Additional Positive Nodes Research Articles

PD60-11 PROGNOSTIC SIGNIFICANCE OF PERIVESICAL LYMPH NODE STATUS IN PATIENTS WITH MUSCLE-INVASIVE BLADDER CANCER UNDERGOING RADICAL CYSTECTOMY

You have accessJournal of UrologyBladder Cancer: Invasive VI (PD60)1 Apr 2020PD60-11 PROGNOSTIC SIGNIFICANCE OF PERIVESICAL LYMPH NODE STATUS IN PATIENTS WITH MUSCLE-INVASIVE BLADDER CANCER UNDERGOING RADICAL CYSTECTOMY Nathan C. Wong*, Melissa Assel, Cristina Falavolti, Chun Huang, Nima Almassi, Shawn Dason, Victor A. McPherson, Lucas W. Dean, Daniel Sjoberg, Nicole Benfante, Hikmat Al-Ahmadie, Guido Dalbagni, Andrew VIckers, Eugene Cha, and Bernard H. Bochner Nathan C. Wong*Nathan C. Wong* More articles by this author , Melissa AsselMelissa Assel More articles by this author , Cristina FalavoltiCristina Falavolti More articles by this author , Chun HuangChun Huang More articles by this author , Nima AlmassiNima Almassi More articles by this author , Shawn DasonShawn Dason More articles by this author , Victor A. McPhersonVictor A. McPherson More articles by this author , Lucas W. DeanLucas W. Dean More articles by this author , Daniel SjobergDaniel Sjoberg More articles by this author , Nicole BenfanteNicole Benfante More articles by this author , Hikmat Al-AhmadieHikmat Al-Ahmadie More articles by this author , Guido DalbagniGuido Dalbagni More articles by this author , Andrew VIckersAndrew VIckers More articles by this author , Eugene ChaEugene Cha More articles by this author , and Bernard H. BochnerBernard H. Bochner More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000977.011AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Although the prognostic significance of pelvic lymph node metastasis at radical cystectomy is well described, the implications of positive perivesical nodes are less clear. Herein, we investigated the prognostic significance of perivesical nodal metastases detected at cystectomy. METHODS: We retrospectively reviewed patients who underwent radical cystectomy and packeted pelvic lymph node dissection at our institution between 2000 and 2015, excluding patients with locally advanced disease or who received non-standard preoperative systemic therapies. Nodes identified in the en bloc cystectomy specimen following node dissection were defined as perivesical. We calculated survival outcomes by nodal status and location (perivesical vs other pelvic) and compared hazard ratios for number of positive nodes by location using Cochran’s Q. RESULTS: Of the 2,197 patients included, a median of 19 (IQR 12, 28) lymph nodes were removed, with 397 (18%) patients having nodal metastasis. The majority of node-positive patients had only positive pelvic nodes (306, 77%), while 29 (7%) had only positive perivesical nodes and 62 (16%) had both. Among node-positive patients, there was similar recurrence-free and overall survival based on location (log-rank p=0.4, and 0.8, respectively). Perivesical and other pelvic positive nodes had a similar prognostic impact with hazard ratio for recurrence (adjusted for consensus T-stage) of 1.20 vs 1.09 respectively per additional positive node (p=0.093 for heterogeneity of hazard ratios). CONCLUSIONS: Positive perivesical lymph nodes identified at time of cystectomy carry similar prognostic implications as positive pelvic nodes found during templated packeted lymphadenectomy. Although infrequently found in the absence of positive pelvic nodes, the identification and reporting of perivesical nodes improves staging and can help guide use of adjuvant therapies to improve patient outcomes. Source of Funding: This research was supported by the Sidney Kimmel Center for Prostate and Urologic Cancers and funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1279-e1279 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nathan C. Wong* More articles by this author Melissa Assel More articles by this author Cristina Falavolti More articles by this author Chun Huang More articles by this author Nima Almassi More articles by this author Shawn Dason More articles by this author Victor A. McPherson More articles by this author Lucas W. Dean More articles by this author Daniel Sjoberg More articles by this author Nicole Benfante More articles by this author Hikmat Al-Ahmadie More articles by this author Guido Dalbagni More articles by this author Andrew VIckers More articles by this author Eugene Cha More articles by this author Bernard H. Bochner More articles by this author Expand All Advertisement PDF downloadLoading ...

Sentinel Lymph Node Biopsy in Head and Neck Melanoma: Long-term Outcomes, Prognostic Value, Accuracy, and Safety.

