Sentinel Lymph Node Biopsy Status Research Articles

Abstract PO5-23-04: Clinical utility of sentinel lymph node biopsy in women ≥ 70 years with early breast cancer – an international, retrospective multi-center cohort study

Abstract Introduction Traditionally, sentinel lymph node biopsy (SLNB) has been used to stage the axilla in early breast cancer (EBC) to guide adjuvant treatment recommendations. Following advances in tumor biology understanding, targeted systemic therapies and genomic testing, with increasing de-escalation of axillary surgery, its role may be less critical especially in selected groups of women. Aims Evaluate clinical utility of SLNB in adjuvant treatment recommendations for women ≥ 70 years with EBC. Methods Retrospective cohort study of women ≥ 70 years with cT1-2N0 EBC undergoing primary surgery and SLNB between 01/2017-12/2022 at The Royal Marsden Hospital (RMH), University Hospital Zurich (USZ) and Seoul National University Hospital (SNUH) in the United Kingdom, Switzerland and South Korea respectively. Simple descriptive statistics and non-parametric tests were performed as appropriate. Results A total of 884 patients were included in the analysis, with 584 patients from RMH, 148 from USZ and 152 from SNUH. The median age was 75 (IQR 72-79) years. Most cancers were invasive ductal (82.9%), grade 2 (61.4%), hormone receptor (HR) positive/HER2 negative (82.9%) with a median tumor size of 17 (IQR 4-50) mm. SLNB was positive in 116 (13.1%) patients. Of these 116 patients, 20 (17.2%) had completion ALND; 7/20 had further RT up to levels 3&4 of the axilla. Of these 116 patients, 96 patients (82.8%) avoided ALND; 25/96 had no further treatment, and 71/96 patients had loco-regional axillary RT (8/71 had RT to levels 1&2 and 63/71 had RT up to levels 3&4). As per international guidelines for patients with EBC with 1-2 positive macrometastases on SLNB treated with breast conserving surgery and breast RT, 5/20 could have been spared ALND, and 50/71 axillary RT. Completion ALND was more likely to be performed at SNUH compared to the other 2 units (p< 0.0001). Axillary RT was more likely to be administered at SNUH and less likely at RMH (p< 0.0001). The multidisciplinary team (MDT) recommended adjuvant chemotherapy (AC) in 146 (16.5%) patients and 100 received it. Of those with a positive SLNB (n=116), AC was recommended in 35, and received by 29. Recommendation for AC was significantly associated with younger age (p=0.021), fewer comorbidities (p=0.003), higher tumor grade (p< 0.0001), increased tumor size (p< 0.0001), HR negative status (p< 0.0001), high genomic risk profile (p< 0.0001) and positive SLNB status (p< 0.0001), but not center (p=0.497). A subgroup analysis of 505 patients with cT1N0, HR+/HER2- EBC, representing a more favorable prognosis group, was performed. Here, 52/505 (10.3%) patients had positive SLNB, of whom 11 had no further axillary treatment, 9 underwent ALND and 32 axillary RT, where 4/9 could have been spared ALND and 28/32 axillary RT as per international guidelines mentioned above. AC was recommended in 26/505 (5.15%) women and 23 received it. AC was not recommended in 39/52 (75%) cases, despite a positive SLNB. MDT recommendation for AC was associated with grade 3 (p< 0.0001), multifocal disease (p=0.021), positive SLNB status (p< 0.0001), high genomic risk profile (p< 0.0001), lower age (p=0.044), fewer co-morbidities (p=0.001) and center (p=0.007) with SNUH being more likely than the other 2, but not ethnicity (p=0.130); AC receipt was associated with the same factors except age (p=0.347). Conclusions Real-world data demonstrates axillary overtreatment despite evidence of the safety of de-escalation of axillary management in EBC. Only a small proportion of women ≥ 70 years with EBC had positive SLNB that may influence adjuvant treatment recommendations, especially with favorable prognosis tumors. In such cases, where clinical morbidity and financial burden of SLNB may outweigh the benefits, a nuanced discussion for opting in SLNB rather than routine performance should be considered. Citation Format: Radhika Merh, Denise Vorburger, Ji-Jung Jung, Han-Byoel Lee, Marios Tasoulis. Clinical utility of sentinel lymph node biopsy in women ≥ 70 years with early breast cancer – an international, retrospective multi-center cohort study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-23-04.

The Role of Sentinel Node Biopsy in the Era of Adjuvant Therapy for Melanoma.

