Article

Enhanced Axillary Evaluation Using Reflector-Guided Sentinel Lymph Node Biopsy: A Prospective Feasibility Study and Comparison With Conventional Lymphatic Mapping Techniques

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Abstract

Objective Recently there are efforts to utilize sentinel lymph node biopsy (SLNB) techniques after neoadjuvant chemotherapy (NAC) to minimize axillary surgery. However, studies have demonstrated higher false-negative rates in this scenario, which may result in inaccurate assessment of treatment response and patient prognosis as well as leaving residual disease behind. In this study, we describe the use of reflector-guided excision of the percutaneously biopsied node (PBN) as an aide to conventional SLNB and its predictor of the axillary status following NAC. Methods Single-institution analysis of patients undergoing axillary fiducial-reflector placement and subsequent SLNB compared with conventional SLNB. Results Nineteen patients in the reflector-group were matched with 19 patients who underwent conventional SLNB (conventional-group). The PBN was identified in the SLNB in 19 patients (100%) in the reflector-group and in 9 patients (47.3%) in the conventional-group (p=0.002). In the remaining 10 patients in the conventional-group, the PBN was identified in the axillary lymph node dissection (ALND) specimen in 4 patients (21%) and not identified in 6 patients (31.7%). Among the 38 patients, traditional mapping failed to identify the PBN in 13 patients (34.2%). The PBN was negative in 10 patients (36%) and positive in 18 patients (64%); no additional positive nodes were identified among patients with a negative PBN, correctly reflecting the status of the axilla in 100% of cases. Conclusion Mapping failure after neoadjuvant chemotherapy may compromise SLNB. Reflector-guided excision of the PBN is not only facile and feasible, but more accurately reflects the status of the axilla following NAC.

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... Subset analysis of this group demonstrated that a 6.8% FNR for SLNB after NAC could be achieved with excision of two or more SLN and confirmation that one of the lymph nodes excised was the biopsy positive clipped axillary lymph node (CALN) [5]. A number of studies have since been published evaluating different methods of targeted excision of the CALN for identification and retrieval at the time of SLNB after NAC [6][7][8][9][10][11]. ...
... Several devices for axillary lymph node localization exist such as radioactive seed marker, radar reflectors, magnetic seeds, and radiofrequency identification labeling technology, but wire localization has been the most commonly used modality [6][7][8][9][10][11][12][13]. A retrospective study by Plecha et al. demonstrated 97% successful CALN excision with wire localization [14]. ...
... Taback et al. established the feasibility and success of using day prior to surgery placement of a radar-based reflector for localization of the previously biopsied CALN. In a cohort of 19 patients, there was 100% identification of the clipped node [9]. In a similar study, Sun et al. reported similar results in a cohort of 45 patients with a median reflector placement time of 8 days [17]. ...
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PurposeClipped axillary lymph node (CALN) localization after neoadjuvant chemotherapy (NAC) for axillary node positive breast cancer can be difficult due to significant shrinkage or disappearance of the CALN after NAC. This study compares wire localization to a radar-based localization system utilizing a reflector that can be placed before or during NAC, in the months before definitive surgery, to facilitate accurate localization and excision of the CALN.Methods Between 2016 and 2019, women with T0-4 N1-3 M0 breast cancer who underwent NAC followed by axillary surgery with planned excision of a biopsy positive or clinically suspicious axillary node via wire or reflector localization were identified. A retrospective chart review was performed comparing successful localization and CALN retrieval by each localization technique.ResultsNinety-nine patients met inclusion criteria. Forty-two patients underwent wire localization while 57 patients underwent reflector localization of the CALN. Successful identification of the CALN by wire or reflector was equivalent (83.3% vs 84.2%, respectively). Twenty-two reflectors placed before or during early/mid NAC (early placement) had 100% successful CALN localization and retrieval in the OR. Placement of wire or reflector localization devices within 8 weeks of surgery (late placement) only resulted in 79.2% localization success (p = .02).Conclusion This study suggests a benefit of axillary lymph node reflector placement in the early NAC setting. Early reflector placement allows for more accurate excision of the CALN during axillary surgery after NAC as compared to placement of localization wires or reflectors in the few weeks prior to surgery.
... Full texts (where available) were then examined for the 14 abstracts, which initially met the criteria for SSL efficacy analysis (16,17,(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). In total, three of these publications were excluded from our calculations. ...
... In total, three of these publications were excluded from our calculations. One study was excluded because it assessed the use of SSL for sentinel lymph node biopsy rather than breast lesions (22). A second study was also excluded for including reflectors placed outside of the breast (27) -these could not be differentiated from reflectors placed within the breast in the study's data set. ...
... It is important to note that several studies have reported the use of Savi Scout ® system to successfully localise axillary lymph nodes (22,27), including within our own patient cohort (20). Lack of sufficient available data prevented any meaningful analysis from being conducted as part of our pooled analysis. ...
Article
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Background/aim: With the increase in detection of non-palpable breast lesions through screening, wire-guided localisation (WGL) has long been the favoured method for preoperative localisation. However, this technique comes with several limitations. New methods have been developed, including several non-radioactive, wireless options. We aimed to assess the effectiveness of Savi Scout® localisation (SSL) through this pooled analysis and systematic review. Materials and methods: A number of databases were searched for records reporting data on localisation and retrieval of SSL reflectors, as well as re-excision rate. We included our own data from 20 patients (22 reflectors) at our institution. Results: A total of 842 reflectors were inserted across eleven studies and our own data. Pooled analysis revealed an overall successful deployment rate of 99.64% and a successful retrieval rate of 99.64% using SSL. A statistically significant difference in re-excision rate was found in a smaller pooled analysis conducted across four studies comparing SSL and WGL (12.9% and 21.1% respectively, p<0.01). Conclusion: The Savi Scout® localisation system is a safe and effective alternative to WGL. It facilitates flexible scheduling by decoupling radiology and surgery interventions and may reduce the need for re-excision procedures for positive surgical margins.
... Though, SNNS of gastric carcinoma has not been universal owing to the complicated lymphatic flow from the stomach and skip metastasis, which are sometimes acknowledged in gastric cancer [12][13][14] ; the application of SN biopsy in gastric cancer is still debatable [15][16][17][18] . Few studies have been reported in gastric cancer [18][19][20][21][22] ; the SN detection rate and the predictive values of SNs biopsy must be high enough for the clinical application of SNs in gastric cancer 17 . In the present study, the SN detection rate and the predictive values of the SN biopsy were determined to evaluate its practicality and significance in gastric cancer. ...
... EGCs were confined by preoperative endoscopic snipping since such tumors might not be palpable on the serosal surface; just before surgery, three endoscopic clips (HX-600-090Lw, Olympus, Japan) were located at the mucosal layer roughly 1 cm distant in the oral although blue stained lymphatic vessels were well pictured. The average number of dissected lymph nodes per patient was 13 (range [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Lymph node metastasis was found in two of three patients in those whose SNs were not recognized. ...
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Objective: This study aims to explore the application value and detection rate of sentinel lymph node (SLN) biopsy in accurate detecting of lymph node metastasis in patients with gastric cancer. Patients and Methods: A total of 24 patients with Stage I, II or III gastric cancer, from 2015 to 2017, were admitted to our department and underwent D2-gastrectomy plus lymphadenectomy. All 236 nodes were sectioned and stained with immunohistochemical staining (IHC). Lymph node micro-metastasis was defined as evidencing to be positively stained or via the IHC process. Results: The results indicated that gastric cancer stage 1 was significantly correlated with higher lymphatic metastasis. Conclusions: Given the very low frequency of malignant non-sentinel lymph nodes was detected in stage 1, it could be logic and safe to merely dissected sentinel nodes without extended lymph node dissection while operation.
... The essence of these methods was to reduce FNR by combining the SD-SLNB with a tool that marks the pathologically proven positive lymph nodes [12]. As reported, such tools include metallic clips, radioactive seeds, tattooing with carbon suspension, sonographically visible bioresorbable polymers, hook wires, endomagnetic markers, radio frequency markers [13], and electromagnetic reflection reflector [14]. Although these tools might reduce the FNRs, the drawbacks also exist. ...
... However, IHC of cytokeratin was performed in case of uncertain metastasis in lymph nodes. SLNs with macrometastases, micro-metastases, or isolated tumor cells were considered positive [14]. PCR was defined as absence of invasive cancer in both the breast and axillary nodes, irrespective of ductal carcinoma in situ (ypT0/is ypN0) [25]. ...
Article
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Purpose In order to achieve an optimized method of axillary staging after neoadjuvant chemotherapy (NAC) in breast cancer patients with pretreatment positive axillary lymph nodes, we evaluated the feasibility and accuracy of nanoparticle-assisted axillary staging (NAAS) which combines carbon nanoparticles with standard sentinel lymph node biopsy (SLNB) with radioisotope and blue dye. Methods Invasive breast cancer patients with pre-NAC positive axillary lymph nodes who converted to ycN0 and received surgeries from November 2020 to March 2021 were included. All patients underwent ipsilateral NAAS followed by axillary lymph node dissection. Detection rate (DR), false-negative rate (FNR), negative predictive value (NPV) and accuracy of axillary staging were calculated. Results Eighty of 136 (58.8%) breast cancer patients converted to ycN0 after NAC and received NAAS. The DR, NPV and accuracy was 95.0%, 93.3% and 97.4% for NAAS, respectively. And the FNR was 4.2% (2/48) for NAAS, which was lower than that of standard dual-tracer SLNB (SD-SLNB) (9.5%, 4/42). Pretreatment clinical T4 classification was a risk factor for detection failure in NAAS (p = 0.016). When patients with pretreatment inflammatory breast cancers were excluded from analysis, FNR dropped to 2.2% (1/45) for NAAS. Conclusion NAAS revealed great performance in invasive breast cancer patients with pre-NAC positive axillary lymph nodes who converted to ycN0. The application of NAAS reached a better balance between more accurate axillary evaluation and less intervention. Trial registration Chictr.org.cn (ChiCTR2000039814). Registered Nov 11, 2020.
... In a more recent pilot study of 38 patients, Taback et al. found that compared to traditional SLNB alone which had 33% FNR, preoperative reflector-guided localized excision of the biopsied node correctly reflected the status of the axilla in 100% of cases (positive and negative), with no false negatives [37]. 34 out of 38 patients (89%) had dual mapping and median number of sentinel nodes removed was 2 and 3 for the reflector and conventional group, respectively. ...
