary lymph node dissection (ALND). The MSKCC-BCN was used to calculate the theoretical risk of additional nodal metastasis for all patients. The evaluation of the MSKCC-BCN was performed with calibration test (Cox method) and performance test (Bleeker). Multivariate analysis used a logistic regression model. The input was based on the variables found significant in the univariate analysis. Interaction covariate between ER and HER2 status was included in the model. Our model was then analyzed in terms of discrimination (area under the curve) and of calibration (Hosmer-Lemeshow test). Results: Calibration test showed significant differences between the probability of additional nodal disease predicted by the MSKCC-BCN and the probability observed in our population for the following subgroups of patients: histological grade 3 (p= 0.007), lymphovascular invasion (p=0.03), multifocality (p=0.04), positive ER (p=0.002), micrometastasis in the SLN (p=0.003), isolated tumor cells in the SLN (p=0.02 and positive HER2 (p=0.01). Performance test showed significant differences for the following variables: histological grade (p= 0.02), size of the SLN metastasis (p=0.04) and HER2 status (p=0.01). This shows that the MSKCC-BCN is not well calibrated and cannot be used for our population. A multivariate model to determine the probability of additional nodal metastasis was defined with the following variables: pathologic size of the sentinel node metastasis, interaction covariate between the ER and HER2 status, number of positive SLN and number of SLN removed [Table 1]. This multivariate model resulted in a nomogram tested on the training population. It was discriminating with an area under the curve of 0.76 [0.720−0.808] and well calibrated (Hosmer-Lemeshow test p= 0.51). Conclusions: We showed that HER2 status and pathologic size of the SLN metastasis are determinant to predict additional nodal metastasis after a positive SLN. These two variables were included in a new nomogram that could help in the decision-making concerning further axillary treatment in these patients. Our model has to be validated prospectively in external series to confirm its accuracy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-09.

317 Predictive factors of negative axillary dissection after neoadjuvant chemotherapy (NAC): place of a score in decision-making regarding sentinel lymph node after NAC in patients with locally advanced breast cancer

Although completion axillary lymph node dissection (CALND) is the gold standard for evaluating axillary status after identification of a positive sentinel lymph node (SLN) in breast cancer, almost 40% to 70% of SLN-positive patients will have negative non-SLNs. To predict non-SLN metastases (NSLNM) in patients with a positive SLN biopsy, four different nomograms have been created. The aim of this study was to evaluate the accuracy of four different nomograms in our SLN-positive breast cancer patients.We identified 319 patients who had a positive SLN biopsy and CALND at our hospital during an 8-year period. Breast cancer nomograms developed by Memorial Sloan-Kettering Cancer Center, Tenon Hospital, Cambridge University, and Stanford University were used to calculate the probability of NSLNM. The area under the receiver operating characteristics curve was calculated for each nomogram, and values greater than 0.70 were accepted as demonstrating considerable discrimination.One hundred seven of 319 patients (33.5%) had positive axillary NSLNM. The mean number of SLNs was 2.01 (range, 1 to 11 nodes), and the mean number of positive SLNs was 1.44 (range, 1 to 9 nodes). The area under the curve values were 0.70, 0.69, 0.69, and 0.64 for the Memorial Sloan-Kettering Cancer Center, Tenon, Cambridge, and Stanford models, respectively.We found that the Memorial Sloan-Kettering Cancer Center nomogram was more predictive than the other nomograms, but the Cambridge model and the Tenon model reached borderline values for accurate prediction. Nomograms developed at other institutions should be used with caution when counseling patients about the risk of additional nodal disease.

Why Does No One Want to Perform Lymph Node Dissection Anymore?

