post-Z0011 Era Research Articles

Ultrasound contrast-enhanced patterns of sentinel lymph nodes: predictive value for nodal status and metastatic burden in early breast cancer

In the post-Z0011 era, sentinel lymph node (SLN) status and metastatic burden determine whether axillary management entails conservative sentinel lymph node biopsy (SLNB) or radical axillary lymph node dissection (ALND) in breast cancer patients. However, SLN status and metastatic burden cannot be evaluated preoperatively in clinical practice. This study explored the predictive value of contrast-enhanced ultrasound (CEUS) patterns of SLN to assess the nodal status and metastatic burden in early breast cancer patients. A retrospective study was conducted on 88 consecutive patients who were diagnosed with clinical T1-2N0 breast cancer between December 2020 and November 2021 at the Lanzhou University Second Hospital and scheduled for SLNB. Preoperative CEUS was performed to confirm the location and enhancement pattern of the SLN, and the conventional ultrasonic characteristics of the primary breast lesions and SLN were recorded. Intraoperative localized SLN and postoperative pathological results were used as the gold standard for comparison with preoperative ultrasound findings. CEUS successfully identified at least 1 SLN in 88 patients, with a total of 118 SLNs identified in the entire cohort. Univariate analysis showed that lesion size, blood flow grade, SLN longitudinal diameter, cortical thickness, and enhancement pattern were significant predictive features of SLN metastasis. Further multiple regression analysis indicated that the enhancement pattern of the SLN was an independent risk factor for SLN metastasis, with a sensitivity and a specificity of 84.2% (32/38) and 80.0% (40/50), respectively. Meanwhile, the SLN enhancement pattern could predict the lymph node metastasis burden (P<0.001). In patients presenting with a type I (homogeneous enhancement) or type II (heterogeneous enhancement) SLN, 91.5% (65/71) had ≤2 positive SLNs, whereas in patients with a type III (no enhancement) SLN, 70.6% (12/17) had >2 metastatic nodes. The contrast-enhanced pattern of the SLN is an independent risk factor for SLN status. Patients presenting with a type I or type II SLN enhanced pattern are unlikely to have high-burden metastases detected at their final surgical treatment and omission of ALND may be appropriate.

Omitting axillary lymph node dissection after positive sentinel lymph node in the post-Z0011 era: Compliance with NCCN and ASCO clinical guidelines and Z0011 criteria in a large prospective cohort

In the ACOSOG Z0011 trial, patients with primary breast cancer and 1-2 tumor-involved sentinel lymph nodes (SLNs) undergoing breast-conserving surgery had no oncological outcome benefit after axillary lymph node dissection (ALND), despite a relevant rate of non-SLN metastases of 27%. According to the St Gallen expert consensus, and NCCN and ASCO clinical guidelines, ALND may be avoided in patients who meet all ACOSOG Z0011 inclusion criteria. This recommendation can also be extended to patients undergoing mastectomy, with 1 or 2 positive SLNs and an indication for chest wall radiation, in whom axillary radiotherapy can be proposed as an alternative to completion ALND. The aim of this study was to assess non-compliance with the NCCN and ASCO clinical guidelines and Z0011 criteria, namely the rate of performance of completion ALND when it was not recommended, and the rate of failure to perform completion ALND when recommended. Data were prospectively analysed from T1-2 N0 breast cancer patients undergoing an SLN procedure and treated at the Georges-François Leclerc Cancer Center between November 2015 and May 2017. Factors associated with non-compliance treatment decisions were identified using logistic regression. Among 563 patients included, 122 (21.7%) had at least one positive SLN. ALND was not recommended for 76 patients (62.3%), and was recommended in 46 patients (37.7%). The rate of non-compliant treatment was 32% (39/122) overall: ALND was performed despite not being recommended in 16/76 patients (21.1%) and was not performed in 50% of patients in whom it was recommended (23/46). By multivariate analyses, lymphovascular invasion ((Odds Ratio (OR)=6.1; 95% confidence interval (CI): 1.4-26.7; P=0.02)) and only one SLN removed (OR=9.1; 95%CI: 2.2-33.3; P=0.002) were associated with performance of completion ALND when not recommended. Conversely, >1 SLN removed (OR=5.1; 95%CI: 1.2-22.2; P=0.03) was associated with the failure to perform completion ALND when recommended. Almost one third of patients with invasive breast cancer receive treatment that is not in compliance with recommendations regarding completion ALND.