... Various localization techniques, including I-125 seed, electromagnetic reflector and wire localization, have shown low FNR for TAD (range 0-7%), although identification issues at wire localization reported by some authors limits the use of wires [33,[36][37][38][39][40]. However, Plecha et al. reported a 96.3% ...
Article
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Axillary nodal status is one of the most important prognostic factors in breast cancer. While sentinel lymph node biopsy (SLNB) is a safe and validated procedure for clinically node-negative patients, axillary management of clinically node-positive patients has been more controversial. Patients with clinically detected axillary metastases often benefit from neoadjuvant chemotherapy (NAC). Those who convert to node-negative disease following NAC are important to identify, since they can often be spared significant morbidity from axillary dissection. SLNB has shown widely varying false-negative rates (FNR) but with the use of dual mapping and surgical biopsy of 3 or more nodes, it is considered an acceptable method to stage the axilla in clinically node-positive patients who receive NAC. Various methods including targeted axillary dissection (TAD) have been shown to decrease the FNR of SLNB. We will review appropriate methods to identify a metastatic node and subsequent ultrasound-guided biopsy with tissue marking techniques. We underscore key points in monitoring axillary response, techniques to accurately localize the biopsied and clipped known metastatic node for surgical excision and the effect of various methods in reducing the FNR of SLNB, including the emerging concept of TAD on patient care.
... Other techniques for marking axillary lymph nodes have been reported in small series, e.g., the use of magnetic seeds [41,42] and infrared-activated fiducial reflectors [43]. Greenwood et al. [41] reported their successful retrieval of magnetic seeds in 97 percent of patients, while Taback et al. [43] found a 100 percent success rate in the reflector group. ...
... Other techniques for marking axillary lymph nodes have been reported in small series, e.g., the use of magnetic seeds [41,42] and infrared-activated fiducial reflectors [43]. Greenwood et al. [41] reported their successful retrieval of magnetic seeds in 97 percent of patients, while Taback et al. [43] found a 100 percent success rate in the reflector group. Both localization techniques are non-radioactive and can be implanted to the targeted axillary node at a more flexible time before operation. ...
Article
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Background Marking of cytology-proven metastatic axillary lymph node in breast cancer patients before neoadjuvant treatment and its subsequent surgical retrieval have been shown to reduce the false-negative rate of sentinel lymph node biopsy. A systematic review was performed to evaluate different strategies in nodal marking and localization.Methods PubMed, Embase, EBSCOhost, and the Cochrane library literature databases were searched systematically to address the identification rate and retrieval rate of marked axillary lymph nodes. Studies were eligible if they performed nodal marking before neoadjuvant treatment, followed by selective extirpation of these marked axillary lymph nodes in definitive surgeryResultsFifteen studies with a total of 703 patients were included. Index axillary lymph nodes were marked by clips or tattooed prior to the commencement of neoadjuvant treatment. In our pooled analysis, eighty-eight percent of the clipped nodes and ninety-seven percent of the tattooed nodes were successfully retrieved. Among these patients, seventy-seven percent of these marked axillary lymph nodes were also sentinel lymph nodes.Conclusion Marking and selectively removing cytology-proven metastatic axillary lymph nodes after neoadjuvant treatment is feasible. An acceptably high nodal retrieval rate could be achieved using various methods of nodal marking and localization techniques.
... At present, there is no clear contraindication for TAD with regard to the degree of the involvement of the axilla, and authors use the method in cases with variance in axillary tumor burden. Few restrict TAD to small axillary involvement [19] only, and even fewer (if any) mark > 1 suspicious node pre-NAC. ...
... It is worth mentioning that some researchers do not specifically report the FNR according to N status (N1, N2, etc.), but rather grant an overall FNR of 0% for all N statuses [10,15,17,19]. This indirectly suggests that, for patients with axillary disease >N1, the FNR of TAD is still 0%. ...
Article
Introduction: Targeted axillary dissection (TAD) has been proposed as an alternative method for the staging of patients with node-positive breast cancer who undergo neoadjuvant chemotherapy. However, not much is known yet about the false-negative rate (FNR) of the method and the subsequent risk of underestimation of residual axillary disease. Methods: This study reviews published articles with calculations of false negativity of TAD and potential factors that may influence it. Results: The FNR of TAD is usually reported as being <10%, but this calculation is usually based on small study populations. Lower FNR is a common finding along with lower N status, while not enough data are available yet for greater axillary involvement. When a marked node is revealed to be a sentinel lymph node (SLN) at surgery after neoadjuvant chemotherapy (NAC), this seems to be another factor that contributes to reliable TAD. With regard to the methods used to mark the positive node before chemotherapy and retrieval at surgery, there is no clear advantage of one over the other. The availability of relevant resources, the costs, and local legislation must all be taken into account for the selection of the optimal strategy. Conclusion: Although still in its early days, the FNR of TAD can be low, at least in patients with relatively little axillary involvement and when the marked node is the SLN. All reported methods of lymph node marking seem reliable.
... 16,17 A small study of 19 patients has also demonstrated the feasibility and safety of applying RRL to localize lymph nodes. 18 The goal of this study is to report our experience with RRLguided excision of lymph nodes in node-positive breast cancer patients after NAC. Secondarily, we assess how often metastatic lymph nodes are missed when performing TAD. ...
... 11,20 Traditional methods of SLNlocalization with radiocolloid and isosulfan blue still carry failure rates as high as 34%. 18 ...
Article
Introduction Neoadjuvant chemotherapy (NAC) is commonly used for patients with clinically-detected nodal metastases. Sentinel node biopsy (SLNB) after NAC is feasible. Excision of biopsy-proven positive lymph nodes in addition to SLNB, termed targeted axillary dissection (TAD), decreases the false-negative rate of SLNB alone. Positive nodes can be marked with radar reflector-localization (RRL) clips. We report our institutional experience with RRL-guided TAD and demonstrate its safety and feasibility. Methods We performed an IRB-approved retrospective review of consecutive clinically node-positive female breast cancer patients treated with NAC and RRL-guided TAD between January 2017 and September 2019. Clinicopathologic and treatment data were collected; descriptive statistics reported. Results Forty-five patients were analyzed; median age 55 years (range 20-72) and median BMI 27.2 kg/m² (range 16.5-40.4). All patients received NAC, primary breast surgery and TAD. All clinically-detected nodal metastases were confirmed with percutaneous biopsy and marked with a biopsy clip. RRL clips were implanted a median of 8 days (range 1-167) prior to surgery, all were retrieved without complications. The RRL node was identified as the SLN in 36 (80%) patients. 25 patients had positive nodes of which 24 were identified by RRL node excision and 1 patient (4%) had a positive node identified by SLNB but not RRL. Over median follow-up time of 29.6 months, 5 patients recurred (1 local, 4 distant). Conclusions RRL-guided TAD after NAC is safe and feasible. This technique allows for adequate assessment of the nodal basin and helps confirm excision of the previously biopsied positive axillary node.
... 6 Wire localization may be associated with wire migration/breakage and patient discomfort 7 and is not always technically possible. Savi Scout reflector-guided localization 8 and magnetic seed localization (Magseed) 9 are promising devices but are expensive and not readily available worldwide. To date, several ongoing worldwide trials are still assessing the feasibility of radioactive seed (Radioactive Iodine Seed localization in the Axilla with the Sentinel node -RISAS trial 10 ), Magseed (ClinicalTrials.gov ...
... The radioactive seed carries radiation exposure and requires radiation safety precautions and handling. 14 Other promising modalities include a radar breast localization system (Savi Scout), 8 Magseed 9 or radiofrequency identification technology 15 predominantly used for breast lesions. These devices have no radiation risk and can avoid the use of wire. ...
Article
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Purpose: Removal of clipped nodes can improve sentinel node biopsy accuracy in breast cancer patients post neoadjuvant chemotherapy (NACT). However, the current methods of clipped node localization have limitations. We evaluated the feasibility of a novel clipped node localization and removal technique by preoperative skin marking of clipped nodes and removal by the Skin Mark clipped Axillary nodes Removal Technique (SMART), with the secondary aim of assessing the ultrasound visibility of the various clips in the axillary nodes after NACT. Methods: Invasive breast cancer patients with histologically metastatic axillary nodes, going for NACT, and ≤3 sonographically abnormal axillary nodes were recruited. All abnormal nodes had clips inserted. Patients with M1 disease were excluded. Post-NACT, patients underwent SMART and axillary lymph node dissection. Specimen radiography and pathological analyses were performed to confirm the clipped node presence. Success, complication rates of SMART, and ultrasound visibility of the various clips were assessed. Results: Twenty-five clipped nodes in 14 patients underwent SMART without complications. The UltraCor Twirl, hydroMARK, UltraClip Dual Trigger, and UltraClip were removed in 13/13 (100%), 7/9 (77.8%), 1/2 (50.0%), and 0/1 (0%), respectively (P = .0103) with UltraCor Twirl having the best ultrasound visibility and removal rate. Removal of three clipped nodes in the same patient (P = .0010) and deeply seated clipped nodes (P = .0167) were associated with SMART failure. Conclusion: Skin Mark clipped Axillary nodes Removal Technique is feasible for removing clipped nodes post-NACT, with 100% observed success rate, using the UltraCor Twirl marker in patients with <3 not deeply seated clipped nodes. Larger studies are needed for validation.
... A variety of methods are used to target the pathologically proven positive lymph node: marking with a clip pre-NST followed by placing an iodine seed or wire in the clipped node post-NST 7,33-35,37 and primary marking with an iodine seed, clip, charcoal, or electromagnetic reflector. 36,38 Also, the time of marking the lymph node pre-NST differs: either immediately at time of FNAC/CNB, 7,33,34,37 at a second appointment once metastatic burden of the punctured lymph node is confirmed by the pathologist 35,36 or even at both occasions. 38 Currently, further research has to define which combination procedure is most accurate, patient-friendly, and cost-effective. ...
... 36,38 Also, the time of marking the lymph node pre-NST differs: either immediately at time of FNAC/CNB, 7,33,34,37 at a second appointment once metastatic burden of the punctured lymph node is confirmed by the pathologist 35,36 or even at both occasions. 38 Currently, further research has to define which combination procedure is most accurate, patient-friendly, and cost-effective. Identification of the ML at time of surgery is highly feasible, provided that clipping (with/without secondary localization of the clip) of the node was successful. ...
