Macrometastatic Sentinel Lymph Node Research Articles

Can Axillary Lymph Node Dissection be Omitted in Breast Cancer Patients with Metastatic Sentinel Lymph Nodes Undergoing Mastectomy? A Systematic Review and Meta-Analysis of Real-World Evidence.

The omission of axillary lymph node dissection (ALND) in patients with breast cancer who have metastatic sentinel lymph nodes (SLNs) undergoing mastectomy remains controversial. This meta-analysis explored the clinicopathological factors affecting the selection of ALND and the influences of ALND on survival outcomes in patients receiving mastectomy with positive SLNs. Eligible studies published prior to 31 December 2022 were selected by searching the Embase, Web of Science and PubMed databases. Pooled analyses were performed using the number of events for clinicopathological parameters and HRs with 95% CIs for survival outcomes including disease-free survival (DFS), overall survival (OS), distant recurrence-free survival (DRFS) and locoregional recurrence-free survival (LRFS). A total of 10 retrospective studies enrolling only breast cancer patients with limited SLN metastases (no more than 3 positive SLNs or micrometastatic SLNs) undergoing mastectomy were included. Performing ALND in mastectomy patients who had limited SLN metastases was significantly correlated with invasive ductal carcinomas, larger tumors, lymphovascular invasion, higher tumor grade, macrometastatic SLNs, more positive SLNs, extranodal extension, positive surgical margins, negative ER, administration of adjuvant chemotherapy and nonwhite race (P < 0.05). However, performing ALND did not result in significantly longer OS, DFS, LRFS or DRFS (P > 0.05) in these patients. The present meta-analysis indicated that ALND may be safely avoided in patients with breast cancer who had limited SLN metastases undergoing mastectomy. Further well-designed randomized clinical trials are warranted to validate our results.

Risk factors of non-sentinel lymph node metastasis in breast cancer with 1–2 sentinel lymph node macrometastases underwent total mastectomy: a case-control study

BackgroundThe randomized trials which include ACOSOG Z0011 and IBCSG 23-01 had found that the survival rates were not different in patients with cT1/2N0 and 1–2 sentinel lymph node (SLN)-positive, macro/micrometastases who underwent breast-conserving therapy, and micrometastases who underwent total mastectomy (TM), when axillary lymph node dissection (ALND) was omitted. However, for patients with cT1/2N0 and 1–2 SLN macrometastases who underwent TM; there was still insufficient evidence from clinical studies to support whether ALND can be exempted. This study aimed to investigate the risk factors of non-sentinel lymph node (nSLN) metastasis in breast cancer patients with 1–2 SLN macrometastases undergoing TM.MethodsThe clinicopathological data of 1491 breast cancer patients who underwent TM and SLNB from January 2017 to February 2022 were retrospectively analyzed. Univariate and multivariate analyses were performed to analyze the risk factors for nSLN metastasis.ResultsA total of 273 patients with 1–2 SLN macrometastases who underwent TM were enrolled. Postoperative pathological data showed that 35.2% patients had nSLN metastasis. The results of multivariate analysis indicated that tumor size (TS) (P = 0.002; OR: 1.051; 95% CI: 1.019–1.084) and ratio of SLN macrometastases (P = 0.0001; OR: 12.597: 95% CI: 4.302–36.890) were the independent risk factors for nSLN metastasis in breast cancer patients with 1–2 SLN macrometastases that underwent TM. The ROC curve analysis suggested that when TS ≤22 mm and ratio of SLN macrometastases ≤0.33, the incidence of nSLN metastasis could be reduced to 17.1%.ConclusionsThe breast cancer patients with cT1/2N0 stage, undergoing TM and 1–2 SLN macrometastases, when the TS ≤22 mm and macrometastatic SLN does not exceed 1/3 of the total number of detected SLN, the incidence of nSLN metastasis is significantly reduced, but whether ALND can be exempted needs further exploration.

Abstract OT1-06-01: Preservation of axillary lymph nodes in breast cancer patients undergoing mastectomy with 1-2 metastatic sentinel lymph nodes: The current status and future perspectives of the multicenter randomized clinical trial SINODAR-ONE

