Accuracy Of Sentinel Lymph Node Biopsy Research Articles

Can a machine-learning model improve the prediction of nodal stage after a positive sentinel lymph node biopsy in breast cancer?

Background: The current standard for evaluating axillary nodal burden in clinically node negative breast cancer is sentinel lymph node biopsy (SLNB). However, the accuracy of SLNB to detect nodal stage N2-3 remains debatable. Nomograms can help the decision-making process between axillary treatment options. The aim of this study was to create a new model to predict the nodal stage N2-3 after a positive SLNB using machine learning methods that are rarely seen in nomogram development.Material and methods: Primary breast cancer patients who underwent SLNB and axillary lymph node dissection (ALND) between 2012 and 2017 formed cohorts for nomogram development (training cohort, N = 460) and for nomogram validation (validation cohort, N = 70). A machine learning method known as the gradient boosted trees model (XGBoost) was used to determine the variables associated with nodal stage N2-3 and to create a predictive model. Multivariate logistic regression analysis was used for comparison.Results: The best combination of variables associated with nodal stage N2-3 in XGBoost modeling included tumor size, histological type, multifocality, lymphovascular invasion, percentage of ER positive cells, number of positive sentinel lymph nodes (SLN) and number of positive SLNs multiplied by tumor size. Indicating discrimination, AUC values for the training cohort and the validation cohort were 0.80 (95%CI 0.71–0.89) and 0.80 (95%CI 0.65–0.92) in the XGBoost model and 0.85 (95%CI 0.77–0.93) and 0.75 (95%CI 0.58–0.89) in the logistic regression model, respectively.Conclusions: This machine learning model was able to maintain its discrimination in the validation cohort better than the logistic regression model. This indicates advantages in employing modern artificial intelligence techniques into nomogram development. The nomogram could be used to help identify nodal stage N2-3 in early breast cancer and to select appropriate treatments for patients.

Effect of delay between nuclear medicine scanning and sentinel node biopsy on outcome in patients with cutaneous melanoma.

Sentinel lymph node biopsy (SLNB) is an important staging tool for the management of melanoma. A multicentre study was done to validate previous findings that the timing of lymphoscintigraphy influences the accuracy of SLNB and patient outcomes, particularly survival. Data were reviewed on patients undergoing SLNB for melanoma at three centres in the UK and Sweden, examining the effect of timing of SLNB after nuclear medicine scanning. Kaplan-Meier survival analysis was used to assess overall (OS), disease-specific (DSS) and progression-free (PFS) survival, stratified by timing of lymphoscintigraphy. Independent risk factors for survival were identified by Cox multivariable regression analysis. A total of 2270 patients were identified. Median follow-up was 56 months. Univariable analysis showed a 4·2 per cent absolute and 35·5 per cent relative benefit in DSS (hazard ratio 1·36, 95 per cent c.i. 1·05 to 1·74; P = 0·018) for 863 patients whose SLNB was performed up to 12 h after lymphoscintigraphy compared with 1407 patients who had surgery after more than 12 h. There were similar OS and PFS benefits (P = 0·036 and P = 0·022 respectively). Multivariable analysis identified timing of lymphoscintigraphy as an independent predictor of OS (P = 0·017) and DSS (P = 0·030). There was an excess of nodal recurrences as first site of recurrence in the group with delayed surgery (4·5 versus 2·5 per cent; P = 0·008). Delaying SLNB beyond 12 h after lymphoscintigraphy with 99 Tc-labelled nanocolloid has a significant negative survival impact in patients with melanoma.

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.

Does The Tumor Location Affect The Accuracy of Sentinel Lymph Node Biopsy In Breast Cancer? A Single Institute Experience

Background: Sentinel lymph node biopsy (SLNB) can give an idea about the nodal status with high accuracy. Objective: To assess the effect of breast cancer location on SLNB accuracy regarding identification rate (IR), accuracy rate and false negativity rate (FNR). Methods: Breast cancer patients with positive axilla who were scheduled for axillary lymph node dissection (ALND) were included. They were randomly allocated into two groups: Group I (G I) included patients with laterally located breast cancer while Group II (G II) included patients with medially located breast cancer. Four ml of Methylene blue (1%) was injected in the peritumoral tissue. SLNB was taken for histopathological examination while ALND was completed in all cases. SLN IR, FNR and accuracy rate were assessed in both groups. Results: This study included 104 female patients; 63 (60.6%) in GI whereas 41(39.4%) in GII. SLN identification was done successfully in 92% in G I and 87.8% in G II with no significant difference. In G I; Out of the 58 patients in whom SLN was identified; SLN was positive in 54 (93.1%) cases and negative in 4(6.9%) cases while in G II; SLN was positive in 31 out of 36 (86.1%) cases and negative in 5 (13.9%) cases with no significant difference regarding SLN accuracy or FNR. Conclusion: The tumor location doesn’t affect axillary SLNB regarding identification rate, accuracy rate and false negativity rate. Methylene blue alone is still efficacious in SLNB lymphatic mapping especially in developing countries because of its low cost.

