The Exportability of the ACOSOG Z0011 Criteria for Omitting Axillary Lymph Node Dissection After Positive Sentinel Lymph Node Biopsy Findings: A Multicenter Study

Purpose

To determine the exportability of the criteria defined by the American College of Surgeons Oncology Group Z0011 trial for selecting patients who are eligible for omitting completion axillary lymph node dissection (cALND) after a positive sentinel lymph node (SLN) biopsy result and to investigate whether not following the Z0011 criteria might affect patient outcomes.

Methods

From a multicenter database, we selected 188 patients with positive SLNs and then excluded patients with positive SLNs on immunohistochemistry only. We retrospectively applied the Z0011 criteria and grouped the patients as eligible or ineligible for omitting cALND. The eligible group was compared with the cohort included in the Z0011 trial and with the ineligible group. Kaplan–Meier survival curves were calculated for each group, and univariate analyses assessed associations between the groups and clinicopathological variables.

Results

The final analysis involved 125 patients with positive SLNs. Eighty-seven patients (69.6 %) were potentially eligible for omitting cALND. The estrogen receptor status, T stage, grade, and number of positive non-SLNs were not statistically different between the eligible group and the Z0011 cohort. The ineligible group had significantly more positive non-SLNs (P = 0.01) and a lower 5-year overall survival rate than the eligible group (P < 0.001).

Conclusions

The similarity of clinical characteristics between the Z0011 trial cohort and our eligible group confirms the exportability of these criteria to another population. The worse prognosis of patients who did not meet the Z0011 criteria suggests prudence before disregarding or enlarging broadening the indications for omitting cALND.     

Application of ACOSOG Z0011 Criteria Reduces Perioperative Costs

Background

The ACOSOG Z0011 (Z0011) trial concluded that sentinel lymph node biopsy (SLNB) without completion axillary lymph node dissection (ALND) provides excellent regional control in women with T1–T2 sentinel lymph node (SLN) positive breast cancers receiving breast conservation therapy. We determined whether application of Z0011 guidelines would reduce costs.

Methods

A retrospective chart review of patients with invasive breast cancer treated with lumpectomy and SLNB at our institution during 2009 was performed. We determined the number of overnight hospital admissions following ALND and estimated costs pertaining to the perioperative surgical management of the axilla patients actually received, and compared those to the estimated number of inpatient days and perioperative costs if Z0011 guidelines had been followed for eligible patients. The 2011 Medicare Fee Schedule was used to estimate costs for procedures, and costs for OR time were estimated using procedure length and cost of OR time per minute.

Results

A total of 71 patients underwent lumpectomy with SLNB and had at least 1 positive SLN. Estimated costs related to perioperative surgical management of the axilla were $322,775, and there were 36 overnight admissions. Applying Z0011 criteria, 51 patients (72 %) would have been eligible to forego completion ALND. Estimated costs would have been $264,513 with 13 overnight admissions, translating into a cost savings of $58,262 and 23 fewer overnight admissions.

Conclusion

Application of Z0011 guidelines resulted in cost savings, with a 64 % reduction in inpatient hospital days and an 18 % reduction in early perioperative costs.     

American College of Surgeons Oncology Group (ACOSOG) Z0011: Impact on Surgeon Practice Patterns

Introduction

The ACOSOG Z0011 trial has been described as practice-changing. The goal of this study was to determine the impact of the trial on surgeon practice patterns at our institution.

Methods

This is a review of practice patterns comparing the year before release of Z0011 to the year after an institutional multidisciplinary meeting discussing the results. Patients meeting Z0011 inclusion criteria were identified. Clinicopathologic data were compared between the cohorts.