Sentinel lymph node biopsy (SLNB) is a surgical procedure aimed to detect nodal metastases in patients with clinically occult disease. Since the advent of new systemic therapies, its role in melanoma has been extensively debated over the last years. In this article, three possible scenarios are discussed, considering the SLNB impact on the management of melanoma patients. First, pT1b and pT2a patients with negative SLNB (stages IA and IB) and those with positive SLNB (stage IIIA) would all not benefit from adjuvant treatment. Therefore, SLNB might be avoided in these categories of patients. Second, in IIB and IIC, melanoma patients are already candidates for adjuvant treatment; therefore, SLNB in patients with T3b, T4a, or T4b melanoma would not change treatment decisions. On the other end of the spectrum, patients with pT2b and pT3a melanomas (clinical stage IIA) represent the only two groups whose management would be significantly affected by the SLNB status, being adjuvant therapy only indicated for SLN-positive patients. Further studies are needed to investigate which melanoma patient deserves SLNB.

Clinical utility of sentinel lymph node biopsy in women ≥ 70 years with early breast cancer.

e12512 Background: Sentinel lymph node biopsy (SLNB) has traditionally been used to stage the axilla in early breast cancer (EBC) to guide adjuvant treatment recommendations. Following advances in genomic testing and tumor biology understanding, its role may be less critical especially in selected groups of women. The aim was to evaluate clinical utility of SLNB in adjuvant treatment recommendations for women ≥ 70 years with EBC in a tertiary unit in the United Kingdom. Methods: Retrospective cohort study of women ≥ 70 years with cT1-2N0 EBC undergoing primary surgery and SLNB between 01/2018-12/2022. Simple descriptive statistics and non-parametric tests were performed, including cost analysis of the SLNB procedure. Results: A total of 528 patients were included. The median age was 75 (IQR 72-79) years. Most cancers were invasive ductal (84.7%), grade 2 (66.9%), hormone receptor (HR) positive/HER2 negative (84.4%) with a median tumor size of 17 (IQR 4-50) mm. SLNB was positive in 64 (12.1%) patients. Of these 64 patients, 13 (20.3%) had completion ALND and 39 (60.9%) had adjuvant locoregional nodal radiotherapy (RT) including levels 1 & 2 of the axilla; adjuvant RT to levels 3 & 4 after ALND was given to 5/13. As per ACOSOG Z0011 criteria, 2/13 could have been spared ALND and 31/39 axillary RT. The multidisciplinary team (MDT) recommended adjuvant chemotherapy (AC) in 72 (13.6%) patients and 45 received it. Of those with a positive SLNB (n = 64), AC was recommended in 15, and received by 11. Recommendation for AC was significantly associated with age (p = 0.006), tumor grade (p < 0.0001), size (p = 0.001), receptor status (p < 0.0001) and positive SLNB status (p = 0.02) but not with comorbidities (p = 0.06). A subgroup analysis of 294 patients with cT1N0, HR+/HER2- EBC, representing a more favorable prognosis group, was performed. Here, 31/294 (10.5%) patients had positive SLNB, of whom 5 underwent ALND and 16 regional nodal RT, where 2/5 could have been spared ALND and 13/16 axillary RT as per ACOSOG Z0011 criteria. AC was recommended in 11/294 (3.7%) women and 9 received it. AC was not recommended in 20/31 (64.5%) cases, despite a positive SLNB. MDT recommendation for AC was associated with SLNB status (p = 0.02), grade 3 (p = 0.002) and multifocal disease (p = 0.02), while AC receipt was only associated with grade 3 (p = 0.017) and multifocal disease (p = 0.009) but not SLNB status (p = 0.058). Given an average cost of $6504.95 / £5359.38 per SLNB procedure in this unit, avoiding routine SLNB in the subgroup population may have potentially saved $1,912,493.95 / £1,575,657.72 in this 5 year period. Conclusions: Only a small proportion of women ≥ 70 years with EBC had positive SLNB that may influence adjuvant treatment recommendations, especially with favorable prognosis tumors. In such cases, where clinical morbidity and financial burden of SLNB may outweigh the benefits, a nuanced discussion for opting in SLNB rather than routine performance should be considered.

Validation of a microRNA liquid biopsy assay for diagnosis and risk stratification of invasive cutaneous melanoma.