In this issue of Annals of Surgical Oncology, Kingham et al. from Memorial Sloan-Kettering Cancer Center present their single-institution retrospective experience of melanoma patients who did not undergo completion lymph node dissection (CLND) for a tumor-positive sentinel lymph node (SLN). Of 313 patients who had a tumorpositive SLN, 271 underwent CLND and 42 did not. Of the 42 patients who did not undergo CLND, 5 did not do so because they were found to have stage IV disease on further workup, leaving 37 patients who should reasonably have considered CLND. The nodal recurrence rates were no different in the no-CLND group (7%) versus the CLND group (6%). Because the disease-free and disease-specific survival rates were similar between the groups, the authors question the value of CLND. We must recognize the limitations of this study. It is a small, retrospective review from a single institution. The groups are not well balanced in terms of clinicopathologic factors. Patients in the no-CLND group versus the CLND group were older (median age, 70 vs. 56 years, P .01), more often had lower-extremity melanomas (40% vs. 13%, P .01), and had a trend toward thicker (3.5 vs. 2.8 mm, P .06), more often ulcerated (62 vs. 44%, P = .09) melanomas. Why did the patients not undergo CLND in this study? In 33% of cases, it seems that the surgeon essentially talked the patient out of having a CLND. Although patient refusal was cited as the most common reason for failure to perform CLND (45%), it is likely that the surgeon’s opinion strongly influenced the patients’ decisions in these cases as well. The patients who chose to forego CLND did not do so for random reasons; selection bias is a major drawback of this study. In my experience, most patients choose CLND if recommended by their surgeon. So what does this study really tell us? I believe it tells us that the experienced melanoma surgeons at Memorial Sloan-Kettering Cancer Center were very good at selecting patients who were unlikely to have nodal recurrence and/or were very likely to develop distant metastatic disease, and thus were unlikely to benefit from CLND. It does not tell us that CLND is of no value. The authors cite population studies that indicate that only 50–69% of melanoma patients in the United States who have a tumor-positive SLN undergo CLND. So why are surgeons so reluctant to perform CLND these days? To address this question, we must consider the reasons for performing CLND. There are two goals: regional disease control and cure. The patients who undergo CLND for a tumor-positive SLN fall into three camps: (1) those who do not need CLND because they do not have, and never will have, additional nodal disease; (2) those who will not benefit from CLND because they are going to die of distant metastatic disease or because their disease will recur in the regional nodes, despite the best possible lymph node dissection; and (3) those who have nonsentinel node metastases for whom CLND will prevent regional nodal recurrence and, in some cases, result in cure. The third camp undoubtedly represents the smallest group. The article by Kingham et al. implies that the third camp does Society of Surgical Oncology 2009

Comparison of Three Micromorphometric Pathology Classifications of Melanoma Metastases in the Sentinel Node

The purposes of this study were to determine which classification best predicts additional lymph node disease and survival, and to suggest a threshold below which a completion dissection may be omitted. Three micromorphometric parameters of melanoma sentinel node metastases were compared: invasion depth from the capsule (Starz-classification), maximum diameter (Rotterdam-criteria), and location within the node (Dewar-classification). The pathology slides of 116 patients with tumor-positive sentinel nodes were reviewed. The follow-up data were obtained from the prospectively kept database. The median follow-up duration was 53 months. Metastases with an invasion depth under 0.3 mm or diameter less than 0.1 mm were not associated with additional involved nodes. Four percent of the patients with metastases with an invasion depth of 0.3 to 1.0 mm had other involved nodes and 3% of the patients with metastases with a diameter of 0.1 to 1.0 mm. Other nodes were involved in 3% of subcapsular metastases, 9% of both subcapsular and parenchymal metastases, and 33% in case of multifocal or extensive disease. The smallest tumor invasion depth and diameter associated with additional involved nodes was 0.4 mm. Only 5-year overall survival in the 3 successive invasion depth categories were statistically significant: 92%, 83%, and 68%. Five-year overall survival was 81% in patients with one involved sentinel node and 60% if there were more. Invasion depth and diameter of the metastasis correlate best with the presence of additional nodal disease. Invasion depth best predicts overall survival. It seems justified to refrain from completion dissection in patients with a sentinel node tumor invasion depth up to 0.4 mm.

