Non-sentinel Node Research Articles

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.

Prediction of Non-sentinel Lymph Node Metastases After Positive Sentinel Lymph Nodes Using Nomograms.

Only 30-50% of patients with sentinel lymph node (SLN) metastases present with further axillary lymph node metastases. Therefore, up to 70% of patients with positive SLN are overtreated by axillary dissection (AD) and may suffer from complications such as sensory disturbances or lymphedema. According to the current S3 guidelines, AD can be avoided in patients with a T1/T2 tumor if breast-conserving surgery with subsequent tangential irradiation is performed and no more than two SLNs are affected. Additionally, use of nomograms, that predict the probability of non-sentinel lymph node (NSLN) metastases, is recommended. Therefore, models for the prediction of NSLN metastases in our defined population were constructed and compared with the published nomograms. In a retrospective study, 2,146 primary breast cancer patients, who underwent SLN biopsy at the University Women's Hospital in Tuebingen, were evaluated by dividing the patient group in a training and validation collective (TC or VC). Using the SLN-positive TC patients, three models for the prediction of the likelihood of NSLN metastases were adapted and were then validated using the SLN-positive VC patients. In addition, the predictive power of nomograms from Memorial Sloan Kettering Cancer Center (MSKCC), Stanford, and the Cambridge model were compared with regard to our patient collective. A total of 2,146 patients were included in the study. Of these, 470 patients had positive SLN, 295 consisted the training collective and 175 consisted the validation collective. In a regression model, three variants - with 11, 6 and 2 variables - were developed for the prediction of NSLN metastases in our defined population and compared to the most frequently used nomograms. Our variants with 11 and with 6 variables were proven to be a particularly suitable model and showed similarly good results as the published MSKCC nomogram. Our developed nomograms may be used as a prediction tool for NSLN metastases after positive SLN.

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.

Risk factors for lymph node metastasis in non-sentinel node basins in early gastric cancer: sentinel node concept.

Sentinel node (SN) concept is being applied to early gastric cancer. However, when SNs are positive for metastasis, it is unclear how often LNs in other LN basins show metastasis. We aimed to investigate LN metastasis possibility in LN basins without SNs (non-SN basins). We determined risk factors for metastasis in non-SN basins and identified a prediction model for non-SN basin metastasis using classification and regression tree (CART) analysis. We enrolled 550 patients who were diagnosed with cT1N0M0 or cT2N0M0 gastric cancer with a single lesion and underwent SN mapping. We adopted a dual-tracer method using a radioactive colloid and blue dye to detect SNs. Of all, 45 (8.2%) patients had SN metastasis; we divided them into two groups: LN metastasis positive and LN metastasis negative in non-SN basins. Univariate analysis showed that the groups differed significantly regarding lymphatic invasion (p = 0.007), number of identified SNs (p = 0.032), and macrometastasis in SN basins (p = 0.005). The CART decision tree for predicting LN metastasis in non-SN basins had area under the curve value of 0.86. Moreover, there were significantly differences in cancer-specific survival (CSS) between the two groups (p = 0.028). Macrometastasis in SN basins, lymphatic invasion, and number of identified SNs ≥ 5 are risk factors for LN metastasis in non-SN basins among gastric cancer patients. We identified a prediction model with CART analysis; patients with macrometastasis in SN basins and lymphatic invasion were considered to be at the highest risk for LN metastasis.

A new model to predict risk of nonsentinel lymph node status in Chinese sentinel lymph node-positive patients after neoadjuvant chemotherapy.