Abstract Introduction: Axillary lymph node dissection (ALND) has always been part of breast cancer (BC) treatment. However, during the past 25 years, the surgical management of the axilla has shifted towards a more conservative approach. Until now, ALND has remained the standard surgical technique when the sentinel lymph node (SLN) is macrometastatic. However, ALND may now be considered overtreatment for early-stage BC. The SINODAR-ONE trial is a prospective non-inferiority multicenter randomized study aimed at assessing the role of ALND in patients undergoing either breast-conserving surgery (BCS) or mastectomy for T1-2 BC presenting 1-2 macrometastatic SLNs. Objectives: The primary endpoint was to evaluate whether sentinel lymph node biopsy (SLNB) only was associated with clinically relevant worsening of the prognosis compared with ALND in terms of overall survival (OS). The secondary endpoint was to evaluate whether there was increased regional (lymph node recurrence) or distant recurrence in terms of recurrence-free survival (RFS) in patients with macrometastatic SLN who did not undergo ALND. Methods: Patients were randomly assigned (1:1 ratio) to either removal of ≥10 axillary level I/II non-SLNs followed by adjuvant therapy (standard arm) or no further axillary treatment (experimental arm). Results: The trial started in April 2015 and ceased in April 2020, involving 889 patients. The majority of the patients (75.2%) underwent BCS; 328 of 439 patients (74.7%) in the standard treatment arm, and 333 of 440 patients (75.7%) in the experimental treatment arm. 218 patients (24.8%) underwent mastectomy. SLN status at randomization was comparable between the two groups of treatment, with a median number of two SLNs removed and a median number of one positive SLN in both arms. The median number of non-SLNs identified at definitive histopathological evaluation was 16 (interquartile range [IQR] 12–21) in the ALND group. Overall, 193 of 439 patients (44.0%) in the standard treatment arm had additional macrometastases in the removed axillary lymph nodes. However, the median number of positive non SLNs was 0 (IQR 0–1) in the ALND group. Median follow-up was 34.0 months. There were eight deaths (ALND, 4; SNLB only, 4), with a 5-year cumulative mortality of 5.8% and 2.1% in the standard and experimental arm, respectively (p = 0.984). There were 26 recurrences (ALND 11; SNLB only, 15), with a 5-year cumulative incidence of recurrence of 6.9% and 3.3% in the standard and experimental arm, respectively (p = 0.444). Only one axillary lymph node recurrence was observed in each arm. The 5-year OS rates were 98.9% and 98.8%, in the ALND and SNLB only arm, respectively (p = 0.936). Conclusion: The 3-year survival and relapse rates of T1-2 BC patients with 1-2 macrometastatic SLNs treated with SLNB only, and adjuvant therapy, were not inferior to those of patients treated with ALND. These results do not support the use of routine ALND in patients undergoing BCS. However, given the low number of patients treated with mastectomy, there is no certainty that ALND omission can be extended also to this sub-group. In order to collect further evidence regarding the safety of the experimental treatment in patients candidates for mastectomy, the reopening of the enrollment of these patients as part of a single-arm experimental study started in June 2022. Citation Format: Damiano Gentile, Wolfgang Gatzemeier, Andrea Sagona, Erika Barbieri, Alberto Testori, Valentina Errico, Alberto Bottini, Simone Di Maria Grimaldi, Giulia Caraceni, Luca Boni, Paolo Bruzzi, Bethania Fernandes, Davide Franceschini, Ruggero Spoto, Rosalba Torrisi, Marta Scorsetti, Armando Santoro, Giuseppe Canavese, Corrado Tinterri. Preservation of axillary lymph nodes in breast cancer patients undergoing mastectomy with 1-2 metastatic sentinel lymph nodes: The current status and future perspectives of the multicenter randomized clinical trial SINODAR-ONE [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-06-01.

Presence of Dendritic Cell Subsets in Sentinel Nodes of Breast Cancer Patients Is Related to Nodal Burden.

BACKGROUND: Sentinel lymph nodes (SLNs) are both the first site where breast cancer (BC) metastases form and where anti-tumoral immunity develops. Despite being the most potent antigen-presenting cells, dendritic cells (DCs) located in a nodal tissue can both promote or suppress immune response against cancer in SLNs. METHODS: In SLNs excisions obtained from 123 invasive BC patients, we performed immunohistochemistry (IHC) for CD1a, CD1c, DC-LAMP, and DC-SIGN to identify different DCs populations. Then we investigated the numbers of DCs subsets in tumor-free, micrometastatic, and macrometastatic SLNs with the use of a light microscope. RESULTS: We observed that CD1c+ and DC-SIGN+ DCs were more numerous in SLNs with a larger tumor size. More abundant intratumoral DC-LAMP+ population was related to a higher number of metastatic lymph nodes. Conversely, more abundant CD1a+ DCs were associated with a decreasing nodal burden in SLNs and a lower number of involved lymph nodes. Moreover, densities of the investigated DC populations differed with respect to tumor grade, HER2 overexpression, hormone receptor status, and histologic type of BC. CONCLUSIONS: According to their subtype, DCs are associated with either lower or higher nodal burden in SLNs from invasive BC patients. These relationships appear to be dependent not only on the maturation state of DCs but also on the histological and biological characteristics of the tumor.

Preservation of Axillary Lymph Nodes Compared with Complete Dissection in T1-2 Breast Cancer Patients Presenting One or Two Metastatic Sentinel Lymph Nodes: The SINODAR-ONE Multicenter Randomized Clinical Trial.