Results

There were 658 patients with clinical T1-2 tumors planned for breast conservation: 335 in the pre-Z0011 cohort and 323 post-Z0011. Sixty-two (19?%) patients were sentinel lymph node (SLN) positive in the pre-Z0011 group versus 42 (13?%) post-Z0011 (p?=?0.06). Before Z0011, 85?% (53/62) of SLN-positive patients underwent axillary node dissection (ALND) versus 24?% (10/42) after Z0011 (p?p?=?0.09), lobular histology (p?=?0.01), fewer SLNs (1 vs. 3, p?=?0.09), larger SLN metastasis size (4 vs. 2.5?mm, p?=?0.19), extranodal extension present (20 vs. 6?%, p?=?0.16), or a higher probability of positive non-SLNs (p?=?0.03). Surgeons were less likely to perform intraoperative nodal assessment post-Z0011 (26 vs. 69?%, p?p?Conclusions Surgeons at our institution have implemented Z0011 results for the majority of patients; however, clinicopathologic factors still impact the decision to perform ALND. Z0011 results have significantly impacted practice by decreasing rates of ALND, use of intraoperative nodal evaluation, and operative times.     

Omission of Axillary Dissection after a Positive Sentinel Node Dissection may Influence Adjuvant Chemotherapy Indications in Operable Breast Cancer Patients

Background

This study was designed to evaluate how the omission of axillary dissection would have altered the indication for adjuvant chemotherapy (ACT) in patients with early breast cancer submitted to conservative surgery with one or two positive sentinel lymph nodes (SLNs).

Methods

We identified 321 women in our institutional database who fulfilled the characteristics. All underwent completion axillary lymph node dissection (AD). Each case was blindly reviewed by our breast team in two rounds, and the total number of positive lymph nodes was disclosed only in the second. At each round, the panel chose between: (1) recommend, (2) discuss, (3) do not recommend ACT. Changes between round 1 and 2 were studied by the marginal homogeneity test. Exploratory logistic regression analyses were performed to study predictors of non-SLN involvement and of changes in the indication for ACT.

Results

AD revealed non-SLNs metastases in 96 patients (30?%). Fifty-two patients (16?%) had their initial indication changed at round 2 (p?<?0.001). Most of the changes were toward ACT (83?%), and all except two occurred in patients with immunohistochemically defined luminal A and luminal B/HER2-negative tumors. In these two subgroups, a Ki67 above the median value (21?%) was the only independent predictor of no change in the indication to ACT at round 2.

Conclusions

Omission of AD in patients with one or two positive SLNs may change the indication to ACT in a significant proportion of patients with hormone receptor-positive/HER2-negative tumors. All implications should be taken into account before abandoning AD, including a possible biologically tailored surgical approach.     

Impact of Omission of Axillary Lymph Node Dissection After Negative Sentinel Lymph Node Biopsy: 70-Month Follow-up

Background  

The objective of this study is to assess the oncologic safety of sentinel lymph node biopsy (SLNB), especially with regard to the axillary recurrence (AR) rate, and to determine the risk factors for AR and disease-free survival (DFS) and overall survival (OS) after negative SLNB.     

Changing Behavior in Clinical Practice in Response to the ACOSOG Z0011 Trial: A Survey of the American Society of Breast Surgeons

Background

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated no difference in overall survival or local?Cregional recurrence rates between patients planned for breast conservation therapy including whole breast irradiation (WBI) with one or two positive sentinel lymph nodes (SLNs) randomly selected to undergo axillary lymph node dissection (ALND) versus no further surgery. The current study was undertaken to evaluate the impact of Z0011 on surgical practice nationally.

Methods

A survey was sent by e-mail to 2,759 members of the American Society of Breast Surgeons (ASBrS). Questions assessed the respondents?? practice, familiarity with Z0011, and preferences for treating patients with one or two positive SLNs.

Results

Of those surveyed, 849 (30.8?%) responded. The majority (97?%) indicated familiarity with the data. Of those respondents, 468 (56.9?%) would not routinely perform ALND in patients planned to receive WBI, while 279 (36.0?%) would consider omission of completion ALND in patients planned to receive accelerated partial breast irradiation (APBI), and 218 (26.6?%) would consider omission of ALND in patients not planned to receive radiation. Academic and private practice surgeons were equally likely to incorporate Z0011 into practice.