There is no previous predictive model to assess risk of nonsentinel lymph node metastases (NSLN) in sentinel lymph node (SLN)-positive breast cancer patients after neoadjuvant chemotherapy (NAT). Our goal was to develop a new predictive model for SLN-positive patients after NAT, and validate this new model. A series of 513 patients with metastases in SLN who received NAT were used to evaluate factors affecting NSLN status. Logistic regression analysis was performed to develop a predictive model, which was validated by a subsequent prospective 138 patients. There were 115 (22.4%) patients with metastases in NSLN followed by axillary lymph node dissection (ALND). Multivariate analysis indicated that tumor (T) stage, number of positive SLN,micrometastases, extracapsular extension (ECE), and clinical response of primary tumor after NAT were significant independent predictors for the NSLN metastases. Area under the curve (AUC) of the model was 0.795 (95% CI, 0.734-0.861). When applied to the prospective series, the model accurately predicted the risk of NSLN disease, AUC was 0.772 (95% CI, 0.653-0.845). We present a new predictive model to assess the risk of NSLN status in Chinese SLN-positive breast cancer patients after NAT. The predictive model performed well in prospective validation but needs to be further studied in external center patients before application to clinical use.

Post SABCS local therapy and radiology

SummaryThis year there were three interesting oral presentations and several posters presenting important new data regarding local therapy (surgery and radiotherapy) as well as radiological aspects. This minireview is a personal view of the clinically most relevant data in this respect with the following conclusions: A micrometastasis is no indication for axillary dissection. The number of involved sentinel lymph nodes predicts non-sentinel lymph node metastasis and should be taken into account regarding omitting axillary dissection. Neoadjuvant chemotherapy reduces the risk of non-sentinel lymph node metastasis. A 2 mm margin shows an optimal rate of local recurrences after breast conservation. The question of the correct definition for an R0 resection after neoadjuvant therapy remains open. We should omit radiotherapy for women with low risk ductal carcinoma in situ (DCIS) below 2.5 cm in size and pT1a G1 after breast conservation. Risk of finding invasive cancer after having a B3 biopsy is very low depending on the type of lesion, thus, questioning the surgical approach of some of these entities. The use of magnetic resonance imaging is a standard procedure before and after neoadjuvant therapy. Data regarding correlation between complete radiologic response (rCR) with pathologic complete response (pCR) and real tumor size are rare. For women with micrometastases or isolated tumor cells in the sentinel node postmastectomy radiotherapy has little benefit. After neoadjuvant therapy only women with ypN2 had a significant benefit of postmastectomy radiotherapy for local, disease-free and overall survival.

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.

One-Step Nucleic Acid Amplification (OSNA): A fast molecular test based on CK19 mRNA concentration for assessment of lymph-nodes metastases in early stage endometrial cancer.

IntroductionThe aim of the current study is to evaluate the detection rate of micro- and macro-metastases of the One-Step Nucleic Acid Amplification (OSNA) compared to frozen section examination and subsequent ultra-staging examination in early stage endometrial cancer (EC).Material and methodsFrom March 2016 to June 2016, data of 40 consecutive FIGO stage I EC patients were prospectively collected in an electronic database. The sentinel lymph node mapping was performed in all patients. All mapped nodes were removed and processed. Sentinel lymph nodes were sectioned and alternate sections were respectively examined by OSNA and by frozen section analysis. After frozen section, the residual tissue from each block was processed with step-level sections (each step at 200 micron) including H&E and IHC slides.ResultsSentinel lymph nodes mapping was successful in 29 patients (72.5%). In the remaining 11 patients (27.5%), a systematic pelvic lymphadenectomy was performed. OSNA assay sensitivity and specificity were 87.5% and 100% respectively. Positive and negative predictive values were 100% and 99% respectively, with a diagnostic accuracy of 99%. As far as frozen section examination and subsequent ultra-staging analysis was concerned, we reported sensitivity and specificity of 50% and 94.4% respectively; positive and negative predictive values were 14.3% and 99%, respectively, with an accuracy of 93.6%. In one patient, despite negative OSNA and frozen section analysis of the sentinel node, a macro-metastasis in 1 non-sentinel node was found.ConclusionsThe combination of OSNA procedure with the sentinel lymph node mapping could represent an efficient intra-operative tool for the selection of early-stage EC patients to be submitted to systematic lymphadenectomy.

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.