Article
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Objective: The aim of this study was to perform a systematic review and meta-analysis to assess the accuracy of different surgical axillary staging procedures compared with ALND. Summary of background data: Optimal axillary staging after neoadjuvant systemic therapy (NST) in node-positive breast cancer is an area of controversy. Several less invasive procedures, such as sentinel lymph node biopsy (SLNB), marking axillary lymph node with radioactive iodine seed (MARI), and targeted axillary dissection (a combination of SLNB and a MARI-like procedure), have been proposed to replace the conventional axillary lymph node dissection (ALND) with its concomitant morbidity. Methods: PubMed and Embase were searched for studies comparing less invasive surgical axillary staging procedures to ALND to identify axillary burden after NST in patients with pathologically confirmed node-positive breast cancer (cN+). A meta-analysis was performed to compare identification rate (IFR), false-negative rate (FNR), and negative predictive value (NPV). Results: Of 1132 records, 20 unique studies with 2217 patients were included in quantitative analysis: 17 studies on SLNB, 1 study on MARI, and 2 studies on a combination procedure. Overall axillary pathologic complete response rate was 37%. For SLNB, pooled rates of IFR and FNR were 89% and 17%. NPV ranged from 57% to 86%. For MARI, IFR was 97%, FNR 7%, and NPV 83%. For the combination procedure, IFR was 100%, FNR ranged from 2% to 4%, and NPV from 92% to 97%. Conclusion: Axillary staging by a combination procedure consisting of SLNB with excision of a pre-NST marked positive lymph node appears to be most accurate for axillary staging after NST. More evidence from prospective multicenter trials is needed to confirm this.
... In pursuit of this objective, novel approaches are consistently emerging, underscoring the imperative for heightened precision in the acquisition of lymph node biopsy specimens. [32][33][34][35] ...
... Accordingly, Savi-Scout offers a safe alternative to WGL with multiple benefits including minimal ref lector migration, in contrast to the recognised limitation of wire migration with WGL [5]. Furthermore, Savi-Scout implementation prior to neoadjuvant therapy, at the time of percutaneous biopsy of axillary lymph nodes (PBN), has been found to facilitate 100% PBN excision following neoadjuvant therapy, compared with 75.8% PBN excision rate with conventional sentinel lymph node biopsy with technetium 99 and intraoperative isosulfan blue dye [6]. ...
Article
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This case describes a 48-year-old female who the first patient in Australia treated surgically with Savi-Scout™ assisted breast cancer localization, utilizing electromagnetic wave signalling for accurate depth guidance. After initial breast cancer diagnosis at age 44 treated with bilateral mastectomies and DIEP flap reconstructions, clinical surveillance found recurrent right chest wall disease. US and MRI identified a 4-6 mm interpectoral lesion; poorly differentiated metastatic micropapillary carcinoma on core biopsy. Savi-Scout™ was selected to assist localization and removal of the lesion due it's technically challenging location. Informed consent was gained and one month pre-operatively a 12× 1.6 mm electromagnetic wave Savi-Scout™ reflector was inserted via US-guidance. A Savi-Scout™ probe guided marking, incision and dissection of subcutaneous tissues and pectoralis muscles, through localization to the reflector. The lesion and reflection were excised and confirmed on specimen radiograph, with clear histopathology margins. This technology has potential applications for challenging breast cancer cases.
... Radiofrequency and radar guided localisations have been recently reported to be effective breast lesion localisation modalities without the challenges of RSL and Magseed but are in early stages of being adopted for routine use in the UK. 19 The ideal localisation technique should precisely localise the lesion and facilitate successful surgical excision with minimal morbidity. 20 Advantage of WGL includes familiarity of procedure, use of traditional materials such as guidewire and universal availability of technique. ...
Article
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Breast cancer screening has seen an increase in the detection of non-palpable breast lesions. Wire guided localisation (WGL) and Radio-guided occult lesion localisation (ROLL) are well established modalities of localisation of non-palpable breast lesions in the UK. We aimed to compare the outcomes of WGL and ROLL in this updated meta-analysis. We searched Cochrane Central Register of Controlled Trials (CENTRAL), and LILACS using free text search words as well as relevant MESH-terms. We also searched Medline (02/03/2021), Embase and registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Outcomes considered were re-excision rates, margin involvement, specimen volume and weight, accurate localisation of lesions and operative time. We assessed the risk of bias in included studies and performed random effects meta-analyses using Review Manager (version 5.3). Heterogeneity was estimated using the I²-statistic. Nine included studies enrolled 1096 patients undergoing localization in breast surgery (534 in WGL and 562 in ROLL). There was a statistically significant benefit in favour of ROLL for non-involved resection margins (OR 0.60; 95% CI, 0.44–0.97); based on seven studies. Nine trials assessed operative time favouring ROLL (OR 1.95; 95% CI, 0.27–3.63). No significant difference in re-excision rates was reported (OR 1.42; 95% CI, 0.83–2.43) based on seven studies. Current evidence favourably supports ROLL, compared to WGL, with respect to margin involvement, localisation and operative time in the treatment of non-palpable breast lesions.
... Given the idea that a combination procedure is most accurate for axillary staging after NST, and radioactive iodine seeds are not allowed to be used for this purpose in various countries, several variations of TAD have been investigated. Mostly in small and retrospective cohorts, markers such as wire [32][33][34], carbon ink [35][36][37][38], magnetic seeds [39,40], and clips [29] have been used, which all have certain benefits and downsides with regard to identifying the marked lymph node. Wire, carbon ink, and clips are non-radioactive and less expensive than radioactive iodine and magnetic seeds, and therefore often preferred options for TAD. ...
Article
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Background: There is a trend towards de-escalating axillary staging and treatment in breast cancer patients. On account of neoadjuvant systemic therapy, node-positive breast cancer patients can achieve a pathological complete response of the axilla. It is hypothesized that these patients do not benefit from an axillary lymph node dissection (ALND), and thus may be spared the risk of severe post-surgical morbidity. In an effort to omit standard ALND, less invasive axillary staging procedures are being implemented to establish response-guided treatment. However, it is unclear which less invasive staging procedure is most accurate, and long-term data are missing with regard to their oncologic safety. Summary: This article provides an overview of the literature on currently used less invasive axillary staging procedures, the accuracy and feasibility of these procedures in clinical practice, important issues concerning axillary treatment, and issues to be addressed in ongoing or future studies. Key messages: More evidence is needed regarding the safety of replacing standard ALND by less invasive axillary staging procedures in terms of long-term prognosis. These less invasive staging procedures not only serve to select patients who may benefit from treatment de-escalation, but also to select patients who may benefit from treatment escalation.
... The SAVI SCOUT ® localisation system has also been approved for use in targeted axillary lymph node dissection (TAD) (Figure 6). Although published data are limited, several existing studies have reported the successful use of the reflector system to localise axillary lymph nodes [30][31][32]. Sun et al. reported the successful retrieval of all SAVI SCOUT ® reflectors with no intra-or postoperative complications [32]. ...
Article
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Wire-guided localisation (WGL) has been the mainstay for localising non-palpable breast lesions before excision. Due to its limitations, various wireless alternatives have been developed. In this prospective study, we evaluate the role of radiation-free wireless localisation using the SAVI SCOUT® system at the London Breast Institute. A total of 72 reflectors were deployed in 67 consecutive patients undergoing breast conserving surgery for non-palpable breast lesions. The mean interval between deployment and surgery for the therapeutic cases was 18.8 days (range: 0–210). The median deployment duration was 5 min (range: 1–15 min). The mean distance from the lesion was 1.1 mm (median distance: 0; range: 0–20 mm). The rate of surgical localisation and retrieval of the reflector was 98.6% and 100%, respectively. The median operating time was 28 min (range: 15–55 min) for the therapeutic excision of malignancy and 17 min (range: 15–24) for diagnostic excision. The incidence of reflector migration was 0%. Radial margin positivity in malignant cases was 7%. The median weight for malignant lesions was 19.6 g (range: 3.5–70 g). Radiologists and surgeons rated the system higher than WGL (93.7% and 98.6%, respectively; 60/64 and 70/71). The patient mean satisfaction score was 9.7/10 (n = 47, median = 10; range: 7–10). One instance of signal failure was reported. In patients who had breast MRI after the deployment of the reflector, the MRI void signal was <5 mm (n = 6). There was no specific technique-related surgical complication. Our study demonstrates that wire-free localisation using SAVI SCOUT® is an effective and time-efficient alternative to WGL with excellent physician and patient acceptance.
... Newer methods utilize implantation of devices at the time of core needle biopsy. Taback et al. used a non-radioactive infrared-activated fiducial reflector (SAVI Scout™) to localize the clipped node at the time of SLNB after NAC in 19 patients; the clipped node was retrieved in 100%, compared with 47.3% seen in a similar control group [27] (Fig. 1). Furthermore, Greenwood et al. reported a 97% successful retrieval rate in 35 patients using a magnetized stainless steel seed (Magseed TM ) [28]. ...
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Purpose of Review The use of neoadjuvant chemotherapy (NAC) for breast cancer (BC) can eradicate axillary disease in > 40% of patients. The standard of care for node-positive BC has been axillary lymph node dissection. In this review, we examine the data for de-escalating axillary surgery after NAC. Recent Findings Studies have shown that sentinel lymph node biopsy (SLNB) is accurate after NAC. False negative rates (FNR) of SLNB after NAC in node-positive patients have been reduced with a combination of dual tracers and localization of the clipped positive node. Clipped nodes may be localized with a variety of methods. Summary Targeted axillary dissection (removal of clipped node in conjunction with SLNB) results in an acceptable FNR and can be considered in certain patients with axillary clinical response to neoadjuvant chemotherapy. Patient selection is important, as those with persistently positive nodes on clinical exam should proceed directly to axillary dissection.
... In previous cohorts that received combination procedures 17,20,21 , sometimes ten or more lymph nodes were retrieved, even though these procedures aim to offer a less invasive alternative to ALND. In the present cohort, only one to three lymph nodes were excised in half of the patients. ...
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Background Marking the axilla with radioactive iodine seed and sentinel lymph node (SLN) biopsy have been proposed for axillary staging after neoadjuvant systemic therapy in clinically node‐positive breast cancer. This study evaluated the identification rate and detection of residual disease with combined excision of pretreatment‐positive marked lymph nodes (MLNs) together with SLNs. Methods This was a multicentre retrospective analysis of patients with clinically node‐positive breast cancer undergoing neoadjuvant systemic therapy and the combination procedure (with or without axillary lymph node dissection). The identification rate and detection of axillary residual disease were calculated for the combination procedure, and for MLNs and SLNs separately. Results At least one MLN and/or SLN(s) were identified by the combination procedure in 138 of 139 patients (identification rate 99·3 per cent). The identification rate was 92·8 per cent for MLNs alone and 87·8 per cent for SLNs alone. In 88 of 139 patients (63·3 per cent) residual axillary disease was detected by the combination procedure. Residual disease was shown only in the MLN in 20 of 88 patients (23 per cent) and only in the SLN in ten of 88 (11 per cent), whereas both the MLN and SLN contained residual disease in the remainder (58 of 88, 66 per cent). Conclusion Excision of the pretreatment‐positive MLN together with SLNs after neoadjuvant systemic therapy in patients with clinically node‐positive disease resulted in a higher identification rate and improved detection of residual axillary disease.