SENTINEL LYMPH NODE BIOPSY AS GUIDANCE FOR CENTRAL NECK DISSECTION IN PATIENTS WITH PAPILLARY THYROID CARCINOMA

Background: Occult lymph node metastasis of papillary thyroid carcinoma (PTC) can be detected by sentinel lymph node (SLN) biopsy. Aim of the work: Our objective in this study was to evaluate the accuracy of using sentinel lymph node biopsy as a marker to identify occult metastases early. Patients and methods: The present study was a prospectivestudy that was conducted in Ain Shams University Hospitals in Egypt, and included sixty (60) patients who had papillary thyroid carcinoma. The patients underwent sentinel lymph node biopsy with total thyroidectomy during the period between 1st of December 2016 and 1st of December 2018. Results: The study included 60 patients with papillary thyroidcarcinoma, 16 males and 44 females. Size of nodules ranged from 0.5- 4 cm and more nodules were confined to the left lobe (63.3%). SLNs were identified in 44 of 60 malignant cases (73.3%). 38 of identified SLN were positive for metastasis and 22 were negative while non SLN were positive in 31/60 and negative for 29/60. Thus, the sensitivity, specificity, negative predictive values, positive predictive values and accuracy of SLN biopsy were 86.7%, 100%, 72,7%, 100% and 73.3%, respectively. Post-operative complications included temporary symptomatic hypocalcaemia in 3 patients and temporary recurrent laryngeal nerve injury in 2 patients then recovered. Conclusion: SLN biopsy for patients with papillary thyroid carcinoma and negative LNs clinically and radiologically is an accurate and noninvasive means to identify subclinical lymph node metastasis.

Sentinel lymph node biopsy in clinically node-negative Merkel cell carcinoma: the Westmead Hospital experience.

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with a propensity to metastasize to regional lymph nodes. Sentinel lymph node biopsy (SLNB) in patients with clinically node-negative MCC has been utilized to identify patients with subclinical nodal metastases. This study aims to review the accuracy of SLNB in MCC and to evaluate the impact of SLNB on management. Patients with clinically node-negative MCC who underwent SLNB were identified from a prospective database of patients treated at the Westmead Hospital, Sydney, between 1998 and 2017. Data from these patients were reviewed and analysed. Forty-one patients were identified: 28 men and 13 women, median age 70 years. Median duration of follow-up was 27 months. Sixteen (39%) patients had a positive SLNB and all underwent nodal treatment which consisted of radiotherapy (n = 13), completion lymphadenectomy and adjuvant radiotherapy (n = 2), and completion lymphadenectomy alone (n = 1). Following negative SLNB, 24 of 25 patients did not undergo further nodal treatment. The false-negative rate was 16% as three patients developed in-field nodal recurrence subsequent to a negative SLNB. At last follow-up, 29 patients had no evidence of disease, six were alive with disease and three had died from other causes. Three SLN-positive patients have died of MCC. SLNB has a high rate of positivity and can improve the accuracy of staging and prognostication in MCC, and guide management. The relatively low risk of a false-negative SLNB justifies close observation in SLNB-negative patients.

Lymph node harvest in breast cancer patients with and without preoperative scintigraphy

Background: Sentinel lymph node biopsy (SLNB) is the standard of care for women with node negative breast cancer. Tc99 nanocolloid is a popular tracer, facilitating preoperative lymphoscintigraphy to identify sentinel nodes. This study compares the number of sentinel lymph nodes identified at the time of surgery in women who had lymphoscintigraphy with those who did not.Method: All women with primary breast cancer undergoing a SLNB from 2003-2017 who were node negative and did not have neoadjuvant chemotherapy were retrospectively reviewed in this study.Results: 576 women who had Tc99 preoperative injection were included in the study. Three hundred patients (Group 1) underwent lymphoscintigraphy preoperatively and 276 (Group 2) had no lymphoscintigraphy. The mean age at diagnosis for Groups 1 and 2 were 56 and 58 years. respectively. Both groups were also found to be similar in terms of histological subtype, tumour location, size, and HER2- and Estrogen receptor (ER) status. The surgery for the breast primal) was similar in groups 1 and 2. While both groups had a median number of 2 nodes identified, the mean number of nodes identified for Group 2 (2.12) was 10% higher than for Group 1 (1.92) (p = 0.0026).Conclusion: This is the largest series to show that a preoperative lymphoscintigram (scan) can safely be omitted when performing a SLNB. As newer tracers are being used (e.g. Iron Oxide). it is important to know that accuracy of SLNB is not compromised by omission of a scan.