The SINODAR-ONE trial is a prospective noninferiority multicenter randomized study aimed at assessing the role of axillary lymph node dissection (ALND) in patients undergoing either breast-conserving surgery or mastectomy for T1-2 breast cancer (BC) and presenting one or two macrometastatic sentinel lymph nodes (SLNs). The endpoints were to evaluate whether SLN biopsy (SLNB) only was associated with worsening of the prognosis compared with ALND in terms of overall survival (OS) and relapse. Patients were randomly assigned (1:1 ratio) to either removal of ≥ 10 axillary level I/II non-SLNs followed by adjuvant therapy (standard arm) or no further axillary treatment (experimental arm). The trial started in April 2015 and ceased in April 2020, involving 889 patients. Median follow-up was 34.0 months. There were eight deaths (ALND, 4; SNLB only, 4), with 5-year cumulative mortality of 5.8% and 2.1% in the standard and experimental arm, respectively (p = 0.984). There were 26 recurrences (ALND 11; SNLB only, 15), with 5-year cumulative incidence of recurrence of 6.9% and 3.3% in the standard and experimental arm, respectively (p = 0.444). Only one axillary lymph node recurrence was observed in each arm. The 5-year OS rates were 98.9% and 98.8%, in the ALND and SNLB-only arm, respectively (p = 0.936). The 3-year survival and relapse rates of T1-2 BC patients with one or two macrometastatic SLNs treated with SLNB only, and adjuvant therapy, were not inferior to those of patients treated with ALND. These results do not support the use of routine ALND.

Abstract GS4-05: Preservation of axillary lymph nodes compared to complete dissection in T1-T2 breast cancer patients presenting 1-2 metastatic sentinel lymph nodes. A multicenter randomized clinical trial. Sinodar One

Abstract Introduction: Sentinel lymph node (SLN) staging is currently used to avoid complete axillary lymph node dissection (ALND) in breast cancer (BC) patients. The SLN is the only site of axillary metastasis (MTS) in ≥60% of cases. Recently, a randomized controlled trial (Z0011) comparing SLN biopsy (SLNB) alone with SLNB followed by ALND in patients with 1-2 SLNs+ demonstrated no significant statistical difference in relapse and overall survival (OS) rates among the two different groups. However, this study had some limitations: small tumor size (≤2cm in 70% of cases), frequent presence of only microMTS in SLN (40%), prevalent use of “whole breast” adjuvant radiotherapy (&amp;gt;90%). Given these considerations, the SINODAR-ONE study started in April 2015. Objectives: The aims are to assess whether ALND omission in BC patients with 1-2 SLNs+ is associated with worse survival and/or increased rate of regional/distant relapse. Thus evaluating whether SLNB is or is not inferior to ALND. Primary endpoint is OS. Secondary endpoints are disease-free survival (DFS) referring to distant MTS and loco-regional recurrence. Methods: Patients received either mastectomy or conservative surgery plus radiotherapy. They all underwent SLNB and were randomly divided into two arms of treatment: standard (SLNB plus ALND) or experimental treatment (only SLNB). According to multidisciplinary evaluation, patients could undergo additional adjuvant radiotherapy, chemo- and/or hormonal therapy, or no further therapy. Eligibility criteria: age 40-75 years; primary invasive T1-T2 tumor; axillary nodes cN0; no more than 2 macro-metastatic SLNs; no distant MTS; no neo-adjuvant therapy; no previous invasive BC. Exclusion criteria: in situ, inflammatory, contralateral BC; micro-metastatic SLNs; pregnancy or breast feeding; comorbidity impeding adjuvant therapy. All analyses were performed both on all patients according to the Intention-To-Treat principle and excluding those patients who did not receive the axillary treatment randomly assigned. Statistical analysis: OS and DFS were calculated using the Kaplan-Meier Product Limit Estimator and differences between arms were assessed with the log-rank test. Results: The enrollment of patients ended in April 2020 with a total of 889 cases (443: standard arm; 446: experimental arm). In April 2021, we conducted a preliminary analysis on 889 patients. We found the two groups homogeneous for epidemiologic characteristics (age and menopausal status), tumor characteristics (tumor size, pTNM, immunohistochemistry, histology, grading, vascular and lymphatic invasion), and adjuvant therapies. The majority of patients (77.2%) received breast conserving surgery, while 22.8% of patients underwent mastectomy. A median of 2 SLNs were removed in both arms. Overall, only 3 micro-metastatic SNLs were found (1 in the standard arm and 2 in the experimental arm). Conclusion: In sum, OS rate is 99.1% and 99.3% in the standard and experimental arm, respectively; DFS rate is 96.8% and 95.9% in the standard and experimental arm, respectively. After a median follow-up of 36 months, there has been only one axillary recurrence in the experimental arm. Additionally, we found seven distant relapses in both arms; four and three deaths in the standard and experimental arm, respectively. Citation Format: Damiano Gentile, Wolfgang Gatzemeier, Erika Barbieri, Andrea Sagona, Alberto Bottini, Valentina Errico, Alberto Testori, Marta Scorsetti, Giuseppe Canavese, Corrado Tinterri. Preservation of axillary lymph nodes compared to complete dissection in T1-T2 breast cancer patients presenting 1-2 metastatic sentinel lymph nodes. A multicenter randomized clinical trial. Sinodar One [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS4-05.