Economic implications of ACOSOG Z0011 trial application into clinical practice at the European Institute of Oncology

Background and objectivesThe American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated that in clinically node-negative women undergoing breast-conserving therapy (BCT) and found to have metastases to 1 or 2 sentinel nodes, sentinel lymph node biopsy (SLNB) alone resulted in rates of local control, disease-free survival, and overall survival equivalent to those seen after axillary lymph node dissection (ALND), but with significantly lower morbidity. Application of the Z0011 guidelines resulted in fewer ALNDs without affecting locoregional recurrence or survival. Changes in practice inevitably affect health care costs. The current study investigated the actual impact of applying the Z0011 guidelines to eligible patients and determined the costs of care at a single institution. Patients and methodsWe compared axillary nodal management and cost data in breast cancer patients who met the Z0011 criteria and were treated with BCT and SLNB. Patients were allocated into two mutually exclusive cohorts based on the date of surgery: pre-Z0011 (June 2013 to December 2015) and post-Z0011 (June 2016 to December 2018). ResultsOf 3912 patients, 433 (23%) and 357 (17.6%) patients in the pre- and post-Z0011 era had positive lymph nodes. ALND decreased from 15.3% to 1.57% in the post-Z0011 era. The mean overall cost of SLNB in the pre-Z0011 cohort was €1312 per patient, while that for SLNB with completion ALND was €2613. Intraoperative frozen section (FS) use decreased from 100% to 12%. Omitting the FS decreased mean costs from €247 to €176. The mean total cost in the pre-Z0011 cohort was €1807 per patient, while in the post-Z0011 cohort it was €1498. The application of Z0011 resulted in an overall mean cost savings of €309 for each patient. ConclusionsApplication of the Z0011 criteria to patients undergoing BCT at our institution results in more than half a million Euro cost savings.

The value of the intraoperative assessment of the SLN via frozen section in the post Z0011 era

IntroductionSentinel node (SN) assessment via frozen section (FS) has declined since the publication of Z0011 which modified the management of a specific group of patients with positive SN. The risk of misleading the surgeons to a preventable ALND and the cost are among the main factors for that. The aim of our study is to assess the value of FS in the post Z0011. Material and methods244 patients out of 434 were eligible for an upfront SLNB. Based on the final histology and the clinical data we selected the eligible for breast conserving surgery patients (55.4%). 78 patients had positive SN and 26 of them fulfilled the criteria of Z0011. We assessed the false negative findings, the impact on the management and the indications and value of FS in the post Z0011 era. ResultsOverall, there were 12 FN cases out of which 7 were macrometastases (8.97%). Only in one case there were > 2 positive LN and 3 patients needed mastectomy. The remaining cases fulfilled the criteria of Z0011 and needed no further surgery hence in 96.1% of the cases the axillary status was correctly assessed via FS and the reoperation rate was 1.2%. On the contrary, if FS was not used, at least 21.3% of the patents would have needed reoperation based on the today’s guidelines. DiscussionWe believe FS is still valuable and may spare a significant percentage of patients from a second operation (SNB) without leading to axillary overtreatment if used wisely.

Axillary Management in Women with Early Breast Cancer and Limited Sentinel Node Metastasis: A Systematic Review and Metaanalysis of Real-World Evidence in the Post-ACOSOG Z0011 Era.