Conclusions

ACOSOG Z0011 has changed surgical practice. ASBrS respondents have embraced Z0011 and have changed their practice, omitting ALND in patients with one or two positive SLNs who will undergo WBI. However, many also omit ALND in patients undergoing surgery without radiation or with APBI. As these clinical scenarios were not studied in Z0011, further evaluation is required prior to changing clinical practice.     

Impact of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial on Clinical Management of the Axilla in Older Breast Cancer Patients: A SEER-Medicare Analysis

Background

American College of Surgeons Oncology Group (ACOSOG) Z0011 demonstrated that eligible breast cancer patients with positive sentinel lymph nodes (SLN) could be spared an axillary lymph node dissection (ALND) without sacrificing survival or local control. Although heralded as a “practice-changing trial,” some argue that the stringent inclusion criteria limit the trial’s clinical significance. The objective was to assess the potential impact of ACOSOG Z0011 on axillary surgical management of Medicare patients and examine current practice patterns.

Methods

Medicare beneficiaries aged ≥66 years with nonmetastatic invasive breast cancer diagnosed from 2001 to 2007 were identified from the Surveillance, Epidemiology and End Results-Medicare database (n = 59,431). Eligibility for ACOSOG Z0011 was determined: SLN mapping, tumor <5 cm, no neoadjuvant treatment, breast conservation; number of positive nodes was determined. Actual surgical axillary management for eligible patients was assessed.

Results

Twelve percent (6,942/59,431) underwent SLN mapping and were node positive. Overall, 2,637 patients (4.4 % (2,637/59,431) of the total cohort, but 38 % (2,637/6,942) of patients with SLN mapping and positive nodes) met inclusion criteria for ACOSOG Z0011, had 1 or 2 positive lymph nodes, and could have been spared an ALND. Of these 2,637 patients, 46 % received a completion ALND and 54 % received only SLN biopsy.

Conclusions

Widespread implementation of ACOSOG Z0011 trial results could potentially spare 38 % of older breast cancer patients who undergo SLN mapping with positive lymph nodes an ALND. However, 54 % of these patients are already managed with SLN biopsy alone, lessening the impact of this trial on clinical practice in older breast cancer patients.     

Factors Associated With Local-Regional Recurrence After a Negative Sentinel Node Dissection: Results of the ACOSOG Z0010 Trial

OBJECTIVE:: To determine factors important in local-regional recurrence (LRR) in patients with negative sentinel lymph nodes (SLNs) by hematoxylin and eosin (H&E) staining. BACKGROUND:: Z0010 was a prospective multicenter trial initiated in 1999 by the American College of Surgeons Oncology Group to evaluate occult disease in SLNs and bone marrow of early-stage breast cancer patients. Participants included women with biopsy-proven T1-2 breast cancer with clinically negative nodes, planned for lumpectomy and whole breast irradiation. METHODS:: Women with clinical T1-2,N0,M0 disease underwent lumpectomy and SLN dissection. There was no axillary-specific treatment for H&E-negative SLNs, and clinicians were blinded to immunohistochemistry results. Systemic therapy was based on primary tumor factors. Univariable and multivariable analyses were performed to determine clinicopathologic factors associated with LRR. RESULTS:: Of 5119 patients, 3904 (76.3%) had H&E-negative SLNs. Median age was 57 years (range 23-95). At median follow-up of 8.4 years, there were 127 local, 20 regional, and 134 distant recurrences. Factors associated with local-regional recurrence were hormone receptor-negative disease (P = 0.0004) and younger age (P = 0.047). In competing risk-regression models, hormone receptor-positive disease and use of chemotherapy were associated with reduction in local-regional recurrence. When local recurrence was included in the model as a time-dependent variable, older age, T2 disease, high tumor grade, and local recurrence were associated with reduced overall survival. CONCLUSIONS:: Local-regional recurrences are rare in early-stage breast cancer patients with H&E-negative SLNs. Younger age and hormone receptor-negative disease are associated with higher event rates, and local recurrence is associated with reduced overall survival.     