To evaluate the long-term outcomes of sentinel lymph node biopsy (SLNB) for head and neck cutaneous melanoma (HNCM). Retrospective cohort study. Tertiary academic medical center. Longitudinal review of a 356-patient cohort with HNCM undergoing SLNB from 1997 to 2007. Descriptive characteristics included the following: age, 53.5 ± 19 years (mean ± SD); sex, 26.8% female; median follow-up, 4.9 years; and Breslow depth, 2.52 ± 1.87 mm. Overall, 75 (21.1%) patients had a positive SLNB. Among patients undergoing completion lymph node dissection following positive SLNB, 20 (27.4%) had at least 1 additional positive nonsentinel lymph node. Eighteen patients with local control and negative SLNB developed regional disease, indicating a false omission rate of 6.4%, including 10 recurrences in previously unsampled basins. Ten-year overall survival (OS) and melanoma-specific survival (MSS) were significantly greater in the negative sentinel lymph node (SLN) cohort (OS, 61% [95% CI, 0.549-0.677]; MSS, 81.9% [95% CI, 0.769-0.873]) than the positive SLN cohort (OS, 31% [95% CI, 0.162-0.677]; MSS, 60.3% [95% CI, 0.464-0.785]) and positive SLN/positive nonsentinel lymph node cohort (OS, 8.4% [95% CI, 0.015-0.474]; MSS, 9.6% [95% CI, 0.017-0.536]). OS was significantly associated with SLN positivity (hazard ratio [HR], 2.39; P < .01), immunosuppression (HR, 2.37; P < .01), angiolymphatic invasion (HR, 1.91; P < .01), and ulceration (HR, 1.86; P < .01). SLN positivity (HR, 3.13; P < .01), angiolymphatic invasion (HR, 3.19; P < .01), and number of mitoses (P = .0002) were significantly associated with MSS. Immunosuppression (HR, 3.01; P < .01) and SLN status (HR, 2.84; P < .01) were associated with recurrence-free survival, and immunosuppression was the only factor significantly associated with regional recurrence (HR, 6.59; P < .01). Long-term follow up indicates that SLNB showcases durable accuracy, safety, and prognostic importance for cutaneous HNCM.

Regional nodal irradiation for early breast cancer; clinical benefit according to risk stratification

Three recently published prospective trials on regional nodal irradiation (RNI) in early breast cancer showed a reduction on breast cancer mortality, any first breast recurrence and/or distant recurrence rate. The positive outcomes of the modern trials reflect the development in radiotherapy by being more precise nowadays in radiation dose delivery to the lymph nodes, while reducing the radiation dose to heart and lungs. The possibility of axillary radiotherapy (ART) to replace axillary node dissection (ALND) after positive sentinel node (SLNB) biopsy is explored in a few trials. In the AMAROS trial both ALND and ART provide excellent and comparable LRR in SN+ patients. While the lymphedema was 2 times higher after ALND compared to ART. The ACOSOG Z0011 10 years results did not show a significant difference in locoregional recurrence rate or survival. These equal results were seen despite that in 27.4% of the patients had additional positive nodes removed beyond SLN in the patients who received axillary dissection (ALND). The IBCSG 23-01 phase III trial showed that there is no need for extra treatment of the axilla after micro-metastases in SLNB, however in this trial nearly all patients received breast irradiation including part of the axilla, often combined with adjuvant therapy.The introduction of neo- adjuvant systemic treatment (NACT) may lead to less RNI in early breast cancer, especially as NACT leads to pCR in axillary lymph nodes in about one third of the patient.

Lobular Histology Does Not Predict the Need for Axillary Dissection Among ACOSOG Z0011-Eligible Breast Cancers.

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated that axillary lymph node dissection (ALND) may be omitted for women with two or fewer positive sentinel nodes (SLNs) undergoing breast-conservation therapy (BCT). Lobular histology comprises a minority of patients, and applicability to these discohesive cancers has been questioned. From August 2010 to March 2017, patients undergoing BCT for cT1-2N0 cancer with positive SLNs were prospectively managed with ALND for three or more positive SLNs or gross extracapsular extension (ECE). In this study, clinicopathologic characteristics and nodal burden were compared between pure/mixed invasive lobular cancer (ILC) and invasive ductal cancer (IDC) patients. Among 813 consecutive patients, 104 (12.8%) had ILC and 709 (87.2%) had IDC. ILC was more often multifocal and low grade, and less frequently had lymphovascular invasion (all p < 0.001). ILC more often had SLN macrometastases (81.7% ILC vs. 69.4% IDC; p = 0.01) and more than 2mm of ECE (30.8% ILC vs. 19.5% IDC; p = 0.03), but the proportions of cases with three or more positive SLNs were similar in the two groups (14.4% ILC vs. 9.9% IDC; p = 0.2). The ALND procedure was performed for 20 ILC patients (19.2%) compared with 97 IDC patients (13.7%) (p = 0.2). Additional positive nodes were found in 80% of the ILC patients versus 56.7% of the IDC patients (p = 0.09). The ALND and nodal burden rates were similar in the estrogen receptor-positive (ER+) subset analysis. In the multivariable analysis, lobular histology (p = 0.03) and larger tumors (p = 0.03) were associated with additional positive nodes. During a median follow-up period of 42months, there were no isolated axillary recurrences. Despite a higher proportion of SLN macrometastases and association with more positive nodes at ALND, lobular histology does not predict the need for ALND. ALND is not indicated on the basis of histology among patients otherwise meeting Z0011 criteria.