Metastases to level IIb in squamous cell carcinoma of the oral cavity: A systematic review and meta‐analysis

In this study, a meta-analysis of level IIb metastases in squamous cell carcinoma (SCC) of the oral cavity was conducted. Two independent reviewers screened abstracts and full text papers deemed potentially relevant. Data were pooled using a random intercept model. In this analysis, 729 abstracts and 177 full text papers were screened (Kappa statistic 0.8 and 1.0, respectively). A total of 332 patients in 9 papers were included in the analysis. Twenty patients had level IIb metastases (mean, 6%; range, 0% to 10.4%). The pooled percentage of level IIb metastases was 6.0% (95% CI: 3.5-8.6). Only 3 patients with level IIb metastases had isolated nodal disease. Eighty-five percent of those with level IIb metastases had additional nodal disease (95% CI: 64.0-94.8), with IIa being a common denominator among all. Level IIb nodal metastases are relatively uncommon in previously untreated SCC of the oral cavity (6%). Furthermore, isolated level IIb nodal disease is uncommon. However, given the quality of evidence to date, it is recommended that dissection of level IIb remain the standard of care in oral cavity squamous cell cancer.

The predictive probability of four different breast cancer nomograms for non-sentinel axillary lymph node metastasis in positive sentinel lymph node biopsy.

Abstract Abstract #204 Introduction: Although completion axillary lymph node dissection (CALND) is the standard for evaluating axillary status after identification of a positive sentinel lymph node (SLN) in breast cancer (BC), almost 50% of SLN positive patients will have negative non-SLN and undergo a non-therapeutic axillary dissection. Accurate estimates of the likelihood of additional disease in the axilla can assist decision-making about further treatment. In order to predict non- sentinel lymph node metastases (NSLNM) in patients with a positive SLN biopsy, four different nomograms have been created. The Memorial Sloan Kettering Cancer Center (MSKCC) nomogram was created in 2003 and validated at sources outside that institution. The other nomograms were developed by the Tenon Hospital, the Cambridge University and the Stanford University group recently, but have not been validated yet. The aim of this study was to evaluate the accuracy of 4 different nomograms in our SLN positive BC patients. Methods: We identified 319 patients who had a positive SLN biopsy and CALND at Magee-Womens Hospital of the University of Pittsburgh Medical Center over an 8 year period. The BC nomograms developed by the MSKCC, the Tenon Hospital, the Cambridge University and the Stanford University were used to calculate the probability of NSLNM. Area Under (AUC) Receiver Operating Characteristics Curve (ROC) was calculated for each nomogram a value more than 0.70 was accepted as providing considerable discrimination. Results: One hundred-seven of 319 patients (33.5%) had positive axillary NSLNM. The mean predicted probability of positive NSLNM was 28.1 % (3-93), 67.1% (4.8-100) and, 39.1% (3.6-97.5) for the MSKCC, the Cambridge, and the Stanford nomograms, respectively. The mean point for the Tenon model was 4.45 (0-7). The AUC values were 0.70, 0.69, 0.69 and 0.64 for the MSKCC, the Tenon, the Cambridge and, the Stanford models, respectively. Conclusion: Breast nomograms can be used in the current practice to provide an accurate prediction for identifying low or high risk for NSLNM in BC. In our study, we found the MSKCC nomogram is more predictive than the other nomograms but the Cambridge model and the Tenon model reached borderline values for the good prediction. A model can provide more accurate results with its original group, but may be insufficient on the different groups. Nomograms developed at other institutions should be used with caution when counseling patients regarding the risk of additional nodal disease. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 204.

Predicting the burden of axillary disease in breast cancer patients with a positive sentinel node.

