Positive Sentinel Lymph Node Biopsy 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.

Abstract PO5-17-12: Impact of HER2-low status on axillary response and surgical management after neoadjuvant chemotherapy in early breast cancer

Abstract Background: Breast cancer (BC) with low expression of HER2 (HER2-low) might constitute a group of tumors with unique clinical and biological characteristics. Little is known about axillary downstaging and nodal surgical outcomes in HER2-low BC after neoadjuvant chemotherapy (NACT). The aim of this study was to evaluate axillary response and surgical management of the axilla in HER2-low BC patients submitted to NACT. Methods: In this cross-sectional single center study, we consecutively included all patients diagnosed with early HER2-negative BC between 2017 to 2021 that were treated with NACT. Patients must have biopsy-confirmed stage II-III BC, submitted to breast surgery after NACT. Clinical and pathological response in the axilla, type of axillary surgery, and surgical outcomes data were collected. HER2-low was defined by IHC score 1+, or 2+ ISH non-amplified; HER2-zero was defined by IHC score 0. Pathological response was determined locally. Results: At diagnosis, 291 patients had clinically involved axillary nodes (cN1: 69.4%; cN2: 25.1%; cN3: 5.5%). Among 136 patients eligible for SLN biopsy after NACT, 77 (26.5%) had pathologically negative SLN. Of those submitted to upfront axillary dissection (n=154), 52 (33.7%) had pN0 disease. In total, 129 (44.3%) patients with clinically involved axillary lymph nodes at diagnosis were converted to cN0 after NACT. There was no difference in the rate of axillary downstaging between HER2-low and HER2-zero tumors, 17.8% vs 26.5%, respectively (p=0.0026). 236 patients were submitted to sentinel lymph node biopsy (SLN), of whom 214 (81.4%) with blue dye-only, 40 (15.2%) with radioactive isotope, and 7 (2.7%) with dual tracer. SLN detection failure were reported for 12 patients (0.046%). Mean number of lymph nodes retrieved were 2.7. Most patients had a negative SLN biopsy (180/263; 68.4%), of whom 91 (50.6%) were HER2-low and 89 (49.4%) were HER2-zero. Positive SLN biopsy were reported in 83 patients (isolated tumor cells: 20,5%; micrometastasis: 24.1%; macrometastasis: 55.4%), with capsular extravasation in 25.3%. A positive SLN biopsy occurred in 61.4% of patients with HER2-low tumors, and in 38.5% of patients with HER2-zero tumors. Among patients with a positive SLN biopsy (n=83), 67 were submitted to axillary dissection, of whom 39 (58.2%) had no additional nodes involved (HER2-low: 61.5%; HER2-zero: 38.4%). Considering N0 tumors at diagnosis, 127 patients were submitted to SNL, and only 18.9% had a positive result (HER2-low: 66.6%; HER2-zero: 33.3%). In the subgroup of initially cN+ disease, 136 (46.7%) underwent SLN biopsy, with 59 (43.4%) with a positive result (HER2-low: 59.3%; HER2-zero: 40.7%). Conclusions: Our results showed that HER2-low BC patients had a statistically significant lower frequency of axillary downstaging after NACT. More than 40% of patients with cN+ at diagnosis were downstaged to cN0 and were submitted to SNL biopsy. Axillary dissection were avoided in roughly 25% of patients with cN+ BC at initial staging. Citation Format: Leonardo Roberto da Silva, Guilherme Sartori, Susana Ramalho, Tomás Reinert, Mahira Lopes Da Rosa, Grazielle Morais Tavares, Higor Mantovani, Vivian Vasconcelos, Ana Elisa Ribeiro Da Silva Cabello, Guilherme Coelho, Jovana Mandelli, Facundo Zaffaroni, Carlos Barrios, Marcia Silveira Graudenz, César Cabello. Impact of HER2-low status on axillary response and surgical management after neoadjuvant chemotherapy in early breast cancer [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 PO5-17-12.

Abstract PO3-23-07: Evaluation of the role of axillary ultrasound to estimate axillary nodal burden to guide de-escalation of upfront axillary surgery in node positive early breast cancer patients