Noninvasive molecular biomarkers are needed to improve the early, accurate and precise diagnosis of invasive cutaneous melanoma. To independently validate a previously identified circulating microRNA signature of melanoma (MEL38), and, secondly, to develop a complementary microRNA signature, optimized for prognostication. MicroRNA expression profiling was performed on plasma samples from a multicentre observational case-control study, involving patients with primary or metastatic melanoma, melanoma in situ, nonmelanoma skin cancer, or benign naevi. MicroRNA profiles from patients with length of survival, treatment and sentinel lymph node biopsy (SLNB) data were used to develop the prognostic signature. The primary outcome of interest for MEL38 was its association with melanoma status, including area under the curve, binary diagnostic sensitivity and specificity, and incidence-adjusted positive and negative predictive values. The prognostic signature was assessed using rates of survival per risk group and relationship to conventional predictors of outcome. Circulating microRNA profiles of 372 patients with invasive melanoma and 210 control individuals were generated. The average age of all participants was 59 years; 49% were male. A MEL38 score > 5.5 indicated the presence of invasive melanoma. Overall, 551/582 (95%) of patients were correctly diagnosed, with 93% sensitivity and 98% specificity. MEL38 score ranged from 0 to 10 with an area under the curve of 0.98 (95% confidence interval 0.97-0.99, P < 0.001). A novel prognostic 12-microRNA signature (MEL12) developed from 232 patients identified low-, standard- or high-risk groups, with 94%, 78% and 58% rates of 10-year melanoma-specificsurvival, respectively (log-rank P < 0.001). MEL12 prognostic risk groups were significantly associated with clinical staging (χ2, P < 0.001) and SLNB status (P = 0.027). Patients who were classified as high risk by MEL12 were approximately three times more likely to have melanoma detected in their sentinel lymph nodes compared to low-risk patients. The circulating MEL38 signature may assist in diagnosing patients with invasive melanoma vs. other conditions associated with a lower - or negligible - risk of mortality. A complementary and prognostic MEL12 signature is predictive of SLNB status, clinical stage and probability of survival. Plasma microRNA profiling may help to optimize existing diagnostic pathways as well as enable personalized, risk-informed melanoma treatment decisions.

Management of the axilla in postmenopausal patients with cN0 hormone receptor-positive/HER2-negative breast cancer treated with neoadjuvant endocrine therapy and its prognostic impact.

To evaluate the differences in nodal positivity if the sentinel lymph node biopsy (SLNB) is performed before or after neoadjuvant endocrine therapy (NET) in breast cancer patients, and its impact on prognosis. A retrospective cohort study was performed in a single center including 91 postmenopausal cases with clinically node-negative and hormone receptor-positive/HER2-negative (HR + /HER2-) breast cancer, treated with NET and SLNB. SLNB was done pre-NET until 2014, and post-NET thereafter. Axillary lymph node dissection (ALND) was indicated only in SLNB macrometastasis, although in selected elderly patients, it was omitted. Kaplan-Meier survival curves were estimated in relation to the status of the axilla, and the differences assessed using the log-rank test. Between December 2006 and March 2022, SLNB was performed pre-NET in 14 cases and post-NET in 77. Both groups were similar in baseline tumor and patient characteristics. SLNB positivity was similar regardless of whether SLNB was performed before (5/14, 35.7%) or after NET (27/77, 37%), with 2/14 SLN macrometastases in the pre-NET cohort and 17/77 in the post-NET cohort. Only three patients (18.7%) with SLN macrometastasis had > 3 positive nodes following ALND. The 5-year overall survival and distant disease-free survival were 92.4% and 94.8%, respectively, with no significant differences according to SLNB status (p 0.5 and 0.8, respectively). SLN positivity did not differ according to its timing (before or after NET). Therefore, NET has no effect on lymph node clearance. Furthermore, the prognosis is good regardless of the axillary involvement. Therefore, factors other than axillary involvement may affect the prognosis in these patients.

Has the advent of modern adjuvant systemic therapy for melanoma rendered sentinel node biopsy unnecessary?

The prognostic value of sentinel node biopsy (SNB) is well established and SNB was therefore adopted as a requirement for pathological staging of melanomas>1 mm thick in the American Joint Committee on Cancer (AJCC) 8th edition. Consequently, a negative SNB status became an eligibility criterion for clinical trials of adjuvant systemic therapy in resected stage IIB/C melanoma. However, since the Keynote 716 trial demonstrated an improvement in relapse-free survival (RFS) in patients with Stage IIB/C melanoma, all of whom had SNB staging, some have argued that SNB is no longer required for patients with T3 and T4 primary melanomas. The rationale for omitting SNB is that these patients will be able to access adjuvant immunotherapy regardless of SNB status, avoiding the costs and potential complications of SNB. However, this argument overlooks the prognostic value of knowing a patient’s nodal status and the therapeutic benefit of SNB in regional disease control. Based on extrapolation of data from multiple sources, we demonstrate that the risk of regional node-field relapse with SNB and immunotherapy for T3b and T4 melanomas is around 7–9% but is 20–27% without SNB. Similarly, the node-field recurrence rate with SNB alone is around 14% compared to around 40% with no SNB or immunotherapy. Consequently, in the absence of prospective data, we propose that the optimal management of the regional node-field for high-risk T3b and T4 primary melanomas is likely to be achieved by combining SNB and adjuvant immunotherapy for those patients who are suitable, rather than either treatment alone.