Abstract Abstract #1010 Background: Current practice is to perform a completion axillary lymph node dissection (ALND) for breast cancer (BC) patients with tumor-positive sentinel lymph nodes (SLNs). However, not all patients with positive SLNs have further ALND. Katz et al suggested a nomogram for predicting having four or more positive nodes for SLN-positive BC which could change the adjuvant radiation treatment fields. Our goal is to validate the accuracy in predicting &amp;gt; 4 positive axillary lymph nodes in BC patients with a positive SLN in our institution. Methods: Katz nomogram was developed from the multivariate logistic regression model using tumor histology, primary tumor size, lymphovascular space invasion, extranodal extension, the number of involved SLNs, the number of uninvolved SLNs, and the size of the largest SLN metastasis. Area Under (AUC) Receiver Operating Characteristics Curve (ROC) was calculated for the nomogram and a value more than 0.70 was accepted as providing considerable discrimination. Results: We reviewed the records of 319 patients with invasive BC and positive SLNs who underwent completion ALND at MWH of UPMC. None of these patients received neoadjuvant chemotherapy The mean age was 54.2 (30-84) years. Eighty-nine patients (27.8%) had four or more positive nodes. Histology was invasive ductal carcinoma for 86.2 % of patients. The median tumor size was 2.22 (0.5-8.0) cm. Seventy percent of patients had only one involved SLN. The median size of the largest SLN metastasis on H&amp;E staining was 9.7 mm (range, &amp;lt; 0.2 to 35 mm), and 24.4% of the patients had micrometastases (2 mm). Ninety nine patients (31%) had extranodal extension. The mean predicted probability of having ≥ 4 involved axillary LNs was 31.9 % (range, 1 to 99) in patients with ≥ 4 involved axillary LNs while it was it is 9.1% (range, 0.5 to 80) in patients having &amp;lt; 4 axillary LN metastases (P&amp;lt;0.001). The AUC value was 0.809. Conclusions: The Katz nomogram developed to predict having ≥ 4 involved axillary lymph nodes in BC patients with a positive SLNs is validated in our patients. Nomograms developed at other institutions should be used with caution when counseling patients regarding the risk of additional nodal disease. This nomogram will be helpful to clinicians making adjuvant treatment recommendations in practice. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1010.

Predictive Probability of Four Different Breast Cancer Nomograms for Nonsentinel Axillary Lymph Node Metastasis in Positive Sentinel Node Biopsy

Although completion axillary lymph node dissection (CALND) is the gold standard for evaluating axillary status after identification of a positive sentinel lymph node (SLN) in breast cancer, almost 40% to 70% of SLN-positive patients will have negative non-SLNs. To predict non-SLN metastases (NSLNM) in patients with a positive SLN biopsy, four different nomograms have been created. The aim of this study was to evaluate the accuracy of four different nomograms in our SLN-positive breast cancer patients. We identified 319 patients who had a positive SLN biopsy and CALND at our hospital during an 8-year period. Breast cancer nomograms developed by Memorial Sloan-Kettering Cancer Center, Tenon Hospital, Cambridge University, and Stanford University were used to calculate the probability of NSLNM. The area under the receiver operating characteristics curve was calculated for each nomogram, and values greater than 0.70 were accepted as demonstrating considerable discrimination. One hundred seven of 319 patients (33.5%) had positive axillary NSLNM. The mean number of SLNs was 2.01 (range, 1 to 11 nodes), and the mean number of positive SLNs was 1.44 (range, 1 to 9 nodes). The area under the curve values were 0.70, 0.69, 0.69, and 0.64 for the Memorial Sloan-Kettering Cancer Center, Tenon, Cambridge, and Stanford models, respectively. We found that the Memorial Sloan-Kettering Cancer Center nomogram was more predictive than the other nomograms, but the Cambridge model and the Tenon model reached borderline values for accurate prediction. Nomograms developed at other institutions should be used with caution when counseling patients about the risk of additional nodal disease.

The likelihood of additional nodal disease following a positive sentinel lymph node biopsy in breast cancer patients: validation of a nomogram

Background Sentinel lymph node (SLN) biopsy examination is the current modality for evaluating the axilla in breast cancer patients. A nomogram has been developed to predict the likelihood of non-SLN metastases after a positive SLN biopsy examination. The purpose of this study was to validate the nomogram in a community breast center. Methods A prospective database was used to identify breast cancer patients with a positive SLN biopsy examination who underwent a completion axillary lymph node dissection. The nomogram was used to calculate the probability of having non-SLN involvement, and was compared with the observed numbers. Results The observed incidence of non-SLN involvement showed excellent correlation with the nomogram predicted probability (chi-square test statistic = 5.87; P = .83). Conclusions Predicting the risk of additional nodal metastases allows the surgeon and patient to make an individualized decision regarding the need for completion axillary lymph node dissection.