Abstract Background: Axillary surgery is now routinely de-escalated in clinically node negative breast cancer patients with limited axillary nodal burden (up to 2 involved sentinel nodes) based on the results of ACOSOG-Z0011 and AMAROS trials. However, patients with proven axillary metastasis following on ultrasound (AUS) guided core needle biopsy (CNB), undergoing primary surgery are still subjected to an axillary lymph node dissection (ALND) irrespective of the magnitude of the axillary nodal burden. If we could predict axillary nodal burden with a low false negative rate (FNR) for the presence of extensive axillary nodal involvement, we can then hypothesize that axillary surgery could be safely de-escalated in this cohort of patients. We investigated whether pre-operative AUS suggesting limited axillary burden is sensitive enough to rule out gross axillary disease burden. Methods: A single institution retrospective study. We undertook an electronic chart review of all T1 to T3 patients undergoing upfront ALND with either mastectomy or breast conserving surgery between January 2019 and June 2023. Patients with palpable axillary nodes, locally advanced breast cancer or a completion ALND after positive sentinel lymph node biopsy (SLNB) were excluded from the study. Clinical and pathological characteristics associated with nodal burden of disease were evaluated. Limited axillary burden was defined as < 2 involved nodes with ≥3 taken as gross nodal burden for primary analyses. Sensitivity analyses were carried out with limited axillary burden defined as < 3 involved nodes (N1) and ≥4 (N2) taken as gross nodal burden. Subgroup analyses in T1 or T2 tumors were carried out as well. The probabilities of discordant events, defined as limited burden on AUS-CNB but gross burden on final histopathology evaluation (HPE), assuming 10% FNR, were estimated using inverse cumulative binomial distribution function. Results: Data on the exact number of suspicious nodes on AUS were missing for 2 patients, therefore, the final study cohort included 39 patients. The correlation between AUS nodal burden and that on HPE was moderate (Spearman’s rho = 0.48; p = 0.0018). The sensitivity and specificity of AUS in identifying gross nodal burden were 61% and 81% respectively. Observation of 9 discordant events in 22 patients with low burden on AUS ruled out an FNR of < 10% with 99.99% certainty. The sensitivity and specificity in T1/T2 subgroup were 60% and 75% respectively. The sensitivity analyses classifying N1 as limited and N2 as gross axillary burden showed the sensitivity and specificity of 35% and 82% respectively and an FNR of < 10% was ruled out with 99.996% certainty. Conclusion: Pre-operative AUS alone lacks the sensitivity and specificity to accurately predict the true axillary nodal burden to safely guide de-escalation of axillary surgery. AUS followed by targeted axillary dissection (TAD) in conjunction with a dual technique SLNB may provide the desired sensitivity and specificity to guide de-escalation of axillary surgery. A prospective evaluation of this approach is merited. Given the limited number of patients that could be enrolled in such prospective study from individual institutions, an international collaborative effort is needed to address this important research question. Citation Format: Nidhi Garg, Mangesh Thorat, Hisham Hamed, Ashutosh Kothari. Evaluation of the role of axillary ultrasound to estimate axillary nodal burden to guide de-escalation of upfront axillary surgery in node positive early breast cancer patients [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 PO3-23-07.

Abstract PO3-02-08: Risk factors and a new predictive nomogram for predicting the Non-sentinel Lymph Node Metastasis in 708 early-stage Breast Cancer Patients with Positive Sentinel Nodes in China

Abstract Objective: The management of positive sentinel lymph node biopsies (SLNB) in patients with early-stage breast cancer remains a matter of controversy. Some studies have shown that not all breast cancer patients with positive sentinel lymph nodes (SLNs) benefit from further axillary lymph node dissection (ALND). Our study aims to analyse the risk factors and construct a new nomogram to predict non-sentinel lymph node (NSLN) metastasis in Chinese early-stage breast cancer patients with positive sentinel lymph nodes. Methods: The clinical data of 708 patients with early-stage breast cancer who attended The Fourth Hospital of Hebei Medical University for surgical treatment from January 2016 to December 2021 was retrospectively analyzed. All of them were female breast cancer patients with positive sentinel lymph nodes and underwent ALND. The patients were divided into modeling group and validation group according to the time of treatment. The patients in the modeling group were divided into a positive NSLN group and a negative NSLN group. The characteristics: age, maximum tumor diameter, the number of positive SLNs, proportion of positive SLNs, vessel carcinoma embolus, nerve invasion, status of ER, PR, HER-2 and Ki-67 were included in the analysis. And the independent risk factors of NSLN metastasis were screened by univariate (chi-square test) and multivariate (logistic regression) analysis. A nomogram model was established according to the screened independent risk factors, and the model was externally validated by the validation group. The ROC curve was plotted to calculate the area under the curve (AUC) and evaluate the predictive power of the nomogram model. A calibration curve and decision curve analysis (DCA) were used to evaluate the performance of the model. Results: Among the 708 patients, (modeling group n=410, validation group n=298), the average age, average number of positive SLNs, and NSLN positive rate were 50.9±11.1, 1.55±0.87 and 25.71%. The univariate analysis revealed statistically significant differences in the number of positive SLNs (P< 0.001), the proportion of positive SLNs (P < 0.001), vessel carcinoma embolus (P=0.001), nerve invasion (P=0.012), and ER status (P=0.029) in the NSLN-positive group compared with the negative group. The multifactorial logistic regression analysis revealed that the number of positive SLN (P=0.002; OR: 1.700; 95% CI: 1.219-2.370), the proportion of positive SLN (P=0.048; OR: 3.214; 95% CI: 1.001-10.490), vessel carcinoma embolus (P=0.010; OR: 2.076; 95% CI: 1.194-3.612), nerve invasion (P=0.024; OR: 2.119; 95% CI: 1.221-3.678), and ER status (P=0.045; OR: 2.978; 95% CI: 1.022-8.675) were independent risk factors for NSLN positivity. Furthermore, the nomogram was built using these 5 factors and validated on 298 patients in the validation group. The AUC was 0.728 (P< 0.001; 95%CI: 0.673-0.784) in the modeling group and 0.810 (P<0.001; 95%CI: 0.735-0.886) in the validation group. The calibration curves of the modeling and validation groups were close to the ideal curve, and DCA also showed that the model could be applied in clinical practice. Conclusion: For early-stage breast cancer with positive SLNs, these factors as the positive number of SLNs > 2, the ratio of positive SLNs > 50%, vessel carcinoma embolus, nerve invasion and ER-positive could predict NSLN metastasis well. The proposed nomogram appears to accurately estimate the likelihood of positive NSLNs and may greatly help the surgeon to decide intraoperatively whether to perform further ALND and avoid non-essential ALND as well as postoperative complications. Citation Format: Zhenchuan Song, Xueyi Zhao, Liu Yang. Risk factors and a new predictive nomogram for predicting the Non-sentinel Lymph Node Metastasis in 708 early-stage Breast Cancer Patients with Positive Sentinel Nodes in China [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 PO3-02-08.