Investigation of the pathomechanism of smoke-induced pancreatic damage

The need for completion axillary lymph node dissection (ALND) in breast cancer patients with micrometastases in the sentinel nodes (SNs) is controversial. The aim of this retrospective observational study is to determine if the method of detection of early breast cancer is predictive for additional positive nodes in patients with micrometastases in the SNs.Between 2001 and 2011 a total of 1993 women with primary unilateral breast cancer had surgery at Skåne University Hospital, Lund. Of 1993 patients, 1458 had an SN biopsy and nearly all patients with micro- and macrometastases had ALND.Micrometastases defined as >0.2 mm/>200 cells and ≤2.0 mm were found in 62 of 757 screen-detected patients and in 81 of 701 patients with symptomatic breast cancer. Only 3 of the screen-detected patients with micrometastases, all with tumour size >15 mm (range 18–39 mm), had metastases in the completion ALND whereas this was found in 18 of the symptomatic patients with micrometastases (p = 0.01), (tumour size, range 10–30 mm). Logistic regression analysis adjusted for method of detection, tumour size and histological grade showed 5 times higher odds for further metastases in ALND in patients with symptomatic presentation vs. screen-detected breast cancer.Despite the small number of patients with micrometastases in this large cohort of breast cancer patients, these results support the contention that completion ALND can safely be omitted in screen-detected breast cancer patients with micrometastases in the SNs.

Abstract P3-03-14: Clinical utility of one-step nucleic acid amplification (OSNA) in axillary surgery after neoadjuvant chemotherapy (NAC)

Abstract Introduction NAC has been used for downsizing of the tumour in breast and axilla to allow more conservative surgery. In the NAC setting, intraoperative assessment of sentinel lymph node(s) (SLN) is still considered necessary1. Current awareness of the prognostic value for axillary nodal down-staging has renewed interest in analysis of SLN post-NAC. In this study we want to examine the clinical utility of OSNA (based on CK19 mRNA detection) as a method of intra-operative analysis of SLN to assist real-time decision-making for axillary surgery post-NAC in early breast cancer (EBC). Methods Retrospective analysis of prospective data on 399 consecutive patients with EBC who received NAC followed by breast surgery with SLN biopsy (408 axillae) and assessment by OSNA, from September 2011 to January 2018 at the Royal Marsden Hospital (UK). OSNA readouts from the Sysmex RD-100i were collected separate to and blinded from clinico-pathological data. A negative or benign pre-treatment axillary ultrasound scan or indeterminate ultrasound with negative or benign axillary cytology/histology prior to NAC was considered cN0. Univariate analysis (significance at p&amp;lt;0.05) was used to identify risk of recurrence. Patients had a median (mean) follow up of 32.5 (36) months. Results The median age at diagnosis was 49 years, median BMI 26, 41 EBC (10%) were screen-detected, 292 (72%) were grade 3 and the most frequent phenotype was receptor triple negative (n=132, 32%). Of 408 axillae, 248 (60%) were initially cN0, of which 113 (46%) had a pathological complete response (pCR) in the breast. SLN in 54 (22%) cN0 patients were positive on OSNA, of which only 6 (9%) had further involved axillary nodes all 6 of which were ER+ Her2-. The remaining 160 (40%) axillae were cN1 of which 87 (54%) had conversion to ypN0 including 55 (34%) with both ypT0ypN0. Axillary lymphadenectomy (AL) was performed in 79 (19%) patients overall, of which n=22 (28%) were cN0 and 57 (72%) were cN1. Of these, 30 (53%) of the cN1 and 6 of 22 (45%) of cN0 had at least 1 additional positive AL node. Overall 59 (14.4%) patients relapsed. A significantly worse rate of relapse was observed in cN1 compared to cN0 patients (37/159 (23.3%) versus 22/244 (9%), p&amp;lt;0.001). Combined pCR of both breast and axilla (in cN1, n=54) was associated with a significantly reduced risk of relapse and death (p&amp;lt;0.001) compared to those without pCR of either breast or axilla (n=62). Of the latter 18 (29%) relapsed (including 10 deaths). The mean of both the single highest node tumour load (and total nodal tumour load), as measured by CK19mRNA copies/ul on OSNA, were significantly higher at 90,000 (98,300) for those who relapsed versus 23,100 (25,100) for those without relapse (p=0.027). Conclusions The OSNA assay is an accurate tool for axillary SLN analysis in patients after NAC and was helpful in intra-operative axillary management. OSNA reduces the need for a second surgery for AL in 20% of breast cancer patients with a positive-SLN after NAC and might offer additional prognostic value. Reference 1. NCCN. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology Breast Cancer.2016.Version 2.2016. Citation Format: Muscara F, Christaki G, Richardson C, O'Connell R, Padmanabhan P, Warwick J, Lee Y, Smith I, Nerurkar A, Osin P, Krupa K, Rusby J, Roche N, Gui G, MacNeil F, Barry P. Clinical utility of one-step nucleic acid amplification (OSNA) in axillary surgery after neoadjuvant chemotherapy (NAC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-14.

