American College Of Surgeons Oncology Group Research Articles

The prevalence of non-sentinel lymph node metastasis among breast cancer patients with sentinel lymph node involvement and its impact on clinical decision-making: a single-centred retrospective study.

Sentinel lymph node biopsy (SLNB) has become standard procedure for early breast cancer patients with clinically node negative disease. The patients with SLN metastasis normally underwent axillary lymph node dissection (ALND). However, the metastatic status of non-sentinel Lymph nodes (non-SLNs) varied significantly in different reports. Here, we evaluated the prevalence of non-SLNs metastasis among breast cancer patients with sentinel lymph node metastasis and its impact on clinical decision-making. We identified 892 female patients with operable cT1-3N0 invasive breast cancer who underwent ALND in our center due to SLN metastasis from 2017 to 2023, retrospectively. The prevalence of non-SLN metastasis among different clinicopathological traits and its correlation with the number of positive SLNs were analyzed. The optimal clinical decision-making was generalized. The median number of SLN+, SLN, non-SLN+ and non-SLN was 2, 4, 1 and 14 among the enrolled 892 female patients, respectively. 504 (56.50%) patients with SLN + had at least one metastatic lymph node in the harvested non-SLNs. Among the enrolled 892 female patients, 435 (48.77%) patients with 1 positive SLN, of which 180 (41.38%) had at least one additional metastatic non-SLNs. 242 (27.13%) patients with 2 positive SLNs, of which 146 (60.33%) had at least one metastatic non-SLNs. For the rest 215 (24.10%) patients with at least 3 metastatic SLNs, 178 (82.79%) had at least one metastatic non-SLNs. In the univariate analysis, the non-SLNs metastatic status was correlated with the number of SLNs+, tumor size, tumor grade, lymphovascular invasion (LVI) and molecular subtypes, but not histopathologic type. In the multivariate analysis, the risk of additional non-SLNs metastasis correlated with the number of SLNs+, SLNs, non-SLNs and LVI. Omiting ALND in patients with higher non-SLNs + rate outside the American College of Surgeons Oncology Group (ACSOG) Z0011 and the European Organization for Research and Treatment of Cancer (EORTC) 10,981-22023 AMAROS criteria should be considered with caution in clinical decision-making. To evaluate whether axillary radiotherapy and ALND provides equivalent regional control in breast cancer patients with obvious residual metastatic lymph nodes undesected in the axilla, a well-matched prospective randomized controlled trial is an urgent need.

Should Palpable Nodes Be Exclusionary in Patients Who Are Otherwise Candidates for ACOSOG Z0011-Type Trials?

Palpable nodes were exclusionary in American College of Surgeons Oncology Group (ACOSOG) Z0011, while SINODAR-ONE excluded those with positive axillary nodes by palpation and ultrasound. To determine whether clinical nodal status should be exclusionary in those fulfilling pathologic criteria for ACOSOG Z0011 and similar trials, this study analyzed the accuracy and implications of clinical nodal positivity. Patients ≥ 18years old with cT1-T2, cN0-cN1, M0 breast cancer were identified in the National Cancer Database between 2004 and 2019. Subset characteristics of cN1 and cN0 were compared with respect to final pathologic nodal status and overall survival (OS). Of 57,823 patients identified, 77.0% were cT1 and 23.0% were cT2. Of the 93.9% of patients who were staged as cN0, 16.7% were pN1; of the remaining 6.1% staged as cN1, 9.6% were found to be pN0. Among cN1/pN0 patients, 14.9% underwent axillary dissection without sentinel node biopsy. There was no difference in adjusted OS for patients staged as cN0 versus cN1 who were found to be pN1 (HR 1.13, 95% CI 0.93-1.37, p = 0.22), a finding that persisted on subset analysis in those with two positive nodes (HR 0.91, 95% CI 0.62-1.33, p = 0.63). Clinical nodal stage does not affect OS in pN1 patients. Clinical nodal assessment can both overstage patients and result in unnecessary axillary surgery. These data suggest that cN1 patients who are otherwise candidates for a Z0011-like paradigm should still be considered eligible. Their final candidacy should be determined by surgical lymph node pathology and not preoperative clinical status.

Comparison of clinical characteristics between ACOSOG Z0011-eligible cohort and sentinel lymph node-positive breast cancer patients in Hong Kong.

