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Background: Talimogene laherparepvec (T-VEC) is an FDA-approved oncolytic herpesvirus therapy used for unresectable stage IIIB through IV metastatic melanoma. However, the correlation between clinical complete response (cCR) and pathologic complete response (pCR) in patients treated with T-VEC is understudied., Study Design: We conducted a retrospective study from a prospectively maintained IRB-approved melanoma single-center database in patients treated with T-VEC from October 2015 to April 2022. Patients were categorized into 3 groups: cCR with pCR, cCR without pCR, and less than cCR. The primary endpoint was overall survival. We used descriptive statistics, chi-square tests, and Wilcoxon rank-sum tests to compare key covariates among exposure groups. We used survival analysis to compare survival curves and reported hazard ratio of death (95% CI) across exposure groups., Results: We included 116 patients with a median overall survival (interquartile range) of 22.7 (14.8-39.3) months. The majority were men (69%) and White (97.4%), with a median age of 74.5 years. More than half of patients (n = 60, 51.6%) achieved cCR. Distribution among the groups was as follows: cCR with pCR (35.3%), cCR without pCR (16.3%), and less than cCR (48.4%). Median overall survival time (interquartile range) was 26.5 (18.6-36.0) months for cCR with pCR, 22.7 (14.4-35.5) months for cCR without pCR, and 17.8 (9.2-47.0) months for less than cCR (log-rank p value = 0.0033)., Conclusions: Patients achieving cCR with pCR after T-VEC therapy have the most favorable overall survival outcomes, whereas those achieving cCR without pCR have inferior survival and those achieving less than cCR have the poorest overall survival outcomes. These findings emphasize the importance of histological confirmation and provide insights for optimizing T-VEC therapy in patients with advanced melanoma., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: This is a prospective, single-institution study to evaluate feasibility and accuracy of radar-localized reflector (RLR)-targeted axillary dissection (TAD) in node-positive breast cancer patients after neoadjuvant systemic therapy (NST)., Methods: Patients with biopsy-proven T1-2, N1-3 disease were eligible. Before NST, a marker clip and/or RLR was placed into the positive node. After NST, RLR was inserted if not placed previously. All patients underwent RLR TAD followed by axillary lymph node dissection (ALND). Primary end points of the trial were feasibility of RLR TAD and false negative rate (FNR)., Results: Between 2017 and 2021, 101 patients with N1-3 disease underwent NST. Five patients withdrew from the study, 1 was ineligible, and there were 9 technical failures, thus our final study cohort comprised 86 patients. RLR TAD was performed with probe guidance and confirmed with intraoperative specimen radiograph. After RLR TAD, ALND was performed. Median number of RLR TAD nodes removed was 2 (range 1-10), and the RLR TAD nodes remained positive in 56 patients. Median number of ALND nodes removed was 18 (range 4-46). Accounting for 9 technical failures, feasibility was 90%. All technical failures occurred with attempted placement of RLR after NST. Feasibility rate was 100% when RLR placement occurred at diagnosis. Of the evaluable 86 patients, RLR TAD accurately predicted axillary status in 83 patients, with FNR of 5.1%., Conclusion: We demonstrate high accuracy of RLR TAD, especially when RLR is placed before NST. For patients who present with N1-3 disease, this is another step towards axillary surgery de-escalation strategies., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: We examined the impact of cavity shave margins (CSMs) on margin status in patients with pure ductal carcinoma in situ (DCIS) undergoing partial mastectomy (PM)., Methods: One hundred and nine patients from 2 multicenter, randomized controlled trials were identified with pure DCIS (no invasive cancer). Surgeons performed their best PM, with specimen radiography and resection of selective margins per surgeon discretion. Patients were then randomized to have CSM resected or not. A positive margin was defined as <2 mm from ink., Results: Median patient age was 63 years; median size of DCIS was 1.20 cm; 43.6% of patients had high-grade DCIS; and 58 (53.2%) patients were randomized to take CSM. The "shave" and "no-shave" groups were well-matched for age, race, ethnicity, palpability, grade, and size of DCIS. Although 33 (56.9%) of the patients in the shave group had a positive margin before randomization, only 12 (20.7%) had a positive margin after randomization to CSM (p < 0.001). In the no-shave group, 17 patients (33.3%) had a positive margin. Controlling for size and grade of DCIS, taking CSM resulted in a nearly 65% reduction in the positive-margin rate (odds ratio 0.366; 95% CI, 0.136 to 0.981; p = 0.046). Size of DCIS remained an independent predictor of positive margins in the model (odds ratio 1.646; 95% CI, 1.227 to 2.209; p = 0.001)., Conclusions: CSM reduces positive-margin rates in patients with pure DCIS, and can be a practical solution for DCIS patients who tend to have a high rate of margin positivity., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: In sentinel lymph node (SLN)-positive melanoma, two randomized trials demonstrated equivalent melanoma-specific survival with nodal surveillance vs completion lymph node dissection (CLND). Patients with microsatellites, extranodal