Is the frozen section examination for sentinel lymph node necessary in early breast cancer patients?

PurposeSentinel lymph node (SLN) biopsy (SLNB) is widely performed for axillary staging in patients with breast cancer. Based on the results of frozen section examination (FSE), surgeons can decide to continue further axillary dissections. This study aimed to verify the accuracy of FSE for SLNs.MethodsWe reviewed the records of 4,219 patients who underwent SLNB for primary invasive breast cancer between 2007 and 2016 at the Severance Hospital. We evaluated factors associated with the false-negative results of FSE for SLNs using the Generalized Estimating Equations model.ResultsA total of 1,397 SLNs from 908 patients were confirmed to be metastatic. Seventy-one patients (1.7%) had confirmed pathologic N2 or N3 stage. Among metastatic SLNs, micrometastasis was found in 234 (16.8%). The overall accuracy of SLNB was 98.5%. The sensitivity and false-negative rate of FSE were 86.4% and 13.6%, respectively. Several clinicopathological factors, including the size of SLN metastases, suspicious preoperative axillary lymph nodes, and luminal B subtype, were associated with a higher rate of false-negative results.ConclusionMost patients were not indicated for axillary lymph node dissection. Some patients may show transition in their permanent pathology due to the size of the metastatic node. However, the false-negative results of FSE for SLNs based on the size of the metastatic node did not change our practice. Therefore, intraoperative FSE for SLN should not be routinely performed for all breast cancer patients.

Sentinel Lymph Node Biopsy After Initial Lumpectomy (SNAIL Study)-a Prospective Validation Study.

Tertiary oncology center clinicians are commonly faced with the problem of managing patients with a diagnosis of breast cancer made after lumpectomy in the Primary Health Care (PHC) setting. There are no studies or guidelines that address the further surgical management in this group of patients regarding sentinel lymph node biopsy (SLNB) and need for breast post-operative cavity excision. Prospective observational study was planned to evaluate the feasibility of SLNB and defining the need for definitive breast surgery in patients diagnosed with breast cancer after lumpectomy in PHC. The study was carried out from January 2015 to August 2017 in Tata Medical Center, India, approved by institutional review board (EC/TMC/36/14). Seventy patients who underwent lumpectomy with a definitive histological analysis of breast cancer were included in this study. Each patient had definitive breast surgery and SLNB using subareoral blue dye injection followed by validation axillary dissection. The identification rate (IR) for SLNB was 92% (64/70). The median number of SLNs removed was 2 (IQR 1, 3). There were 2 patients with false negative results resulting in false negative rate (FNR) of 11%. Overall, SLNB procedure has the sensitivity of 89%, NPV of 96%, and accuracy was 97%. Peri-areoral incision of initial surgery was associated with low IR (84%) and high FNR (33%). Final histopathology showed residual invasive cancer in 43% and ductal carcinoma in situ in 14% of patients. Among 21 patients where initial lumpectomy histopathology margin was free of cancer, residual malignancy was found in 57% of patients. Prior excision of lumps for breast cancer does not affect the accuracy of SLNB. Peri-areoral scar may be associated with high FNR and low IR, although further studies are needed to validate this statement. Definitive breast surgery is required for all patients, irrespective of initial lumpectomy histopathological margin status.

High sensitivity and negative predictive value of sentinel lymph node biopsy in a retrospective early stage oral cavity cancer cohort in the Northern Netherlands.