Fat clearance of upper gastrointestinal resection specimens increases lymph node yield and may result in nodal upstaging

IntroductionLymph node retrieval and quantification is an important element in staging upper gastrointestinal cancers. Our department introduced fat clearance for oesophagectomy and gastrectomy specimens in 2014. This study assessed the...

Nomogram-Based Estimate of Axillary Nodal Involvement in ACOSOG Z0011 (Alliance): Validation and Association with Radiation Protocol Variations and Outcomes

Nomograms may be more accurate than experts at predicting risk. Our aim is to use two validated nomograms for axillary node involvement in breast cancer to assess whether protocol variations occurred in higher risk patients in ACOSOG Z0011. We used the M.D. Anderson (MDA) and Memorial Sloan-Kettering (MSK) nomograms to calculate the estimated risk of additional positive axillary nodes using sentinel lymph node biopsy and primary tumor surgery information. In the control arm, we compared findings of axillary dissection (AD) to nomogram-predicted estimates for validation. Logistic regression was used to evaluate whether nomogram-estimated higher risk of nodal involvement was associated with high tangent (HT) or supraclavicular (SCV) radiation field use for patients with known radiation field design. We included radiation fields in multivariate Cox models to evaluate associations with ten-year local-regional failure (LRF), disease-free survival (DFS), and overall survival (OS). Of the 856 evaluable women enrolled, 552 (64.5%) had complete details for the MDA nomogram. Mean MDA risk estimate for patients in both treatment arms was 23.8%. For patients on the AD arm with positive nodes, the estimated risk was 25.9%. Estimated risk did not significantly differ between treatment arms (p-value 0.16). Higher risk estimate was associated with additional positive nodes in the AD arm (OR: 1.04, 95% CI:1.02-1.06, p<0.0001). 78/165 (47.3%) of evaluable patients in the pooled arms with known radiation fields received either HT(n=53) or SCV(n=25) radiation. We observed significant association with higher MDA nomogram estimated risk and SCV radiation (OR=1.07, 95%CI: 1.04-1.10,p<0.0001) but not HT (OR=0.99, 95%CI:0.96-1.02,p=0.52). On multivariable analysis, MDA nomogram estimate was associated with LRF (HR=1.05, 95%CI:1.02-1.08, p=0.003) but not DFS (HR-1.00, 95%CI:0.9901.02, p=0.54) or OS (HR=1.00, 95%CI:0.99-1.02, p=0.66). Receiving SCV radiation was associated with worse DFS (HR=1.83, 95%CI:0.77-4.36, p=0.045) and OS (HR=2.72, 95%CI:1.03-7.18, p=0.027) but not LRF (p=0.27) The MSK nomogram had similar associations for all endpoints. MDA and MSK nomogram risk estimates were associated with confirmed additional lymph node risk in ACOSOG Z011 in the AD arm and appeared balanced in both arms. Radiation oncologists’ use of SCV fields was associated with treating higher risk patients with a worse prognosis.

The Role of Completion Lymph Node Dissection for Sentinel Lymph Node-Positive Melanoma.