extension (ENE) in the SLN, or >3 positive SLNs constitute a high-risk group largely excluded from the randomized trials, for whom appropriate management remains unknown., Study Design: SLN-positive patients with any of the three high-risk features were identified from an international cohort. CLND patients were matched 1:1 with surveillance patients using propensity scores. Risk of any-site recurrence, SLN-basin-only recurrence, and melanoma-specific mortality were compared., Results: Among 1,154 SLN-positive patients, 166 had ENE, microsatellites, and/or >3 positive SLN. At 18.5 months median follow-up, 49% had recurrence (vs 26% in patients without high-risk features, p < 0.01). Among high-risk patients, 52 (31%) underwent CLND and 114 (69%) received surveillance. Fifty-one CLND patients were matched to 51 surveillance patients. The matched cohort was balanced on tumor, nodal, and adjuvant treatment factors. There were no significant differences in any-site recurrence (CLND 49%, surveillance 45%, p = 0.99), SLN-basin-only recurrence (CLND 6%, surveillance 14%, p = 0.20), or melanoma-specific mortality (CLND 14%, surveillance 12%, p = 0.86)., Conclusions: SLN-positive patients with microsatellites, ENE, or >3 positive SLN constitute a high-risk group with a 2-fold greater recurrence risk. For those managed with nodal surveillance, SLN-basin recurrences were more frequent, but all-site recurrence and melanoma-specific mortality were comparable to patients treated with CLND. Most recurrences were outside the SLN-basin, supporting use of nodal surveillance for SLN-positive patients with microsatellites, ENE, and/or >3 positive SLN., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Background: For patients with sentinel node-positive melanoma (SNPM), randomized trials, first reported in 2015, found no benefit for routine completion lymph node dissection (CLND) in selected patients. This study examines time trends in CLND and explores institutional and clinical factors associated with CLND., Study Design: The National Cancer Database was queried for patients older than 18 years from 2012 to 2016 with SNPM. A high-volume center was defined as >80th percentile for number of sentinel node procedures. Poisson regression assessed temporal trends and identified patient, pathologic, and institutional characteristics associated with CLND., Results: From 2012 to 2016, we identified 7,146 patients with SNPM. The proportion of patients undergoing CLND was steady in 2012 to 2014 (61% to 63%), but decreased to 57% in 2015 and 50% in 2016 (p < 0.0001). The proportion of patients with SNPM who underwent CLND decreased over time for both high- (66% to 52%; p < 0.0001) and lower-volume centers (55% to 45%; p = 0.06). Female sex (relative risk [RR] 0.97; p < 0.001) and increasing age (RR 0.98; p < 0.0001) were associated with lower likelihood of CLND. Increased Breslow depth (RR 1.015; p = 0.006), ulceration (RR 1.067; p = 0.02), and high-volume centers (RR 1.180; p < 0.0001) were associated with higher likelihood of CLND. Regional differences in likelihood of CLND were also present (p < 0.0001)., Conclusions: Completion lymph node dissection in SNPM decreased over time, with the greatest change in 2016. Several patient, pathologic, and institutional characteristics were associated with likelihood of CLND. As evidence supports close observation for selected patients, efforts should be undertaken to improve and standardize patient selection for CLND across institutions caring for patients with melanoma., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Talimogene laherparepvec (TVEC) is an FDA-approved oncolytic herpes virus used to treat unresectable stage IIIB to IV metastatic melanoma via intralesional injection. This study aims to characterize the efficacy TVEC in patients with unresectable stage IIIB to IV melanoma., Methods: We performed a multi-institutional, IRB-approved review of all patients who received TVEC at 3 centers from October 2015 to October 2018. Clinicopathologic characteristics, TVEC treatment data, and outcomes were assessed., Results: One hundred and twenty-one patients received TVEC, of which 80 patients had available treatment response data with at least 3-month follow-up. Anatomic sites treated were 19 (24%) head and neck, 9 (11%) upper extremity, 12 (15%) torso, and 40 (50%) lower extremity. Thirty-four (42.5%) patients did not receive therapy before TVEC. Side effects were mild and self-limited, most commonly flu-like symptoms seen in 22 (28%) patients. Median follow-up was 9 months (range 3 to 28 months), with complete local response in 31 (39%) and partial response in 14 (18%) patients. Of complete responders, 29 (37%) had no evidence of disease at last follow-up and received a median of 6 (range 2 to 12) cycles of therapy., Conclusions: Talimogene laherparepvec is a well-tolerated, durable treatment option for patients with unresectable locoregional melanoma, particularly in stage IIIB/C disease. Additionally, we found that TVEC can be administered safely across anatomic sites that are otherwise not amenable to other local therapies., (Copyright © 2019 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Management of the axilla in stage II/III breast cancer undergoing neoadjuvant systemic therapy (NST) is controversial. To understand current patterns of care, we collected axillary data from 2 NST trials: HER2-positive (Cancer and Leukemia Group B [CALGB] 40601) and triple-negative (CALGB 40603)., Study