The Practical Value of Prediction: A Semireliable Assistant

The proposed utility of a nomogram is to assist decision making for complete axillary lymph node dissection (CLND) in breast cancer patients who have a positive sentinel lymph node (SLN). According to the American Joint Committee on Cancer Cancer Staging Manual (sixth edition, 2002), a positive SLN is defined as tumor deposits >.2 mm. Isolated tumor cells, clusters smaller than .2 mm, are classified as N0. Of all patients with a positive SLN, about 30% to 50% will have additional non-SLNs that contain tumor cells detectable by hematoxylin and eosin. The size of these metastases is not well documented since only in the most recent update of the American Joint Committee on Cancer staging system has size been relevant. The standard of care is to perform CLND on all patients who have positive SLNs. Accurately predicting which patients with a positive SLN are the 50% to 70% with no additional nodal disease might spare them the morbidity of a CLND. However, the therapeutic impact of such management has not been determined. Small studies suggest that further dissection may not be necessary. Indeed, extrapolation from National Surgical Adjuvant Breast and Bowel Project B04 data might even suggest that axillary surgery itself may not impact survival. Van Zee et al. published an excellent nomogram for predicting the likelihood of additional nodal metastases in 2003. The Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram used eight clinical and tumor characteristics that are readily available to most clinicians to predict the likelihood that additional positive nodes will be found if the patient undergoes CLND. These variables include tumor size, histological type, nuclear grade, presence of lymphovascular invasion, multifocality, estrogen receptor status, number of positive and negative SLNs, and the method of detection of the SLN metastases. Lambert et al. applied the nomogram to 200 consecutive patients at the University of Texas M. D. Anderson Cancer Center to assess its performance. They found that the area under the receiver operating characteristic (ROC) curve was .71. The area under the ROC curve is an overall assessment of the test s ability to predict accurately. ROC curves were developed in the 1950s in the study of how to interpret radio signals contaminated by noise. An ROC curve plots a test s performance with varying thresholds of sensitivity and specificity. As sensitivity improves, specificity suffers. For fewer missed diagnoses, there are more false positives. A value of .5 represents no ability to predict, and a value of 1.0 represents perfect accuracy. ROC curves are being used more frequently to describe the accuracy of radiological tests. Surgeons are often less familiar with this kind of tool because they are trained to manage uncertainty through a less quantitative process known as surgical judgment. ROC curves are compared by measuring the area under the curve as a quantification of accuracy. A rough correlation of surgical judgment and the area under the ROC curve values in terms of reliability might coincide like this: .9 to 1.0, intuitive genius professor; .8 to .9, dedicated midcareer surgeon; .7 to .8, average chief resident; .6 to .7, disinterested intern; and .5 to .6, motivated passer-by. In their original description of the MSKCC nomogram, Van Zee et al. explained the concept of a value of .77 of the ROC as follows: Received November 10, 2005; accepted November 16, 2005; published online February 1, 2006. Address correspondence and reprint requests to: Armando E. Giuliano, MD; E-mail: giulianoa@jwci.org.

Factors predictive of tumor-positive nonsentinel lymph nodes after tumor-positive sentinel lymph node dissection for melanoma.

Approximately 20% of sentinel node (SN) positive melanoma patients have additional non-SN (NSN) metastasis. The rationale for this study was to identify the factors associated with additional nodal disease, as a method to determine which patients may most benefit from completion lymph node dissection (CLND). During 1990 to 2002, 1,599 patients have undergone SN biopsy at our institute. 19.5% underwent CLND for tumor-positive SN. One hundred ninety-one of these patients had clinicopathologic information available for review. Univariate analyses used chi2 test, Wilcoxson rank sum test, and chi2 test for trend. Multivariate analyses used logistic regression and Wald test. Forty-six (24%) patients had tumor-positive NSN. Univariate analyses showed that primary thickness (Breslow and Clark), primary site, SN tumor size, and number of tumor-positive SNs were significantly associated with tumor-positive NSN. Multivariate analysis (167 patients), confirmed that Breslow and SN tumor size were independently predictive. Sex, histology, ulceration, mitotic index, and SN basin location were not predictive. Risk stratification by the number of prognostic factors present (Breslow > or = 3 mm and SN tumor size > or = 2 mm) showed that probability of finding tumor-positive NSN was 12.3% in the low-risk group (0 factors), 30.9% in the intermediate-risk group (1 factor), and 41.9% in the high-risk group (2 factors). Thicker primary and larger SN tumor size are factors that correlate best with tumor-positive NSN. Although none of these factors are absolutely predictive of residual nodal disease, these factors must be strongly considered if the SN contains metastasis, as they provide enhanced risk assessment for NSN tumor-positivity.

