Non-sentinel Node Research Articles

CK19 in peripheral blood to indicate the status of non-sentinel lymph nodes: An independent predicative factor.

e12047 Background: CK19 mRNA level of lymph node tissue detected by RT-PCR has been used in sentinel lymph node biopsy (SLNB) in breast cancer. This study was designed to figure out whether CK19 ex...

Non-sentinel lymph node analysis with one-step nucleic acid amplification in breast cancer patients

BackgroundOne-step nucleic acid amplification (OSNA) examines lymph node metastasis in a semiquantitative manner with molecular biology techniques. In this study, we conducted a whole-node analysis of non-sentinel lymph nodes (SLNs) using the OSNA method in SLN metastasis-positive breast cancer patients. MethodsWith the OSNA method, we compared the rates of positivity of non-SLN metastasis in cases with both SLN micro- and macrometastases. ResultsThe rates of non-SLN metastasis positivity in those with SLN micrometastasis and macrometastasis were 44% and 48%, respectively, and this difference was not significant. When the study of non-SLN metastasis positivity was focused only on macrometastases, the rates of non-SLN metastasis positivity in patients with SLN micrometastasis and macrometastasis were 19% and 22%, respectively, and there was no significant difference. ConclusionRegardless of the copy number of SLN metastases, non-SLN metastases were found in approximately half of the cases.

P043. Specialist Masters Degree in Oncoplastic Breast Surgery: An update of student engagement and feedback

P043. Specialist Masters Degree in Oncoplastic Breast Surgery: An update of student engagement and feedback

P042. One Step Nucleic Acid Amplification copy number as a predictor for non-sentinel lymph node positivity

Introduction: OSNA (One-Step Nucleic Acid Amplification) is an established technique for intra-operative assessment of sentinel lymph node (SLN) metastasis, used in 26 hospitals in the UK. The Z0011 and AMAROS trials prompted controversy over whether axillary lymph node dissection (ALND) should be performed at all. Currently we use a CK19 copy number of > 5000 (macrometastasis) to identify patients requiring ALND. We investigated whether a higher copy number of 7700 is a better predictor of non-sentinel lymph node (NSLN) positivity.

P116. Effects of trastuzumab treatment on the patterns of survival and metastasis in Her-2 positive breast cancers

P116. Effects of trastuzumab treatment on the patterns of survival and metastasis in Her-2 positive breast cancers

P169. In patients with micrometastatic sentinel lymph node biopsies, involvement of the non-sentinel lymph nodes cannot be predicted by clinicopathological variables

P169. In patients with micrometastatic sentinel lymph node biopsies, involvement of the non-sentinel lymph nodes cannot be predicted by clinicopathological variables

P114. Acellular dermal matrix versus latissimus dorsi breast reconstruction: An investigation of the costs

P114. Acellular dermal matrix versus latissimus dorsi breast reconstruction: An investigation of the costs

P075. A predicitive model for axillary non-sentinel node involvement by one-step nucleic acid amplification (OSNA) and tumour-related factors in the treatment of breast cancer

P075. A predicitive model for axillary non-sentinel node involvement by one-step nucleic acid amplification (OSNA) and tumour-related factors in the treatment of breast cancer Shramana Banerjee, Timothy Davidson, NormanWilliams, Soha ElSheikh, My-Annh Tran-Dang, Debashish Ghosh, Stephen Davison, Mohammed Keshtgar 1 Royal Free London NHS Foundation Trust, London, UK University College London, London, UK

Evaluating One Day versus Two Days Preoperative Lymphoscintigraphy Protocols for Sentinel Lymph Node Biopsy in Breast Cancer

Sentinel lymph node biopsy (SLNB) is used to detect axillary lymph node metastases in breast cancer. Preoperative radiocolloid injection with lymphoscintigraphy (PL) is performed before SLNB. Few comparisons between 1- and 2-day PL protocols exist. Opponents of a 2-day protocol have expressed concerns of radiotracer washout to nonsentinel nodes. Proponents cite lack of scheduling conflicts between PL and surgery. A total of 387 consecutive patients with clinically node-negative breast cancer underwent SLNB with PL. Lymphoscintigraphy images were obtained within 30 minutes of radiocolloid injection. Axillary lymph node dissection was performed if the sentinel lymph node (SLN) could not be identified. Data were collected regarding PL technique and results. In all, 212 patients were included in the 2-day PL group and 175 patients in the 1-day PL group. Lymphoscintigraphy identified an axillary sentinel node in 143/212 (67.5%) of patients in the 2-day group and 127/175 (72.5%) in the 1-day group (P = 0.28). SLN was identified at surgery in 209/212 (98.6%) patients in the 2-day group and 174/175 (99.4%) in the 1-day group (P = 0.41). An average of 3 SLN was found at surgery in the 2-day group compared with 3.15 in the 1-day group (P = 0.43). SLN was positive for metastatic disease in 54/212 (25.5%) patients in the 2-day group compared with 40/175 (22.9%) in the 1-day group (P = 0.55). A 2-day lymphoscintigraphy protocol allows reliable detection of the SLN, of positive SLN and equivalent SLN harvest compared with a 1-day protocol. The timing of radiocolloid injection before SLNB can be left at the discretion of the surgeon.