Design: Axillary evaluation pre- and post-NST was per the treating surgeon and could include sentinel node biopsy. Post-NST, node-positive patients were recommended to undergo axillary lymph node dissection (ALND). We report pre-NST histopathologic nodal evaluation and post-NST axillary surgical procedures with correlation to clinical and pathologic nodal status., Results: Seven hundred and forty-two patients were treated, 704 had complete nodal data pre-NST and post-NST. Pre-NST, 422 (60%) of 704 patients underwent at least 1 procedure for axillary node evaluation (total of 468 procedures): fine needle aspiration (n = 234; 74% positive), core needle biopsy (n = 138; 72% positive), and sentinel node biopsy (n = 96; 33% positive). Pre-NST, 304 patients were considered node-positive. Post-NST, 304 of 704 patients (43%) underwent sentinel node biopsy; 44 were positive and 259 were negative (29 and 36 patients, respectively, had subsequent ALND). Three hundred and ninety-one (56%) patients went directly to post-NST ALND and 9 (1%) pre-NST node-positive patients had no post-NST axillary procedure. Post-NST, 170 (24%) of the 704 patients had residual axillary disease. Agreement between post-NST clinical and radiologic staging and post-NST histologic staging was strongest for node-negative (81%) and weaker for node-positive (N1 31%, N2 29%), with more than half of the clinically node-positive patients found to be pathologic negative (p < 0.001)., Conclusions: Our results suggest there is no widely accepted standard for axillary nodal evaluation pre-NST. Post-NST staging was highly concordant in patients with N0 disease, but poorly so in node-positive disease. Accurate methods are needed to identify post-NST patients without residual axillary disease to potentially spare ALND., (Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Patients with stage II melanoma have a considerable risk for recurrence. Current guidelines are imprecise as to optimal follow-up. We hypothesized that by examining recurrence patterns, we could help to better inform guidelines., Study Design: We queried IRB-approved melanoma databases of Thomas Jefferson University and University of North Carolina, identifying 581 patients with stage II melanoma between 1996 and 2015 with at least 1 year of follow-up. Data included location of first recurrence and how recurrence was detected (ie patient symptom, physician examination, or routine surveillance imaging). Cox regression with backward elimination was used for multivariable analysis., Results: One hundred and seventy-one patients had a recurrence (29.4%), the incidence increased considerably by stage sub-group. Significant predictors of recurrence included male sex (p = 0.003), ulceration (p = 0.03), and stage (p < 0.001). On multivariable analysis, male sex and stage continued to be significant (p < 0.01). For overall survival, regression, ulceration, stage, and age were significant predictors of survival. Stage, regression, and age remained significant by multivariable analysis. Patient symptoms were the most frequent mode of detection (40%), followed by physician examination (30%) and surveillance imaging (26%)-this did not differ significantly by stage. Regional nodes were the most common site of recurrence (30%), followed by lung (27%) and in-transit (18%)., Conclusions: The majority of recurrences in stage II melanoma are detected by patients and their physicians and rarely by routine imaging. As such, clinical follow-up and patient education are critical factors in detection of recurrence. With the prevalence of regional nodal recurrences, ultrasound might prove to be an important strategy in early recurrence detection., (Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Practice variation in breast cancer surgery has raised concerns about the quality of treatment decisions. We sought to evaluate the quality of decisions about surgery for early-stage breast cancer by measuring patient knowledge, concordance between goals and treatments, and involvement in decisions., Study Design: A mailed survey of stage I/II breast cancer survivors was conducted at 4 sites. The Decision Quality Instrument measured knowledge, goals, and involvement in decisions. A multivariable logistic regression model of treatment was developed. The model-predicted probability of mastectomy was compared with treatment received for each patient. Concordance was defined as having mastectomy and predicted probability >0.5 or partial mastectomy and predicted probability <0.5. Frequency of discussion about partial mastectomy was compared with discussion about mastectomy using chi-square tests., Results: Four hundred and forty patients participated (59% response rate). Mean overall knowledge was 52.7%; 45.9% knew that local recurrence risk is higher after breast conservation and 55.7% knew that survival is equivalent for the 2 options. Most participants (89.0%) had treatment concordant with their goals. Participants preferring mastectomy had lower concordance (80.5%) than those preferring partial mastectomy (92.6%; p = 0.001). Participants reported more frequent discussion of partial mastectomy and its advantages than of mastectomy, and 48.6% reported being asked their preference., Conclusions: Breast cancer survivors had major knowledge deficits, and those preferring mastectomy were less likely to have treatment concordant with goals. Patients perceived that discussions focused on partial mastectomy, and many were not asked their