Completion lymph node dissection (CLND) for sentinel lymph node (SLN)-positive melanoma patients has been guideline-concordant standard of care since adoption of lymphatic mapping and SLN biopsy for the management of clinically node-negative melanoma patients more than 20years ago. However, a trend for omission of CLND has been observed over the past decade, and we now have randomized, controlled clinical trial data to help guide treatment recommendations. Publication of these data prompted an American Society of Clinical Oncology-Society of Surgical Oncology 2018 clinical practice guideline update for these patients. Systematic review of current evidence supports a selective, individualized approach to CLND for SLN-positive melanoma. For low-risk, low-volume micrometastatic disease, SLN biopsy may be both diagnostic and therapeutic, and close clinical follow-up with imaging or CLND are reasonable options for appropriately selected patients. For higher-risk patients, omission of CLND requires careful consideration of risks versus benefits, relevant histopathology, and individualized patient discussion. This should address patient comorbidities and life expectancy, the predicted likelihood of additional positive nodes, availability of imaging surveillance, likelihood of adherence to imaging and clinical follow-up, consequences of regional recurrence, and the prognostic value of complete nodal staging and its impact on adjuvant therapy recommendations or clinical trial participation. Data on long-term outcomes, cost, and patient-reported quality of life measures are not yet available.

The Potential Impact of AMAROS on the Management of the Axilla in Patients with Clinical T1-2N0 Breast Cancer Undergoing Primary Total Mastectomy.

Recent trials have demonstrated that axillary observation or axillary radiation therapy (AxRT) is equivalent to axillary node dissection (ALND) for patients with one or two positive sentinel lymph nodes (SLNs). These strategies have been widely adopted for patients having breast conservation. This report demonstrates the potential impact of the AMAROS trial on axillary therapy in a retrospective cohort of mastectomy patients. Patients undergoing primary mastectomy for cT1-2N0 breast cancer who had one or two positive SLNs were identified from institutional databases (2005-2015). Locoregional management strategies were evaluated, and variables predictive of the use of postmastectomy radiation therapy (PMRT) were identified. Among 2594 mastectomies, 193 (7%) met the AMAROS eligibility criteria. The median patient age was 50years (range 22-83years). Locoregional treatment consisted of ALND + PMRT for 102 patients (53%), ALND alone for 66 patients (34%), PMRT alone for 11 patients (6%), and observation for 14 patients (7%). Overall, 59 ALND patients (35%) had additional positive nodes. In the multivariate analysis, age younger than 50years (odds ratio [OR] 3.55; 95% confidence interval [CI] 1.57-8.45), lymphovascular invasion (LVI) (OR 5.78; 95% CI 2.53-4.78), macrometastases (OR 3.99; 95% CI 1.54-10.97), and extracapsular extension (OR 11.66; 95% CI 2.55-88.34) were associated with receipt of PMRT. In this cohort of AMAROS-eligible patients, 168 (87%) underwent ALND, 102 (61%) of whom also received PMRT, suggesting that AxRT could have been used instead of ALND for a significant number of patients. Preoperative factors associated with the receipt of PMRT, such as young age and LVI, may be useful for defining a multidisciplinary decision-making framework for axillary management in this population.

PCN8 - Patterns of Treatment and Recurrence In Patients with Non-Metastatic Melanoma WHO Underwent Lymph Node Dissection Surgery

Describe real-world patterns of treatment and locoregional/distant recurrence in patients with non-metastatic melanoma who underwent lymph node surgery (LNS, dissection or lymphadenectomy). Adults with non-metastatic melanoma who underwent LNS were identified in Truven MarketScan (Q1/2008 – Q2/2017; n=6,400). LNS test results were not available in Truven, so the study included patients with and without additional positive lymph nodes. Treatment patterns were identified after LNS (median follow-up: 1.9 years). Locoregional and distant recurrence(s) during follow-up were identified based on patterns of melanoma therapy (initiation of new pharmacotherapy, radiotherapy, or new skin excision/LNS) and secondary malignancy diagnoses (excluding 2nd primary melanoma and non-melanoma cancers) during follow-up. Of 6,400 patients, 219 (3.4%) initiated adjuvant therapy within 3 months of LNS, mostly with interferon-alfa2B (n=206/219, 94.1%; mean duration therapy: 6.4 months); overall, 257/6,400 (4.0%) received adjuvant therapy anytime during follow-up. Other treatments observed during follow-up included: pharmacotherapy for metastatic melanoma (n=32/6,400, 0.5%), radiotherapy (n=186/6,400, 2.9%), new skin excision/LNS (n=1,014/6,400, 15.8%). In addition, 651/6,400 (10.2%) were diagnosed with secondary malignancy and 196/6,400 (3.1%) had a BRAF test. Of 219 patients initiated on adjuvant therapy within 3 months of LNS, 73 (33.3%) experienced recurrence(s) during the follow-up (60 locoregional, 10 distant, 3 both). The first recurrence occurred within a year of the LNS for 51/73 (69.9%), within 2 years for 54/73 (74.0%), and within 3 years for 66/73 (90.4%). Over Q1/2008 – Q2/2017, few patients with high-risk non-metastatic melanoma managed in real-world practice received adjuvant therapy within 3 months of LNS. Among those patients, one third experienced a recurrence. It remains to be determined how the new generation of adjuvant therapies, such as immune checkpoint inhibitors and targeted agents, will increase the use of adjuvant therapies and reduce the risk of recurrence.