Abstract P2-01-29: Axillary involvement in lobular breast cancer

Abstract Purpose: Since the beginning of the use of the technique of selective sentinel node biopsy (SLNB), multiple models have been proposed to predict both the probability of involvement of the sentinel lymoh node (SLN), and, in case it is positive, the likelihood of non-sentinel lymph node (NSLN) involvement. Some of the factors that increase the likelihood of SN involvement (multifocallity, hormonal receptors, larger size…)are frequently found in invasive lobular carcinoma. Invasive lobular carcinoma (ILC) is the second most common histologic type of invasive mammary carcinoma, comprising 5%– 15% of all invasive breast carcinomas. However, in recent decades an increase in the relative incidence of this variant has been reported in the literature. This has been linked to the employment of hormone replacement therapy, the use of assisted reproduction techniques (IVF) or greater availability of diagnostic tools such as breast ultrasound or MRI that allow their better detection. The aim of this study is to determine the extent of axillary involvement in both SLN and NSLN in patients with ILC Patients and Methods 369 cases of infiltrating carcinoma candidates for SLNB technique between April 2010 and April 2013 were reviewed retrospectively. Patients must have a diagnosis of breast cancer of any histological type, with a screening ultrasound without clinical suspicion of axillary involvement. Cases of intraductal carcinoma that underwent SLNB were excluded and even those that were performed prior to neoadjuvant treatment Data on age, histological type, positivity / negativity of the SLN, implementation or not of axillary lymphadenectomy and outcome of involvement of NSLN were collected. Statistical calculations were performed with SPSS. Results Of the 369 selected patients, 291 (79.9%) had invasive ductal carcinoma (IDC), 55 (15.1%) ILC and 18 other histological types (mucinous, colloid, tubular, papillary or mixed). The median age was 58.6 years. SLN could not be found in 5 patientes. 225 (61.8%) had a negative SLN. In 139 (38.2%) patients, SLN was positive, 64 of these cases showed micrometastasis while 75 presented macrometastasis. Among IDC, 108 (37.1%) of the cases had a positive SLN, 53 (49.1%) of them with macrometastases. Among ILC, 27 (49.1%) of the cases presented positive SLN, in 20 of them (74.1%) with macrometastasis. Differences in both the SLN involvement and the presence of macrometastases observed between IDC and ILC were statistically significant (p< 0.001). In those cases were a lymph node dissection was performed, the probability of finding NSLN affection was 18.8% in the case of IDC compared to 55% in patients with ILC (p< 0.001). Conclusions Axillary lymph node involvement in the case of candidates for SLNB is more frequent and more extensive in patients with ILC than in patients with IDC. Citation Format: Pilar Zamora, Covadonga Marti, Ana Roman, Jose M Oliver, Javier de Santiago, Jose I Sanchez-Mendez. Axillary involvement in lobular breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-29.

Abstract P2-01-27: In patients with micrometastatic in sentinel lymph node biopsies, involvement of the non-sentinel lymph nodes cannot be predicted by clinicopathological variables

Abstract Background: The Sentinel Lymph Node Biopsy (SLNB) procedure is recognised to be an accurate method of staging the axilla in patients with early stage breast cancer. There remains a debate as to whether patients with micrometastases should undergo completion axillary lymph node dissection (CALND). We aimed to assess the indicators for positive non-sentinel lymph nodes (n-SLN) following CALND. Methods: We retrospectively analysed our experience of SNLB between July 2008 to July 2013. A total of 1152 breast cancer patients underwent SLNB based on lymphoscintigraphy, intra-operative gamma probe detection, and blue dye mapping using 99mTc-nanocolloid and Patent Blue V injected peri-areola. Statistical analysis was performed using Fisher’s exact and c2 for categorical data. Results: Out of 1152 SLNB biopsies performed, 224 (19.5%) were positive for metastatic disease; macrometastases in 150 (67%), micrometastases in 72 (32%) and ITC in 2. CALND was not performed in 20 cases (9 macrometastases, 10 micrometastases, and 1 ITC), largely due to concerns regarding fitness for anesthesia. Macrometastases on SNLB were more likely to predict positive n-SLN on ANC {macrometastases; 39/141(27.7%) vs micrometastases; 9/62 (14.5%), p=0.029}. On univariate analysis, positive n-SLN in CALND for patients with micrometastases on SLNB was not predicted by grade (G0-G2; 6/43, and G3; 3/19, p=0.565), size of primary breast tumour (<40mm; 8/58, 340mm; 1/4, p=0.475), lymphovascular invasion (5/30 vs 4/31, p=0.503), age (<50 years; 3/24 vs 350 years; 6/38, p=0.496), or number of positive SLNB (all patients had <2 positive nodes on SLNB). Recurrences were detected in 4 patients, of which 1 was in a patient with micrometastases on SLNB. Out of the 4 recurrences, 3 were distant (liver and bone) and one was locoregional, with new disease in the contralateral breast). Conclusion In our series, 14.5% (9/62) of patients with micrometastases had positive n-SLB on CALND, which was not predicted by any clinicopathological characteristics. We have recently changed our practice toward not routinely offering CALND in patients with micrometastases, in keeping with current vogue. However, it is important to inform our patients that 14.5% of patients with micrometastases on SLNB may have positive n-SLN. Citation Format: Muhammad N Chauhan, Rajiv V Dave, Mauria Ghaus, Sana Ahmad, Craig Sayers, Zbigniew Kryjak, Deedar Ali. In patients with micrometastatic in sentinel lymph node biopsies, involvement of the non-sentinel lymph nodes cannot be predicted by clinicopathological variables [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-27.