Can Conization Specimens Predict Sentinel Lymph Node Status in Early-Stage Cervical Cancer? A SENTICOL Group Study.

Simple SummaryLymph node involvement is one of the major prognosis factors for early-stage cervical cancer. Improvement in preoperative identification of node-positive patients may lead to a more accurate triage to primary chemoradiation for these patients instead of radical surgery followed by adjuvant radiotherapy, given the increased morbidity of combined treatment. Several studies have well established risk factors for node involvement, but they are based on final pathologic examination of radical hysterectomy specimens and are usually extrapolated for preoperative risk assessment. Among these risk factors, tumor size, lymphovascular space invasion (LVSI) and depth of stromal invasion might be assessed in conization specimens. Our findings suggest that patients with depth of stromal invasion lower than 10 mm and no LVSI in conization specimens had lower risk of micro- and macrometastatic SLN. In this subpopulation, full node dissection may be questionable in case of SLN unilateral detection.Background: The prognosis of patients with cervical cancer is significantly worsened in case of lymph node involvement. The goal of this study was to determine whether pathologic features in conization specimens can predict the sentinel lymph node (SLN) status in early-stage cervical cancer. Methods: An ancillary analysis of two prospective multicentric database on SLN biopsy for cervical cancer (SENTICOL I and II) was carried out. Patients with IA to IB2 2018 FIGO stage, who underwent preoperative conization before SLN biopsy were included. Results: Between January 2005 and July 2012, 161 patients from 25 French centers fulfilled the inclusion criteria. Macrometastases, micrometastases and Isolated tumor cells (ITCs) were found in 4 (2.5%), 6 (3.7%) and 5 (3.1%) patients respectively. Compared to negative SLN patients, patients with micrometastatic and macrometastatic SLN were more likely to have lymphovascular space invasion (LVSI) (60% vs. 29.5%, p = 0.04) and deep stromal invasion (DSI) ≥ 10 mm (50% vs. 17.8%, p = 0.04). Among the 93 patients with DSI < 10 mm and absence of LVSI on conization specimens, three patients (3.2%) had ITCs and only one (1.1%) had micrometastases. Conclusions: Patients with DSI < 10 mm and no LVSI in conization specimens had lower risk of micro- and macrometastatic SLN. In this subpopulation, full node dissection may be questionable in case of SLN unilateral detection.

Correlation between outcome and extent of residual disease in the sentinel node after neoadjuvant chemotherapy in clinically fine-needle proven node-positive breast cancer patients

BackgroundWhether the extent of residual disease in the sentinel lymph node (SLN) after neoadjuvant chemotherapy (NAC) influences the prognosis in clinically node-positive breast cancer (BC) patients remains to be ascertained. MethodsOne hundred and thirty-four consecutive cN+/BC-patients received NAC followed by SLN biopsy and axillary lymph node dissection. Cumulative incidence of overall (OS) and disease-free (DFS) survival, BC-related recurrences and death from BC were assessed using the Kaplan-Meier method both in the whole patient population and according to the SLN status. The log rank test was used for comparisons between groups. ResultsThe SLN was identified in 123/134 (91.8%) patients and was positive in 98/123 (79.7%) patients. Sixty-five of them (66.3%) had other axillary nodes involved. SLN sensitivity and false-negative rate were 88.0% and 2.0%, Median follow-up was 10.2 years. Ten-year cumulative incidence of axillary, breast and distant recurrences, and death from BC were 6.5%, 11.9%, 33.4% and 31.3%, respectively. Ten-year OS and DFS were 67.3% and 55.9%. When stratified by SLN status, 10-year cumulative incidence of BC-related and loco-regional events, and death from BC were similar between disease-free SLN and micrometastatic SLN subgroups (28.9% vs 30.2%, p = 0.954; 21.6% vs 13.4%, p = 0.840; 12.9 vs 24.5%, p=0.494). Likewise, 10-year OS and DFS were comparable (80.0% vs 75.5%, p=0.975 and 68.0% vs 69.8, p=0.836). Both OS and DFS were lower in patients presenting a macrometastatic SLN (60.2% and 47.5%). ConclusionOutcome of patients with micrometastatic SLN was similar to that of patients with disease-free SLN, which was more favorable as compared to that of patients with macrometastatic SLN.