Is Low-Volume Disease in the Sentinel Node After Neoadjuvant Chemotherapy an Indication for Axillary Dissection?

Intraoperative evaluation of sentinel lymph nodes (SLNs) after neoadjuvant chemotherapy (NAC) has a higher false-negative rate than in the primary surgical setting, particularly for small tumor deposits. Additional tumor burden seen with isolated tumor cells (ITCs) and micrometastases following primary surgery is low; however, it is unknown whether the same is true after NAC. We examined the false-negative rate of intraoperative frozen section (FS) after NAC, and the association between SLN metastasis size and residual disease at axillary lymph node dissection (ALND). Patients undergoing SLN biopsy after NAC were identified. The association between SLN metastasis size and residual axillary disease was examined. From July 2008 to July 2017, 702 patients (711 cancers) had SLN biopsy after NAC. On FS, 181 had metastases, 530 were negative; 33 negative cases were positive on final pathology (false-negative rate 6.2%). Among patients with a positive FS, 3 (2%) had ITCs and no further disease on ALND; 41 (23%) had micrometastases and 125 (69%) had macrometastases. Fifty-nine percent of patients with micrometastases and 63% with macrometastases had one or more additional positive nodes at ALND. Among those with a false-negative result, 10 (30%) had ITCs, 15 (46%) had micrometastases, and 8 (24%) had macrometastases; 17 had ALND and 59% had one or more additional positive lymph nodes. Overall, 1/6 (17%) patients with ITCs and 28/44 (64%) patients with micrometastases had additional nodal metastases at ALND. Low-volume SLN disease after NAC is not an indicator of a low risk of additional positive axillary nodes and remains an indication for ALND, even when not detected on intraoperative FS.

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

BackgroundRecently there are efforts to use sentinel lymph node biopsy (SLNB) techniques after neoadjuvant chemotherapy (NAC) to minimize axillary surgery. However, studies have shown higher false negative rates in this scenario, which might result in inaccurate assessment of treatment response and patient prognosis as well as leaving residual disease behind. In this study, we describe the use of reflector-guided excision of the percutaneously biopsied node (PBN) as an aid to conventional SLNB and its predictor of the axillary status after NAC. Patients and MethodsThis was a single-institution analysis of patients who underwent axillary fiducial-reflector placement and subsequent SLNB compared with conventional SLNB. ResultsNineteen patients in the reflector group were matched with 19 patients who underwent conventional SLNB (conventional group). The PBN was identified in the SLNB in 19 patients (100%) in the reflector group and in 9 patients (47.3%) in the conventional group (P = .002). In the remaining 10 patients in the conventional group, the PBN was identified in the axillary lymph node dissection specimen in 4 patients (21%) and not identified in 6 patients (31.7%). Among the 38 patients, traditional mapping failed to identify the PBN in 13 patients (34.2%). The PBN was negative in 10 patients (36%) and positive in 18 patients (64%); no additional positive nodes were identified among patients with a negative PBN, correctly reflecting the status of the axilla in 100% of cases. ConclusionMapping failure after NAC might compromise SLNB. Reflector-guided excision of the PBN is not only facile and feasible, but more accurately reflects the status of the axilla after NAC.

Risk factors associated with outcomes following neoadjuvant chemoradiotherapy prior to esophagectomy in patients with adenocarcinoma of the esophagus.