After the publication of the Z0011 trial, the American Society of Clinical Oncology published an updated clinical practice guideline stating that clinicians should not recommend axillary lymph node dissection (ALND) for early-stage breast cancer patients with the involvement of one or two sentinel lymph nodes (SLNs). However, these recommendations have been challenged because they were mainly based on data from limited studies. The aim of the current study is to systematically compare the real-world outcomes of SLN biopsy (SLNB) alone and SLNB + ALND in patients with early-stage breast cancers and limited positive SLN metastasis in the post-Z0011 era PATIENTS AND METHODS: We searched articles in the PubMed, EMBASE, and Cochrane library databases. The primary endpoints were overall survival (OS) and disease-free survival (DFS). The secondary endpoints were recurrence rate and the incidence of lymphedema. One randomized controlled trial and six retrospective studies with 8864 patients were retrieved. For patients with early-stage breast cancer with one or two SLN metastases, receiving SLNB alone showed no significant difference in OS, DFS, and recurrence rate compared with receiving SLNB + ALND. The incidence of lymphedema in patients who received SLNB alone was significantly lower than those who received SLNB + ALND (odds ratio 1.95, 95% confidence interval 1.02-3.71). Current real-world evidence proved that the Z0011 strategy is safe with respect to survival outcomes and effective in reducing the incidence of lymphedema. ALND should be avoided in patients with early-stage breast cancer with one or two SLN metastases in the post-Z0011 era.

National Trend of Axillary Management in Clinical T3/T4 N0 Patients Having Breast Conserving Therapy

BackgroundThe ACOSOG Z0011 trial has essentially eliminated axillary lymph node dissection (ALND) in breast conserving therapy (BCT) patients with clinical T1/T2 and 1-2 positive sentinel lymph nodes (SLNs). Currently, ALND is recommended for positive SLNs unless ACOSOG Z0011 criteria are applicable. We aimed to assess the national trends and axillary management before and after the publication of ACOSOG Z0011 for larger tumors. MethodsAn IRB-approved study evaluated the National Cancer Database from 2006 to 2016. Women with clinical T3/T4, N0 who otherwise fit ACOSOG Z0011 criteria were included. Neoadjuvant systemic therapy or known nodal disease was excluded. Clinicopathologic data were compared between two timeframes based on ACOSOZ Z0011 publication and by axillary management. Patients were categorized into SLNB alone (1-5 lymph nodes examined) and ALND (≥10 lymph nodes examined) groups. ResultsA total of 230 women fit inclusion criteria, of whom 36% underwent ALND. ALND use decreased from 54% in 2006 to 14% in 2016 (P < 0.01). Comparing ALND to SLNB alone within the pre-Z0011 era, comprehensive community cancer programs had higher proportions of ALND, whereas academic centers had higher rates of SLND alone (P = 0.03). Comparing similar axillary management between eras, SLNB-alone patients in the post-Z0011 era had higher pT and pN stages, were less likely to be Her2 positive, and were more likely to receive systemic treatment. ConclusionsThere is a national trend to forgo ALND in women who have tumors larger than those included in the Z0011 criteria without any clear clinicopathologic indications.

Role of sonoelastography in assessment of axillary lymph nodes in breast cancer: a systematic review and meta-analysis

To evaluate the effectiveness of shear-wave elastography (SWE) and strain elastography (SE) for axillary lymph nodes (ALNs). PubMed, Embase, and Cochrane Library databases were searched until September 2018. Weighted mean difference was calculated for continuous variables. The accuracy of sonoelastography was assessed by calculating pooled sensitivity, specificity, area under the curve (AUC), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). All data were analysed using Stata 12.0. Ten studies with 1,038 ALNs were included in the meta-analysis. Five studies evaluated the use of SE, and the other five evaluated the SWE. The SWE stiffness values of malignant ALNs were significantly higher than those of benign nodes. Both SE and SWE have relatively high specificity and sensitivity. The max stiffness in SWE showed the highest specificity (0.94; 95% confidence interval [CI], 0.81-0.98), PLR (12.1; 95% CI, 4-36.5), NLR (0.29; 95% CI, 0.12-0.69), AUC (0.94; 95% CI, 0.91-0.96), and DOR (42; 95% CI, 12-154); in contrast, the mean stiffness showed the highest sensitivity (0.80; 95% CI, 0.61-0.91). Sonoelastography demonstrated high sensitivity and specificity for differentiating between malignant and benign ALNs. The max and mean stiffness on SWE appeared to exhibit the highest accuracy. Thus, SWE is an effective accompaniment to sentinel node biopsy, and is appropriate for preoperative assessment of ALNs in the post-Z0011 era.