In cT1-2N0, oral squamous cell carcinoma (OSCC) occult metastases are detected in 23%-37% of cases. Sentinel lymph node biopsy (SLNB) was introduced in head and neck cancer as a minimally invasive alternative for an elective neck dissection in neck staging. Meta-analyses of SLNB accuracy show heterogeneity in the existing studies for reference standards, imaging techniques and pathological examination. The aim of this study was to assess the sensitivity and negative predictive value (NPV) of the SLNB in detecting occult metastases in cT1-2N0 OSCC in a well-defined cohort. Retrospective study. The SLNB procedure consisted of lymphoscintigraphy, SPECT/CT-scanning and gamma probe detection. Routine follow-up was the reference standard for the SLNB negative neck. Histopathological examination of sentinel lymph nodes (SLN) consisted of step serial sectioning, haematoxylin-eosin and cytokeratin AE1/3 staining. Two comprehensive oncology centres. A total of 91 consecutive patients with primary cT1-2N0 OSCC treated by primary resection and neck staging by SLNB procedure between 2008 and 2016. Sensitivity and negative predictive value. In all cases, SLNs were harvested. A total of 25 (27%) patients had tumour-positive SLNs. The median follow-up was 32months (range 2-104). Four patients were diagnosed with an isolated regional recurrence in the SLNB negative neck side resulting in an 85% sensitivity and a 94% NPV. In our cohort, the SLNB detected occult metastases in early OSCC with 85% sensitivity and 94% NPV. This supports that SLNB is a reliable procedure for surgical staging of the neck in case of oral cT1-2N0 SCC.

Management of the axilla in metaplastic breast carcinoma.

Metaplastic breast cancer (MBC), characterized by admixed epithelial, squamous or mesenchymal elements, constitutes <1% of breast cancers and has a poor prognosis but a paradoxically low reported rate of axillary lymph node (LN) involvement. Due to its rarity, data on appropriate axillary management is lacking, prompting this investigation of LN status and outcomes. We identified 41 MBC patients treated at our institution 2001-2011 who were followed for a median of 66 months. Statistical analyses evaluated axillary ultrasound (AUS), fine needle aspiration (FNA), and sentinel LN biopsy (SLNB) in association with LN status. Median tumor size was 2.7 cm and 76% were triple-negative. Twenty-three patients (56%) had preoperative AUS: 9 (39%) showed ≥1 suspicious LN, 6 proceeded to LN FNA and 3 were confirmed positive. Six patients had neoadjuvant chemotherapy, including 2 FNA LN+. Ten patients were LN+ at operation. Among 19 patients undergoing AUS and axillary surgery, AUS ± FNA sensitivity was 100% and specificity was 94%. LN positivity correlated with increasing tumor size, grade and angiolymphatic invasion. 16 patients recurred, 63% with distant disease (10/16) and one with isolated axillary disease after a negative SLNB not preceded by AUS. Overall SLNB accuracy was 96% (23/24), but absent preoperative AUS, 1/7 (14%) of SLNBs were falsely negative. Our study is the first to specifically address the performance and utility of AUS/FNA and SLNB for MBC patients. AUS/FNA at diagnosis followed by SLN surgery provided accurate nodal staging and critical prognostic information to inform treatment recommendations. We recommend this approach for axillary management of MBC patients.

Abstract P3-01-01: Management of the axilla in metaplastic breast carcinoma

Abstract Background Metaplastic breast cancer (MBC), characterized by a mixture of epithelial, squamous or mesenchymal elements and a usually triple-negative (TN) phenotype, accounts for &amp;lt;1% of breast cancer diagnoses. MBC has a poor prognosis with frequent distant spread, but, paradoxically, a lower than expected rate of nodal positivity (6 to 40%). Due to its rarity there is little data on how best to evaluate and manage the axilla in women with these tumors. Thus we undertook this study to evaluate axillary management and oncologic outcomes. Methods With IRB approval, we identified adult patients diagnosed with MBC at our institution from 2001 to 2011 from our prospective surgical pathology database. Patient, pathology, imaging, treatment and outcome data were obtained from electronic medical record, tumor registry, pathology slide and imaging review. Median follow-up for surviving patients was 66 months. Statistical analyses were performed using JMP 10.0 software. Results We identified 41 MBC patients, median age 60 years (range 33-89 years), with a median tumor size of 2.7 cm; 33 (80%) were TN. 23 patients (56%) had a preoperative axillary ultrasound (AUS): 9 (39%) showed at least one suspicious axillary lymph node (LN) of whom 6 had a preoperative fine needle LN biopsy (FNA) of which 3 were positive for metastasis. 6 patients, including the 3 LN+ on FNA, had neoadjuvant chemotherapy (NAC). Operation included axillary dissection (ALND) in 14, sentinel LN biopsy (SLNB) in 23, and SLNB followed by ALND in 1, while 3 patients had no axillary surgery. 10 patients were LN+ at operation. Among 22 patients who had both an AUS and axillary surgery, AUS had a sensitivity of 100% and specificity of 78%. Patient and tumor variables in association with pathologic LN status are summarized in the table. LN positivity correlated with increasing tumor size, T stage, grade and angiolymphatic invasion. 16 patients recurred, most with distant disease (10/16, 63%), although there was a solitary axillary recurrence 8 months after a negative SLNB in one patient who did not have a preoperative AUS. Thus the accuracy of SLNB was 96% (23/24) overall, but among those without preoperative AUS, 1/7 (14%) SLNBs were falsely negative. 5-year disease-free and breast cancer-specific survival estimates were 49% and 63%. LN- N=28 (74%)LN+ N=10 (26%)p-valueSize, median (IQR), cm2.7 (1.6-4.6)6.6 (2.5-16.5)0.001T stage 0.03T19 (100%)0 (0%) T214 (78%)4 (22%) T33 (60%)2 (40%) T42 (33%)4 (67%) Grade 0.04Low6 (16%)0 (0%) Intermediate/High22 (58%)10 (26%) Estrogen Receptor 0.61Positive (&amp;gt;1%)5 (71%)2 (29%) Negative (&amp;lt;1%)23 (74%)8 (26%) Angiolymphatic Invasion 0.002No26 (87%)4 (13%) Yes2 (25%)6 (75%) Dominant Histology 0.65Adenosquamous2 (100%)0 (0%) Matrix producing4 (80%)1 (20%) Spindle cell14 (74%)5 (26%) Squamous*8 (67%)4 (33%) *any squamous component Conclusion Our study is the first to specifically address AUS and SLNB for patients with metaplastic breast cancer. AUS had 100% sensitivity and 78% specificity, while one patient without a preoperative AUS had a falsely negative SLNB. Further, AUS with FNA of suspicious LNs was useful for staging at the time of diagnosis and informing treatment. We recommend this approach for patients with MBC. Citation Format: Murphy BL, Fazzio RT, Hoskin TL, Glazebrook KN, Keeney MG, Habermann EB, Hieken TJ. Management of the axilla in metaplastic breast carcinoma [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-01-01.