Abstract PO4-16-10: Overall survival in sentinel node biopsy and axillary dissection: a real-world data

Abstract Background: Information about the status of the axilla (presence or absence of lymph node disease) is important for breast cancer (BC) treatment decision-making. Axillary dissection (AD) has been gradually substituted by sentinel node biopsy (SLNB) in clinical node negative patients and intraoperative evaluation became a routine. Most of the patients with a positive node in an intraoperative evaluation were submitted to AD, and when a negative intraoperative evaluation but a positive paraffin evaluation was found a new axillary surgery was a routine. Both approaches were gradually abandoned with the publication of the ACOSOG Z011 study showing no difference in local recurrence or overall survival (OS). Objective: To evaluate the number of patients with BC who meet the criteria of Z011 trial and could be spared of AD and compare the outcomes of the SLNB only and those that had AD. Methods: Patients with BC that were submitted to upfront surgery and had at least one positive node in SLNB were included in these retrospective analyses at Pérola Byington Hospital database, diagnosed between 1992 and 2019. Clinical and pathological characteristics were extracted from the database and patient medical records. T-test or chi-square test was used to individually analyze the association of each variable between the groups. Multivariate analysis was used to calculate odds ratio (OR) and 95% confidence intervals (CI) for independent variables correlated with positive AD. Cox regression was used for survival analysis, and survival curves were plotted using the Kaplan-Meier method, analyzing the difference between curves using the Log-rank test. R software version 4.1.1 was used for all analyses, with a p-value < 0.05 considered statistically significant. Results: A total of 729 patients were analyzed, with a mean age of 54.1 (±11.6) years at diagnosis. Most patients (n=633, 86.8%) underwent AD after a positive SLNB and 40,3% of the patients that were submitted to AD the only positive node was the sentinel node. After AD, 63,3% of these patients had 1 or 2 lymph nodes positive and met the Z011 criteria trial. The mean number of lymph node in AD was 12.2. Most patients (72.7%) were diagnosed at clinical stage II, 62% had nuclear grade 2 tumors, 52.9% had Luminal B subtype, and 63% were postmenopausal. Furthermore, 58.5% of patients underwent breast-conserving surgery, and 5.2% of patients experienced recurrence. The chance of AD was observed 2,2 times for the luminal B (OR 2.163, 95% CI 1.104-4.239, p=0.025), 2,1 times HER2-positive with receptor positive (OR 2.125, 95% CI 1.160-3.893, p=0.015), and 2,8 times for triple-negative (OR 2.806, 95% CI 1.013-7.757, p=0.047) compared to Luminal A. Patients that were submitted to AD had worse outcome when compared to SLNB, the overall survival showed a 94.4% higher risk of death with a median survival of 11 years (HR 1.944, 95% CI 1.20-3.14, p=0.006). Conclusion: These retrospective analyses showed 63,3% of the patients that had a positive node in a SLNB could be spared from AD (based on Z011 trial). Patients submitted to AD had worse outcome and these findings needs to be clarified. Citation Format: Renata Pares, Andre Mattar, Juliana de Lima, Marcelo Antonini, Francisco Pimentel Cavalcante, Luiz Henrique Gebrim. Overall survival in sentinel node biopsy and axillary dissection: a real-world data [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 PO4-16-10.