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial resulted in de-escalation of axillary surgery among early-stage breast cancer patients with low-volume sentinel lymph node (SLN) disease undergoing breast-conserving surgery and radiation therapy. Nevertheless, the mastectomy rate in the Chinese population remains high. This study compared the clinical characteristics of the ACOSOG Z0011-eligible cohort with SLN-positive breast cancer patients in Hong Kong. This retrospective analysis of a prospectively maintained database at a university-affiliated breast cancer centre in Hong Kong was performed from June 2014 to May 2019. The database included all patients with clinical tumour (T) stage T1 or T2 invasive breast carcinoma, no palpable adenopathy, one or two positive SLNs on histological examination, and no prior neoadjuvant systemic treatment. Comparisons were made between the mastectomy and breast-conserving treatment groups in our cohort, along with the sentinel-alone arm in the ACOSOG Z0011 trial. One hundred and seventy-one patients met the inclusion criteria: 112 underwent mastectomy and 59 underwent breast-conserving treatment. Our mastectomy group had higher prevalences of T2 tumours (P<0.001), lymphovascular invasion (P<0.001), and SLN macrometastases (P=0.004) compared with the ACOSOG Z0011 cohort. However, in our patient population, mean pathological size slightly differed between the mastectomy and breast-conserving treatment groups (2.2 cm vs 1.8 cm; P=0.005). Other histopathological features were similar. This study demonstrated that clinicopathological features were comparable between SLN-positive breast cancer patients undergoing mastectomy and those undergoing breast-conserving treatment. Low-risk SLN-positive mastectomy patients may safely avoid completion axillary lymph node dissection.

A nomogram for predicting three or more axillary lymph node involvement before breast cancer surgery

Based on the American College of Surgeons Oncology Group (ACOSOG)-Z0011, a useful nomogram has been constructed to identify patients who do not require intraoperative frozen sections to evaluate sentinel lymph nodes in the previous study. This study investigated the developed nomogram by ultrasonography (US) and positron emission tomography (PET)/computed tomography (CT) as a modality. In the training set, 89/1030 (8.6%) patients had three or more positive nodes. Larger tumor size, higher grade ultrasonographic ALN classification, and findings suspicious of positive ALN on PET/CT were associated in multivariate analysis. The areas under the receiver operating characteristic curve (AUC) of the nomogram were 0.856 [95% CI 0.815–0.897] in the training set. The AUC in the validation set was 0.866 [95% CI 0.799–0.934]. Application of the nomogram to 1067 patients who met the inclusion criteria of ACOSOG-Z0011 showed that 90 (8.4%) patients had scores above the cut-off and a false-negative result was 37 (3.8%) patients. And the specificity was 93.8%, and the negative predictive value was 96.4%. The upgraded nomogram improved the predictive accuracy, using only US and PET/CT. This nomogram is useful for identifying patients who do not require intraoperative analysis of sentinel lymph nodes and considering candidates for identifying neoadjuvant chemotherapy. The patients consisted of clinical T1-2 and node-negative invasive breast cancer. The training and validation set consisted of 1030 and 781 patients, respectively. A nomogram was constructed by analyzing factors related to three or more axillary lymph node metastases. The patients who matched the ACOSOG-Z0011 criteria were selected and applied to the new nomogram.

Axillary Needle Biopsy in the Era of American College of Surgeons Oncology Group (ACOSOG) Z0011: Institutional Experience With a Largely Urban Minority Population and Review of the Literature

Background: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated that sentinel lymph node biopsy (SLNB) alone is adequate for axillary control in patients with one to two positive axillary lymph nodes. However, axillary lymph node dissection (ALND) is required in patients with N1 disease diagnosed with a preoperative needle biopsy. In this report, we determined how many patients could potentially have had SNB alone based on finding only one to two positive nodes in the axilla.Methods: A retrospective review of patients with positive preoperative axillary needle biopsy undergoing ALND was used to identify rates of high volume axillary disease (>2 positive nodes). Wilcoxon’s rank-sum and Fisher’s exact test were used for statistical analysis. A review of the literature is included for comparison.Results: 73% of 51 total patients with a positive needle biopsy had >2 positive nodes on axillary dissection. The high-volume axillary disease was significantly more likely with the presence of lymphovascular invasion and extranodal extension.Conclusions: Patients with positive preoperative axillary needle biopsies have a significantly higher rate of high volume axillary disease. However, at least one-quarter of these patients will have <3 positive nodes and potentially could have been treated with SNB alone.

Avoiding unnecessary intraoperative sentinel lymph node frozen section biopsy of patients with early breast cancer.