Abstract ES7-1: Challenges in the management of locoregional recurrence

Abstract The increasing trend toward tailoring treatment of the primary breast cancer with limited surgery of both the breast and axilla has increased the challenge of managing locoregional recurrence (LRR). In the era when patients uniformly had axillary dissection, the appropriateness of repeat sentinel node biopsy was not a question. Similarly, the dogma that all ipsilateral breast tumor recurrences must be treated with mastectomy if the breast has been previously irradiated is also being challenged. LRR events are infrequent with modern multi-modality therapy, and there are no randomized trials to address these questions. Re-operative sentinel node (SN) biopsy after breast conserving surgery therapy (BCT) has been shown to be feasible, with the likelihood of identifying additional SNs related to the number of nodes excised at the time of initial SN biopsy. The accuracy of SN biopsy after mastectomy is less clear. However, the impact of identification of nodal disease on management of LRR is controversial. In a study of 12 patients with isolated chest wall recurrence post mastectomy, 10/12 had successful mapping and 7/10 had an axillary SN. The absence of nodal metastases was an indication to avoid supraclavicular RT (Johnson J. Ann Surg Oncol 2016;23:715). In a study of 83 patients with in breast (n=79) or chest wall recurrence who were clinically node negative, 47 had axillary surgery and 36 did not. At a median of 4.2 years after LR, rates of axillary and non-axillary local recurrence, distant metastases, and death did not differ significantly between groups (Ugras S. Ann Surg Oncol 2016). With the findings of the CALOR trial that systemic chemotherapy is beneficial in the management of LRR, the finding of axillary metastases is less likely to influence systemic therapy than in the past and repeat axillary staging could potentially be avoided. In the untreated breast, drainage to the contralateral axilla is very rare and contralateral axillary metastases classify a patient as Stage IV. After initial axillary dissection, between 4% and 33% of patients with local recurrence will have contralateral axillary drainage. In a systemic review of 48 cases of contralateral nodal recurrence without other distant metastatic disease, at a mean follow-up of 50.3 months disease free survival was 65% and overall survival 83% after treatment that included both local and systemic therapy (Moossdorff M. Eur J Surg Oncol 2015;41:1128). These findings raise the possibility that in the setting of LR, contralateral axillary metastases should be treated aggressively for cure after excluding distant metastases. Citation Format: Morrow M. Challenges in the management of locoregional recurrence [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES7-1.