Axillary lymph node surgical treatment

Nowadays, the overall attention is focused on de-escalating treatments for breast cancer (BC) including surgery, radiotherapy and chemotherapy. The introduction of sentinel lymph node biopsy (SLNB) has led to less invasive surgical approaches for accurately staging the axilla, with axillary lymph node dissection (ALND) progressively confined to a limited group of patients. One of the goal of surgery in de-escalating approaches is to reduce surgical morbidity by restricting or avoiding axillary surgery with no effect on survival. In this context the importance of imaging study for preoperative identification of axillary metastasis, in order to reduce axillary surgery, is gradually improving while the role of intraoperative assessment of sentinel nodes is progressively becoming limited to restricted groups of patients. According to the results of the ACOSOG Z0011 and following the most important guidelines, ALND can be safely omitted in selected patients treated with breast conserving surgery (BCS) with one or two positive SLNB while the adoption of SLNB positive alone in patients undergoing mastectomy is not yet defined. The increased employment of neoadjuvant chemotherapy (NAC) and the use of SLNB in patients after NAC plays an important role in de-escalation of axillary surgery in this group of patients. However current studies on this topic are still controversial, mainly about clinically positive lymph nodes (cN+) pre NAC patients or how to manage positive SLNB in post NAC patients. Some authors have collected predictive factors of positive non sentinel lymph nodes (NSLNs) in nomograms, considered an useful tool to avoid unnecessary further surgery. Elderly women represent specific group of patients where the axillary approach needs to be properly resized. The management of axilla in BC is in continuous evolution and ongoing studies could make even SLNB useless in the next future.

Evaluation of sentinel lymph node biopsy prior to axillary lymph node dissection: the role of isolated tumor cells/micrometastases and multifocality/multicentricity—a retrospective study of 1214 breast cancer patients

Sentinel lymph node biopsy (SLNB) alone has thus become an accepted surgical approach for patients with limited axillary metastatic disease. We investigated to what extent isolated tumor cells (ITC) or micrometastasis in SLNBs is associated with proven tumor cells or metastasis in non-sentinel lymph nodes. Furthermore, we investigated the feasibility of SLNB in multifocal and multicentric tumors as both entities have been considered a contraindication for this technique. 1214 women suffering from T1 and T2 invasive breast cancer, with clinically and sonographically insuspect axillary status and undergoing primary breast cancer surgery including SLNB and axillary staging in case of SLN (sentinel lymph node) metastases, were recruited into this multicentered study. ITC and micrometastases were found in 2.01 and 21.4% of patients with SLN metastases (n = 299). Among patients with sentinel micrometastases, 4.7% showed further axillary micrometastases, while only two patients (3.1%) had two axillary macrometastases. Multifocal and multicentric tumors were diagnosed in 9.3 and 2.6% of our patients who at least had one SLN resected, respectively. Detection rates of SLNs did not differ between the cohorts suffering from unicentric and multifocal or multicentric disease. Moreover, the portion of tumor-free SLNs, the number of SLNs with metastasis as well as the mean number of resected SLNs did not differ. No patient with sentinel node micrometastases showed more than two axillary macrometastases. Multifocal and multicentric disease is no contraindication for SLNB.

Morphology of Immunomodulation in Breast Cancer Tumor Draining Lymph Nodes Depends on Stage and Intrinsic Subtype

Cancer research of immune-modulating mechanisms mainly addresses the role of tumor-infiltrating immune cells. Mechanisms modulating the adaptive immune system at the primary activation site – the draining lymph node (LN) – are less investigated. Here we present tumor-caused histomorphological changes in tumor draining LNs of breast cancer patients, dependent on the localization (sentinel LN vs. non-sentinel LN), the tumor size, the intrinsic subtype and nodal metastatic status. The quantitative morphological study was conducted in breast cancer patients with at least one sentinel LN and no neoadjuvant therapy. All LNs were annotated considering to their topographical location, stained for IgD/H&E, digitized and quantitatively analyzed. In 206 patients, 394 sentinels and 940 non-sentinel LNs were categorized, comprising 40758 follicles and 7074 germinal centers. Subtype specific immunomorphological patterns were detectable: Follicular density was higher in LNs of Her2 enriched hormone receptor positive and triple-negative breast cancers whereas hormone receptor positive breast cancers showed more macrophage infiltrations in the LN cortex. Follicles are rounder in metastatic LNs and non-sentinel LNs. The identified immunomorphological changes reflect different underlying immunomodulations taking place in the tumor-draining LNs and should therefore be considered as possible prognostic and predictive markers for LN metastasis and therapy associated immunomodulation.