PurposeAfter the publication of the ACOSOG (American College of Surgeons Oncology Group) Z0011 trial, the rate of axillary lymph node dissection has reduced. Thus, the need for intraoperative frozen section biopsy of sentinel lymph nodes (SLNs) has become controversial. We identified patients for whom intraoperative SLN frozen section biopsy could be omitted and found that frozen section biopsy rate can be reduced.MethodsWe reviewed the records of patients with tumors ≤5 cm in diameter who underwent breast-conserving surgery between January 2013 and December 2019 at Seoul St. Mary’s Hospital. Clinicopathological and imaging characteristics were compared according to number of positive SLNs (0–2 SLNs positive vs. ≥3 SLNs positive).ResultsA total of 1,983 patients were included in this study. Thirty-two patients (1.6%) had at least 3 positive SLNs. Patients with ≥3 positive SLNs had significantly larger tumors and were more frequently high-grade tumors (P < 0.001 and P = 0.002, respectively). Identification of suspicious lymph nodes on imaging studies was also associated with the presence of ≥3 positive SLNs (hazard ratio, 11.54; 95% confidence interval, 4.42–30.10). All patients with none or only 1 suspicious lymph node on any imaging modality (n = 647, 32.6%) had 0–2 positive SLNs. Also, among patients with clinical T1-stage tumors and at least 2 suspicious lymph nodes on only 1 imaging modality (n = 514, 25.9%), only 2 cases had ≥3 positive SLNs.ConclusionWe found that intraoperative SLN frozen biopsy could be omitted in patients using tumor size and axillary lymph node status on imaging modality.

Neoadjuvant Endocrine Therapy as an Alternative to Neoadjuvant Chemotherapy Among Hormone Receptor-Positive Breast Cancer Patients: Pathologic and Surgical Outcomes.

BackgroundNeoadjuvant chemotherapy (NCT) is considered more effective in downstaging hormone receptor-positive (HR+) breast cancer than neoadjuvant endocrine therapy (NET), particularly in node-positive disease. This study compared breast and axillary response and survival after NCT and NET in HR+ breast cancer.MethodsBased on American College of Surgeons Oncology Group (ACOSOG) Z1031 criteria, women age 50 years or older with cT2-4 HR+ breast cancer who underwent NET or NCT and surgery were identified in the National Cancer Database 2010–2016. Chi-square and logistic regression analysis determined differences between the NCT and NET groups and therapy response, including downstaging and pathologic complete response (pCR, ypT0/is and ypN0).ResultsOf 19,829 patients, 14,025 (70.7%) received NCT and 5804 (29.3%) received NET. The NET patients were older (mean age, 68.9 vs. 60.3; P < 0.001) and had greater comorbidity (1+ Charlson–Deyo score, 21% vs. 16%; P < 0.001). Therapy achieved T downstaging (any) for 58% of the patients with NCT versus 40.5% of the patients with NET, and in-breast pCR was achieved for 9.3% of the NCT versus 1.3% of the NET patients (P < 0.001). Approximately half of the mastectomy procedures could have been potentially avoided for the patients with in-breast pCR (53.6% of the NCT and 43.8% of the NET patients). For the cN+ patients, N downstaging (any) was 29% for the NCT patients versus 18.3% for the NET patients (P < 0.001), and nodal pCR was achieved for 20.3% of the NCT versus 13.5% of the NET patients (P < 0.001). Among those with nodal pCR, axillary lymph node dissection (ALND) still was performed for 56% of the patients after NCT and 45% of the patients after NET.ConclusionsAlthough the response rates after NCT were higher, NET achieved both T and N downstaging and pCR. Neoadjuvant endocrine therapy can be used to de-escalate surgery for patients who cannot tolerate NCT or when chemotherapy may not be effective based on genomic testing.Supplementary InformationThe online version contains supplementary material available at 10.1245/s10434-021-10459-3.

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.

Costes asociados al diagnóstico y tratamiento quirúrgico del cáncer de mama precoz

ObjectiveThe aim of our study was to identify the costs associated with the diagnosis and surgical procedure in a cohort of patients with early breast cancer. MethodWe performed a costs study, referred to the preoperatory radiological-histological study, surgical procedure and inpatient/outpatient health service in a cohort of 224 patients diagnosed and operated on early-stage breast from June 2012 to December 2016. ResultsBreast conserving surgery in outpatient health service applied to lumpectomy with sentinel lymph node biopsy compared to carrying it out in the inpatient setting, contributed to a saving of 2085€ per patient, and total of 289,815€. Following the ACOSOG (American College of Surgeons Oncology Group) trial in 18 patients with tumor-involved sentinel node, no further axillary specific treatment (completion of lymphadenectomy) was made, allowing a saving of 37,530€. In most patients our study have not showed benefit from diagnostic/preoperative breast MRI, leading to an over cost of 37,179€. The surgical rescission without showing the presence of residual tumor burden, led to an additional cost of 11,592€. Conclusions-Breast conserving surgery with sentinel lymph node biopsy in outpatient health service supposed an important economical saving of resources, without compromising the well-being and prognosis of our patients.-The diagnostic/preoperative MRI in all the patients and the surgical rescissions led to an over cost that could be avoided in most of the cases.