186 Background: The study was conducted to evaluate risk factors associated with treatment outcomes following concurrent chemoradiotherapy (CRT) and esophagectomy in patients diagnosed with resectable esophageal cancer. Methods: IRB approval was obtained to evaluate patients with esophageal cancer treated at our center from 2002 to 2017 with neoadjuvant CRT followed by esophagectomy. Patient characteristics pre and post-surgery including age, number of positive lymph nodes, length of time between neoadjuvant therapy and surgery were evaluated. Univariable and multivariable frailty survival analysis were used to evaluate the association between risk factors and treatment outcomes. Results: 74 patients met inclusion criteria of CRT and esophagectomy. Controlling for the number of days between the end of radiotherapy and surgery, the hazard of death for patients who developed metastatic cancer following completion of therapy was 2.08 (95 CI: 1.04 – 4.13) times higher compared to patients who did not develop metastasis (p = .04). Adjusting for metastatic cancer, for every five additional days between the end of radiotherapy and surgery, patients’ hazard of death increased 5% (HR = 1.05, 95 CI: 1.02 – 1.07, p &lt; .001). Controlling for metastatic cancer and the number of positive nodes, for every one-year increase in age, patients’ hazard of recurrence decreased 5% (HR = 0.95, 95 CI: 0.91 – 0.99, p = .04). Adjusting for age and the number of positive nodes, the hazard of recurrence for patients who developed metastatic cancer was 28.57 (95 CI: 6.58-123.97) times higher compared to patients without metastasis (p &lt; .0001). Conclusions: Longer duration between completion of CRT and surgery as well as developing metastatic disease are associated with a significantly higher hazard of death. Additionally, developing metastatic cancer, increase in age, and additional positive lymph nodes are all associated with a significantly higher hazard of recurrence. Optimal timing between neoadjuvant therapy and surgery needs to be evaluated further, as increasing hazard of death following therapy suggests that there may be a role for adjuvant chemotherapy in these patients.

Frozen section evaluation of sentinel lymph nodes in breast carcinoma: a retrospective analysis

ObjectiveTo determine the false-negative rate, sensitivity, and diagnostic accuracy of the frozen section analysis of the sentinel lymph node (SLN) biopsy in early-stage breast cancer compared to the definitive section and to identify the factors that could be associated with the appearance of false-negative cases. Secondarily, to evaluate the pathological results of cases submitted to completion axillary lymph node dissection (ALND) for positive SLN.MethodsWe performed a five-year review of cases (2011–2015), including patients with early-stage breast cancer undergoing SLN biopsy, with frozen section evaluation and subsequent definitive pathological analysis. These results were compared to calculate the false-negative rate and the factors associated with it. The histopathological findings were also evaluated in patients submitted to completion ALND.ResultsA total of 281 patients were evaluated, identifying 18 cases with frozen section results as false negative (false-negative rate: 23.7%), and 55.5% of these cases were micrometastases. The false-negative rate in SLN with macrometastasis was 13.1% and for micrometastasis cases was 66.7% (p < 0.001). True-positive patients that were submitted to completion ALND had additional axillary lymph nodes with metastases in 28% of cases, whereas the group of false negatives had additional positive axillary lymph nodes in 40% of patients (p = 0.62).ConclusionFrozen section analysis had a false-negative rate acceptable in SLN biopsy in our institution, and the micrometastasis in the SLN was the most important factor associated with the appearance of this phenomenon.

Minimal Clinical Impact of Intraoperative Examination of Sentinel Lymph Nodes in Patients With Ductal Carcinoma In Situ: An Opportunity for Improved Resource Utilization.

There is little information regarding sentinel lymph node (SLN) frozen-section examination in patients with a history of ductal carcinoma in situ (DCIS). We evaluated the usage, clinical impact, and pathology resources used for SLN cryosectioning in mastectomy cases with a DCIS history. Mastectomies with SLNs submitted from 2012 to 2013 at a tertiary care center were analyzed. Medicare reimbursement was used to estimate pathology health care expenditures of intraoperative frozen sections. There was no difference in the rate of SLN frozen-section examination or parts submitted, total blocks frozen, total blocks submitted, or total SLNs identified per case between the DCIS (n = 139) and invasive (n = 369) groups. Nine patients with DCIS had SLN metastases (three macrometastases, two micrometastases, and four isolated tumor cells), all of which were examined by frozen section. Only the macrometastases were identified by cryosectioning, which led to two synchronous axillary lymph node dissections that did not yield any additional positive nodes. A total of $19,313 was spent for pathology per DCIS patient with surgical management affected, whereas only $1,019 was spent per invasive carcinoma patient affected. Decreasing SLN frozen-section use in patients with a history of DCIS represents an opportunity for pathology cost containment.

The Sentinel Node with Isolated Breast Tumor Cells or Micrometastases. Benefits and Risks of Axillary Dissection.