Abstract GS02-06: Recurrence-free survival following sentinel node-positive breast cancer without completion axillary lymph node dissection – first results from the international randomized SENOMAC trial

Abstract Background The omission of a completion axillary lymph node dissection (cALND) after a positive sentinel lymph node (SLN) biopsy in patients with clinically node-negative breast cancer has been demonstrated to yield survival outcomes non-inferior to routine cALND in breast-conserving surgery followed by whole-breast irradiation (ACOSOG Z0011 and IBCSG 23-01 trials), and to axillary radiotherapy (RT) regardless of breast surgery (EORTC AMAROS trial). Mainly due to the under-representation of mastectomy patients, and a limited number of observed events compromising statistical power, the international randomized SENOMAC trial was initiated in 2015. The main aim of this non-inferiority trial was to address knowledge gaps relating to individuals treated by mastectomy, those with larger tumors and those with SLN extracapsular extension. Method The SENOMAC trial (NCT 02240472) enrolled patients with cT1-3cN0 primary breast cancer and 1-2 SLN macrometastases at 67 sites in five countries between January 27, 2015, and December 31, 2021. Participants were randomized 1:1 between cALND (standard) and omission of cALND (intervention). Stratification was per country. Breast-conserving surgery and mastectomy were eligible surgical interventions. Preoperative axillary ultrasound was mandatory; patients with non-palpable suspicious axillary lymph nodes, even if proven metastatic by biopsy, were eligible. SLN extracapsular extension was allowed. Adjuvant radiotherapy was dictated by national guidelines and not by the trial protocol. Statistical sample size calculation was based on the primary outcome overall survival. Non-inferiority was defined as a 5-year overall survival not worsened by more than 2.5% when refraining from cALND after the observation of 190 all-cause deaths in a target sample size of 3000 included patients. In the present analysis, the pre-specified secondary outcome of recurrence-free survival is reported. Results Out of 2766 randomized individuals, 2539 comprised the per-protocol population: 1204 in the standard and 1335 in the intervention group. Median follow-up was 37.1 months (1.5-75.0) and median age at inclusion 61 years (range 20-94). Most tumors belonged to the luminal subtype (93.6%); tumor stage was T1 in 1358 (53.5%), T2 in 1034 (40.7%) and T3 in 146 participants (5.8%). Out of 347 participants with suspicious lymph nodes on ultrasound, 36 had confirmed non-palpable metastasis. SLN extracapsular extension was reported in 866 (34.1%). The breast was conserved in 1621 (63.8%) and a mastectomy performed in 918 (36.2%) patients. Most patients (2127, 83.8%) received radiotherapy including nodal target volumes. In 34.1% of the standard group, additional non-SLN metastases were identified on cALND. Overall, 104 recurrences were reported, 54 (4.5%) in the standard and 50 (3.7%) in the intervention group. Of these, 11 recurrences were found in the ipsilateral axilla: 5 (0.4%) and 6 (0.5%), respectively. Recurrence-free survival did not differ between groups (country-adjusted HR 0.89, 95% CI 0.65-1.20). Conclusion Despite extended inclusion criteria, there was no difference in recurrence-free survival whether cALND was omitted (intervention) or not (standard). Patients undergoing mastectomy will specifically be addressed in subgroup analyses. Long-term follow-up is crucial considering the high proportion of luminal cancers. Citation Format: Jana de Boniface, Tove Tvedskov, Bergkvist Leif, Jan Frisell, Yvette Andersson, Sara Alkner, Malin Sund, Roger Olofsson Bagge, Dan Lundstedt, Oreste Davide Gentilini, Michalis Kontos, Toralf Reimer, Birgitte Offersen, Thorsten Kühn, Lisa Rydén, Peer Christiansen. Recurrence-free survival following sentinel node-positive breast cancer without completion axillary lymph node dissection – first results from the international randomized SENOMAC trial [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 GS02-06.

Does Sentinel Lymph Node Biopsy Influence Subsequent Management Decisions in Women With Breast Cancer ≥ 70 Years Old?