ACOSOG Z-0011 criteria impact on axillary surgery for early breast cancer in clinical practice: Evaluation in a retrospective cohort of 1900 patients

BackgroundThere is a trend towards de-escalation in early breast cancer axillary surgery. In the American College of Surgeons Oncology Group (ACOSOG) Z-0011 trial, observation was shown to be non-inferior in terms of overall survival to complementary axillary lymph node dissection (cALND) in patients with up to two sentinel lymph node (SLN) metastases. The study included patients with T1-T2 invasive breast cancer, clinically node negative, undergoing breast-conserving surgery with SLN biopsy, followed by systemic therapy and radiotherapy. The aim of our study was to evaluate the impact of applying these ACOSOG Z-0011 inclusion criteria in routine practice. Patients and methodsThis retrospective observational study was conducted in a French comprehensive cancer center where patients treated for breast cancer with primary surgery were prospectively included between 2010 and 2016. Patients meeting ACOSOG Z-0011 inclusion criteria were analyzed. ResultsAmong the 1900 included patients, 1497 (79 %) met the ACOSOG Z-0011 criteria before surgery. Of these, 390 (20 %) had one or two metastatic SLN and could have avoided cALND. Out of these patients, 319 (81 %) presented cT1 tumors. During the study period, cALND was performed in 320 (82 %) patients and was free of metastases in 80 % of cases, having an impact on eligibility for adjuvant chemotherapy in only 3 (0.8 %) patients. ConclusionsIn situations of primary breast cancer surgery, use of ACOSOG Z-0011 criteria could reduce the rate of cALND by 20 %. Further studies are needed to help select patients for whom abstention from any axillary surgery would be reasonable.

Impact of Axillary Dissection Among Patients With Sentinel Node-Positive Breast Cancer Undergoing Mastectomy.

Results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial supports omission of completion axillary lymph node dissection (CLND) after breast-conservation surgery with a positive sentinel lymph node biopsy (SLNB). We hypothesized that CLND also does not impact outcomes in women with clinically node-negative (cN0), pathologically node-positive breast cancer undergoing mastectomy. A single-institution retrospective review was performed of patients with SLN-positive breast cancer treated from July 1999 through May 2018. Clinicopathologic and outcome data were collected. Patients with SLNBs were compared with those receiving SLNB and CLND. The Kruskal-Wallis, chi-square, and Fisher exact tests were used to assess for differences between continuous and categorical variables. The log-rank test was used for time-to-event analyses, and Cox proportional hazards models were fit for locoregional and distant recurrence and overall survival (OS). Of 329 patients with SLN-positive breast cancer undergoing mastectomy, 60% had CLND (n=201). Median age at diagnosis was 53 years (interquartile range [IQR], 46-62 years). The median number of SLNs sampled was 3 (IQR, 2-4), and the median number of positive SLNs was 1 (IQR, 1-2). Patients receiving CLND had higher tumor grades (P=.02) and a higher proportion of hormone receptor negativity (estrogen receptor, 19%; progesterone receptor, 27%; both P=.007). A total of 44 patients (22%) had increased N stage after CLND. Median follow-up was 51 months (IQR, 29-83 months). No association was found between CLND and change in OS and locoregional or distant recurrence. Completion of postmastectomy radiotherapy was associated with improved OS (P=.04). CLND is not significantly correlated with reduced recurrence or improved OS among patients who have cN0, SLN-positive breast cancer treated with mastectomy. CLND was significantly correlated with receipt of adjuvant systemic therapy. Completion of postmastectomy radiotherapy was associated with improved OS.

Extranodal Tumor Deposits in the Axillary Fat Indicate the Need for Axillary Dissection Among T1-T2cN0 Patients with Positive Sentinel Nodes.