A Clinical Decision Tool to Calculate Pretest Probability of Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma.

Although sentinel lymph node biopsy (SLNB) status is a strong prognostic indicator for cutaneous melanoma, unnecessary SLNBs have substantial cost and morbidity burden. This study was designed to develop, validate, and present a personalized, clinical, decision-making tool using nationally representative data with clinically actionable probability thresholds (Expected Lymphatic Metastasis Outcome [ELMO]). Data from the Surveillance, Epidemiology, and End Results (SEER) Registry from 2000 to 2017 and the National Cancer Database (NCDB) from 2004 to 2015 were used to develop and internally validate a logistic ridge regression predictive model for SLNB positivity. External validation was done with 1568 patients at a large tertiary referral center. The development cohort included 134,809 patients, and the internal validation cohort included 38,518 patients. ELMO (AUC 0.85) resulted in a 29.54% SLNB reduction rate and greater sensitivity in predicting SLNB status for T1b, T2a, and T2b tumors than previous models. In external validation, ELMO had an accuracy of 0.7586 and AUC of 0.7218. Limitations of this study are potential miscoding, unaccounted confounders, and effect modification. ELMO ( https://melanoma-sentinel.herokuapp.com/ ) has been developed and validated (internally and externally) by using the largest publicly available dataset of melanoma patients and was found to have high accuracy compared with other published models and gene expression tests. Individualized risk estimates for SLNB positivity are critical in facilitating thorough decision-making for healthcare providers and patients with melanoma.

Alternatives and reduced need for sentinel lymph node biopsy (SLNB) staging for melanoma

Sentinel lymph node biopsy (SLNB) has been introduced in the 1990s to identify patients who might benefit from completion lymph node dissection. Neither SLNB nor CLND improved survival, but SLNB staging did provide the best staging, above Breslow thickness and ulceration. The SLN status and SLN tumour burden were used in all trials until date looking at modern adjuvant systemic therapy with immune checkpoint inhibition (ICI) or targeted therapies (TT). Adjuvant ICI and TT are shifting towards stage II melanoma. The question is whether there is still role for SLNB in melanoma, in this day and age, and if so, how does the future look for SLNB staging? The SLN status and SLN tumour burden might be useful for a consultation to discuss the number needed to treat in a risk/benefit discussion. For stage IIB/C patients, it seems likely, however, that patients will forego a nuclear scan followed by the risk of surgical intervention and morbidity associated with SLNB if they opt to receive adjuvant therapy regardless of the SLNB result. For stage I/IIA, it is still required to detect high-risk patients who might benefit from adjuvant therapy. However, biomarkers are emerging, such as gene expression profilers (GEP), immunohistological signatures and liquid biopsies with ctDNA. There still is a role for SLNB staging in melanoma today, but we expect that the availability of therapeutic option independent of SLNB status as well as emergence of validated biomarkers to predict risk will reduce the need for SLNB staging in the upcoming decade to the point it will no longer be used.

Sentinel lymph node biopsy status improves adjuvant therapy decision-making in patients with clinical stage IIB/C melanoma: A population-based analysis

Given the results of the recent KEYNOTE-716 trial, the performance of sentinel lymph node (SLN) biopsy for patients with clinical stage IIB/C melanoma has been questioned. Determine the utility of SLN status in guiding the recommendations for adjuvant therapy. Patients with clinical stage IIB/C cutaneous melanoma who underwent wide local excision and SLN biopsy between 2004 and 2011 were identified from the Surveillance, Epidemiology, and End Results database. Two prognostic models, with and without SLN status, were developed predicting risk of melanoma-specific death (MSD). The primary outcome was net benefit at treatment thresholds of 20% to 40% risk of 5-year MSD. For the 4391 patients included, the 5-year MSD rate was 46%. The model estimating 5-year MSD risk that included SLN status provided greater net benefit at treatment thresholds from 30% to 78% compared to the model without SLN status. The added net benefit for the SLN biopsy-containing model persisted in subgroup analysis of patients in different age groups and with various T stages. Retrospective study. A prognostic model with SLN status estimating patient risk for 5-year MSD provides superior net benefit compared to a model with primary tumor staging factors alone for threshold mortality rates ≥30%.