Could axillary clearance be avoided in clinically node-negative breast cancer patients with positive nodes diagnosed by ultrasound guided biopsy in the post-ACOSOG Z0011 era?

Background and objectivesThe role of ultrasound (US) guided biopsy in selecting patients for an upfront lymph node dissection (ALND) has been controversial following the publication of the American College of Surgeons (ACOSOG) Z0011 data. The purpose of this study was to investigate if patients with positive axillary lymph nodes (LNs) proven by US guided biopsy should be recommended for ALND and to analyze the utility of preoperative US and US guided biopsy in planning axillary surgery to avoid both unnecessary ALND and unnecessary SLNB.MethodsPatients with a positive preoperative LN biopsy were identified and evaluated to determine their suitability for inclusion according to the criteria proposed in the Z0011 data. The correlation of the number of suspicious nodes found using US with the number of positive nodes on ALND was studied.ResultsA total of 261 breast cancer patients who had a positive preoperative LN needle biopsy were identified, among them, 79 patients with cT1–2N0 breast cancer and ALND were enrolled in the study. Thirty-one patients (39.2%) had ≤2 positive nodes identified in pathology and 10 patients (12.7%) met all of the Z0011 criteria and might have been spared ALND. A significantly greater proportion of women with ≥3 positive nodes during ALND had >1 abnormal LN identified using US compared to women with ≤2 positive LNs found using ALND (66.7% vs. 6.5%, p<0.0001).ConclusionUS with needle biopsy is valuable to patients with multiple suspicious nodes found using US while SLND without US guided needle biopsy is suggested if only one abnormal LN is detected on US in the post-Z0011 era.

Axillary lymph node dissection (ALND) training in a post-Z0011 Era–A national survey of UK breast surgery trainees

Axillary lymph node dissection (ALND) training in a post-Z0011 Era–A national survey of UK breast surgery trainees

Predicting Nodal Burden in Clinically N0 Breast Cancer: A Comparison Between Ultrasound-Guided Fine Needle Aspiration Cytology (FNAC) and Sentinel Lymph Node Biopsy (SLNB)

Post-Z0011 era there is much debate on omitting axillary clearance in select group of patients. However, there is difference in nodal burden in SLNB and FNAC positive group even though both are clinically N0. This study compares the nodal burden in SLNB and FNAC positive patients of clinically N0 breast cancer. Retrospective data collection was done for a period between June 2014 and May 2016 from institutional-based cancer registry for clinically N0 breast cancer patients. A total of 72 patients with SLNB and image-guided FNAC positive node and who underwent complete ALND were found to be eligible for the present study. Out of 72 patients, who underwent complete ALND, 45 were US-FNAC positive and 27 were SLNB positive. Ultrasound-guided FNAC positive patients had higher nodal burden N2 (31.1 vs. 7.4%) and N3 (22.22% vs. 0) compared with SLNB positive patients. Ultrasound-guided FNAC positive patients had higher hormone receptor negative and Her2/neu positive tumor with high Ki 67 (>20%) compared with SLNB positive group. Mean positive lymph nodes in FNAC group were 5.16 ± 4.781 compared to 1.67 ± 1.074 in SLNB positive groups. Among 27 SLNB positive patients, sentinel lymph node was the only positive node in 20 patients and 5 had just one additional positive node. Ultrasound FNAC positivity predicts higher nodal burden in clinically N0 patients compared with SLNB positive patients. Further studies are needed to support above findings and to define patients in FNAC positive group which can be exempted from complete ALND.

Healthcare Costs Reduced After Incorporating the Results of the American College of Surgeons Oncology Group Z0011 Trial into Clinical Practice.