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated the safety of omitting axillary lymph node dissection (ALND) in T1-T2cN0 patients with fewer than three positive sentinel nodes (SLNs) undergoing breast-conservation therapy. While microscopic extracapsular extension (mECE) > 2mm is associated with increased nodal burden, the significance of extranodal tumor deposits (ETDs) in the axillary fat is uncertain. Consecutive patients with T1-T2cN0 breast cancer undergoing sentinel node biopsy and ALND for SLN metastases from January 2010 to December 2018 were identified. ETDs were defined as intravascular tumor emboli or metastatic deposits in the axillary fat. Clinicopathologic characteristics and nodal burden were compared by ETD status. Among 1114 patients, 113 (10%) had ETDs: 81 (72%) were intravascular tumor emboli and 32 (28%) were soft tissue deposits. Patients with ETDs had larger tumors (median 2.2 vs. 2.1cm; p = 0.033) and more often had mECE (83% vs. 44%; p < 0.001). On univariable analysis, presence of ETDs (odds ratio [OR] 9.66, 95% confidence interval [CI] 6.36-14.68), larger tumors (OR 1.47, 95% CI 1.25-1.72), and mECE (OR 10.73, 95% CI 6.86-16.78) were associated with four or more additional positive non-SLNs (NSLNs; all p < 0.001). On multivariable analysis, ETDs remained associated with four or more positive NSLNs (OR 5.67, 95% CI 3.53-9.08; p < 0.001). ETDs were strongly associated with four or more positive NSLNs (OR 7.15, 95% CI 4.04-12.67) among patients with one to two positive SLNs (n = 925). Among T1-T2cN0 patients with SLN metastases, ETDs are strongly associated with four or more positive NSLNs at ALND. Even among those who may otherwise meet the criteria for omission of ALND, the presence of ETDs in axillary fat warrants consideration of ALND.

Application of the Z1071 criteria: classification of axillary lymph nodes on ultrasound after neoadjuvant chemotherapy in initially node-positive breast cancer.

The American College of Surgeons Oncology Group (ACOSOG) Z1071 trial assessed the accuracy of sentinel lymph node biopsies in clinically node-positive patients who underwent neoadjuvant chemotherapy (NAC). Axillary ultrasound (US) images after NAC were reviewed, and the accuracy of classifying nodes into six types according to the ACOSOG Z1071 trial was determined. This study included 69 patients who underwent NAC followed by curative surgery for breast cancer including axillary lymph node dissection between January 2010 and July 2019. All patients were pathologically confirmed as being initially node positive. Lymph nodes were retrospectively classified into one of six types based on the appearance of the nodal cortex and hilum. Types I and II were classified as having normal nodal morphology, whereas types III, IV, V, and VI were classified as having suspicious nodal morphology. These node types on US images after NAC were compared between patients with an axillary complete response (Ax-pCR) and those with residual metastatic lymph nodes (Ax-non-pCR) using Chi-square tests. Twenty-four (35%) of the 69 patients achieved Ax-pCR. Patients with nodes classified as type I or II were more likely to achieve Ax-pCR (83% vs. 36%, p = 0. 0002). The classification of six node types was associated with nodal status.