Sentinel lymph node biopsy in extramammary Paget disease: A 13-year institutional experience.

Whether sentinel lymph node biopsy status is a prognostic factor or effective in determining treatment strategies in extramammary Paget disease remains unclear. This study aimed to investigate the significance of sentinel lymph node biopsy in extramammary Paget disease. We retrospectively reviewed the clinical information of previously untreated patients with invasive extramammary Paget disease who underwent wide local excision of the primary tumor and sentinel lymph node biopsy at our hospital between April 2008 and March 2021. Clinical data including the baseline neutrophil-to-lymphocyte ratio and recurrence-free survival were analyzed. Sentinel lymph node metastases were classified as macrometastases and micrometastases, with a cut-off value for sentinel lymph node tumor burden of 2 mm. Univariate and multivariate analyses of factors affecting sentinel lymph node biopsy positivity and recurrence-free survival rates were performed. Overall, 85 patients were included in the analysis. Patients in the sentinel lymph node biopsy-positive group (n=26) had a significantly higher invasion level and neutrophil-to-lymphocyte ratio. According to multivariate analyses, invasion level and a high neutrophil-to-lymphocyte ratio were independent predictive factors for sentinel lymph node biopsy positivity, and the sentinel lymph node biopsy status was an independent prognostic factor for recurrence-free survival. In conclusion, sentinel lymph node biopsy provides an accurate risk classification and clinical indication for postoperative follow-up in patients with invasive extramammary Paget disease.

Prediction of Sentinel Lymph Node Biopsy Status in Breast Cancers with PET/CT Negative Axilla.

Background and Aim Prior knowledge of axillary node status can spare a lot of patients with early breast cancer morbidity due to an unnecessary axillary dissection. Our study compared various metabolic and pathological features that can predict the sentinel lymph node biopsy (SLNB) status in patients with positron emission tomography/computed tomography (PET/CT) negative axilla. Patients and Methods All consecutive patients with early breast cancers (< 5 cm) with PET/CT negative axilla who underwent breast surgery and SLNB from November 2016 to February 2020 were included. Various primary tumor (PT) pathological variables and metabolic variables on PET/CT such as maximum standardized uptake value (PT-SUV max ), metabolic tumor volume (PT-MTV), and total lesion glycolysis (PT-TLG) were compared using univariate and multivariate analyses for prediction of SLNB status. Results Overall 70 patients, all female, with mean age 55.6 years (range: 33–77) and mean tumor size 2.2 cm (range: 0.7–4.5), were included. SLNB was positive in 20% of patients ( n = 14) with nonsentinel nodes positive in 4% ( n = 3) patients. Comparing SLNB positive and negative groups, univariate analysis showed significant association of SLNB with low tumor grade, positive lymphovascular invasion (LVI), positive estrogen receptor (ER) status with lower mean K i -67 index (34.41 vs. 52.02%; p = 0.02), PT-SUV max (5.40 vs. 8.68; p = 0.036), PT-MTV (4.71 cc vs. 7.46 cc; p = 0.05), and PT-TLG (15.12 g/mL.cc vs. 37.10 g/mL.cc; p = 0.006). On multivariate analysis, only LVI status was a significant independent predictor of SLNB status (odds ratio = 6.23; 95% confidence interval: 1.15–33.6; p = 0.033). Conclusion SLNB is positive in approximately 20% of early breast cancers with PET/CT negative axilla and SLNB status appears to be independent of PT size. SLNB+ PTs were more likely to be LVI+ and ER + ve, with lower grade/K i -67/metabolic activity (SUV max /MTV/TLG) compared with SLNB–ve tumors. Logistic regression analysis revealed LVI status as the only significant independent predictor of sentinel lymph node status.

Use of Merlin Assay to identify patients with a low-risk for SN metastasis in a prospective multicenter Dutch study of a primary melanoma gene-signature (CP-GEP model) to predict sentinel node status during COVID-19.