Abstract PD4-01: Preservation of axillary lymph nodes compared to complete dissection in T1-T2 breast cancer patients presenting 1-2 metastatic sentinel lymph nodes : A multicenter randomized clinical trial. Sinodar One.

Abstract Introduction: Sentinel lymph node (SLN) staging is currently used to avoid complete axillary lymph node dissection (ALND) in breast cancer (BC) patients. The SLN is the only site of axillary metastasis (MTS) in ≤60% of cases. Recently, a randomized controlled trial (Z0011) comparing SLN biopsy (SLNB) alone with SLNB followed by ALND in patients with 1-2 SLNs+ demonstrated no significant statistical difference in relapse and overall survival rates among the two different groups. However, this study had some limitations: small tumor size (≤2cm in 70% of cases), frequent presence of only microMTS in SLN (40%), prevalent use of “whole breast” adjuvant radiotherapy (&amp;gt;90%). Given these considerations, the SINODAR-ONE study started in April 2015.Objectives: The aims are to assess whether ALND omission in BC patients with 1-2 SLNs+ is associated with worse survival and/or increased rate of regional/distant relapse. Thus evaluating whether SLNB is or is not inferior to ALND. Primary endpoint is overall survival (OS). Secondary endpoints are disease-free survival (DFS) referring to distant MTS and loco-regional recurrence. Methods: Patients receive either mastectomy or conservative surgery plus radiotherapy. They all undergo SLNB and are randomly divided into two arms of treatment: standard (SLNB plus ALND) or experimental treatment (only SLNB). According to multidisciplinary evaluation, patients may undergo additional adjuvant radiotherapy, chemo- and/or hormonal therapy , or no further therapy. Eligibility criteria: age 40-75 years; primary invasive T1-T2 tumor; axillary nodes clinically N0; no more than 2 macro-metastatic SLNs; no distant MTS; no neo-adjuvant therapy; no previous invasive BC; signed informed consent. Exclusion criteria: in situ, inflammatory, contralateral BC; micro-metastic SLNs; pregnancy or breast feeding; comorbidity impeding adjuvant therapy. All analyses are performed both on all patients according to the Intention-To-Treat principle and excluding those patients who did not receive the axillary treatment randomly assigned. Statistical analysis: OS and DFS are calculated using the Kaplan-Meier Product Limit Estimator and differences between arms are assessed with the log-rank test. Results: The enrollment of patients ended in April 2020 with a total of 889 cases (443: standard arm; 446: experimental arm). In June 2020, we conducted an ad interim analysis on 889 patients. We found the two groups homogeneous for epidemiologic characteristics (age and menopausal status), tumor characteristics (tumor size, pTNM, immunohistochemistry, histology, grading, vascular and lymphatic invasion), adjuvant therapies and surgery on T. In particular we have performed a 23,1% of mastectomies in the standard arm and 20,1% in the experimental arm. We found a median of 2 sentinel lymph nodes removed in both arms and 1 non-sentinel positive lymph node in the experimental arm, and only 3 micro-metastases (1 in the standard arm and 2 in the experimental arm). Conclusion: In sum, with a median follow-up of 30 months, there have been no axillary recurrence in both arms. In the standard arm we found 8 total events (2 deaths and 6 distant relapses) and in in the experimental arm 6 events (1 death and 5 distant relapses), with a projected 5-years cumulative incidence of 6,5% in standard arm and 4,85% in the experimental arm. Citation Format: Corrado Tinterri, Emilia Marrazzo, Chiara Anghelone, Erika Barbieri, Andrea Sagona, Alberto Bottini, Arianna Rubino, Damiano Gentile, Wolfgang Gatzemeier, Valentina Errico, Alberto Testori, Giuseppe Canavese. Preservation of axillary lymph nodes compared to complete dissection in T1-T2 breast cancer patients presenting 1-2 metastatic sentinel lymph nodes : A multicenter randomized clinical trial. Sinodar One. [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 PD4-01.