Abstract P4-02-14: Impact of ACOSOG Z0011 trial at University Hospital in Brazil

Abstract Background: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trialwas a milestone in the surgical treatment of the axilla. Its results have made significant contributions in reducing the extent of breast surgery. In Brazil, this new approach was questioned, since the survival of the disease remains lower in the developing countries due to the difficulty in the early diagnosis, delay in the treatment and diagnosis in more advanced stages. Objective: To evaluate the overall survival and locoregional recurrence in patients with sentinel lymph node (SLN) metastatic from breast cancer with or without complete axillary lymph node dissection (ALND) treated at our institution. Methods: This retrospective cohort study evaluated patients with primary invasive breast cancer and clinically negative axilla who underwent lumpectomy and sentinel lymph node dissection (SLND) at the São Paulo Hospital, from February 2008 to December 2018. Patients with metastatic SLN were treated with SLND (group 1) or ALND (group 2). Group 1 was composed by the patients who met the inclusion criteria of ACOSOG Z0011 trial. Group 2 was composed by patients treated previous to the publication or by patients that had exclusion criteria according ACOSOG Z0011 trial. Overall survival was defined as the time relapsed from the date of surgery to death from any cause. Locoregional recurrence was determined by the presence of disease in the breast or ipsilateral lymph nodes in the axilla, supraclavicular, infraclavicular or internal mammary. Survival was analyzed with Kaplan-Meier method and comparison among groups with log-rank. Cox proportional-hazards model were applied. Statistical analysis was performed in SPSS version 20.0 and STATA12, with p value &amp;lt;0.05 considered significant. Results: A total of 415 patients were included in this study, 23.3% (97 patients) were identified as metastatic SLN, 56 patients were treated with SLND only (group 1) and 41 patients with ALND (group 2). The groups were homogeneous in relation to the variables: age group (50 years versus 51 years and over) (p = 0.279), race (p = 0.120), level of education (p = 0.142), pathological diagnosis (p = 0.210), histological grade (p = 0.983), hormonal receptors (p = 0.708), HER2 status (p = 0.695), pT (p = 0.334). Average age was 58.3 years (group 1) and 56.3 years (group 2), p = 0.456; and average tumor size was 1.8 cm (group 1) and 2.2 cm (group 2), p = 0.048. In group 1, the average number of resected lymph nodes was 2.7 and 91% of the cases only 1 lymph node was positive. In group 2, the average number of positive lymph nodes was 3.5 and only 17% had additional axillary disease. The SLND presented 35.7% micrometastasis compared to 2.4% in ALND (p &amp;lt;0.001) and a lower number of capsular extravasation (8.9%), in contrast to 41.5% in the ALND group (p &amp;lt;0.001). In addition, ALND group also had greater axillary involvement as evidenced by axillary pathological staging, with N1 (73.2%), N2 (19.5%), N3 (4.9%) and SLND group with N1 (62.5%) and no cases N2 or N3 (p &amp;lt;0.001). The average survival time, estimated using the Kaplan-Meier model, was 9.18 years (95% CI: 8.47-9.90). There was no difference in overall survival between patients who underwent SLND alone or ALND. The 5-year survival was 80.1% in the SLND and 87.5% in the ALND (p = 0.376). The locoregional recurrence was a rare event, average time of 5 years was 1.8% SLND and 7.7% ALND (p = 0.196). Only 4 locoregional recurrences were described and all occurred within 18 months of follow-up. Conclusions: Overall survival and locoregional recurrence in patients with metastatic axillary sentinel lymph node treated with SLND alone did not differ from those who underwent ALND, corroborating ACOSOG Z0011 data. The omission of axillary lymph node dissection and the implementation of this practice in our service benefits the patients treated with less aggressive surgeries and, potentially, produces lower morbidity. Citation Format: Afonso CelsoPinto Nazário, Simone Elias, Gil Facina, Vanessa Monteiro Sanvido. Impact of ACOSOG Z0011 trial at University Hospital in Brazil [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-02-14.

Assessment of prognosis in patients with invasive breast cancer and metastatic sentinel lymph node treated with or without axillary lymphadenectomy

Introduction: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial was a landmark in axillary surgical treatment. Its results brought significant contributions to the reduction of the extension of breast cancer surgery. However, this approach was questioned at first. Objectives: To assess the global survival and the locoregional recurrence in patients with metastatic sentinel lymph node biopsy treated with or without axillary lymphadenectomy (AL). Method: A historical cohort study was carried out with patients with primary invasive breast carcinoma and clinically negative axilla who underwent breast-conserving surgery and SLNB between February 2008 and December 2018. Results: We included 415 patients who were submitted to conserving surgery. In 23.3% (97 patients), SLNB was positive, 56 patients were submitted only to SLNB, and 41 patients were treated with AL. The groups were homogeneous regarding the variables: age group (p=0.279), anatomopathological diagnosis (p=0.210), histological grade (p=0.983), hormone receptor expression (p=0.708), HER 2 expression (p=0.695) and pT (p=0.334). Global survival, in the mean period of 5 years, was 80.1% in the SLNB group, and 87.5% in the AL group (p=0.376). The locoregional recurrence was a rare event; in the mean period of 5 years, there was 1.8% in the SLNB group, and 7.7% in the AL group (p=0.196). Only 4 locoregional recurrences were described, and all took place in up to 18 months of follow-up. Conclusions: Global survival and locoregional recurrence in patients with metastatic axillary sentinel lymph node treated only with sentinel lymph node biopsy did not present differences in relation to patients who underwent axillary lymphadenectomy, which corroborates the data from ACOSOG Z0011. The omission of axillary lymphadenectomy and the implantation of such a practice in our service benefitted the patients treated with less aggressive surgery, and, potentially, with lower morbidity.