9571 Background: Approximately 70%-85% of patients who undergo sentinel lymph node biopsy (SLNb) show no nodal metastasis in the sentinel node (SN). The clinicopathological and gene expression profile (CP-GEP) model ( Merlin Assay) was developed and validated to identify patients that may forgo the SLNb surgery due to their low risk for for nodal metastasis This study was initiated during the first wave of Covid-19 pandemic to allow for surgical triage on SLNb and evaluate the implementation of the Merlin assay in clinical practice. Methods: This study was conducted in four designated melanoma centers in the Netherlands. Patients (age &gt; 18y) with newly diagnosed melanoma of the skin, eligible to undergo SLNb were screened for study inclusion. Main exclusion criteria was prior history of primary melanoma ( &gt; T1b) in the past 5 years. After enrollment, tissue sections of the primary melanoma were centrally reviewed at the Erasmus MC Cancer Institute to determine Breslow thickness at primary diagnosis. FFPE tumor tissue was dispatched for molecular analysis of eight target genes known to play a role in cancer development. In combination with age, Breslow thickness, and GEP outcome, risk of having nodal metastasis was calculated. Results were binary presented as 'CP-GEP low risk' and 'CP-GEP high risk'. SLNb status was used as gold standard for comparison. Results: A total of 177 patients were analyzed using the CP-GEP model. Median age was 64 years (IQR 52-73) Median Breslow thickness was 1.4mm (IQR 1.0-2.4). Of all patients 28.2% was diagnosed with T1, 40.7% with T2 and 20.9% with T3 melanoma. Corresponding positivity rate was 7%, 14% and 29% respectively. A total of 24 out of 177 patients had a positive SLNb. Median turn-around time from inclusion to CP-GEP result was 15 days. Overall 37.1.% of patients had a CP-GEP low risk profile. The CP-GEP model had a NPV of 94.6%. Conclusions: This is the first prospective multicenter implementation study for the Merlin assay. Results are in line with previous validation studies. The CP-GEP model could accurately identify patients at low risk for SN metastasis. Implementation in clinical practice is feasible based on current turn-around time. In the future, using the Merlin assay to deselect patients for SLNB may allow for a reduction of surgery in patients with melanoma.

Sentinel lymph node biopsy in Merkel cell carcinoma: Rates and predictors of compliance with the National Comprehensive Cancer Network guidelines

To the Editor: Primary Merkel cell carcinoma (MCC) has a 25% to 30% risk of occult nodal metastasis,1 and the National Comprehensive Cancer Network (NCCN) guidelines recommend sentinel lymph node biopsy (SLNB) in all patients without clinical nodal disease or known metastasis.2 SLNB status guides the prognosis and indications for adjuvant therapy.1 The rates of SLNB compliance have not been studied for MCC.

Deep Learning Algorithms for Predicting Breslow Thickness from Dermoscopic Images of Acral Lentiginous Melanomas

Breslow thickness (BT) is the length from the top of the epidermis to the greatest depth of invasion of a melanoma. BT is a crucial prognostic indicator because patients’ 5-year survival considerably decreases with every increase in BT. The positive rate of sentinel lymph node biopsy status varies depending on BT and corresponds to 7.7%, 14.5%, and 32.6–47.4% for BT ≤ 1.0, 1.1–2.0, and >2.0 mm, respectively (Stiegel et al., 2018). Wide excision according to the magnitude of the BT is recommended for the treatment of cutaneous melanoma; however, this is more challenging to implement in acral lesions.

Sentinel Node Biopsy after Neoadjuvant Chemotherapy for Breast Cancer: Preliminary Experience with Clinically Node Negative Patients after Systemic Treatment.

Sentinel lymph node biopsy (SLNB) following neoadjuvant treatment (NACT) has been questioned by many studies that reported heterogeneous identification (IR) and false negative rates (FNR). As a result, some patients receive axillary lymph node dissection (ALND) regardless of response to NACT, leading to a potential overtreatment. To better assess reliability and clinical significance of SLNB status on ycN0 patients, we retrospectively analyzed oncological outcomes of 399 patients treated between January 2016 and December 2019 that were either cN0-ycN0 (219 patients) or cN1/2-ycN0 (180 patients). The Endpoints of our study were to assess, furthermore than IR: oncological outcomes as Overall Survival (OS); Distant Disease Free Survival (DDFS); and Regional Disease Free Survival (RDFS) according to SLNB status. SLN identification rate was 96.8% (98.2% in patients cN0-ycN0 and 95.2% in patients cN+-ycN0). A median number of three lymph nodes were identified and removed. Among cN0-ycN0 patients, 149 (68%) were confirmed ypN0(sn), whereas regarding cN1/2-ycN0 cases 86 (47.8%) confirmed an effective downstaging to ypN0. Three year OS, DDFS and RDFS were significantly related to SLNB positivity. Our data seemed to confirm SLNB feasibility following NACT in ycN0 patients, furthermore reinforcing its predictive role in a short observation timing.