Application of OSNA Nomogram in Patients With Macrometastatic Sentinel Lymph Node: A Retrospective Assessment of Accuracy

Introduction:Almost 50% to 70% of patients who undergo axillary lymph node dissection (ALND) because of a single metastatic sentinel lymph node (SLN) have no further metastatic nodes at the axillary histology. On these grounds, the one-step nucleic acid amplification (OSNA) nomogram was designed and validated. As a mathematical model, calculated through tumor size (expressed in millimeters) and CK19 mRNA copy number, it is thought to predict nonsentinel lymph node (NSLN) status. The aim of the study is to verify the diagnostic accuracy of the OSNA nomogram in a group of patients with macrometastatic SLN, with a retrospective analysis.Methods:The OSNA nomogram was retrospectively applied to a group of 66 patients with macrometastatic SLN who underwent ALND. The result of the final histology of the axillary cavity was compared to the nomogram prediction. We calculated the prevalence of NSLN metastasis in patients who underwent ALND, sensitivity and specificity, negative and positive predictive value of the nomogram.Results:In patients with macrometastasis in SLN, the prevalence of patients with metastatic NSLN was 45%. The sensitivity of the nomogram was excellent (90%). The specificity was low (36%). Positive predictive value amounted to 54%, while negative predictive value was good (81%).Conclusions:These results suggest that the OSNA nomogram is a valid instrument that can help choose the best surgical strategy for the treatment of axillary cavity. The mathematical model is useful to avoid surgery in a selected group of patients because it accurately predicts NSLN status.

Can risk groups accurately predict non-sentinel lymph node metastasis in sentinel lymph node-positive endometrial cancer patients? A Turkish Gynecologic Oncology Group Study (TRSGO-SLN-004).

The purpose of this study was to find out the risk factors associated with non-sentinel lymph node metastasis and determine the incidence of non-sentinel lymph node metastasis according to risk groups in sentinel lymph node (SLN)-positive endometrial cancer patients. Patients who underwent at least bilateral pelvic lymphadenectomy after SLN mapping were retrospectively analyzed. Patients were categorized into low, intermediate, high-intermediate, and high-risk groups defined by ESMO-ESGO-ESTRO. Out of 395 eligible patients, 42 patients had SLN metastasis and 16 (38.1%) of them also had non-SLN metastasis. Size of SLN metastasis was the only factor associated with non-SLN metastasis (p = .012) as 13/22 patients with macrometastasis, 2/10 with micrometastasis and 1/10 with isolated tumor cells (ITCs) had non-SLN metastasis. Althoughall 4 metastases (1.8%) among the low-risk group were limited to SLNs, the non-SLN involvement rate in the high-risk group was 42.9% and all of these were seen in patients with macrometastatic SLNs. Non-SLN metastasis was more frequent in higher-risk groups and the risk of non-SLN metastasis increased with the size of SLN metastasis. Proceeding to complete lymphadenectomy when SLN is metastatic should further be studied as the effect of leaving metastatic non-SLNs in-situ is not known.

Prediction of nodal staging in breast cancer patients with 1-2 sentinel nodes in the Z0011 era.

The aim of this study was to provide an innovative nomogram to predict the risk of >2 positive nodes in patients fulfilling the Z0011 criteria with 1-2 sentinel lymph nodes (SLNs) only retrieved.From 2007 to 2017, at the Breast Unit of ICS Maugeri Hospital 271 patients with 1-2 macrometastatic SLNs, fulfilling the Z0011 criteria, underwent axillary dissection and were retrospectively reviewed.A mean of 1.5 SLNs per patient were identified and retrieved. One hundred eighty-seven (69.0%) had 1-2 positive nodes, and 84 (31.0%) had >2 metastatic nodes. Independent predictors of axillary status were: positive SLNs/retrieved SLNs ratio (odds ratio [OR] 10.95, P = .001), extranodal extension (OR 5.51, P = .0002), and multifocal disease (OR 2.9, P = .003). A nomogram based on these variables was constructed (area under curve after bootstrap = 0.74).The proposed nomogram might select those patients fulfilling the Z0011 criteria, with 1-2 SLNs harvested, in whom a high axillary tumor burden is expected, aiding to guide adjuvant treatments.

Pre-operative surgical algorithm: sentinel lymph node biopsy as predictor of parametrial involvement in early-stage cervical cancer

IntroductionRadical hysterectomy is the gold standard in the management of early-stage cervical cancer. Parametrectomy aims to remove occult disease but is associated with significant surgical morbidity. Avoiding unnecessary parametrectomy in...

Associated Features with Non-Sentinel Lymph Node Involvement in Early Stage Breast Cancer Patients who Have Positive Macrometastatic Sentinel Lymph Node.

The main goal of this study is to determine the clinico-pathological factors that correlate non-sentinel lymph nodes (LNs) involvement in clinically node negative breast cancer (BC) patients with positive macrometastatic sentinel lymph node (SLN) in order to derive future evidence to define a subgroup where completion axillary lymph node dissection (cALND) might not be recommended. Total 289 SLN biopsies were performed in clinically node negative BC patients between March 2014 and April 2017. Seventy patients who performed cALND due to positive macrometastatic SLN were retrospectively selected and classified into two groups, according to non-SLN involvement (NSLNI). Clinico-pathological features of patients were examined computerized and documentary archives. Extracapsular extension (ECE) of SLN, number of harvested SLNs, metastatic rate of SLNs, absence of ductal carcinoma in situ (DCIS) and presence of multilocalization were significantly associated with the likelihood of non-SLN involvement after univariate analysis (p<0,05). Absence of DCIS and presence of multilocalization were found to be significant after multivariate analysis. Careful examination of clinico-pathological features can help to decide avoiding cALND if enough LNs are removed and the rate of SLN metastases is low, particularly in case DCIS accompanying invasive cancer in patients without multi localized tumour.