Does the number of sentinel lymph nodes removed affect the false negative rate for head and neck melanoma?

Head and neck (HN) cutaneous melanoma is associated with worse disease-free survival compared to non-HN cutaneous melanoma, possibly due to inadequate staging. We aim to determine if a higher yield of sentinel lymph nodes (SLNs) affected rates of sentinel lymph node biopsy (SLNB) positivity. Two Cancer Registries were used to identify patients who underwent SLNB for HN melanoma. A false negative (FN) was defined by nodal recurrence after negative SLNB. Out of 333 patients who underwent SLNB, 20% (n = 69) had a positive SLN with a FN rate of 6.3%. Those with three or more SLNs had a higher rate of SLN positivity (23.8% [17.5-29.9% CI] vs 16.4% [10.7-23.6% CI]), a lower FN rate (16.7% [10.2-21.2% CI] vs 35.3% [27.1-42.9% CI]), and higher sensitivity (83.3% [82.59-84.09% CI] vs 65.7% [64.87-66.53% CI]) compared to those with one or two SLNs. Of patients in Group 1 (one or two SLNs) with a positive SLN who underwent completion lymph node dissection (20/23), 47% (33-61% CI) had one or more positive non-sentinel nodes compared to 29% (16-51%) of patients in Group 2 (three or more SLNs) (42/46). In HN melanoma cases in which multiple nodes are identified, removal of all SLNs will more adequately stage patients.

Unique Genes in Tumor-Positive Sentinel Lymph Nodes Associated with Nonsentinel Lymph Node Metastases in Melanoma.

Current risk assessment tools to estimate the risk of nonsentinel lymph node metastases after completion lymphadenectomy for a positive sentinel lymph node (SLN) biopsy in cutaneous melanoma are based on clinical and pathologic factors. We identified a novel genetic signature that can predict non-SLN metastases in patients with cutaneous melanoma staged with a SLN biopsy. RNA was collected for tumor-positive SLNs in patients staged by SLN biopsy for cutaneous melanoma. All patients with a tumor-positive SLN biopsy underwent completion lymphadenectomy. A 1:10 case:control series of positive and negative non-SLN patients was analyzed by microarray and quantitative RT-PCR. Candidate differentially expressed genes were validated in a 1:3 case:control separate cohort of positive and negative non-SLN patients. The 1:10 case:control discovery set consisted of 7 positive non-SLN cases matched to 70 negative non-SLN controls. The cases and controls were similar with regards to important clinicopathologic factors, such as gender, primary tumor site, age, ulceration, and thickness. Microarray and RT-PCR identified six potential differentially expressed genes for validation. In the 40-patient separate validation set, 10 positive non-SLN patients were matched to 30 negative non-SLN controls based on gender, ulceration, age, and thickness. Five of the six genes were differentially expressed. The five gene panel identified patients at low (7.1%) and high risk (66.7%) for non-SLN metastases. A novel, non-SLN gene score based on differential expressed genes in a tumor-positive SLN can identify patients at high and low risk for non-SLN metastases.

In transit sentinel node drainage as a prognostic factor for patients with cutaneous melanoma.

Minor basin or in transit node drainage can be found in patients with cutaneous melanoma who undergo sentinel node biopsy. Its clinical impact is still unclear. Our objective is to evaluate clinical outcomes in patients who presented with in transit sentinel node (ITN) drainage. Retrospective analysis of patients who underwent sentinel node biopsy (SNB) in a single Brazilian institution between 2000 and 2015. Our cohort comprised 1223 SNB. There were 64 patients (5.2%) with ITN. Melanoma of the limbs (OR 10.61, P < 0.0001) and acral subtype (OR 3.49, P < 0.0001) were associated with ITN drainage. Among these 64 patients, 14 (21.9%) had a positive SNB. The ITN was positive for metastases in five patients, four in a popliteal basin and one on the trunk. Regarding completion node dissection (CND), two patients had positive non-sentinel nodes (NSN), both in major basins. In patients who developed recurrence, time to recurrence was shorter (mean time 18 vs 31.4 months, P = 0.001) and time to death was shorter (mean time 31.6 vs 40 months, P = 0.039) in those who had ITN drainage. ITN drainage was associated with earlier recurrences and deaths from melanoma.