Abstract PD4-02: Sentinel node biopsy should not be routine in older patients with ER positive breast cancer

Abstract Background:Based on randomized controlled trials demonstrating no survival benefit of axillary dissection in elderly breast cancer patients, the SSO/Choosing Wisely campaign recommended against the routine use of sentinel lymph node biopsy (SLNB) in clinically node negative patients aged ≥70 with estrogen receptor (ER) positive breast cancer in 2016. SLNB is still performed in &amp;gt;80% of such patients and we have previously shown that at our institution, SLNB positivity influences adjuvant therapy decisions in this population. In this study, we sought to validate the association of SLNB positivity and adjuvant treatment in a larger population-based cohort, and to evaluate the impact of this finding on oncologic outcomes. Methods:The Breast Cancer Outcome Unit (BCOU) prospectively collects demographic, pathologic, treatment and outcomes data on all patients referred to BC Cancer with breast cancer in British Columbia, Canada. Female patients aged ≥70 with newly diagnosed estrogen receptor-positive invasive breast cancer who underwent SLNB from 2010-2016 were included. Patients with HER2-positive disease or those treated with neoadjuvant therapy were excluded. Multivariable analysis was used to assess the effect of SLNB positivity on adjuvant treatment. Overall survival (OS) and breast cancer specific survival (BCSS) were assessed using Kaplan-Meier analysis and Cox regression was used to assess contribution of SLNB positivity and adjuvant treatment. A nomogram was created to model the effect of nodal positivity and adjuvant treatment on BCSS. Results:We identified 2580 patients who met study criteria with a median age of 75 and a median tumor size of 15 mm. SLNB was positive in 23%. Sixty-seven percent of patients had breast conserving surgery (BCS) and 62% of patients had RT (BCS 79%, mastectomy 25%). As systemic therapy 5% of patients had chemotherapy (CT) and 78% of patients had hormone therapy (HT). Use of adjuvant therapies was associated with SLNB positivity: Systemic therapy (HR = 2.4, 95% CI: 1.84-3.14, p &amp;lt;0.0001), RT (HR = 4.94, 95% CI: 3.91-6.25, p &amp;lt;0.0001) and nodal RT (HR = 61.4, 95% CI: 26.6-141.7, p &amp;lt;0.0001). The 5-year OS was 86% and BCSS was 96% with a median follow-up of 4.33 years (95% CI 4.21-4.47 years). There was improved BCSS with receipt of HT (HR 0.51 95% CI 0.301-0.875, p=0.0142) and worse BCSS with grade 3 vs grade 1 disease (HR 4.09, 95% CI 2.06-8.10, p&amp;lt;0.0001). Age, tumor size, status of SLNB and use of RT were not significant prognostic variables. Patients with a positive SLNB who did not receive any adjuvant therapy had lower BCSS (HR 3.22 95% CI 1.235-8.418, p=0.0168) than those with a negative SLNB. However, amongst those who received any combination of CT, HT and RT, there was no significant difference in BCSS regardless of nodal status. A nomogram was developed incorporating tumor size, grade, SLNB status and adjuvant treatment. Using the nomogram, patients aged 75-79 with T1, grade 1-2 tumors, with or without positive SLNB and treated with or without adjuvant therapy had 5-year BCSS ≥95%. The nomogram also indicated that 5-year BCSS was similar for patients with positive and negative SLNB for all combinations of tumor features when patients received HT. Conclusions:In this modern, population-based cohort of patients over 70 with ER-positive breast cancer, 5-year BCSS was excellent at 96%. Although the use of adjuvant treatment was associated with a positive SLNB, BCSS was not changed based on nodal status when patients received HT. Our results support the Choosing Wisely recommendations; SLNB can be safely omitted in elderly patients willing to take HT, and we advocate that SLNB can be omitted in low-risk patients aged ≥75 even in the absence of planned HT. Citation Format: Elaine McKevitt, Rona Cheifetz, Kimberly DeVries, Alison Laws, Rebecca Warburton, Lovedeep Gondara, Caroline Lohrisch, Alan Nichol. Sentinel node biopsy should not be routine in older patients with ER positive breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD4-02.

Regional lymph node metastases in cutaneous melanoma: a single-center analysis from southeast europe