Diagnostic accuracy of sentinel lymph node biopsy in determining the axillary lymph node metastasis.

Sentinel lymph node biopsy (SLNB) is accepted as the standard procedure to determine the axillary lymph node metastasis in breast cancer at early stage. However, in many cases with sentinel lymph node positivity, the axilla does not contain any tumor cells. As a result, the accuracy of SLNB to predict axillary lymph node metastasis must be evaluated. Thousand hundred and fourteen women operated for breast cancer were retrospectively examined. Breast cancer patients without axillary metastasis on clinical examination who had undergone SLNB were included in the study. Sentinel lymph node positivity and axillary lymph node positivity were compared. Among 1114 women operated for breast cancer, 230 were clinically node negative preoperatively and undergone SLNB. Eighty-three (36%) of the patients were SLNB positive and undergone axillary dissection. Forty-three (51.8%) of them had tumor positive axillary lymph nodes and 40 (48.2%) of them had tumor negative axillary lymph nodes. In 48.2% of the patients, positive sentinel lymph node does not demonstrate a positive axilla. This finding supports sparing axillary dissection in patients with favorable prognostic factors even if the sentinel lymph node is found to be positive. Axillary lymph node dissection(ALND) may be spared even if there are macrometastatic sentinel lymph nodes in patients with favorable tumor types who will undergo breast-conserving surgery.

Sentinel lymph node biopsy in early stage endometrial cancer: a Turkish gynecologic oncology group study (TRSGO-SLN-001)

ObjectiveThe aim of this multicenter study was to evaluate the feasibility of sentinel lymph node (SLN) mapping in clinically uterine confined endometrial cancer.MethodsPatients who underwent primary surgery for endometrial cancer...

Abstract P3-03-30: Validity and safety of omission of axillary lymph node dissection among sentinel lymph node-positive breast cancer patients treated with mastectomy

Abstract Background:American College of Surgeons Oncology Group Z0011 trial showed that axillary lymph node dissection (ALND) had no impact on recurrence and survival in patients with positive sentinel lymph node (SLN) after breast-conserving surgery. However, it is still unknown if the omission of ALND can be applicable to patients treated with mastectomy. The aim of this study wasto evaluate whether ALND could be safely omitted for patients with SLN–positive breast cancer after mastectomy. Methods: From a prospective database of 296 patients with clinically node-negative breast cancer who underwent mastectomy and sentinel lymph node biopsy (SLNB) from March 2006 to December 2016, 81 patients who had positive SLNs were selected. Patient characteristics and prognosis were compared between SLN-positive patients with and without ALND. Patients treated with neoadjuvant chemotherapy were excluded from the analysis. Lymphatic mapping was performed using a combined method of blue dye and radioisotope. Results: The median age of entire patients was 57.0 (range: 32-85) years and the median tumor size was 2.5 (range: 0.6-7.9) cm. Of 81 patients, 23 (28.4%) patients omitted ALND. Patients with SLNB alone were more likely to have smaller SLN involvements (p&amp;lt;0.001): micrometastasis was identified in 13 (56.5%) patients in SLNB-alone group and 9 (15.5%) patients in ALND group. The number of positive SLN was comparable between SLNB-alone (median: 1.0, range: 1-6) and ALND groups (median: 1.0, range: 1-5) (p=0.063). There was no significant difference in characteristics including age, tumor size and tumor subtypes between the two groups. Post-mastectomy radiotherapy was performed in 5 (21.7%) patients with SLNB alone and 16 (27.6%) patients with ALND (p=0.588). The majority of patients with macrometastatic SLN received adjuvant chemotherapy in both groups (83.3% vs. 75.5%, p=0.562). Twenty (87.0%) and 51 (87.9%) patients received adjuvant endocrine therapy in SLNB-alone and ALND group, respectively (p=0.584). After a median follow-up of 54.7 months, no axillary recurrence was observed in both groups and 5-year disease-free survival was not significantly different between the two groups (75.0% vs. 88.8%, p=0.489). Lymphedema was observed significantly more often after ALND than after SLNB (22.4% vs. 4.3%, p=0.045). Conclusions: These data suggested that ALND could be safely omitted in SLN-positive breast cancer patients treated with mastectomy and appropriate systemic therapy. Citation Format: Matsumoto A, Umemoto Y, Jinno H. Validity and safety of omission of axillary lymph node dissection among sentinel lymph node-positive breast cancer patients treated with mastectomy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-30.