preference. Improvements in the quality of decisions about breast cancer surgery are needed., (Copyright © 2012 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Atypical melanocytic neoplasms present a therapeutic dilemma. Current consensus is to perform a sentinel lymph node (SLN) biopsy as part of management. However, it is unclear whether this is required in all patients. We present our experience with sentinel lymphadenectomy in these patients and examine the clinical and pathologic variables associated with a positive SLN., Study Design: A prospectively maintained melanoma database was queried for patients with controversial melanocytic lesions. All patients between January 1997 and January 2009 were included. Demographic and pathologic information was collected and correlated with results of SLN biopsy., Results: Thirty-one patients underwent SLN biopsy. Median patient age was 19 years (range 5 to 59 years) and median tumor Breslow depth was 1.35 mm. Five patients (16%) had a positive SLN. Those with a positive SLN were younger (median 11 vs 23.5 years, p = 0.02) and had a greater Breslow depth (median 1.90 vs 1.09; p = 0.03) than those who were SLN negative. Median follow-up was 16 months for patients with at least 6 months of follow-up time and there have been no recurrences identified., Conclusions: We report an SLN positive rate of 16% in patients with atypical melanocytic tumors. Younger age and greater Breslow depth are associated with having a positive SLN. These results confirm earlier work demonstrating the importance of SLN biopsy in this disease and highlight the need to measure Breslow depth in these lesions so that they can be appropriately stratified as to the need for SLN biopsy., (Copyright © 2010 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this survey was to ascertain the most common surgical practices for attaining negative (tumor-free) surgical margins in patients desiring breast-conservation treatment for breast cancer to see if a consensus exists for optimal treatment of patients., Study Design: We sent a survey to 1,000 surgeons interested in the treatment of breast cancer. Three hundred eighty-one surgeons responded to this survey and 351 were used for the analysis (response rate of 38%)., Results: Answers showed a large variety in clinical practices among breast surgeons across the country. There was little intraoperative margin analysis; only 48% of surgeons examine the margins grossly with a pathologist and even fewer used frozen sections or imprint cytology. Decisions to reexcise specific margins varied greatly. For example, 57% of surgeons would never reexcise for a positive deep margin, but 53% would always reexcise for a positive anterior margin. Most importantly, there was a large range in answers about acceptable margins with ductal carcinoma in situ and invasive carcinoma. Fifteen percent of surgeons would accept any negative margin, 28% would accept a 1-mm negative margin, 50% would accept a 2-mm negative margin, 12% would accept a 5-mm negative margin, and 3% would accept a 10-mm negative margin., Conclusions: Results of this survey highlight the wide variety of practice patterns in the US for handling surgical margins in breast-conservation treatment. This issue remains controversial, with no prevailing standard of care. Consequently, additional study is needed in the modern era of multimodality treatment to examine the minimal amount of surgical treatment necessary, in conjunction with chemotherapy and radiation, to attain adequate local control rates in breast-conservation treatment.

Background: How to best risk-stratify patients with metastatic melanoma in the sentinel node (SN) is controversial. Not all node-positive disease is equivalent in terms of disease-free or overall survival, and some have suggested that submicrometastatic disease, characterized by <0.1 mm tumor burden, can represent a distinct classification not associated with a chance for recurrence or death. We hypothesize that all patients with metastatic melanoma cells in the sentinel node have potentially life-threatening disease., Study Design: This is a retrospective review of an IRB-approved, prospectively maintained melanoma database of >1,100 patients. All invasive melanoma patients who had an SN biopsy and at least 1 year of followup were included. Patients with metastatic melanoma in the SN were divided into groups according to diameter of SN tumor burden: node-negative, <0.1 mm (submicrometastatic), 0.1 to 1.0 mm, and >1.0 mm. Statistical methods included the Jonckheere-Terpstra method, Fisher's exact tests, and Kaplan-Meier method., Results: From July 1, 1998 to July 1, 2007, 578 patients with invasive melanoma underwent SN procedure. Median followup was 2.2 years. There was a statistically significant difference in the proportion of patients who experienced a recurrence between the node-negative group (11%) and the <0.1 mm group (24%) (p = 0.049). Patients in the submicrometastatic group have a statistically significant (p = 0.048) earlier recurrence than those in the node-negative group., Conclusions: These results suggest that patients with submicrometastatic SN disease should not be treated as node-negative, as it appears to represent a more biologically aggressive melanoma, associated with a substantially faster time to recurrence. We cannot agree with recent proposals that patients with very small tumor burden in the SN can be treated as node-negative and be spared completion node dissection.