Microscopic Extracapsular Extension in Sentinel Lymph Nodes Does Not Mandate Axillary Dissection in Z0011-Eligible Patients

In the ACOSOG (American College of Surgeons Oncology Group) Z0011 trial and the AMAROS (After Mapping of the Axilla: Radiotherapy or Surgery?) trial, matted nodes with gross extracapsular extension (ECE), a risk factor for locoregional recurrence, were an indication for axillary lymph node dissection (ALND), but the effect of microscopic ECE (mECE) in the sentinel lymph nodes (SLNs) on recurrence was not examined. Between 2010 and 2017, 811 patients with cT1-2N0 breast cancer and SLN metastasis were prospectively managed according to Z0011 criteria, with ALND for those with more than two positive SLNs or gross ECE. Management of mECE was not specified. In this study, we compare outcomes of patients with one to two positive SLNs with and without mECE, treated with SLN biopsy alone (n = 685). Median patient age was 58years, and median tumor size was 1.7cm. mECE was identified in 210 (31%) patients. Patients with mECE were older, had larger tumors, and were more likely to be hormone receptor positive and HER2 negative, have two positive SLNs, and receive nodal radiation. At a median follow-up of 41months, no isolated axillary failures were observed. There were 11 nodal recurrences; two supraclavicular ± axillary, four synchronous with breast, and five with distant failure. The five-year rate of any nodal recurrence was 1.6% and did not differ by mECE (2.3% vs. 1.3%; p = 0.84). No differences were observed in local (p = 0.08) or distant (p = 0.31) recurrence rates by mECE status. In Z0011-eligible patients, nodal recurrence rates in patients with mECE are low after treatment with SLN biopsy alone, even in the absence of routine nodal radiation. The presence of mECE should not be considered a routine indication for ALND.

Comparative Age-Based Prospective Multi-Institutional Observations of 12,367 Patients Enrolled to the American College of Surgeons Oncology Group (ACOSOG) Z901101 Trials (Alliance).

The risk of surgery, particularly for older cancer patients with serious, extensive comorbidities, can make this otherwise curative modality precarious. Leveraging data from the American College of Surgeons Oncology Group, this study sought to characterize age-based comparative demographics, adverse event rates, and study completion rates to define how best to conduct research in older cancer patients. This study relied on clinical data from 21 completed studies to assess whether older patients experienced more grade 3 or worse adverse events and were more likely to discontinue study participation prematurely than their younger counterparts. The study enrolled 12,367 patients. The median age was 60years, and 36% of the patients were 65years of age or older. Among 4008 patients with adverse event data, 1067 (27%) had experienced a grade 3 or worse event. The patients 65years or older had higher rates of grade 3 or worse adverse events compared to younger patients [32% vs. 24%; odds ratio (OR), 1.5; 95% confidence interval (CI), 1.3-1.7; p < 0.0001]. This association was not observed in multivariate analyses. The study protocol was completed by 97% of the patients. No association was observed between age and trial completion (OR 0.8; 95% CI 0.7-1.1; p = 0.14). Only the older gastrointestinal cancer trial patients were less likely to complete their studies compared to younger patients (OR 0.50; 95% CI 0.30-0.70; p < 0.0001). Despite higher rates of adverse events, the older patients typically completed the study protocol, thereby contributing relevant data on how best to render care to older cancer patients and affirming the important role of enrolling these patients to surgical trials.