Sentinel lymph node biopsy is the standard of care for nodal staging in clinically node-negative melanoma patients. Our goal was to present 10-year results of sentinel lymph node biopsy at our institution and to evaluate the clinicopathologic factors as potential predictors of sentinel lymph node and non-sentinel lymph node metastatic involvement in patients with cutaneous melanoma. We have analyzed clinicopathologic and lymphoscintigraphic characteristics in 420 patients with cutaneous melanoma who underwent sentinel lymph node biopsy between 2010 and 2019. In addition, we have examined the results of group of patients with positive sentinel lymph node biopsy undergoing complete lymph node dissection. The overall detection rate of sentinel lymph node biopsies was 97.1%, of which 18.8% was metastatic. Drainage to one regional basin was seen in 345 patients (83.1%) and to multiple drainage regions in 71 patients (17%). In-transit lymph nodes were detected in 20 patients. On univariate logistic regression analysis, male gender, primary tumor thickness with nodular histology, acral location, presence of ulceration, and the number of nodes harvested were significantly associated with sentinel lymph node biopsy status (p < 0.05). On multivariate analysis, the Breslow thickness was the only independent predictor of sentinel lymph node biopsy status. The metastases in non-sentinel lymph node found in 26 patients with positive sentinel lymph node (35.6%) correlated on univariate, as well as on multivariate logistic regression, with tumor subtype and number of sentinel lymph node harvested. In addition to the well-established primary tumor thickness as a predictor of sentinel lymph node biopsy positivity, we observed acral location and nodular melanoma subtype to significantly enhance the risk of metastases in sentinel lymph node(s). Primary tumor histology and number of nodes harvested were the only statistically significant variables predicting the non-sentinel lymph node status on multivariate analysis. Lymphoscintigraphy imaging characteristics were not significantly associated with sentinel lymph node status.

Clinical implications of intrinsic molecular subtypes of breast cancer for sentinel node status

Axillary lymph node status is an important prognostic factor for breast cancer patients and sentinel lymph node biopsy (SLNB) is a less invasive surgical proxy. We examined if consecutively derived molecular subtypes from primary breast cancers provide additional predictive value for SLNB status. 1556 patients with a breast cancer > 10 mm underwent primary surgical procedure including SLNB and tumor specimens were assigned with a transcriptomics-based molecular subtype. 1020 patients had a negative sentinel node (SN) and 536 a positive. A significant association between tumor size and SN status (p < 0.0001) was found across all samples, but no association between size and SN status (p = 0.14) was found for BasL tumors. A BasL subtype was a predictor of an SN-negative status (p = 0.001, OR 0.58, 95% CI 0.38;0.90) and among the BasL, postmenopausal status was a predictor for SN-negative status (p = 0.01). Overall survival was significantly lower (p = 0.02) in patients with BasL tumors and a positive SN. Interestingly, we identified a significant correlation between hormone receptor activity and SN status within the BasL subtype. Taken together, molecular subtypes and hormone receptor activity of breast cancers add predictive value for SLNB status.

Sentinel Node Status is the Most Important Prognostic Information for Clinical Stage IIB and IIC Melanoma Patients.

Sentinel node biopsy (SNB) for melanoma patients has been questioned. We aimed to study high-risk stage II melanoma patients who underwent SNB to determine what the prognostic factors regarding recurrence and mortality were, and evaluate how relevant SNB status is in this scenario. This was a retrospective analysis of clinical stage IIB/IIC melanoma patients who underwent SNB from 2000 to 2015 in a single institution. Prognostic factors related to distant recurrence-free survival (DRFS) and melanoma-specific survival (MSS) were assessed from multiple Cox regression. Relevant variables were used to create risk predictor nomograms for DRFS and MSS. From 1213 SNB, 259 were performed for clinical stage IIB/IIC melanoma patients. SNB status was the most important variable for both endpoints. Patients with positive SNB presented median DRFS of 35.73months (95% CI 21.38-50.08, SE 7.32) and median MSS of 66.4months (95% CI 29.76-103.03, SE 18.69), meanwhile both median DRFS and MSS were not achieved for those with negative SNB (logrank < 0.0001). Both nomograms have been internally validated and presented adequate calibration (C-index was 0.734 for DRFS and 0.718 for MSS). SNB status was the most important risk factor in our cohort of clinical stage IIB and IIC patients and, in conjunction with well-established primary tumor characteristics, should not be abandoned. Their use in prognosis for these patients remains extremely useful for daily practice.

Sentinel lymph node biopsy for lung cancer.

Sentinel lymph node biopsy is a technique to identify the first lymph node (or nodes) draining a tumor. The underlying principle is that as the first site of cancer spread, evaluation of the sentinel node will be most predictive for wider nodal involvement. The introduction of sentinel node biopsy revolutionized the surgical management of cutaneous melanoma and breast cancer, becoming a key component in the management of such patients. For over 20years, thoracic surgeons have similarly worked to apply this technique to lung cancer but have thus far not had the same impact on lung surgery. In this review, we will summarize the ongoing discussions on the role of sentinel node biopsy in lung cancer, the methods for identifying the sentinel node, and the techniques for evaluating the sentinel node specimen. We will also highlight some of the pressing questions investigators should consider when designing a trial for sentinel node mapping. This will clarify the current status of sentinel node biopsy in lung cancer and thus highlight important future directions for research.