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Tailored axillary surgery (TAS) is a new approach for selective removal of metastatic lymph nodes. This study evaluated the safety and utility of TAS using a breast biopsy clip inserted into a metastatic lymph node and a point marker consisting of a short hook wire and nylon thread to remove the clipped lymph node. Patients with breast cancer and clinically confirmed metastases to one-to-three axillary lymph nodes were included in this study. A breast biopsy clip was inserted into the metastatic lymph nodes before neoadjuvant chemotherapy. TAS was performed in patients with ycN0 disease after neoadjuvant chemotherapy. The lymph nodes containing the clips were removed using a point marker. The success criteria for TAS were the removal of the lymph node into which the clip was inserted using a point marker and the identification of the sentinel lymph node. The false-negative rate was calculated for cases in which TAS and axillary lymph node dissection were performed. Thirty individuals from two institutions were enrolled between May 2021 and November 2022, of whom 20 underwent TAS. Ten patients had clinically positive axillary lymph nodes and underwent axillary lymph node dissection. No adverse events were observed in any patient using the clips or point markers. TAS was successful in 18 of the 20 patients (90%). Seven patients underwent TAS and axillary lymph node dissection with a false-negative rate of 0%. The use of clips and point markers to perform TAS is clinically feasible.
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Purpose: To be aware of the feasibility of targeted axillary dissection (TAD) injecting 99mTechnetium-labeled macroaggregated albumin (99mTc-MAA) preoperatively into the clipped lymph node of patients with axillary complete clinical response (ycN0), after neoadjuvant chemotherapy (NAC) for breast cancer. Patients and methods: A retrospective observational study was performed on N1 patients with a clipped positive node and a clinically negative axilla (ycN0) after NAC in one center. The pretreatment positive lymph node was injected with 99mTc-MAA the day before surgery and identified intraoperatively with a radioguided occult lesion localization (ROLL) technique. Patients were subjected to a TAD with the intent of identifying the clipped node and other/s sentinel nodes through a standard sentinel lymph node biopsy (SLNB). Results: 54 patients and 55 axillary clipped nodes were included. The clip was intraoperatively encountered in every patient, accomplishing a 100% detection rate, although in one case no lymphatic tissue could be found in the intraoperative frozen section. An axillary lymph node dissection (ALND) was avoided in 62.9% of the cases (34/54). Conclusion: The use of the ROLL technique is a highly valuable tool since it allows a 100% success rate in retrieving the marker (and a 98.1% rate in detecting the clipped lymph node) in ycN0 breast cancer patients.
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Background: De-escalation of axillary surgery for lymph node (LN) positive breast cancer is facilitated by marking involved nodes which, when removed with sentinel nodes constitute risk-adapted targeted axillary dissection (TAD). Whether after chemotherapy or for primary surgery, selected patients with biopsy-proven involvement of nodes may be eligible for axillary conservation. Likewise, impalpable recurrence or stage 4 patients with localised axillary disease may benefit. In these contexts, several devices are used to mark biopsied nodes to facilitate their accurate surgical removal. We report our experience using the paramagnetic MAGSEED (Endomag®, Cambridge, UK). Methods: Local approval (BR2021_149) was obtained to interrogate a prospective database of all axillary markers. The primary endpoint was successful removal of the marked LN. Results: Of 241 markers (in 221 patients) inserted between October 2018 and July 2022, all were retrieved. Of 74 patients who had Magseeds® inserted after completion of NACT (involved nodes initially marked using an UltraCor™Twirl™ marker), the Magseeds® were found outside the node in neighbouring axillary tissue in 18 (24.3%) patients. When Magseeds® were placed at commencement of NACT in 54 patients, in only 1 (1.8%) was the marker found outside the node - a statistically significantly lower rate (Chi2 10.7581 p = 0.001038). For 'primary TAD' patients and those localised for recurrent or stage IV disease, all 93 had the Magseed® found within the biopsied node. Conclusion: This series supports our axillary nodal marking technique as safe and reliable. For TAD following NACT, placement at the start of treatment led to a significantly higher localisation rate.
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Introduction: In patients with non-palpable breast cancer, the availability of wireless localization techniques facilitates removal of the target lesion. One such technique uses a radar reflector for localization (RRL). This study evaluates the feasibility and effectiveness of RRL to guide excision of axillary lymph nodes in patients with node-positive breast cancer. Methods: Our Breast Cancer Database was queried for patients diagnosed with breast cancer, between 5/2017 and 10/2021, who underwent preoperative placement of a radar reflector into a biopsy proven axillary lymph node. Clinicopathologic data were reported using descriptive statistics. Results: Twenty patients underwent preoperative placement of a radar reflector into the axilla. Intraoperatively, the clip and radar reflector were successfully removed in all patients. Among the 10 patients treated with NAC, 5 patients achieved an axillary pathologic complete response (pCR) and were spared a complete axillary lymph node dissection (cALND). Among the entire cohort, RRL resulted in a 53% reduction in the number of lymph nodes removed. Conclusions: Wireless localization of axillary lymph nodes is safe and feasible. The technique ensures excision of biopsy proven positive axillary lymph nodes and enables a targeted approach to assessing the axilla, both in the setting of NAC and upfront surgery.
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Across breast imaging modalities, breast MRI provides the best anatomic delineation including the axilla. This chapter will review the imaging of the axilla and its clinical relevance including treatment planning. In addition, this chapter will discuss the role of breast MRI in evaluating breast cancer of unknown primary along with current research involving artificial intelligence.
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Traditionally, patients with newly diagnosed invasive breast cancer underwent axillary US to assess for suspicious axillary lymph nodes (LNs), which were then targeted for image-guided needle biopsy to determine the presence of metastasis. Over the past decade, there has been a shift towards axillary preservation. For patients with palpable lymphadenopathy, the decision to perform axillary imaging with documentation of the number and location of abnormal LNs in preparation for image-guided LN sampling is straightforward. Since LN involvement correlates with cancer size, it is reasonable to image the axilla in patients with tumors larger than 5 cm; however, for tumors smaller than 5 cm, axillary imaging is often deferred until after the tumor molecular subtype and treatment plan are established. Over the last decade, neoadjuvant chemotherapy (NACT) is increasingly used for smaller cancers with more aggressive molecular subtypes. In most cases, detecting axillary metastasis is critical when deciding whether the patient would benefit from NACT. There is increasing evidence that abnormal axillary US findings correlates with LN metastases and reliably establishes a baseline to monitor response to NACT. Depending on hormone receptor status, practices may choose to image the axilla in the setting of clinical stage T1 and T2 cancers to evaluate nodal status and help determine further steps in care. Radiologists should understand the nuances of axillary management and the scope and challenges of LN marking techniques that significantly increase the precision of limited axillary surgery.
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Background Targeted axillary dissection (TAD), the combination of sentinel lymph node biopsy (SLNB) and targeted lymph node biopsy (TLNB), can reduce the false negative rates of sentinel node biopsy alone dramatically in breast cancer patients, who received neoadjuvant chemotherapy (NAC). However methods for TAD are still under investigation. Methods Magseed®, a non-radioactive magnetic marker was used to mark the biopsied positive TLN after NAC. The SLNB with the standard technetium-based method and the selective TLNB with Magseed® localization were performed in 40 patients. The TLNs were identified with the Sentimag® probe and excised in all patients. Specimen x-ray was performed to confirm the Magseed® within the prior to NAC biopsied and clipped lymph node. Results The TLN identification rate was 100% (40/40), the SLN identification rate was 82.5% (33/40), the concordance rate between the TLN and the SLN was 65% (26/40). Complications according Magseed® deployment or identification could not be observed. Conclusion Magseed® is a reliable and feasible marker for the identification of TLNs after NAC.
Article
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Purpose of Review Axillary nodal disease is significantly less likely in both clinically node-negative (cN0) and node-positive (cN+) breast cancer patients after neoadjuvant chemotherapy (NAC). There have thus been significant efforts to “de-escalate” axillary surgery in this setting. This review discusses modern axillary surgical paradigms and techniques after NAC. Recent Findings In cN0 patients, the accuracy and feasibility of sentinel lymph node biopsy (SLNB) after NAC is well-established, with prospective evidence supporting its oncologic safety. SLNB is also acceptable in select cN+ patients when certain criteria are met. There is mounting “real-world” evidence for the technical feasibility of this approach, including various methods of localizing and excising biopsy-proven nodes, with the ability to avoid axillary lymph node dissection in a substantial proportion of patients. However, outcome data is limited to small retrospective series. Summary In appropriately selected patients, there is increasing opportunity to leverage the benefits of NAC to minimize the burden of axillary surgery.
Article
Background Targeted axillary dissection (TAD) involves sentinel lymph node biopsy (SLNB) and excision of a biopsy-proven node marked by a clip. This study evaluates the feasibility of non-radioactive wireless localizers for targeted excision of clipped axillary lymph nodes.Methods We identified biopsy-proven, node-positive breast cancer patients treated with neoadjuvant therapy (NAT) and TAD from 2016 to 2020, and included those with a clipped node localized using SAVI SCOUT, Magseed, or RFID Tag. Primary outcome measures were (1) successful localization (ultrasound or mammographic-guided placement < 10 mm from target), and (2) retrieval of the clipped node during TAD, documented by specimen radiography or gross visualization. Secondary outcomes included rates of completion axillary lymph node dissection (cALND) and complications.ResultsOverall, 57 patients were included; 1 (1.8%) patient had no clip visible at the time of localization, and no radiographic confirmation of clip placement at the time of biopsy, and was therefore excluded. In the remaining 56 patients, localization was successful in 53 (94.6%) patients and the clipped node was retrieved during TAD in 51 (91.1%) patients. Twenty-three of 27 (85.2%) ypN0 patients were spared cALND; 3 (11.1%) patients had cALND for failed clipped node retrieval during TAD, and 1 (3.7%) for false-positive frozen section. In patients with TAD alone, the rates of axillary seroma and infection were 20.0% and 8.6%, respectively.Conclusions Wireless non-radioactive localizers are feasible for axillary localization after NAT, with high success rates of retrieving clipped nodes. The lack of signal decay is an advantage of these devices, allowing flexibility in timing of placement.