Role of frozen section in sentinel lymph node biopsy for breast cancer in the era of the ACOSOG Z0011 and IBCSG 23-10 trials

Background

Intraoperative frozen sections (FS) of sentinel lymph nodes (SLN) were evaluated to avoid the need for deferred axillary lymph node dissection (ALND) in patients with early breast cancer (EBC). However, FS has low sensitivity for detecting micro-metastases (<2 mm), resulting in patients who later undergo deferred ALND. The aim of the study was to determine the best clinical approach for selecting patients who would derive real benefit from ALND, as well as to minimize the functional and psychological damage caused by delayed surgery, and the risk of undertreating EBC patients.

Extensive Frozen Section Examination of Axillary Sentinel Nodes to Determine Selective Axillary Dissection

As experience accumulates on the use of sentinel node biopsy in breast cancer, it is becoming clear that the method can reliably predict the state of the axilla and thus be used to decide whether to perform complete axillary dissection. Ongoing controlled trials will soon provide definitive evidence on the latter point. The key issue regarding sentinel node biopsy is pathologic evaluation of the biopsied node, which should be done intraoperatively whenever possible. In our initial experience with a conventional intraoperative frozen section method, the false-negative rate was 19% compared to examination of permanent sections of the biopsied node. We therefore devised a new intraoperative method in which pairs of sections are obtained every 50 mm for the first 15 sections and every 100 mm for any remaining node, which essentially samples the entire node; the method takes about 40 minutes. Sentinel node metastases were found in 119 of 295 (40%) of T1N0 breast cancer patients examined by this new method. This high rate of positivity indicates that the new method is reliable. In all cases, metastases were identified on hematoxylin-eosin (HE)-stained sections, although in 4% of positive cases the HE sections were doubtful, and cytokeratin immunostaining on the adjacent section was useful for confirming malignancy. Of 295 patients, 8 (2.7%) had a negative sentinel node but another axillary node metastasis. In conclusion, we found that extensive intraoperative frozen section examination of sentinel nodes correctly predicts a metastasis-free sentinel node in 95.4% of cases (negative predictive value), it is therefore suitable for identifying patients in whom axillary dissection might be avoided. Immunocytochemical staining for cytokeratins or other epithelial markers may be helpful for reducing the risk of missing micrometastatic foci.     

Impact of American College of Surgeons Oncology Group Z0011 and National Surgical Adjuvant Breast and Bowel Project B-32 trial results on surgeon practice in the Pacific Northwest

BackgroundRecent clinical trials have suggested no survival benefit for completion axillary node dissection (CALND) after sentinel lymph node biopsy (American College of Surgeons Oncology Group Z0011) and no clinically meaningful benefit for the routine use of immunohistochemistry (National Surgical Adjuvant Breast and Bowel Project B-32) in clinically node-negative breast cancer.MethodsA 12-question electronic survey was distributed to members of 3 Pacific Northwest surgical societies. Surgeons were queried regarding the impact of the trial results on their surgical management of breast cancer.ResultsThe 181 respondents reported performing fewer CALNDs (63%), fewer intraoperative frozen sections (21%), and no immunohistochemistry (12%) because of trial data. However, 28% of surgeons continued to perform CALND in patients with 1 to 2 positive sentinel lymph nodes undergoing lumpectomy and postoperative radiation.ConclusionsRecent trial data have impacted the performance of CALNDs and the pathological evaluation of sentinel lymph nodes among Pacific Northwest surgeons. Our results suggest a need for regional surgical societies to disseminate practice-changing trial data to members.     