Abstract P3-01-05: A feasibility study of sentinel lymph node detection and analysis of safety to omit axillary lymph node dissection in clinically node-negative breast cancer patients after neoadjuvant chemotherapy

Abstract Background: Concerns still remain about lower sentinel node (SN) detection and higher false-negative rates (FNR) in breast cancer patients treated with neoadjuvant chemotherapy (NAC), especially those who are clinically node-positive before NAC. It is necessary to analyze the validity of sentinel node biopsy (SNB) after NAC and evaluate whether the SN identification rate and FNR for clinically N0 (cN0) patients after NAC would be acceptable or not in order to omit axillary lymph node dissection (ALND). Objectives and methods: We identified SN by radioisotopic methods followed by completion of ALND in cN0 patients after NAC from 2013 to 2016 as part of a clinical research study (SNB group, N=68) to analyze the accuracy of SNB, and retrospectively investigated the prognosis of patients treated with NAC from 2006 to 2012 (control group, N=92) to evaluate whether the validity of SNB would be acceptable or not. Results: Mean patient ages in the SNB group and control group were 51.0 years and 49.5 years, respectively (p=0.17), and the distribution of intrinsic subtypes was not significantly different between the two groups. The numbers of cN1≤ before NAC in the SNB group and control group were 85.5% (57/68) and 80.4% (74/92), respectively (p=0.58), and the pathological complete response rates were 25.0% (17/68) and 19.6% (18/92), respectively (p=0.41). Lymphoscintigraphy using 99mTc-phytate acid was performed in the SNB group, and hot spots were detected at the ipsilateral axilla in 62 of 68 (91.2%) patients, in all of whom SNs could be identified by using a gamma-probe. The FNR, which indicates no metastasis in SNs and metastasis in non-SN, was 5.9% (4/68). Among these four patients, three were of the luminal type while one was triple negative. The number of patients without metastasis in both SN and non-SN, which are candidates for omission of ALND, was 26 of 68 (38.2%). They included eight of nine HER2-enriched patients and six of 13 luminal-HER2 patients. Conversely, there were no false-negative cases in these subtypes. Moreover, all SNs were identified even if there were metastases in SNs. Regarding the prognosis of the control group, the 10-year disease free survival of post-NAC N0 (ypN0) (52/92, 56.5%) and ypN1≤ (40/92, 43.5%) were 80.7% and 61.2%, respectively (p=0.08); in addition, the 10-year overall survival of yN0 and ypN1≤ were 90.4% and 72.6% (p=0.26). Thus, the prognosis of ypN1≤ was not significantly inferior to that of ypN0. If omission of ALND were performed for false negative cases, then the risk of axillary relapse would be a concern. However, these data indicate the possibility that 5.9% of FNR as shown in the SNB group would not have much influence on prognosis. Conclusion: The accuracy of SN detection by radioisotopic methods for cN0 breast cancer after NAC was not maintained like that for -early breast cancer although it was better than the results of previous studies. However, there were no false-negative cases in HER2-enriched and luminal-HER2 subtypes, which could be potential candidates for omission of ALND. In addition, omission of ALND for false-negative patients would have less influence on the prognosis. Citation Format: Maeno K, Yamamoto K, Ono M, Oba T, Iesato A, Ono K, Ito T, Kanai T, Ito K-I. A feasibility study of sentinel lymph node detection and analysis of safety to omit axillary lymph node dissection in clinically node-negative breast cancer patients after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-01-05.

Prospective Randomized Trial of Use of In-House Prepared Low-Cost Radiopharmaceutical Versus Commercial Radiopharmaceutical for Sentinel Lymph Node Biopsy in Patients with Early Stage Invasive Breast Cancer.

The current standard-of-care for surgical staging of the axilla in clinically node-negative (N0) early breast cancers is sentinel lymph node biopsy (SLNB), which requires expensive radiopharmaceuticals for efficacious results. In-house produced low-cost radiopharmaceuticals may be the solution and have shown efficacy in earlier observational/pilot studies. Wecompared SLNB using in-house prepared radiopharmaceutical (99mTc-Antimony-colloid) versus commercially marketed radiopharmaceutical (99mTc-Sulphur-colloid)in this prospective randomized study. 78 clinically N0 early breast cancer patients (T1/2, N0 stages), undergoing primary surgery were prospectively randomized 1:1 into two groups; to receive SLNB using methylene blue, and either 99mTc-Antimony colloid(Group-1) or 99mTc-Sulphur colloid(Group-2). Completion axillary dissection was done in all (validation SLNB). SLNB indices were compared between the groups. The groups were comparable with regard to age, stage, tumour size, hormone receptors and HER2neu status. Cost of thein-house prepared 99mTc-antimony colloid was 16-times lesser compared to 99mTc-sulphur colloid. SLN identification rates (IR) in Groups 1 and 2 were 100 and 97.4% respectively, (p>0.05). False negative rates (FNR) in Group 1 and 2 were 6.3% (1/16 patients) and 7.7% (1/13 patients), respectively, (p>0.05). There were no major allergic reactions in either group. In this prospective randomized trial on early breast cancer patients, accuracy of SLNB was comparable using in-house prepared, 99mTc-antimony colloid and commercially marketed 99mTc-sulphur colloid as radiopharmaceutical, while 99mTc-antimony colloid was much cheaper than 99mTc-sulphur colloid.