Predictors for Nonsentinel Node Involvement in Breast Cancer Patients with Micrometastases in the Sentinel Lymph Node

Sentinel lymph node (SLN) biopsy in breast cancer allows for a more thorough pathologic assessment with serial sectioning and cytokeratin staining. This has resulted in increased detection of micrometastatic disease (tumor size <2 mm) in the SLN. Unfortunately, the value of completion axillary dissection after finding micrometastatic disease in the SLN remains poorly defined. Over a 2-year period, a prospective database of 305 patients who underwent SLN biopsy for breast cancer at Baylor University Medical Center was reviewed. Eighty-four (27.5%) of the patients had evidence of metastatic disease in the SLN. Twenty-four of the 41 patients identified as having micrometastatic disease in the SLN underwent completion axillary lymph node dissection. In these patients, all nonsentinel nodes were further studied by serial sectioning and immunohistochemistry. The median age of these 24 patients was 52 years (range, 34–83). Their primary tumor stages were T1a and T1b (n = 5), T1c (n = 15), and T2 (n = 4). A total of 328 nonsentinel lymph nodes were examined, including 225 from patients with infiltrating ductal carcinoma (n = 17) and 103 from patients with infiltrating lobular carcinoma (n = 7). In the patients with infiltrating ductal carcinoma, no additional nodal metastases were identified, while in those with infiltrating lobular carcinoma, additional nodal disease was found in 5 lymph nodes (2 of 12 patients, 17%). Primary tumor characteristics were not predictive of additional nodal disease. These data suggest that patients with micrometastasis in the SLN from infiltrating lobular carcinoma have a significant risk of harboring additional nodal disease and should undergo completion axillary dissection. However, those with micrometastatic disease from infiltrating ductal carcinoma have a very low incidence of additional metastasis and may not need completion axillary dissection.

Lymphatic Mapping for Gastric Adenocarcinoma

The role of lymphadenectomy for gastric carcinoma has been debated for decades. Lymphatic mapping has revolutionized the treatment of melanoma and breast cancer. However, its potential utility in guiding lymphadenectomy for gastric carcinoma is unknown. Therefore we initiated a trial to investigate lymphatic mapping for gastric carcinoma at Wake Forest University Baptist Medical Center. Lymphatic mapping for gastric carcinoma was attempted in 14 cases of gastric carcinoma. Mapping was performed by perilesional injection of isosulfan blue and the first node in the draining basin was harvested and sent fresh to pathology. Sentinel lymph nodes (SLNs) were evaluated by hematoxylin and eosin (H&E) staining. Immunohistochemical analysis was performed on all SLNs that were found to be negative on initial histologic studies. Radical gastrectomy with celiac node dissection was performed in all cases. SLNs were identified in 14 cases. In one case the technique was abandoned because of bulk nodal disease. The average number of SLNs found in each case was 2.8 with a range of one to five. Eight of 14 patients were found to have SLNs positive for metastatic carcinoma. In seven of these patients pathologic analysis of the final resection specimen confirmed the presence of nodal disease. In one case carcinoma was found in a SLN on touch preparation and no nodal disease was noted in the resection specimen. Immunohistochemical studies performed on SLNs found to be negative on initial H&E histologic analysis failed to reveal the presence of carcinoma. The overall sensitivity and specificity were found to be 72.7 and 75 per cent, respectively. Lymphatic mapping is technically possible in the setting of gastric carcinoma and SLNs can be successfully identified in the majority of cases. Upstaging occurred in one case which may have ramifications for adjuvant therapy. SLN positivity accurately predicts the presence of additional nodal disease beyond the SLN in the final resection specimen (positive predictive value 89%). However, SLN negativity does not definitively prove that the remaining nodal basin is free of disease (negative predictive value 50%). Lymphatic mapping for gastric carcinoma is a promising technique worthy of further investigation.