Article
Introduction After neoadjuvant chemotherapy (NAC) for clinically node-positive breast cancer (NPBC), targeted axillary dissection (TAD) reduces the false negative rate (FNR) of axillary node sampling. Axillary lymph node dissection (ALND) is indicated if the clipped node cannot be identified. Prior studies have indicated that a sentinel lymph node harvest (SLNH) of ≥3 also leads to low FNR. We investigated the performance of SLNH thresholds at inferring the status of the axilla during TAD. Methods Retrospective review of the Legacy Health System Tumor Registry was performed. We identified NPBC patients between 2011 and 2016 managed with NAC and TAD. Results In 29 patients, the FNR of the SLNB component of TAD was 11% with SLNH of ≥3; with SLNH of ≤2 nodes the FNR was 20%. Conclusions In patients with NPBC receiving NAC, adequate SLNH is associated with acceptably low FNR. The decision to pursue ALND for clip identification should be made on a case-by-case basis.
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Background. Current techniques for localization and resection of lung nodules carry many intraoperative challenges for surgeons. This article proposes a new localization method for diagnosis and treatment of pulmonary nodules, which provides a navigational system for more accurate lung resection. Methods. We report the case of a 77-year-old female with a pulmonary nodule of the right lower lobe. A nonradioactive localization technology, known as SAVI SCOUT (Cianna Medical Inc, Aliso Viejo, CA), was placed by interventional radiology under computed tomography guidance preoperatively. Using the SCOUT Wire-Free Radar Localization System, the pulmonary nodule was robotically localized and resected. SCOUT removal was confirmed using the Trident Specimen Radiology System. The efficacy of this procedure was evaluated in terms of ease of use and procedure time by interventional radiology, surgical resection accuracy, diagnostic accuracy, simplicity, and ease to implement this technology in an existing hospital. Results. The SCOUT system allowed for the first reported case of successful SCOUT placement in lung tissue, targeted the pulmonary nodule intraoperatively, and facilitated accurate lung resection. Conclusions. The SCOUT system shows promising advancements in the ability to eliminate many challenges currently seen with lung nodule localization and resection.
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Invasive breast cancer is a common disease, and the most common initial site of metastatic disease are the axillary lymph nodes. As the standard of care shifts towards less invasive surgery in the axilla for patients with invasive breast cancer, techniques have been developed for axillary node localization that allow targeted dissection of specific lymph nodes without requiring full axillary lymph node dissection. Many of these techniques have been adapted from technologies developed for localization of lesions within the breast and include marker clip placement with intraoperative ultrasound, carbon-suspension liquids, localization wires, radioactive seeds, magnetic seeds, radar reflectors, and radiofrequency identification devices.The purpose of this article is to summarize these methods and describe benefits and drawbacks of each method for performing localization of lymph nodes in the axilla.
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Background: Sentinel lymph node biopsy (SNB) is the standard treatment of node-negative breast cancer; however, whether SNB should be performed for patients with node-positive disease before neoadjuvant chemotherapy (NAC) is controversial. We evaluated the accuracy of SNB after NAC in patients with breast cancer with nodal metastasis before chemotherapy to determine the false-negative rate (FNR) and detection rate for SNB. Patients and methods: In the present multicenter prospective study performed from September 2011 to April 2013, 143 patients with breast cancer and positive axillary nodes, proved by fine needle aspiration cytology at the initial diagnosis (stage T1-T3N1M0), were enrolled. All patients underwent breast surgery with SNB and complete axillary lymph node dissection. Results: After NAC, the pathologic complete nodal response rate was 52.4%. The sentinel lymph node could be identified in 130 cases (90.9%); the FNR was 16.0% (13 of 81). The FNR of each clinical subtype was 42.1% (8 of 19) for the estrogen receptor-positive and human epithelial growth factor 2 (HER2)-negative (luminal type), 16.7% (2 of 12) for ER-positive and HER2-positive (luminal-HER2 type), 3.2% (1 of 31) for HER2-positive (HER2-enriched type), and 10.5% (2 of 19) for ER-negative and HER2-negative (triple-negative breast cancer; P = .003). The FNR was significantly greater in the luminal than in the nonluminal type (odds ratio, 9.91; 95% confidence interval, 6.77-14.52). Conclusion: SNB after NAC in patients with initially node-positive breast cancer was technically feasible but should not be recommended for the luminal subtype. However, the tumor subtype can guide patient selection, and axillary lymph node dissection could be omitted for the luminal-HER2, HER2-enriched, and triple-negative breast cancer subtypes.
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To evaluate factors affecting sentinel lymph node (SLN) identification after neoadjuvant chemotherapy (NAC) in patients with initial node-positive breast cancer. SLN surgery is increasingly used for nodal staging after NAC and optimal technique for SLN identification is important. The American College of Surgeons Oncology Group Z1071 prospective trial enrolled clinical T0-4, N1-2, M0 breast cancer patients. After NAC, SLN surgery and axillary lymph node dissection (ALND) were planned. Multivariate logistic regression modeling assessing factors influencing SLN identification was performed. Of 756 patients enrolled, 34 women withdrew, 21 were ineligible, 12 underwent ALND only, and 689 had SLN surgery attempted. At least 1 SLN was identified in 639 patients (92.7%: 95% CI: 90.5%-94.6%). Among factors evaluated, mapping technique was the only factor found to impact SLN identification; with use of blue dye alone increasing the likelihood of failure to identify the SLN relative to using radiolabeled colloid +/- blue dye (P = 0.006; OR = 3.82; 95% CI: 1.47-9.92). The SLN identification rate was 78.6% with blue dye alone; 91.4% with radiolabeled colloid and 93.8% with dual mapping agents. Patient factors (age, body mass index), tumor factors (clinical T or N stage), pathologic nodal response to chemotherapy, site of tracer injection, and length of chemotherapy treatment did not significantly affect the SLN identification rate. The SLN identification rate after NAC was higher when mapping was performed using radiolabeled colloid alone or with blue dye compared with blue dye alone. Optimal tracer use is important to ensure successful identification of SLN(s) after NAC.
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Sentinel lymph node biopsy (SLNB) has replaced conventional axillary lymph node dissection (ALND) in axillary node-negative breast cancer patients. However, the use of SLNB remains controversial in patients after neoadjuvant chemotherapy (NAC). The aim of this review is to evaluate the feasibility and accuracy of SLNB after NAC in clinically node-positive patients. Systematic searches were performed in the PubMed, Embase, and Cochrane Library databases from 1993 to December 2013 for studies on node-positive breast cancer patients who underwent SLNB after NAC followed by ALND. Of 436 identified studies, 15 were included in this review, with a total of 2,471 patients. The pooled identification rate (IR) of SLNB was 89% [95% confidence interval (CI) 85-93%], and the false negative rate (FNR) of SLNB was 14% (95% CI 10-17%). The heterogeneity of FNR was analyzed by meta-regression, and the results revealed that immunohistochemistry (IHC) staining may represent an independent factor (P = 0.04). FNR was lower in the IHC combined with hematoxylin and eosin (H&E) staining subgroup than in the H&E staining alone subgroup, with values of 8.7% versus 16.0%, respectively (P = 0.001). Thus, SLNB was feasible after NAC in node-positive breast cancer patients. In addition, the IR of SLNB was respectable, although the FNR of SLNB was poor and requires further improvement. These findings indicate that IHC may improve the accuracy of SLNB.
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The MARI procedure [marking the axillary lymph node with radioactive iodine (I) seeds] is a new minimal invasive method to assess the pathological response of nodal metastases after neoadjuvant systemic treatment (NST) in patients with breast cancer. This method allows axilla-conserving surgery in patients responding well to NST. Prior to NST, proven tumor-positive axillary lymph nodes were marked with a I seed. This marked lymph node is the so-called MARI-node. After NST, the MARI node was selectively removed using a γ-detection probe. A complementary axillary lymph node dissection was performed in all patients to assess whether pathological response in the MARI node was indicative for the pathological response in the additional lymph nodes. A tumor-positive axillary lymph node was marked with a I seed in 100 patients. The MARI node was successfully identified in 97 of these 100 patients (identification rate 97%). Two patients did not undergo subsequent axillary lymph node dissection, leaving 95 patients for further analysis. The MARI node contained residual tumor cells in 65 of these 95 patients. In the other 30 patients, the MARI node was free of tumor, but additional positive lymph nodes were found in 5 patients. Thus, the MARI procedure correctly identified 65 of 70 patients with residual axillary tumor activity (false negative rate 5/70 = 7%). This study shows that marking and selectively removing metastatic lymph nodes after neoadjuvant systemic treatment has a high identification rate and a low false negative rate. The tumor response in the marked lymph node may be used to tailor further axillary treatment after NST.