Patients with sentinel lymph node positive melanoma: Who needs completion lymph node dissection?

IntroductionCompletion lymph node dissection (CLND) for melanoma after positive sentinel lymph node biopsy (SLNB) was recently shown to improve regional but not overall survival, likely due to the majority of patients harboring no further nodal disease. We sought to determine predictors of non-sentinel node (NSN) positivity. MethodsRetrospective review of prospectively collected data on melanoma patients undergoing SLNB. Results116 patients underwent 119 CLNDs. The incidence of NSN positivity was 17.6%; the average number of positive NSNs in those cases was 1.5. Cervical and inguinofemoral location were most likely to yield positive NSN(s) (40% each). Conversely, the axilla was least likely at 18% (p < 0.001). The average number of nodes harvested was 13 for NSN negative cases and 20 for NSN positive cases (p = 0.005). Tumor thickness increased the probability of positive NSN(s) (OR 1.2, p = 0.02). ConclusionsTumor thickness and nodal basin were predictors of NSN metastasis, factors that could help determine which patients may benefit from CLND. Further, CLNDs with fewer nodes may inadequately clear residual nodal disease.

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.

Abstract OT2-01-05: Sentinel lymphnode biopsy (SLNB) and targeted axillary surgery (TAS) by indocyaningreen (ICG) and a novel near-infrared color camera system - a prospectively randomised, multicenter study to avoid radioactivity in a time-/cost-saving procedure in primary breast cancer

Abstract Background: Sentinel lymph node biopsy (SLNB) by radioactively labelled 99mTechnetium +/- patent blue is so far the current standard in SLN detection. However, it remains a time- and cost-consuming procedure requiring the availability of a nuclear medicine department and a precise coordination with the subsequent surgery. It could be desirable to empower surgeons to be independent from availability of a nuclear source and to spare patients from radioactivity. Indocyanine green (ICG) as a fluorescent coloring agent is already known as safe in diagnostics for heart, circulation, liver and eye disease and may represent a valid alternative to 99mTc and patent blue (PBD), especially as it does not cause aesthetic impairment of the breast, with ICG being only visible with near infra-red light. Methods: This prospective, randomized study is a non-inferiority trial to evaluate ICG-fluorescence as an alternative to either 99mTc and/or patent blue dye for sentinel lymph node detection of primary breast cancer with and without neoadjuvant chemotherapy. Patients, aged 18 - 80 years, with unilateral or bilateral, unifocal or multifocal/ multicentric primary breast cancer without signs of metastases and written consent are eligible for this study. ECOG status of 0-2 and life expectancy &amp;gt; 1 year is required. All BMI classes are admitted to the study, with predefined subgroups of a) &amp;lt;= 20 b) &amp;gt;20-30 c) &amp;gt;30-40 d) &amp;gt;40. Tumor stages included are a) Tis (&amp;gt;= 4 cm) b) T1 c) T2 and d) T3. ICG-guided SLNB may be applied in patients in the following settings: a) before neoadjuvant, b) after neoadjuvant chemotherapy. Primary Endpoints: Rate of SLN detection by either of the methods in the following 3 arms of the trial: Arm A: 99mTc + patent blue dye (PBD) Arm B: 99mTc + indocyanine green (ICG) Arm C: Indocyanine green (ICG) Secondary Endpoints: - Time to identify (TTI) sentinel lymph node(s) (min) - Number of sentinel lymph nodes (SLN) and non-sentinel lymph nodes (non-SLN) - Rate of concordance of detection by 99mTc+patent blue dye (PBD) vs. 99mTc + ICG - Dose of radioactivity omitted in Arm C vs. Arm A &amp; B Results: This trial is in progress. Citation Format: Kern P, Kimmig R, Rezai M, Hoffmann O, Bücker I, Braun M. Sentinel lymphnode biopsy (SLNB) and targeted axillary surgery (TAS) by indocyaningreen (ICG) and a novel near-infrared color camera system - a prospectively randomised, multicenter study to avoid radioactivity in a time-/cost-saving procedure in primary breast cancer [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 OT2-01-05.