Axillary Dissection Versus No Axillary Dissection in Elderly Patients with Breast Cancer and No Palpable Axillary Nodes: Results After 15 Years of Follow-Up

Objective

To assess the long-term safety of no axillary clearance in elderly patients with breast cancer and nonpalpable axillary nodes.

Background

Lymph node evaluation in elderly patients with early breast cancer and clinically negative axillary nodes is controversial. Our randomized trial with 5-year follow-up showed no breast cancer mortality advantage for axillary clearance compared with observation in older patients with T1N0 disease.

Methods

We further investigated axillary treatment in a retrospective analysis of 671 consecutive patients, aged ≥70 years, with operable breast cancer and a clinically clear axilla, treated between 1987 and 1992; 172 received and 499 did not receive axillary dissection; 20 mg/day tamoxifen was prescribed for at least 2 years. We used multivariable analysis to take account of the lack of randomization.

Results

After median follow-up of 15 years (interquartile range 14–17 years) there was no significant difference in breast cancer mortality between the axillary and no axillary clearance groups. Crude cumulative 15-year incidence of axillary disease in the no axillary dissection group was low: 5.8% overall and 3.7% for pT1 patients.

Conclusions

Elderly patients with early breast cancer and clinically negative nodes did not benefit in terms of breast cancer mortality from immediate axillary dissection in this nonrandomized study. Sentinel node biopsy could also be foregone due to the very low cumulative incidence of axillary disease in this age group. Axillary dissection should be restricted to the small number of patients who later develop overt axillary disease.     

Standardization of Surgical and Pathologic Variables is Needed in Multicenter Trials of Adjuvant Therapy for Pancreatic Cancer: Results from the ACOSOG Z5031 Trial

Background

Standardization of surgical and pathologic techniques is crucial to the interpretation of studies evaluating adjuvant therapies for pancreatic cancer (PC).

Methods

To assess the degree to which treatment administered prior to enrollment of patients in trials of adjuvant therapy is quality controlled, the operative and pathology reports of patients in American College of Surgeons Oncology Group (ACOSOG) Z5031—a national trial of chemoradiation following pancreaticoduodenectomy (PD)—were rigorously evaluated. We analyzed variables with the potential to influence staging or outcome.

Results

80 patients reported to have undergone R0 (75%) or R1 (25%) pylorus-preserving (38%) or standard (62%) PD were evaluated. A search for metastases was documented in 96% of cases. The proximity of the tumor to the superior mesenteric vein was reported in 69%; vein resection was required in 9% and lateral venorrhaphy in 14%. The method of dissection along the superior mesenteric artery (SMA) was described in 68%, being ultrasonic dissection (17%), stapler (24%), and clamp and cut (59%). SMA skeletonization was described in 25%, and absence of disease following resection was documented in 24%. The surgeon reported marking the critical SMA margin in 25%; inking was documented in 65% of cases and evaluation of the SMA margin was reported in 47%. A range of 1–49 lymph nodes was evaluated. Only 34% of pathology reports met College of American Pathologists criteria.

Conclusions

Trials of adjuvant therapy following PD suffer from a lack of standardization and quality control prior to patient enrollment. These data suggest areas for improvement in the design of multidisciplinary treatment protocols.     

Treatment of Axillary Hyperhidrosis:

OBJECTIVE: To evaluate and permanently improve axillary hyperhidrosis. BACKGROUND: Excessive sweating of the axillae is a common problem for which patients frequently seek dermatologic advice and therapy. Many treatments, including aluminum chloride, topical and systemic anticholinergic agents, tranquilizers, iontophoresis, direct surgical excision, botulinum toxin injection, and thoracic sympathectomy, have been employed to control this problem. All have drawbacks of one sort or another. METHODS: The starch-iodine technique for delineation of preoperative and postoperative axillary sweating is described in detail. A method of sweat gland removal utilizing tumescent liposuction is discussed. RESULTS AND CONCLUSION: The combination of the starch-iodine technique and tumescent liposuction is safe and effective for therapy of axillary hyperhidrosis.