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Importance Sentinel lymph node (SLN) surgery provides reliable nodal staging information with less morbidity than axillary lymph node dissection (ALND) for patients with clinically node-negative (cN0) breast cancer. The application of SLN surgery for staging the axilla following chemotherapy for women who initially had node-positive cN1 breast cancer is unclear because of high false-negative results reported in previous studies.Objective To determine the false-negative rate (FNR) for SLN surgery following chemotherapy in women initially presenting with biopsy-proven cN1 breast cancer.Design, Setting, and Patients The American College of Surgeons Oncology Group (ACOSOG) Z1071 trial enrolled women from 136 institutions from July 2009 to June 2011 who had clinical T0 through T4, N1 through N2, M0 breast cancer and received neoadjuvant chemotherapy. Following chemotherapy, patients underwent both SLN surgery and ALND. Sentinel lymph node surgery using both blue dye (isosulfan blue or methylene blue) and a radiolabeled colloid mapping agent was encouraged.Main Outcomes and Measures The primary end point was the FNR of SLN surgery after chemotherapy in women who presented with cN1 disease. We evaluated the likelihood that the FNR in patients with 2 or more SLNs examined was greater than 10%, the rate expected for women undergoing SLN surgery who present with cN0 disease.Results Seven hundred fifty-six women were enrolled in the study. Of 663 evaluable patients with cN1 disease, 649 underwent chemotherapy followed by both SLN surgery and ALND. An SLN could not be identified in 46 patients (7.1%). Only 1 SLN was excised in 78 patients (12.0%). Of the remaining 525 patients with 2 or more SLNs removed, no cancer was identified in the axillary lymph nodes of 215 patients, yielding a pathological complete nodal response of 41.0% (95% CI, 36.7%-45.3%). In 39 patients, cancer was not identified in the SLNs but was found in lymph nodes obtained with ALND, resulting in an FNR of 12.6% (90% Bayesian credible interval, 9.85%-16.05%).Conclusions and Relevance Among women with cN1 breast cancer receiving neoadjuvant chemotherapy who had 2 or more SLNs examined, the FNR was not found to be 10% or less. Given this FNR threshold, changes in approach and patient selection that result in greater sensitivity would be necessary to support the use of SLN surgery as an alternative to ALND.Trial Registration clinicaltrials.gov Identifier: NCT00881361
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An important benefit of neoadjuvant chemotherapy is the increased potential for breast-conserving surgery. At present the response of axillary lymph node metastases to chemotherapy is not easily assessed, rendering axilla-conserving treatment difficult. The aim was to assess a new surgical method for evaluating the axillary response to chemotherapy. Before neoadjuvant chemotherapy, proven tumour-positive axillary lymph nodes were localized using ultrasound-guided insertion of iodine-125-labelled (I-125) seeds. After neoadjuvant chemotherapy, the marked lymph nodes were removed selectively with the use of a gamma probe. A complete axillary lymph node clearance was carried out to determine whether the pathological response in the marked node was indicative of that in the other lymph nodes. Tumour-positive axillary lymph nodes were localized successfully with I-125 seeds in 15 patients. The marked lymph node was detected and removed selectively after neoadjuvant chemotherapy in all patients. The pathological response to chemotherapy in the marked lymph node was indicative of the overall response in other removed lymph nodes. This study showed that marking and selectively removing metastatic lymph nodes after neoadjuvant chemotherapy was feasible. The tumour response in the marked lymph node may be used to tailor further axillary treatment, making axilla-conserving surgery a possibility.
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Breast cancer is a significant health problem worldwide and is one of the leading causes of cancer-related mortality in women. Preoperative chemotherapy has become the standard of care for patients with locally advanced disease and is being used more frequently in patients with early-stage breast cancer. Sentinel lymph node biopsy has shown great promise in the surgical management of breast cancer patients, but its use following preoperative chemotherapy is yet to be determined. Eleven studies have been published with respect to the accuracy of sentinel lymph node biopsy following neoadjuvant chemotherapy. Ten studies showed favourable results, with the ability to identify a sentinel lymph node in 84% to 98% of cases, and reported false negative rates ranging from 0% to 20%. The accuracy of sentinel lymph node biopsy following preoperative chemotherapy for breast cancer ranges from 88% to 100%, with higher rates when specific techniques and inclusion criteria are applied. The published literature supports the use of sentinel lymph node biopsy for assessment of the axilla in patients with clinically node-negative disease following preoperative chemotherapy.
Article
Background: The treatment of axillary lymph node metastases after neoadjuvant systemic therapy (NST) remains debatable and axillary lymph node dissection (ALND) is still the standard of care. Marking axillary lymph nodes with radioactive iodine seeds (MARI procedure) is accurate in restaging the axilla after NST (false-negative rate 7 per cent). Here, the potential of tailored axillary treatment, determined by combining the results of PET-CT before NST with those of the MARI procedure after NST, was analysed. Methods: A cohort of axillary node-positive patients was used to construct a hypothetical treatment algorithm based on a combination of PET-CT and the MARI procedure. In the algorithm, the number of fluorodeoxyglucose (FDG)-avid axillary lymph nodes (1-3 versus 4 or more) before NST and the tumour status of the MARI node (positive versus negative) after NST were used to tailor axillary treatment. All patients in the cohort underwent ALND, allowing estimation of potential overtreatment and undertreatment. Results: A total of 93 patients were included in the study. Between one and three FDG-avid axillary lymph nodes were observed in 59 patients, and four or more in 34 patients. The MARI node was tumour-negative in 32 patients and showed residual disease in 61. Treatment according to the constructed algorithm would have resulted in 74 per cent of patients avoiding an ALND, with potential undertreatment in three patients (3 per cent) and overtreatment in 16 (17 per cent). Conclusion: Tailored axillary treatment after NST in node-positive patients, by combining PET-CT before NST and the MARI procedure after NST, has the potential for ALND to be avoided in 74 per cent of patients.
Article
Purpose To evaluate outcomes of Savi Scout (Cianna Medical, Aliso Viejo, Calif) reflector-guided localization and excision of breast lesions by analyzing reflector placement, localization, and removal, along with target excision and rates of repeat excision (referred to as re-excision). Materials and Methods A single-institution retrospective review of 100 women who underwent breast lesion localization and excision by using the Savi Scout surgical guidance system from June 2015 to May 2016 was performed. By using image guidance 0-8 days before surgery, 123 nonradioactive, infrared-activated, electromagnetic wave reflectors were percutaneously inserted adjacent to or within 111 breast targets. Twenty patients had two or three reflectors placed for bracketing or for localizing multiple lesions, and when ipsilateral, they were placed as close as 2.6 cm apart. Target and reflector were localized intraoperatively by one of two breast surgeons who used a handpiece that emitted infrared light and electromagnetic waves. Radiographs of the specimen and pathologic analysis helped verify target and reflector removal. Target to reflector distance was measured on the mammogram and radiograph of the specimen, and reflector depth was measured on the mammogram. Pathologic analysis was reviewed. Re-excision rates and complications were recorded. By using statistics software, descriptive statistics were generated with 95% confidence intervals (CIs) calculated. Results By using sonographic (40 of 123; 32.5%; 95% CI: 24.9%, 41.2%) or mammographic (83 of 123; 67.5%; 95% CI: 58.8% 75.1%) guidance, 123 (100%; 95% CI: 96.4%, 100%) reflectors were placed. Mean mammographic target to reflector distance was 0.3 cm. All 123 (100%; 95% CI: 96.4%, 100%) targets and reflectors were excised. Pathologic analysis yielded 54 of 110 malignancies (49.1%; 95% CI: 39.9%, 58.3%; average, 1.0 cm; range, 0.1-5 cm), 32 high-risk lesions (29.1%; 95% CI: 21.4%, 38.2%), and 24 benign lesions (21.8%; 95% CI: 115.1%, 30.4%). Four of 54 malignant cases (7.4%; 95% CI: 2.4%, 18.1%) demonstrated margins positive for cancer that required re-excision. Five of 110 radiographs of the specimen (4.5%; 95% CI: 1.7%, 10.4%) demonstrated increased distance between the target and reflector distance of greater than 1.0 cm (range, 1.1-2.6 cm) compared with postprocedure mammogram the day of placement, three of five were associated with hematomas, two of five migrated without identifiable cause. No related postoperative complications were identified. Conclusion Savi Scout is an accurate, reliable method to localize and excise breast lesions with acceptable margin positivity and re-excision rates. Bracketing is possible with reflectors as close as 2.6 cm. Savi Scout overcomes many limitations of other localization methods, which warrants further study. (©) RSNA, 2017.
Article
Background: In 1 of 3 patients with initial lymph node-positive (cN(+)) breast cancer, neoadjuvant chemotherapy (NAC) results in an axillary pathologic complete response (ax-pCR). This urges the need for a less-invasive axillary staging method. Recently introduced less-invasive procedures have been insufficient in accurately identifying ax-pCR. Therefore, we propose a novel less-invasive axillary staging procedure: the Radioactive Iodine Seed localization in the Axilla with the Sentinel node procedure (RISAS), a combination of the procedure of marking axillary lymph nodes with radioactive iodine seeds (MARI) and sentinel lymph node biopsy (SLNB). Patients and methods: In the present open single-arm multicenter validation study, 225 cN(+) (biopsy-proven) patients will undergo the RISAS procedure, in which a positive lymph node is marked by an iodine-125 seed before NAC. After NAC completion, this iodine-125 seed-marked lymph node is removed, together with any additional sentinel lymph nodes. The RISAS procedure is subsequently followed by completion axillary lymph node dissection (ALND). The RISAS lymph nodes will be compared with the lymph nodes from the completion ALND specimen. The primary endpoint is accuracy of the RISAS procedure. The identification rate, false-negative rate, negative predictive value, and possible concordance between the MARI and SLNB will be reported. Conclusion: The present prospective multicenter RISAS trial will enable us to validate the combination of MARI and SLNB for assessing the axillary response to NAC in cN(+) patients. If RISAS proves to be an accurate axillary staging procedure, ALND could safely be abandoned in the case of ax-pCR confirmed using the RISAS procedure.
Article
Background: Although morbidity is reduced when sentinel lymph node (SLN) biopsy is performed with dual isotopic and blue dye identification, the effectiveness of adding blue dye to radioisotope remains debated because side effects including anaphylactic reactions. Patients and methods: Using data from a prospectively maintained database, 1884 lymph node-negative breast cancer patients who underwent partial mastectomy with SLN mapping by a dual-tracer using patent blue dye (PBD) and radioisotope were retrospectively studied between January 2000 and July 2013. Patients with tumors <3 cm and with >1 node detected by one of the two techniques (N = 1024) were included in this real-life cross-sectional study. Results: Among the 1024 patients, 274 had positive SLN detected by isotopic and/or PBD staining. Only 4 patients having no detectable radioactivity in the axilla had SLN identified only by PBD staining (blue-only) while 26 patients had SLN only identified by isotopic detection (hot-only) illustrating failure rates of 9.5% (26/274) and 1.5% (4/274), respectively. Among these four patients, two had negative lymphoscintigraphy. Therefore, the contribution of PBD to metastatic nodes identification was relevant for only 2/274 patients (0.8%). Three patients (0.3%) had an allergic reaction with PBD, and anaphylactic shock occurred in two cases (0.2%). Conclusions: The added-value of PBD to reduce the false-negative rate of SLN mapping is only limited to the rare cases in which no radioactivity is detectable in the axilla (<1%). When a radioisotope mapping agent is available, the use of PBD should be avoided, because it can induce anaphylaxis.
Article
Objective: The purpose of this study is to evaluate the feasibility of the SAVI SCOUT surgical guidance system, which uses a nonradioactive infrared-activated electromagnetic wave reflector, to localize and excise nonpalpable breast lesions. We evaluated the system's use in 15 nonpalpable breast lesions in 13 patients. Conclusion: Image-guided placement was successful for 15 of 15 (100%) reflectors. The final pathologic analysis found that lesion excision was successful, including five malignancies with negative margins. No patients required reexcision or experienced complications. SAVI SCOUT is a feasible method for breast lesion localization and excision.