The purpose of our study was to quantitate the changes in axillary lymph node dissection (ALND), frozen section (FS), and the impact on costs after the publication of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial. We compared axillary nodal management and cost data in breast cancer patients who met Z0011 criteria and were treated with lumpectomy and sentinel lymph nodes (SLN) biopsy from 2007 to July 2013. Of 800 patients, 67 (13.5%) and 34 (12.5%) patients in the pre- and post-Z0011 era had 1-2 positive SLN. ALND decreased from 78% to 21% (p < 0.001) after publication of Z0011. The mean overall cost of SLN biopsy was $41,059 per patient, while SLN biopsy with completion ALND was $50,999 (p < 0.001). Intraoperative FS use decreased from 95% to 66% (p = 0.015). Omitting the FS decreased mean costs from $4,319 to $2,036. The application of Z0011 resulted in an overall mean cost savings of $571,653 from 2011 to July 2013. ACOSOG Z0011 significantly impacted axillary management resulting in a 20% reduction in the mean overall cost per patient by omitting ALND. In these patients, intraoperative FS analysis had poor sensitivity (56%) and doubled the cost of pathologic examination. Fewer ALND and intraoperative FS were performed after the publication of ACOSOG Z0011. Eliminating FS and ALND in patients who met Z0011 criteria, results in significant cost savings.

Personalization of loco-regional care for primary breast cancer patients (part 1).

ABSTRACT Kyoto Breast Cancer Consensus Conference, Kyoto, Japan, 18-20 February 2014 The loco-regional management of breast cancer is increasingly complex with application of primary systemic therapies, oncoplastic techniques and genetic testing for breast cancer susceptibility. Personalization of loco-regional treatment is integral to optimization of breast cancer care. Clinical and pathological tumor stage, biological features and host factors influence loco-regional treatment strategies and extent of surgical procedures. Key issues including axillary staging, axillary treatment, radiation therapy, primary systemic therapy (PST), preoperative hormonal therapy and genetic predisposition were identified and discussed at the Kyoto Breast Cancer Consensus Conference (KBCCC2014). In the first of a two part conference scene, consensus recommendations for axillary management are presented and focus on the following topics: indications for completion axillary lymph node dissection in primary surgical patients with ≤2 macrometastases or any sentinel nodal deposits after PST; the timing of sentinel lymph node biopsy in the context of PST; use of axillary irradiation as a component of primary treatment plans and the role of intraoperative node assessment in the post-Z0011 era.

The clinical utility of assessment of the axilla in women with suspicious screen detected breast lesions in the post Z0011 era.

Axillary ultrasound (AUS) and biopsy are now part of the preoperative assessment of breast cancer based on the assumption that any nodal disease is an indication for axillary clearance (AC). The Z0011 trial erodes this assumption. We applied Z0011 eligibility criteria to patients with screen detected cancers and positive axillary assessment to determine the relevance of AUS to contemporary practice. Women screened between 1/1/2012 and 30/6/2013 and assessed for lesions with highly suspicious imaging features are included. We analysed demographic and assessment data and ascertained the final histopathology with particular reference to axillary nodal status. Among 449 lesions, AUS was recorded in 303 lesions (67.5 %). 290 (96 %) were carcinomas, 30.3 % with nodal disease. AUS was abnormal in 46 (15.9 %). AUS had a sensitivity of 39.8 %, specificity 94.6 %, positive predictive value (PPV) 79.2 % and negative predictive value (NPV) 78.1 %. Axillary FNAB was positive in 27 women, suspicious in two, benign in 16 and not performed in one. In one FNA positive case, the lesion was a nodular breast primary in the axillary tail in a multifocal breast cancer. Combining AUS and FNAB, the sensitivity was 76.5 %, specificity 90.9 %, PPV 96.3 % and NPV 55.6 %. Applying the Z0011 inclusion criteria, 24 of the 27 (88.9 %) women with abnormal AUS and positive FNA were ineligible for Z0011-based management. Of three women eligible for Z0011, one proceeded to AC after SN biopsy, leaving only two women (7.4 %) who might have been considered for SN only management had it not been for the results of the axillary assessment. Among women with negative AUS, nodal metastasis was demonstrated in 21.7 %, 86.8 % of these women having only 1-2 positive nodes. Abnormal AUS and FNA preferentially identify candidates for AC. Negative AUS predicts negative or low nodal burden. Axillary assessment streamlines care.