Sentinel lymph node (SLN) biopsy has become the standard procedure to identify metastases in axillary nodes in breast cancer. Even after careful SLN examination additional micrometastases and isolated tumor cells (ITCs) are sometimes found, resulting in a need for delayed axillary lymph node dissection (ALND). This study was undertaken to assess prognostic factors identifying additional axillary lymph node (ALN) metastases at delayed ALND. To define the impact of late ALND regarding their outcome, 162 breast cancer patients with 169 operated breasts treated between 2010 and 2012 were evaluated, with follow-up through 2016. Data were collected on the patients, histology and biologic profile of the cancer, lymph node involvement, recurrence of breast cancer and adverse effects of ALND. With thorough examination and immunohistochemical stainings twenty-nine of 168 SLN biopsies (28 patients, 17% of the patients) showed micrometastases or ITC, and a full ALND was performed at a later time. During these ALNDs 13 to 31 lymph nodes were removed. Additional ALN metastases were found in three (10%) patients. Two (7%) of the 28 patients with triple-negative cancer deceased of metastatic breast cancer. Three patients (11%) reported adverse effects of ALND requiring physiotherapy due to pain, stiffness, swelling or arm oedema. Tumor factors such as molecular subtype (p=0.002), tumor size (p=0.004), and proliferation index (Ki-67) (p=0.003) correlated with higher numbers of ALN metastases. Since most patients with micrometastases found in the primary operation showed no additional positive lymph nodes, completion ALND may not be required in patients with micrometastases or ITCs in the SLN. In our study, the predictive factors for additional ALN metastases were tumur size, molecular subtype and proliferation index. It is conceivable that the features of the primary tumor, rather than the amount of cancer cells in the SLN, might serve to identify patients in whom ALDN can be avoided.

Is the non-sentinel lymph node compartment the next site for melanoma progression from the sentinel lymph node compartment in the regional nodal basin?

Melanoma patients with additional positive lymph nodes in the completion lymph node dissection (CLND) following a positive sentinel lymph node (SLN) biopsy would have a poorer prognosis than patients with no additional positive lymph nodes. We hypothesize that the progression of disease from the SLN to the non-SLN compartment is orderly and is associated with the worsening of the disease status. Thus, the SLN and non-SLN compartments are biologically different in that cancer cells, in general, arrive in the SLN compartment before spreading to the non-SLN compartment. To validate this concept, we used a large cohort of melanoma patients from our prospective SLN database in an academic tertiary medical center. Adult cutaneous melanoma patients (n = 291) undergoing CLND after a positive SLN biopsy from 1994 to 2009 were analyzed. Comparison of 5-year disease-free survival and 5-year overall survival between positive (n = 66) and negative (n = 225) CLND groups was made. The 5-year disease-free survival rates were 55% (95% CI 49-62%) for patients with no additional LN on CLND versus 14% (95% CI 8-26%) in patients with positive LN on CLND (p < 0.0001, log-rank test). The median disease-free survival time was 7.4 years with negative CLND (95% CI 4.4-15+ years) and 1.2 years with positive CLND (95% CI 1.0-1.8 years). The 5-year overall survival rates were 67% (95% CI 61-74%) for negative CLND versus 38% (95% CI 28-52%) for positive CLND (p < 0.0001, log-rank test). The median overall survival time was 12.1 years for negative CLND (95% CI 9.3-15+ years) and 2.5 years for positive CLND (95% CI 2.2-5.7 years). This study shows that CLND status is a significant prognostic factor for patients with positive SLNs undergoing CLND. Also, it suggests an orderly progression of metastasis from the SLN to the non-SLN compartment. Thus, the SLN in the regional nodal basin draining the primary melanoma may serve as an important gateway for metastasis to the non-SLN compartment and beyond to the systemic sites.

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.

Use of axillary lymph node dissection (ALND) in patients with micrometastatic breast cancer

BackgroundSentinel lymph node (SLN) biopsy is the current prognostic tool for clinically node-negative breast cancer patients. If the SLN reveals macrometastasis, axillary lymph node dissection (ALND) is recommended. However, the use of ALND in patients with micrometastasis is debated. The objective of this study was to assess the utilization of ALND in the treatment of micrometastatic breast cancer. MethodsAn IRB approved, retrospective study of a pooled dataset of breast cancer patients with micrometastatic disease on SLN biopsy was performed. Patients diagnosed from 1999-2016 were identified via query of a single-institution National Comprehensive Cancer Network (NCCN) breast cancer database as well as a prospective tumor board. ResultsA total of 91 patients were diagnosed with micrometastatic nodal disease. The median age at diagnosis was 56 y (range: 31-85); median follow-up time was 47 mo (range: 0-203 mo). 42/91(46.2%) patients had ALND of which 37/42 (88.1%) were a second operation; 3/42(7.1%) patients had additional positive nodes found at ALND. 44/91 (48.4%) patients received radiation. 7/91 (7.7%) patients had a recurrence, 5/7 local, including one axillary (2.1%; patient declined ALND). ConclusionsGiven that the risk of lymphedema after ALND ranges between 20%-53%, the morbidity of ALND may far exceed the likelihood of detecting further nodal involvement in women with micrometastatic disease: 7.1% in this series.