Article
Purpose: Placing clips in nodes with biopsy-confirmed metastasis before initiating neoadjuvant therapy allows for evaluation of response in breast cancer. Our goal was to determine if pathologic changes in clipped nodes reflect the status of the nodal basin and if targeted axillary dissection (TAD), which includes sentinel lymph node dissection (SLND) and selective localization and removal of clipped nodes, improves the false-negative rate (FNR) compared with SLND alone. Methods: A prospective study of patients with biopsy-confirmed nodal metastases with a clip placed in the sampled node was performed. After neoadjuvant therapy, patients underwent axillary surgery and the pathology of the clipped node was compared with other nodes. Patients undergoing TAD had SLND and selective removal of the clipped node using iodine-125 seed localization. The FNR was determined in patients undergoing complete axillary lymphadenectomy (ALND). Results: Of 208 patients enrolled in this study, 191 underwent ALND, with residual disease identified in 120 (63%). The clipped node revealed metastases in 115 patients, resulting in an FNR of 4.2% (95% CI, 1.4 to 9.5) for the clipped node. In patients undergoing SLND and ALND (n = 118), the FNR was 10.1% (95% CI, 4.2 to 19.8), which included seven false-negative events in 69 patients with residual disease. Adding evaluation of the clipped node reduced the FNR to 1.4% (95% CI, 0.03 to 7.3; P = .03). The clipped node was not retrieved as an SLN in 23% (31 of 134) of patients, including six with negative SLNs but metastasis in the clipped node. TAD followed by ALND was performed in 85 patients, with an FNR of 2.0% (1 of 50; 95% CI, 0.05 to 10.7). Conclusion: Marking nodes with biopsy-confirmed metastatic disease allows for selective removal and improves pathologic evaluation for residual nodal disease after chemotherapy.
Article
Background: Neoadjuvant chemotherapy (NAC) downstages axillary disease in 55 % of node-positive (N1) breast cancer. The feasibility and accuracy of sentinel lymph node biopsy (SLNB) after NAC for percutaneous biopsy-proven N1 patients who are clinically node negative (cN0) by physical examination after NAC is under investigation. ACOSOG Z1071 reported a false-negative rate of <10 % if ≥3 nodes are removed with dual tracer, including excision of the biopsy-proven positive lymph node (BxLN). We report our experience using radioactive seed localization (RSL) to retrieve the BxLN with SLNB (RSL/SLNB) for cN0 patients after NAC. Methods: We performed a retrospective review of a single-institution, prospectively maintained registry for the years 2013 to 2014. Patients with BxLN who received NAC and had RSL/SLNB were identified. All BxLNs were marked with a radiopaque clip before NAC to facilitate RSL. Results: Thirty patients with BxLN before NAC were cN0 after NAC and underwent RSL/SLNB. Median age was 55 years. Disease stage was IIA-IIIB. Twenty-nine of 30 had ductal cancer (12 triple negative and 16 HER-2 positive). One to 11 nodes were retrieved. Twenty-nine of 30 BxLN were successfully localized with RSL. Note was made of the BxLN-containing isotope and/or dye in 22 of 30. Nineteen patients had no residual axillary disease; 11 had persistent disease. All who remained node positive had disease in the BxLN. Conclusions: RSL/SLNB is a promising approach for axillary staging after NAC in patients whose disease becomes cN0. The status of the BxLN after NAC predicted nodal status, suggesting that localization of the BxLN may be more accurate than SLNB alone for staging the axilla in the cN0 patient after NAC.
Article
Background: The American College of Surgeons Oncology Group Z1071 trial reported a false-negative rate (FNR) of 12.6% with sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy in women presenting with node-positive breast cancer. One proposed method to decrease the FNR is clip placement in the positive node at initial diagnosis with confirmation of clipped node resection at surgery. Methods: Z1071 was a multi-institutional trial wherein women with clinical T0-T4,N1-N2,M0 breast cancer underwent SLN surgery and axillary dissection (ALND) after neoadjuvant chemotherapy. In cases with a clip placed in the node, the clip location at surgery (SLN or ALND) was evaluated. Results: A clip was placed at initial node biopsy in 203 patients. In the 170 (83.7%) patients with cN1 disease and at least 2 SLNs resected, clip location was confirmed in 141 cases. In 107 (75.9%) patients where the clipped node was within the SLN specimen, the FNR was 6.8% (confidence interval [CI]: 1.9%-16.5%). In 34 (24.1%) cases where the clipped node was in the ALND specimen, the FNR was 19.0% (CI: 5.4%-41.9%). In cases without a clip placed (n = 355) and in those where clipped node location was not confirmed at surgery (n = 29), the FNR was 13.4% and 14.3%, respectively. Conclusions: Clip placement at diagnosis of node-positive disease with removal of the clipped node during SLN surgery reduces the FNR of SLN surgery after neoadjuvant chemotherapy. Clip placement in the biopsy-proven node at diagnosis and evaluation of resected specimens for the clipped node should be considered when conducting SLN surgery in this setting.
Article
This study aimed to evaluate whether the use of preoperative ultrasound (US)-guided wire localization of metastatic axillary lymph nodes (LN) assessed previously by core needle biopsy (CNB) and clip placement in breast cancer patients improves successful surgical removal. A retrospective review examined breast cancer patients who underwent US-guided CNB of an axillary LN and biopsy clip placement as well as axillary lymph node dissection (ALND) or sentinel node lymph node biopsy (SLNB) from 1 January 2010 to 30 September 2013. Preoperative needle localization status, neoadjuvant chemotherapy, and type of axillary LN surgery were reviewed. Confirmation that the metastatic LN had been surgically removed was determined on the specimen image, by pathologic report confirmation, or by pre-radiation therapy computed tomography (CT) scan. Preoperative US-guided needle localization was performed for 68.2 % (73/107) of the patients, with 97.3 % (n = 71) demonstrating confirmation of biopsy clip and LN removal versus 79.4 % (n = 27) of the 34 patients showing no performance of needle localization (p = 0.0043). Subgroup analysis showed a significant difference in removal of metastatic LN between the patients who received neoadjuvant chemotherapy [97 % of LNs removed with wire localization (n = 65/67) vs. 83.3 % of LNs removed without wire localization (n = 20/24; p = 0.04)] and the patients who had ALND, [96.3 % of LNs removed with wire localization (n = 52/54) vs. 77.8 % of LNs removed without wire localization (n = 21/27; p = 0.015)]. US-guided wire localization of metastatic axillary LNs that have had biopsy with clip placement significantly improves the success rate of surgical removal, allowing more accurate staging and decreasing the false-negative rates of SLNB after neoadjuvant therapy.
Article
Objective: To determine the impact of tumor biology on rates of breast-conserving surgery and pathologic complete response (pCR) after neoadjuvant chemotherapy. Background: The impact of tumor biology on the rate of breast-conserving surgery after neoadjuvant chemotherapy has not been well studied. Methods: We used data from ACOSOG Z1071, a prospective, multicenter study assessing sentinel lymph node surgery after neoadjuvant chemotherapy in patients presenting with node-positive breast cancer from 2009 through 2011, to determine rates of breast-conserving surgery and pCR after chemotherapy by approximated biologic subtype. Results: Of the 756 patients enrolled on Z1071, 694 had findings available from pathologic review of breast and axillary specimens from surgery after chemotherapy. Approximated subtype was triple-negative in 170 (24.5%), human epidermal growth factor receptor 2 (HER2)-positive in 207 (29.8%), and hormone-receptor-positive, HER2-negative in 317 (45.7%) patients. Patient age, clinical tumor and nodal stage at presentation did not differ across subtypes. Rates of breast-conserving surgery were significantly higher in patients with triple-negative (46.8%) and HER2-positive tumors (43.0%) than in those with hormone-receptor-positive, HER2-negative tumors (34.5%) (P = 0.019). Rates of pCR in both the breast and axilla were 38.2% in triple-negative, 45.4% in HER2-positive, and 11.4% in hormone-receptor-positive, HER2-negative disease (P < 0.0001). Rates of pCR in the breast only and the axilla only exhibited similar differences across tumor subtypes. Conclusions: Patients with triple-negative and HER2-positive breast cancers have the highest rates of breast-conserving surgery and pCR after neoadjuvant chemotherapy. Patients with these subtypes are most likely to be candidates for less invasive surgical approaches after chemotherapy.
Article
Background: The optimum timing of sentinel-lymph-node biopsy for breast cancer patients treated with neoadjuvant chemotherapy is uncertain. The SENTINA (SENTinel NeoAdjuvant) study was designed to evaluate a specific algorithm for timing of a standardised sentinel-lymph-node biopsy procedure in patients who undergo neoadjuvant chemotherapy. Methods: SENTINA is a four-arm, prospective, multicentre cohort study undertaken at 103 institutions in Germany and Austria. Women with breast cancer who were scheduled for neoadjuvant chemotherapy were enrolled into the study. Patients with clinically node-negative disease (cN0) underwent sentinel-lymph-node biopsy before neoadjuvant chemotherapy (arm A). If the sentinel node was positive (pN1), a second sentinel-lymph-node biopsy procedure was done after neoadjuvant chemotherapy (arm B). Women with clinically node-positive disease (cN+) received neoadjuvant chemotherapy. Those who converted to clinically node-negative disease after chemotherapy (ycN0; arm C) were treated with sentinel-lymph-node biopsy and axillary dissection. Only patients whose clinical nodal status remained positive (ycN1) underwent axillary dissection without sentinel-lymph-node biopsy (arm D). The primary endpoint was accuracy (false-negative rate) of sentinel-lymph-node biopsy after neoadjuvant chemotherapy for patients who converted from cN1 to ycN0 disease during neoadjuvant chemotherapy (arm C). Secondary endpoints included comparison of the detection rate of sentinel-lymph-node biopsy before and after neoadjuvant chemotherapy, and also the false-negative rate and detection rate of sentinel-lymph-node biopsy after removal of the sentinel lymph node. Analyses were done according to treatment received (per protocol). Findings: Of 1737 patients who received treatment, 1022 women underwent sentinel-lymph-node biopsy before neoadjuvant chemotherapy (arms A and B), with a detection rate of 99.1% (95% CI 98.3-99.6; 1013 of 1022). In patients who converted after neoadjuvant chemotherapy from cN+ to ycN0 (arm C), the detection rate was 80.1% (95% CI 76.6-83.2; 474 of 592) and false-negative rate was 14.2% (95% CI 9.9-19.4; 32 of 226). The false-negative rate was 24.3% (17 of 70) for women who had one node removed and 18.5% (10 of 54) for those who had two sentinel nodes removed (arm C). In patients who had a second sentinel-lymph-node biopsy procedure after neoadjuvant chemotherapy (arm B), the detection rate was 60.8% (95% CI 55.6-65.9; 219 of 360) and the false-negative rate was 51.6% (95% CI 38.7-64.2; 33 of 64). Interpretation: Sentinel-lymph-node biopsy is a reliable diagnostic method before neoadjuvant chemotherapy. After systemic treatment or early sentinel-lymph-node biopsy, the procedure has a lower detection rate and a higher false-negative rate compared with sentinel-lymph-node biopsy done before neoadjuvant chemotherapy. These limitations should be considered if biopsy is planned after neoadjuvant chemotherapy. Funding: Brustkrebs Deutschland, German Society for Senology, German Breast Group.