MS06.04 Approaches to Overcoming the Nodal Staging Quality Gap

MS06.04 Approaches to Overcoming the Nodal Staging Quality Gap

AB003. Stereotactic body radiation therapy vs. pulmonary resection

: Pulmonary resection remains the accepted standard of care for early stage non-small cell lung cancer (NSCLC) in patients with adequate cardiopulmonary reserve. Radiation therapy, and in particular stereotactic body radiation therapy (SBRT), has traditionally been recommended as curative therapy for medically unfit patients who harbor early stage lung cancer. As a consequence of the rising success of SBRT in patients with medically inoperable early stage NSCLC (evidenced by Radiation Therapy Oncology Group trials 0236 and 0915), there has been keen interest in exploring this modality in operable patients. SBRT to lung is often very well tolerated, thus making it very attractive to patients. The risk of series complications in carefully selected patients is low. Equipoise among surgeons and the medical community for the use of SBRT as curative therapy for patients eligible for surgery has been limited, thus contributing to the poor accrual and early closure of 3 randomized trials attempting to directly compare SBRT to surgery in operable patients. These trials included the STARS trial (Study of Anastrozole and Radiotherapy Sequencing), the ROSEL trial [Either Surgery or Stereotactic Radiotherapy for Early-Stage (IA) Lung Cancer] and the American College of Surgeons Oncology Group (ACOSOG) Z4099 trial. No preliminary data is available from the ACOSOG trial. The STARS and ROSEL trial randomized operable patients with tumors <4 cm (cT1–T2a) and required invasive mediastinal staging in patients harboring radiographically suspicious lymph nodes. Sublobar resection was not permitted in these trials. Since patient accrual was limited (n=58 total patients) the two trials were combined in a controversial publication that showed improved overall survival and decreased toxicity with SBRT compared to surgery. This has spawned additional randomized trials including the STABLE-MATES trial comparing sublobar resection and SBRT in patients with stage I NSCLC (NCT02468024) with an estimated enrollment of 258 patients, a Veterans Affairs Lung Cancer or Stereotactic Radiotherapy (VALOR) trial (NCT02984761) with estimated enrollment of 670 patients, and lastly, a phase II United Kingdom sponsored SABRTooth study (NCT02629458) that is enrolling up to 54 patients. The lack of randomized data has stimulated multiple publications that retrospectively examine these modalities in single center case series and more recently in larger data sets derived from the National Cancer Database (NCDB), the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database and the United States Veterans Affairs Health Care System. These retrospective analyses are clearly limited by patient selection bias and different levels of staging accuracy. Propensity matched retrospective series showed that overall survival was no different at 1 year but favored surgery at 3 years. Cancer-specific survival (clearly a better outcome measure particularly in elderly patients receiving SBRT) was no different compared to surgery, nor was local failure, or the risk of developing distant metastases. Collectively, the studies that used large data with statistical matching demonstrated a survival advantage of surgery (namely lobectomy) over SBRT for stage I NSCLC but raised awareness of the increased post procedure morbidity and mortality for surgery compared to SBRT. Interestingly, sublobar resection versus SBRT in these large data sets had mixed results with some showing survival improvement with surgery and some showing no survival difference. Surgery appears superior at later time points. In a phase II ablate and resect human clinical trial (MISSILE-NSCLC, NCT02136355) for early stage (T1–T2) NSCLC, 35 patients underwent neoadjuvant SBRT using 54–60 Gy in 3–8 fractions followed by surgery at an interval of 10 weeks. The authors reported a 60% pathologic complete response rate, invoking many questions about local control of SBRT. Assessment of local control after SBRT remains the single most challenging real-world clinical problem. The lung injury post ablation is heterogenous and requires very careful observation with imaging modalities that lack sensitivity and specificity for recurrence. At present, the American Society of Radiation Oncology does not recommend SBRT for operable patients with early stage NSCLC outside of a clinical trial.

Patterns in the Use of Axillary Operations for Patients with Node-Positive Breast Cancer After Neoadjuvant Chemotherapy: A National Cancer Database (NCDB) Analysis.

The American College of Surgeons Oncology Group (ACOSOG) Z1071 and Sentinel Neoadjuvant (SENTINA) trials of sentinel node biopsy for node-positive breast cancer treated with neoadjuvant chemotherapy (NAC) demonstrated false-negative rates that varied on the basis of surgical technique. This study evaluated trends in axillary operations before and after publication of these trials. This study analyzed patients from National Cancer Database (NCDB) with clinical T0 through T4, N1 and N2, M0 breast cancer who received NAC from 1 January 2012 to 31 December 2015 and sentinel lymph node biopsy (SNB) or axillary lymph node dissection (ALND). The patients were divided into the following groups: SNB, ALND, and (SNB + ALND). Of the 32,036 evaluable patients identified in this study. 5565 had SNB, 19,930 had ALND, and 6541 had SNB + ALND. Compared with the ALND group, the SNB group was younger, had more invasive ductal cancers, and had lower clinical T- and N-stage disease (p < 0.001). The patients in the SNB group had a higher rate of estrogen receptor-positive and triple-negative breast cancers, but a lower rate of human epidermal growth factor receptor 2 (HER2)-positive cancer (p < 0.001). The nodal pathologic complete response (PCR) rate, defined as no residual invasive cancer, was 66.5% in the SNB group and 33.1% in the ALND group. Since 2013, the rate of ALND has decreased from 88.7 to 77.1% in both community and academic institutions (p < 0.001). Since publication of the ACOSOG Z1071 and SENTINA trials, the national rates of ALND in node positive breast cancer treated with NAC have decreased despite reported false-negative SNB rates and lack of prospective outcome data regarding the oncologic safety of ALND omission.