BackgroundThere have been ongoing attempts to de-escalate surgical intervention in older breast cancer patients in recent years. However, there remains ongoing hesitancy amongst surgeons to de-implement axillary staging in this cohort. The supporting argument for performing a sentinel lymph node biopsy (SLNB) is that it may guide subsequent management. MethodsA retrospective review was performed of 356 SLNBs, in 342 women ≥ 70 years of age with invasive breast cancer, between 2014 and 2022 in a single institution. Data were collected on patient and tumor characteristics and subsequent management for all patients and for patients with ER+/HER2-, early-stage disease. ResultsPositive SLNB significantly increased likelihood of receiving adjuvant chemotherapy (CTh) in patients aged 70-75 in all clinical subtypes (OR 4.0, 95% CI, 1.6-10; P = .0035). Positive SLNB did not significantly increase likelihood of receiving adjuvant CTh in patients aged 75-80, however, an Oncotype Dx score of ≥ 26 did (OR 34.50, 95% CI, 3.00-455.2; P = .0103). Positive SLNB was significantly associated with receiving adjuvant radiotherapy (RTh) in all patients aged 70-75 (OR 4.5, 95% CI, 2.0-11; P = .0004) and 75-80 (OR 9.7, 95% CI, 2.7-46; P = .0015). In patients aged ≥ 80 years, positive SLNB did not have a significant influence on subsequent treatments. ConclusionIn this study, SLNB did not significantly influence subsequent management decisions in patients over 80 and should rarely be performed in this cohort. However, SLNB still had a role in patients aged 70-80 and should be used selectively in this cohort.

Predictors of positive axillary node clearance following positive sentinel node biopsy: A retrospective analysis at royal Glamorgan hospital

Predictors of positive axillary node clearance following positive sentinel node biopsy: A retrospective analysis at royal Glamorgan hospital

De-escalation of axillary treatment in the event of a positive sentinel lymph node biopsy in cT1-2 N0 breast cancer treated with mastectomy: nationwide registry study (BOOG 2013-07).

Trials have demonstrated the safety of omitting completion axillary lymph node dissection in patients with cT1-2 N0 breast cancer operated with breast-conserving surgery who have limited metastatic burden in the sentinel lymph node. The aim of this registry study was to provide insight into the oncological safety of omitting completion axillary treatment in patients operated with mastectomy who have limited-volume sentinel lymph node metastasis. Women diagnosed in 2013-2014 with unilateral cT1-2 N0 breast cancer treated with mastectomy, with one to three sentinel lymph node metastases (pN1mi-pN1a), were identified from the Netherlands Cancer Registry, and classified by axillary treatment: no completion axillary treatment, completion axillary lymph node dissection, regional radiotherapy, or completion axillary lymph node dissection followed by regional radiotherapy. The primary endpoint was 5-year regional recurrence rate. Secondary endpoints included recurrence-free interval and overall survival, among others. In total, 1090 patients were included (no completion axillary treatment, 219 (20.1%); completion axillary lymph node dissection, 437 (40.1%); regional radiotherapy, 327 (30.0%); completion axillary lymph node dissection and regional radiotherapy, 107 (9.8%)). Patients in the group without completion axillary treatment had more favourable tumour characteristics and were older. The overall 5-year regional recurrence rate was 1.3%, and did not differ significantly between the groups. The recurrence-free interval was also comparable among groups. The group of patients who did not undergo completion axillary treatment had statistically significantly worse 5-year overall survival, owing to a higher percentage of non-cancer deaths. In this registry study of patients with cT1-2 N0 breast cancer treated with mastectomy, with low-volume sentinel lymph node metastasis, the 5-year regional recurrence rate was low and comparable between patients with and without completion axillary treatment.

Prognostic significance of sentinel lymph node biopsy in elderly with cutaneous melanoma: systematic review and meta-analysis.

Sentinel lymph node biopsy is the most powerful prognostic indicator to date for cutaneous melanoma. Even though elderly patients have a lower incidence of sentinel node involvement, its results are still necessary for access to adjuvant therapies. This is highly relevant considering that the Western population shows an aging trend, and the incidence of melanoma has grown exponentially over the years, making elderly patients more likely to die from melanoma than younger ones. We performed a systematic review to investigate the prognostic significance of sentinel lymph node biopsy in elderly patients with melanoma. The systematic review was conducted following the PRISMA guidelines and registered in PROSPERO. The authors searched the Cochrane Database, EMBASE, PubMed, and WOS. Eligible studies for the systematic review were clinical trials, observational population studies, clinical or hospital-based cohort studies, and case-control studies. The meta-analysis was conducted using the R software program applying the meta package. Six reports were identified to meet the inclusion criteria. All studies were retrospective, non-randomized cohorts. The results obtained in this systematic review show a statistically significant influence of sentinel lymph node biopsy on disease-specific survival (HR = 2.87; 95% CI: 1.73-4.74) but also suggest that a positive result negatively impacts disease-free survival (HR = 3.41; 95% CI: 0.96-12.11). This meta-analysis shows that a positive sentinel lymph node biopsy does not imply differences in overall survival but significantly influences disease-specific survival and suggests an unfavorable impact on disease-free survival.

Lymphadenectomy After Melanoma-A National Analysis of Recurrence Rates and Risk of Lymphedema.