Article
Sentinel lymph node (SLN) dissection in the management of high-risk melanoma and other cancers, such as breast cancer, has recently increased in use. The procedure identifies an SLN by intradermal or intraparenchymal injection of an isosulfan blue dye, a radiocolloid, or both around the primary malignancy. At the time of selective SLN mapping, 3 to 5 mL of isosulfan blue was injected either intradermally or intraparenchymally around the primary malignancy. From October 1997 to May 2000, 267 patients underwent intraoperative lymphatic mapping with the use of both isosulfan 1% blue dye and radiocolloid injection. Five cases with adverse reactions to isosulfan blue were reviewed. We report 2 cases of anaphylaxis and 3 cases of "blue hives" after injection with isosulfan blue of 267 patients who had intraoperative lymphatic mapping by the procedure described above. The 2 patients with anaphylaxis experienced cardiovascular collapse, erythema, perioral edema, urticaria, and uvular edema. The blue hives in 3 patients resolved and transformed to blue patches during the course of the procedures. The incidence of allergic reactions in our series was 2.0%. As physicians expand the role of SLN mapping, they should consider the use of histamine blockers as prophylaxis and have emergency treatment readily available to treat the life- threatening complication of anaphylactic reaction.
Article
Sentinel lymph node biopsy (SLNB) is an alternative to axillary dissection for many breast cancer patients. Cases of anaphylactic reaction to the isosulfan blue dye used during SLNB have recently been reported. No study on the incidence of serious anaphylactic reactions during SLNB for breast cancer has been reported. We reviewed 639 consecutive SLNBs for breast cancer performed at our institution. Sentinel lymph node biopsy was performed using both isosulfan blue dye and technetium-99m sulfur colloid. Cases of anaphylaxis were reviewed in detail. Overall, 1.1% of patients had severe anaphylactic reactions to isosulfan blue requiring vigorous resuscitation. No deaths or permanent disability occurred. In patients with anaphylaxis, hospital stay was prolonged by a mean of 1.6 days. In 1 patient, the anaphylactic reaction required termination of the operation. Prompt recognition and aggressive treatment of anaphylactic reactions to isosulfan blue are critical to prevent an adverse outcome. Lymphatic mapping with blue dye should be performed in a setting where personnel are trained to recognize and treat anaphylaxis.
Article
Experience with sentinel node biopsy (SNB) after neoadjuvant chemotherapy is limited. We examined the feasibility and accuracy of this procedure within a randomized trial in patients treated with neoadjuvant chemotherapy. During the conduct of National Surgical Adjuvant Breast and Bowel Project trial B-27, several participating surgeons attempted SNB before the required axillary dissection in 428 patients. All underwent lymphatic mapping and an attempt to identify and remove a sentinel node. Lymphatic mapping was performed with radioactive colloid (14.7%), with lymphazurin blue dye alone (29.9%), or with both (54.7%). Success rate for the identification and removal of a sentinel node was 84.8%. Success rate increased significantly with the use of radioisotope (87.6% to 88.9%) versus with the use of lymphazurin alone (78.1%, P = .03). There were no significant differences in success rate according to clinical tumor size, clinical nodal status, age, or calendar year of random assignment. Of 343 patients who had SNB and axillary dissection, the sentinel nodes were positive in 125 patients and were the only positive nodes in 70 patients (56.0%). Of the 218 patients with negative sentinel nodes, nonsentinel nodes were positive in 15 (false-negative rate, 10.7%; 15 of 140 patients). There were no significant differences in false-negative rate according to clinical patient and tumor characteristics, method of lymphatic mapping, or breast tumor response to chemotherapy. These results are comparable to those obtained from multicenter studies evaluating SNB before systemic therapy and suggest that the sentinel node concept is applicable following neoadjuvant chemotherapy.
Article
Lymphatic mapping with sentinel lymph node biopsy has the potential for reducing the morbidity associated with breast carcinoma staging. It has become a widely used technology despite limited data from controlled clinical trials. A systematic review of the world's literature of sentinel lymph node (SLN) biopsy in patients with early-stage breast carcinoma was undertaken by using electronic and hand searching techniques. Only studies that incorporated full axillary lymph node dissection (ALND), regardless of SLN results, were included. Individual study results along with weighted summary measures were estimated using the Mantel-Haenszel method. The correlations of outcomes with the study size, the proportion of positive lymph nodes, the technique used, and the study quality were evaluated. Between 1970 and 2003, 69 trials were reported that met eligibility criteria. Of the 8059 patients who were studied, 7765 patients (96%) had successfully mapped SLNs. The proportion of patients who had successfully mapped SLNs ranged from 41% to 100%, with > 50% of studies reporting a rate < 90%. Lymph node involvement was found in 3132 patients (42%) and ranged from 17% to 74% across studies. The false-negative rate (FNR) ranged from 0% to 29%, averaging 7.3% overall. Eleven trials (15.9%) reported an FNR of 0.0, whereas 26 trials (37.7%) reported an FNR > 10%. Significant inverse correlations were observed between the FNR and both the number of patients studied (r = - 0.42; P < 0.01) and the proportion of patients who had successfully mapped SLNs nodes (r = - 0.32; P = 0.009). Lymphatic mapping with SLN biopsy is used widely to reduce the complications associated with ALND in patients with low-risk breast carcinoma. This systematic review revealed a wide variation in test performance.
Article
In women with breast cancer, sentinel-lymph-node biopsy (SLNB) provides information that allows surgeons to avoid axillary-lymph-node dissection (ALND) if the SLN does not have metastasis, and has a favourable effect on quality of life. Results of our previous trial showed that SLNB accurately screens the ALN for metastasis in breast cancers of diameter 2 mm or less. We aimed to update this trial with results from longer follow-up. Women with breast tumours of diameter 2 cm or less were randomly assigned after breast-conserving surgery either to SLNB and total ALND (ALND group), or to SLNB followed by ALND only if the SLN was involved (SLN group). Analysis was restricted to patients whose tumour characteristics met eligibility criteria after treatment. The main endpoints were the number of axillary metastases in women in the SLN group with negative SLNs, staging power of SLNB, and disease-free and overall survival. Of the 257 patients in the ALND group, 83 (32%) had a positive SLN and 174 (68%) had a negative SLN; eight of those with negative SLNs were found to have false-negative SLNs. Of the 259 patients in the SLN group, 92 (36%) had a positive SLN, and 167 (65%) had a negative SLN. One case of overt clinical axillary metastasis was seen in the follow-up of the 167 women in the SLN group who did not receive ALND (ie, one false-negative). After a median follow-up of 79 months (range 15-97), 34 events associated with breast cancer occurred: 18 in the ALND group, and 16 in the SLN group (log-rank p=0.6). The overall 5-year survival of all patients was 96.4% (95% CI 94.1-98.7) in the ALND group and 98.4% (96.9-100) in the SLN group (log-rank p=0.1). SLNB can allow total ALND to be avoided in patients with negative SLNs, while reducing postoperative morbidity and the costs of hospital stay. The finding that only one overt axillary metastasis occurred during follow-up of patients who did not receive ALND (whereas eight cases were expected) could be explained by various hypotheses, including those from cancer-stem-cell research.
Article
The goals of axillary-lymph-node dissection (ALND) are to maximise survival, provide regional control, and stage the patient. However, this technique has substantial side-effects. The purpose of the B-32 trial is to establish whether sentinel-lymph-node (SLN) resection can achieve the same therapeutic goals as conventional ALND but with decreased side-effects. The aim of this paper is to report the technical success and accuracy of SLN resection plus ALND versus SLN resection alone. 5611 women with invasive breast cancer were randomly assigned to receive either SLN resection followed by immediate conventional ALND (n=2807; group 1) or SLN resection without ALND if SLNs were negative on intraoperative cytology and histological examination (n=2804; group 2) in the B-32 trial. Patients in group 2 underwent ALND if no SLNs were identified or if one or more SLNs were positive on intraoperative cytology or subsequent histological examination. Primary endpoints, including survival, regional control, and morbidity, will be reported later. Secondary endpoints are accuracy and technical success and are reported here. This trial is registered with the Clinical Trial registry, number NCT00003830. Data for technical success were available for 5536 of 5611 patients; 75 declined protocol treatment, had no SLNs removed, or had no SLN resection done. SLNs were successfully removed in 97.2% of patients (5379 of 5536) in both groups combined. Identification of a preincision hot spot was associated with greater SLN removal (98.9% [5072 of 5128]). Only 1.4% (189 of 13171) of SLN specimens were outside of axillary levels I and II. 65.1% (8571 of 13 171) of SLN specimens were both radioactive and blue; a small percentage was identified by palpation only (3.9% [515 of 13 171]). The overall accuracy of SLN resection in patients in group 1 was 97.1% (2544 of 2619; 95% CI 96.4-97.7), with a false-negative rate of 9.8% (75 of 766; 95% CI 7.8-12.2). Differences in tumour location, type of biopsy, and number of SLNs removed significantly affected the false-negative rate. Allergic reactions related to blue dye occurred in 0.7% (37 of 5588) of patients with data on toxic effects. The findings reported here indicate excellent balance in clinical patient characteristics between the two randomised groups and that the success of SLN resection was high. These findings are important because the B-32 trial is the only trial of sufficient size to provide definitive information related to the primary outcome measures of survival and regional control. Removal of more than one SLN and avoidance of excisional biopsy are important variables in reducing the false-negative rate.
Isosulfan blue dye reactions during sentinel lymph node mapping for breast cancer
  • Montgomery