Sentinel node biopsy in early breast cancer: lessons learned from more than 1000 cases at a single institution.

The aims of this paper are to report the development of sentinel node biopsy (SNB) in breast cancer at a single institution and to discuss the relevant issues on SNB still to be elucidated. From 1998 to 2010, 1021 SNBs with frozen section examination were carried out in patients with breast cancer. In the early period (1998-2002) SNB was always combined with axillary lymph node dissection (ALND). From 2002 onwards, only patients with a positive SNB result underwent ALND (late period). The characteristics of patients with infiltrating carcinoma (IC) and ductal carcinoma in situ (DCIS) and the histological status of the sentinel nodes were examined. The survival outcomes of node-negative patients were compared between patients submitted to SNB and ALND (ALND group) during the early period and patients who underwent only SNB during the late period (SNB group). The sentinel node was identified intraoperatively in 98.3% of cases. During the early period the overall accuracy of SNB was 97.0%. During the late period, 700 patients with IC and 140 with DCIS underwent SNB. In the IC group, 149 patients (21.3%) had sentinel node macrometastases and 36 (5.1%) micrometastases; of that subgroup, 21 underwent ALND and no other metastatic lymph nodes were found, and 15 underwent SNB only. Axillary recurrences were observed in 4 patients (0.77%) with negative SNB; none of these were among the patients with micrometastatic SNB. Two patients (1.4%) with DCIS had a positive SNB. In node-negative patients the 5-year overall survival was 96.7% in the ALND group and 96.5% in the SNB group (P = 0.63). The 5-year disease-free survival was 93.8% and 93.2% in the ALND and SNB groups, respectively (P = 0.77). Overall and disease-free survival in patients with a negative SNB result and no further axillary surgery were equal to those in patients with negative ALND. Intraoperative assessment of the sentinel node in expert hands has a low false-negative rate and allows immediate ALND in patients with sentinel node metastases, avoiding the need for a second operation. ALND for sentinel node micrometastases may be safely omitted in most patients with early stage breast cancer.

Intraoperative Ultrasound-Guided Excision of Axillary Clip in Patients with Node-Positive Breast Cancer Treated with Neoadjuvant Therapy (ILINA Trial) : A New Tool to Guide the Excision of the Clipped Node After Neoadjuvant Treatment.

The accuracy of sentinel lymph node biopsy (SLNB) after neoadjuvant therapy (NAT) has been improved with the placement of a clip in the positive node prior to treatment. Several methods have been described for clipped node excision during SLNB after NAT. We assessed the feasibility of intraoperative ultrasound (IOUS)-guided excision of the clipped node during SLNB and investigated whether the accuracy of SLNB is improved. After approval by the Institutional Ethics Committee, all breast cancer patients undergoing NAT had an US-visible clip placed in the positive node. The ILINA trial consisted of IOUS-guided excision of the clipped node along with SLNB and axillary lymph node dissection (ALND). Forty-six patients had a clip placed in the positive node. In two (4.3%) cases, the clip could not be seen prior to surgery and the patient underwent ALND; however, the clipped node was successfully removed by IOUS-guided excision in 44 patients. Thirty-five patients (79.5%) underwent SLNB along with IOUS-guided excision of the clipped node and ALND, and were subsequently included in the ILINA trial. Nine patients were not included (five patients with SLNB only and four patients with ALND without SLNB). SLNB matched the clipped node in 27 (77%) patients. The false negative rate for the ILINA protocol was 4.1% (95% confidence interval 0.1-21.1%). IOUS-guided excision of the axillary clipped node after NAT was feasible, safe, and successful in 100% of cases. The ILINA trial is accurate in predicting axillary nodal status after NAT.