Treatment for melanoma after a positive sentinel lymph node biopsy includes nodal observation or lymphadenectomy. Important considerations for management, however, involve balancing the risk of recurrence and the risk of lymphedema after lymphadenectomy. From the Merative MarketScan Research Databases, adult patients were queried from 2007 to 2021. International Classification of Disease, Ninth (ICD-9) and Tenth (ICD-10) Editions, diagnosis codes and Current Procedural Terminology codes were used to identify patients with melanoma diagnoses who underwent an index melanoma excision with a positive sentinel lymph node biopsy (SLNB). Main outcomes were completion lymph node dissection (CLND) utilization after a positive SLNB, developing lymphedema with or without CLND, and nodal basin recurrence 3 months or more after index excision. Subanalyses stratified by index excision year (2007-2017 and 2018-2021) and propensity score matched were additionally conducted. Demographics and comorbidities (measured by Elixhauser index) were recorded. A total of 153,085,453 patients were identified. Of those, 359,298 had a diagnosis of melanoma, and 202,456 patients underwent an excision procedure. The study cohort comprised 3717 patients with a melanoma diagnosis who underwent an excision procedure and had a positive SLNB. The mean age of the study cohort was 49 years, 57% were male, 41% were geographically located in the South, and 24% had an Elixhauser index of 4+. Among the 350 patients who did not undergo CLND, 10% experienced recurrence and 22% developed lymphedema. A total of 3367 patients underwent CLND, of which 8% experienced recurrence and 20% developed lymphedema. Completion lymph node dissection did not significantly affect risk of recurrence [odds ratio (OR), 1.370, P = 0.090] or lymphedema (OR, 1.114, P = 0.438). After stratification and propensity score matching, odds of experiencing lymphedema (OR, 1.604, P = 0.058) and recurrence (OR, 1.825, P = 0.058) after CLND were not significantly affected. Rates of CLND had significantly decreased (P < 0.001) overtime, without change in recurrence rate (P = 0.063). Electing for nodal observation does not increase the risk of recurrence or reduce risk of lymphedema. Just as CLND does not confer survival benefit, its decreased utilization has not increased recurrence rate.

The Role of Sentinel Lymph Node Biopsy in the Management of Merkel Cell Carcinoma: A Systematic Review and Meta-analysis.

Merkel cell carcinoma (MCC) is a rare cutaneous malignancy with high metastatic potential. Sentinel lymph node biopsy (SLNB) is used to assess locoregional spread, facilitate staging, and inform prognosis. Positive nodal status is associated with higher recurrence rates and reduced overall survival. A systematic search was conducted. Eligible articles included patients diagnosed with MCC, who would be candidates for or who had SLNB. The Covidence tool was used for screening and data extraction, including additional treatments, disease-free survival, overall survival, and recurrence. Methodological quality was assessed using the Newcastle-Ottowa Scale criteria. SLNB was associated with increased likelihood of completion lymphadenectomy (223 versus 41), regional radiotherapy (2167 versus 808), and systemic chemotherapy (138 versus 31). Overall survival for patients undergoing SLNB was 81% at 2 years, 75% at 3 years, and 72% at 5 years (odds ratio: 0.79). Hazard ratio for positive SLNB versus negative was 3.36 (P < 0.001). Five-year disease recurrence was 23.3% in patients undergoing SLNB. Lymph node metastases are associated with reduced overall survival and increased recurrence of MCC. Determining nodal status early can inform prognosis, facilitate staging, and determine need for adjuvant treatment. Adjuvant treatments are associated with reduced mortality and improved overall survival; SLNB is an important influencer of their use. Early prophylactic intervention should be considered in MCC in both positive and negative nodal status to improve overall outcomes. Widespread use of SLNB will allow more accurate assessment of the role of nodal status on adjuvant treatment and long-term outcomes.

De-escalating axillary management after neoadjuvant chemotherapy in breast cancer: The ratio of positive sentinel lymph nodes matters