Factors Influencing Non-sentinel Node Metastasis in Patients with Macrometastatic Sentinel Lymph Node Involvement and Validation of Three Commonly Used Nomograms.

Omitting axillary lymph node dissection (ALND) in a subgroup of patients with sentinel lymph node (SLN) metastasis is becoming a widely accepted practice. Avoiding the well-known complications of ALND is the sole aim without compromising the curative intention of surgery. The data were probed for breast cancer patients that were operated on between February 2014 and June 2016. SLN biopsies were performed in 507 patients and out of 157 patients who underwent ALND for a metastatic SLN, 151 were found eligible for the analyses as having macrometastatic (>2mm) SLN. MD Anderson, Memorial Sloan Kettering Cancer Center and Helsinki nomograms were also tested in our patient population. Pathologic tumor size greater than 2 cm, the ratio of metastatic SLN to dissected SLN, metastatic tumor greater than 1 cm and tumors that extended outside the SLN's capsule were found to be associated with non-sentinel node metastasis in both univariate and multivariate tests. MD Anderson nomogram performed well with an area under the curve (AUC) value of 0.72. Our results suggest that ALND should be considered in patients with macrometastatic SLN greater than 10 mm in size, have extracapsular extension, have metastatic SLNs at a rate of more than 50% and whose primary tumor is greater than 2 cm.

Management of the Axilla in T1-2 Breast Cancer Patients with Macrometastatic Sentinel Node Involvement Who Underwent Breast-Conserving Therapy

ABSTRACTPurpose: The aims of our study were to determine the incidence of axillary recurrence and arm morbidity in T1-2 invasive breast cancer patients with macrometastases on the sentinel lymph node (SLN) who underwent breast-conserving therapy (BCT), with or without axillary lymph node dissection (ALND). Methods: One hundred and nine T1-2 invasive breast cancer patients with macrometastases on the SLN who underwent BCT in our institution were included in the study. Patients with 1–2 positive SLN and without extra nodal extension (ENE) on the SLN did not undergo ALND (SLN-only group) and patients with ENE or patients who had >2 metastatic nodes underwent level I, II ALND (ALND group). The SLN-only group received radiotherapy to three axillary levels, the supraclavicular fossa, and ± mammaria interna. ALND group received radiotherapy to axillary level III, the supraclavicular fossa, and ± mammaria interna. The incidence of axillary recurrence and arm morbidity were investigated. Results: Of the 109 patients, 18 patients with >2 metastatic SLNs and 10 with ENE on the SLN underwent ALND and 81 patients underwent SLN only. Median follow-up time was 37 months (3–77). There was no axillary recurrence in SLN-only group. However, in the ALND group 1 patient had developed axillary metastasis. There were 2 objective lymphoedema and 3 arm-shoulder restriction cases in the SLN-only group, and 2 and 3 in the ALND group, respectively. Conclusions: Axillary dissection could safely be omitted in patients with 1–2 macrometastatic SLN and without ENE who undergo BCT and axillary radiotherapy.

Intraoperative prediction of the two axillary lymph node macrometastases threshold in patients with breast cancer using a one-step nucleic acid cytokeratin-19 amplification assay.

The aim of the present study was to assess the sensitivity, specificity and practicality of using a one-step nucleic acid amplification (OSNA) assay during breast cancer staging surgery to predict and discriminate between at least 2 involved nodes and more than 2 involved nodes and facilitate the decision to provide axillary conservation in the presence of a low total axillary node tumour burden. A total of 700 consecutive patients, not treated with neo-adjuvant chemotherapy, received intraoperative sentinel lymph node (SLN) analysis using OSNA for cT1-T3 cN0 invasive breast cancer. Patients with at least one macrometastasis on whole-node SLN analysis underwent axillary lymph node dissection (ALND). The total tumour load (TTL) of the macrometastatic SLN sample was compared with the non-sentinel lymph node (NSLN) status of the ALND specimen using routine histological assessment. In total, 122/683 patients (17.9%) were found to have an OSNA TTL indicative of macrometastasis. In addition, 45/122 (37%) patients had NSLN metastases on ALND with a total positive lymph node burden exceeding the American College of Surgeons Oncology Group Z0011 trial threshold of two macrometastatic nodes. The TTL negative predictive value was 0.975 [95% confidence interval (CI), 0.962–0.988]. The area under the curve for the receiver operating characteristic curve was 0.86 (95% CI, 0.81–0.91), indicating that SLN TTL was associated with the prediction (and partitioning) of total axillary disease burden. OSNA identifies a TTL threshold value where, in the presence of involved SLNs, ALND may be avoided. This technique offers objective confidence in adopting conservative management of the axilla in patients with SLN macrometastases.