Sentinel lymph node biopsy using indocyanine green fluorescence navigation method after neoadjuvant chemotherapy for patients with clinically node-positive breast cancer.

e12108 Background: Sentinel lymph node biopsy (SNB) for initially clinically node-positive (cN1) after neoadjuvant chemotherapy (NAC) is controversial. Even if approximately 40% of node positive disease converts to node negative after NAC, SNB using blue dye (BD) and/or radioisotope (RI) agent showed the high false-negative rate (FNR) (SENTINA, ACOSOG Z1071). These trials showed the accuracy of SNB was closely related to the number of sentinel lymph nodes (SNs) removed. We presented the efficacy of indocyanine green (ICG) fluorescence navigation method for SNB in clinically node-negative (cN0) patients (ASCO2008). The ICG method can provide higher numbers of SNs and it helps to identify lymph nodes with the remained metastases. Methods: Of 1900 patients (Jan. 2010 - Dec. 2016), 242 women with cN0 or cN1 received NAC: Group 0 (cN0 before NAC, n=150), Group 1 (cN1 converted ycN0 after NAC, n=71) , Group 2 (cN1 remained ycN1 after NAC, n=21). Node status was evaluated by ultrasound. All patients underwent SNB using both ICG- and BD-method together. Fluorescence images were obtained by a CCD camera with a cut filter as a detector, light emitting diodes at 760nm as the light source. ALND was performed in Group1 and Group 2. Results: Pathological complete nodal response rate (pcNRR) was 48.4%. Table shows the number of SNs removed by ICG or BD. SNs detection rates (ICG, BD): Group 0 (98.7%, 84.7%), Group 1 (98.6%, 83.1%), Group 2 (85.7%, 47.6%). Resulting of a FNR (ICG, BD): Group 1 (5.7%, 15.3%), Group 2 (22.2%, 60.0%). Conclusions: The pcNRR and a FNR of BD in Group 1 were similar to those of SENTINA or ACOSOGZ 1071 trials. In patients who converted from cN1 to ycN0, the fluorescent ICG method showed a high detection rate of SNs and a low FNR. [Table: see text]

Swedish prospective multicenter trial evaluating sentinel lymph node biopsy after neoadjuvant systemic therapy in clinically node-positive breast cancer

PurposePatients with clinically node-positive breast cancer planned for neoadjuvant systemic therapy (NAST) may draw advantages from the nodal downstaging effect and reduce the extent of axillary surgery with sentinel lymph node biopsy (SLNB) performed after NAST. Since there are concerns about lower sentinel lymph node (SLN) detection and higher false-negative rates (FNR) in this setting, our aim was to define the accuracy of SLNB after NAST.MethodsThis Swedish national multicenter trial prospectively recruited 195 breast cancer patients from ten hospitals with T1–T4d biopsy-proven node-positive disease planned for NAST between October 1, 2010 and December 31, 2015. Clinically node-negative axillary status after NAST was not mandatory. SLNB was always attempted and followed by a completion axillary lymph node dissection (ALND).ResultsThe SLN identification rate was 77.9% (152/195) but improved to 80.7% (138/171) with dual mapping. The median number of SLNs was two (range 1–5). A positive SLNB was found in 52% (79/152), almost 66% (52/79) of whom had additional positive non-sentinel lymph nodes. The overall pathologic nodal response rate was 33.3% (66/195). The overall FNR was 14.1% (13/92) but decreased to 4% (2/50) when only patients with two or more sentinel nodes were analyzed.ConclusionsIn biopsy-proven node-positive breast cancer, SLNB after NAST is feasible even though the identification rate is lower than in clinically node-negative patients. Since the overall FNR is unacceptably high, the omission of ALND should only be considered if two or more SLNs are identified.

Feasibility, accuracy and prognosis of sentinel lymph node biopsy before neoadjuvant therapy in breast cancer. A prospective study

Background and objectiveIt remains controversial whether sentinel lymph node biopsy (SLNB) should be performed before or after neoadjuvant therapy (NAT). We aimed to evaluate the feasibility and accuracy of SLNB before NAT at a single institution, and to determine its relation to patient prognosis. MethodsA prospective study of T1c-T2-T3 N0 breast cancer patients, after ultrasound examination, who underwent SLNB prior to NAT. Overall, disease-specific and disease-free survival were calculated by Kaplan–Meier curves. ResultsSLNB before NAT was performed in 123 patients from December 2006 to May 2014. The identification rate was 100%. SLNB was positive in 42.3% of cases (27.6% macrometastases). NAT was chemotherapy in 88.6% of cases and endocrine-therapy in 11.4%. Lymphadenectomy was avoided in 72.4% of cases. Median follow-up was 40 months (range 8–100). Overall and disease-free survival was 90.2% and 88.6% respectively.SLN involvement was not related to patient outcome (p 0.72); however there were significant differences in survival according to molecular-like subtypes (p < 0.025) and NAT response (p < 0.0001). ConclusionsSLNB prior to NAT is an accurate method of axillary staging associated with a high identification rate. It avoided lymphadenectomy in more than 70% of patients. SLN involvement did not worsen the prognosis in our cohort.