BackgroundDe-escalation of axillary surgery in breast cancer (BC) patients diminishes sequelae without compromising cancer outcomes. Surgical management of the axilla is challenging after neoadjuvant treatment. We aimed to identify the factors associated with residual axillary disease amenable to lymphadenectomy in patients with positive sentinel lymph node biopsy (SLNB). MethodsWe conducted a retrospective observational study in Hospital 12 de Octubre (Spain). We included BC patients with positive SLNB who underwent axillary dissection after neoadjuvant chemotherapy. Univariate and multivariate logistic regression models were performed to identify independent predictors of residual axillary disease. We estimated the ratio of positive nodes in SLNB and assessed the diagnostic validity of this ratio in relation to residual axillary disease. ResultsWe included 103 patients in the study. Residual axillary disease was identified in 54 patients (52.4%). Clinically node positive status at diagnosis (OR = 18.3, 95%CI: 4.0–83.6) and a ratio of positive nodes in SLNB ≥0.5 (OR = 6.5, 95%CI 41.7–23.7) were associated with residual axillary disease. The sensitivity and negative predictive value of a ratio of positive nodes in SLNB ≥0.5 were 87% (95%CI 75.1%–94.6%) and 75% (95%CI 55.1%–89.3%), respectively. ConclusionsIn our study, for patients with positive SLNB after neoadjuvant chemotherapy, stage N+ at diagnosis and a ratio of positive nodes in SLNB ≥0.5 were independent risk factors of positive residual axillary disease. This ratio is a feasible measure with a good diagnostic validity for residual axillary disease and could be used as a guiding factor in the surgical management of these patients.

Sentinel lymph node biopsy for melanoma in the older population: A prospective analysis of outcomes.

The use of sentinel lymph node biopsy (SLNB) in the older population, defined as those over 70 years old, has been debated since the adoption of SLNBinto routine practice. Interestingly, there remains a paucity of evidence, especially regarding the rates of SLNB positivity, complications, and subsequent adjuvant therapy in those with node positivity. Data on patient's comorbidities, positivity rates, complication rates, and subsequent adjuvant treatments were collected prospectively from 998 patients (644 patients < 70 and 354 patients ≥ 70 years old) between 2016 and 2022. Patients aged ≥ 70 were found to have a higher prevalence of comorbidities, including hypertension, diabetes and hyperlipidaemia. The mean Breslow thickness was 2.2 and 2.5 in the under and over 70 groups respectively (p = 0.03). The mean mitotic rate was found to be 3.3 in the under 70 s and 4.1 in the over 70 s (p = 0.02). Despite these results, no significant differences were observed in the positivity rates of sentinel lymph node biopsies or in the treatment options selected for positive results. The under 70 s were more likely to experience loss of sensation (p < 0.01), but no difference was found in the total number of complications between the two groups. Although patients aged 70 and above had a greater incidence of comorbidities, the study revealed that they had lower complications rates and there was no significant variation in the SLNB positivity rate or chosen treatment options between the two age groups. This study supports the move to physiological rather than chronological age assessments in SLNB of the elderly.

Complete lymph node dissection in cutaneous melanoma patients with positive sentinel lymph node: Outcome and predictors in a retrospective cohort study over 16 years

BackgroundIn melanoma treatment, complete lymph node dissection (CLND) has been considered the therapeutic gold standard in patients with positive sentinel lymph node biopsy (SLNB). This long-held approach was revised in 2017, with recent evidence questioning the therapeutic benefit of CLND in malignant melanoma (MM) therapy. In this study, we aimed to fill this knowledge gap by retrospectively analyzing the impact of CLND on MM patients’ survival. Methods: We retrospectively analyzed the multi-center population-based Clinical Cancer Registry at the Tumor Center Regensburg (TUDOK) database (2004–2020) to identify patients who had been diagnosed with SLN-positive MM and underwent (non)invasive management thereof. Patient cohorts were subdivided according to the treatment received (CLND and waiving CLND). Primary outcomes included overall survival (OS), recurrence-free survival (RFS), and cumulative recurrence rate. Results: We identified 1143 MM patients, of whom 126 (11.0%) had positive SLN status. CLND was waived in the majority of SLN-positive MM cases (n = 71; 56.3%), with 55 (43.7%) patients undergoing CLND. Univariable and multivariable Cox regression revealed no significant advantage for CLND patients compared to non-CLND patients in OS (HR=0.970, p = 0.915 and HR=1.295, p = 0.479, respectively), RFS (HR=1.050, p = 0.849 and HR=1.220, p = 0.544, respectively), and cumulative recurrence rate (HR=1.234, p = 0.441 and HR=1.220, p = 0.544), respectively). Conclusion: We found that CLND had no significant impact on patient survival and MM recurrence rate, thus corroborating the validity of current clinical guidelines.