Abstract P3-01-10: Can we predict the risk for non-sentinel node metastases? Results from the Swedish breast cancer registry on 23053 patients

Abstract Introduction Performing axillary clearance after node positive sentinel node biopsy (SNB) has been challenged. This register study aimed to predict the risk for non sentinel node metastases (non-SN) after axillary clearance in Swedish breast cancer patients. The Swedish Breast Cancer Registry has been in use since 2008 with &amp;gt;99% compliance. National guidelines recommended axillary clearance for macro-and micromets in SN but not for isolated tumor cells (ITC). Breast cancer screening is performed nationwide. Methods Registerdata for 33 314 patients, 2008 until May 2012, was evaluated. SN was performed in 23 053 patients corresponding to 69% of all patients, a stable figure since 2008.This cohort of 23053 patients is further investigated. The median age was 62 years. Breast conserving surgery (BCS) was performed in 61,5%. SN detection mode was radiocolloid and blue dye injection and often (41%) lymphoscintigraphy. Mean tumor size after BCS -16mm and in mastectomy (ME) -23 mm. BCS and ME show positive SN in 19% and 31% respectively (sign.&amp;lt;0.001). Number of excised nodes after axillary clearance was 13 (range 1-50). The dataset is not fully complete in all variables. Results Median harvested SNs was 2 (range 1-8). 5694 SN+ cases were found, distributed as14,9% macromets, 6,4% micromets and 2,0% ITC on the whole SN cohort. Screening detected cancers had metastatic SN in18 % while clinical cases showed positivity in 28% (sign.). Altogether non-SN mets were found for 31% of SN positive patients. The risk of non-SN mets is: if 1 macromet in SN, 35% had further involved nodes. If 2 macromets in SNs, 49 % had non-SN mets and if ≥3 positive SNs the figure was 66% positive non-SN nodes (sign.p&amp;lt;0.01). Evaluating 1299 SN micrometastatic cases gave these figures of freedom of non-SN mets: 1 micromet. node 86%, 2 micromets. 77% was free and ≥3 micromets show 61,5% non-involved mets. These figures are also significant. Data on lymphovascular invasion (LVI) was available for 18754 cases and showed a significant higher risk for non-SN mets in LVI-positive tumors 43% against 27%. Tumours &amp;gt;20 mm and HER2 positive also show significant more non-SN mets. Conclusion The SN diagnostic technique works well in Sweden; 69% of patients had SN as the primary axillary procedure. SN+ was shown in 24,7%.The risk for non-SN mets is significant correlated to 2 or more involved SNs, positive LVI, tumour size &amp;gt;20 mm and HER2+. Is this the group for axillary surgery? We will try to get a Swedish risk score for non-SN+. A new Swedish national randomized study now investigates the need for axillary clearance in a subset of SN+ patients. Figures are collected from The Swedish Breast Cancer Registry-head K. Sandelin, Stockholm, Sweden. Citation Format: VikhePatil E, Arnesson L-G, Fohlin H. Can we predict the risk for non-sentinel node metastases? Results from the Swedish breast cancer registry on 23053 patients [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 P3-01-10.

Discussion of “Patients with sentinel lymph node positive melanoma: Who needs completion lymph node dissection?”

I congratulate the authors on a well done study of a very difficult subject. Melanoma is famous for its unpredictability and also therefore for studies searching for therapies which improve survival. Patients with sentinel lymph node positive melanoma: Who needs completion lymph node dissection?The American Journal of SurgeryVol. 215Issue 5PreviewCompletion lymph node dissection (CLND) for melanoma after positive sentinel lymph node biopsy (SLNB) was recently shown to improve regional but not overall survival, likely due to the majority of patients harboring no further nodal disease. We sought to determine predictors of non-sentinel node (NSN) positivity. Full-Text PDF