Impact of extra-nodal extension and AJCC lymph node staging in predicting recurrence following lymphadenectomy in patients with melanoma

BackgroundRegional lymphadenectomy (RL) has traditionally been recommended in patients with melanoma found to have clinical lymphadenopathy or a positive sentinel lymph node biopsy (SLNB). Regional control of disease is still a relevant issue for patients, even after undergoing lymphadenectomy. The goal of this study was to identify the clinicopathologic characteristics that predict locoregional recurrence in patients who have undergone either therapeutic lymph node dissection (TLND) or completion lymph node dissection (CLND) following SLNB. MethodsRetrospective review of population-based cohort of patients with melanoma lymph node metastasis from the years 2005–2015. Multivariate, proportional hazards regression analysis was performed to determine factors predicting nodal recurrence. Results586 patients underwent a RL, with a median follow up of 35 months. Overall, in-basin recurrence rates in the axilla, groin, and head/neck were 7.7 ​%, 8.7 ​% and 9.2 ​%, respectively. Higher unadjusted recurrence rates occurred following CLND than TLND of the groin (12.8 ​% vs 4.5 ​%) and neck (10.0 ​% vs 4.7 ​%) but not the axilla (7.5 ​% vs 8.0 ​%). Upon multivariate analysis, ENE (HR 2.77; p=<0.0001) and the AJCC lymph node stage (N3 vs N1) (HR 2.51; p ​= ​0.025) were predictive of regional recurrence. ConclusionThe AJCC nodal stage and the presence of extranodal extension were the only variables impacting regional recurrence following regional lymphadenectomy for melanoma. When considering regional disease control, they should be factored into treatment decisions, and surveillance strategies.

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.

Validation of the Melanoma Institute of Australia's Sentinel Lymph Node Biopsy Risk Prediction Tool for Cutaneous Melanoma.

For patients with cutaneous melanoma, sentinel lymph node biopsy (SLNB) is used to stage regional lymph nodes pathologically and inform prognosis, treatment, and surveillance. To reduce unnecessary surgeries, predictive tools aim to identify those at lowest risk for node-positive disease. The Melanoma Institute of Australia (MIA)'s Prediction Tool for Sentinel Node Metastasis Risk estimates risk of a positive SLNB using patient age and primary melanoma Breslow depth, histologic subtype, ulceration, mitotic rate, and lymphovascular invasion. A single-institution validation was performedof the MIA Calculator with 982 cutaneous melanoma patients that included all relevant clinicopathologic factors and SLNB pathology outcomes. The study evaluated discrimination via receiver operating characteristic (ROC) curves, calibration via calibration plots, and clinical utility via decision curve analysis of the MIA model in various subgroups. The data were fit to MIA model parameters via a generalized linear model to assess the odds ratio of parameters in our dataset. The Calculator demonstrated limited discrimination based on ROC curves (C-statistic, 0.709) and consistently underestimated risk of SLN positivity. It did not provide a net benefit over SLNB performed on all patients or reduce unnecessary procedures in the risk domain of 0% to 16%. Compared with the original development and validation cohorts, the current study cohort had thinner tumors and a larger proportion of acral melanomas. The Calculator generally underestimated SLN positivity risk, including assessment in patients who would be counseled to forego SLNB based on a predicted risk lower than 5%. Recognition of the tool's current limitations emphasizes the need to refine it further for use in medical decision-making.

Sentinel lymph node biopsy is unreliable in predicting melanoma mortality for both younger and older patients.

Melanoma disease patterns vary with patient age. To evaluate sentinel lymph node biopsy (SLNB) in managing melanoma at differing patient ages. Online prediction tools were applied to compare SLNB positivity (SLNB+) and survival risk at patient ages 20-80. Tübingen melanoma data were used to determine variations in the hazard ratio of SLNB+ for mortality at different patient ages. Regardless of tumour thickness, predicted SLNB+ rates were markedly higher than mortality rates for 20-year-old patients. For 80-year-old patients, it is the opposite. If 1000 20-year-olds with a 0.4 mm thickness non-ulcerated melanoma underwent SLNB, 100 would likely be positive. If all 100 were to be offered adjuvant drug therapy (ADT), fewer than three more melanoma deaths in those 1000 patients would be avoided. In total, 97 patients would have received medication they may never have needed. If 1000 80-year-olds with a 3 mm thickness non-ulcerated melanoma underwent SLNB, only 40 would likely be positive. In total, 274 patients would be predicted to die of melanoma, 245 being SLNB negative and 29 SLNB+. ADT linked to SLNB+ could deny treatment to 89% of these high-risk patients. The authors relied on published risk data. SLNB has poor specificity at predicting mortality in young melanoma patients and poor sensitivity in older patients. SLNB is not indicated in managing cutaneous melanoma for patients under 40 or over 60 years of age. Many such patients could be managed with wide local excision alone in their clinician's office-based practice. For all cutaneous melanoma patients at all ages, linking ADT to BAUSSS biomarker, (an algorithm of Breslow thickness, age, ulceration, subtype, sex and Site) rather than SLNB+ is likely more appropriate. BAUSSS provides a more accurate melanoma-specific mortality risk assessment for patients without burdening them with added surgery, hospitalization, costs or morbidity risk.

Axillary management of a positive sentinel lymph node biopsy in the era of Abemaciclib in early Breast cancer

Axillary management of a positive sentinel lymph node biopsy in the era of Abemaciclib in early Breast cancer