Abstract P2-01-11: Prospective evaluation of the reliability of the combined use of two models to predict non-sentinel lymph node status in breast cancer patients with metastatic sentinel lymph nodes: The MSKCC nomogram and the Tenon score – PHRC-NOTEGS study

Abstract Background: Several mathematical models have been developed to predict non-SN status in patients with breast cancer with SN metastasis. The Memorial Sloan-Kettering Cancer Center nomogram and Tenon score outperform other methods in academic studies but their exportability at multiple geographic locations and practice settings has never been reported. The purpose of this study was to prospectively evaluate the combined use of the MSKCC nomogram (Memorial Sloan-Kettering Cancer Center) and Tenon score to select, in patients with metastatic sentinel lymph node (SN), those at low risk of metastatic non-SN in whom additional axillary lymph node dissection (ALND) could be avoided. Material and methods: From January 2011 to July 2012, data on 3157 patients with breast cancer from 65 institutions (university affiliated, general, regional hospital, nonprofit private hospital and private practice) were prospectively recorded (NCT01509963). Selection criteria were patients aged over 18 years old with untreated invasive T1-2 breast cancer with an indication of SN procedure. The primary outcome measure was the false negative rate in patients with both a ≤10% probability of metastatic non-SN with the MSKCC nomogram and a Tenon score ≤3.5 (i.e. low risk): proportion of patients with metastatic non-SN at additional ALND. The hypothesis was a 5%±5% rate in this group of patients. Other patients were considered at high risk. Because of the results of the Z011 and IBCSG 23-01 trials, additional ALND was not mandatory.in case of metastatic SN. Results: Among the 2936 patients, at least one SN was metastatic (isolated tumor cells, micro- or macrometastasis) in 696 patients (23.7%). Among them, 178 did not have completion ALND. Among patients with completion ALND (n=518, 74.4%), 67 (13%), 437 (84%) and 14 (3%) patients were at low, high and undetermined combined risk while 47.5% were at low risk in patients without completion ALND (p<.001). This study did not meet its primary objective as the false negative rate in patients with low risk was 16.4% (11/67) [95% confidence interval: 8.5%-27.5%]. The false negative rate was significantly higher in patients in the high risk group: 33.9% (148/437) [95% confidence interval: 29.6%-38.4%] had non-SN metastasis (p=.004). Analyzed individually, Tenon score and MSKCC nomogram had complementary performances (number of patients at low risk: 35.3% and 18.5%, false negative rates: 21.9% and 17%, concordance index: 0.63 and 0.65, respectively). Conclusion: In this controlled prospective trial, metastatic SN patients with both a ≤ 10% probability of metastatic non-SN with the MSKCC nomogram and a Tenon score ≤ 3.5 had completion axillary dissection in 47% of cases: in these patients, the false negative rate was statistically over 5% and did not reach the primary endpoint. Further evaluation is warranted to determine the outcome of patients with and without axillary dissection. Citation Format: Roman Rouzier, Catherine Uzan, Alexandra Rousseau, Eugenie Guillot, Sonia Zilberman, Charles Meyer, Pablo Estevez, Pierre-François Dupre, David Kere, Virginie Doridot, Gauthier D'halluin, Xavier Fritel, Nicolas Pouget, Chafika Mazouni, Tabassome Simon, Charles Coutant. Prospective evaluation of the reliability of the combined use of two models to predict non-sentinel lymph node status in breast cancer patients with metastatic sentinel lymph nodes: The MSKCC nomogram and the Tenon score – PHRC-NOTEGS study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-11.

Abstract P2-01-20: The ratio and size of positive sentinel lymph nodes predicts the involvement of non-sentinel lymph nodes following completion axillary lymph node dissection

Abstract Background: The role of Completion Axillary Lymph Node Dissection (CALND) following positive Sentinel Lymph Node Biopsy (SLNB) is being actively debated. The involvement of our unit in the POSNOC trial (which has a no-treatment arm), has prompted a review of our unit’s CALND results, in order to examine predictors of involvement of non-sentinel lymph nodes (n-SLN), to better inform our patients during recruitment. Methods: We retrospectively analysed our experience of SNLB between July 2008 to 2013. A total of 1152 breast cancer patients underwent SLNB based on lymphoscintigraphy, intraoperative gamma probe detection, and blue dye mapping using 99mTc-nanocolloid and Patent Blue V injected peri-areola. Results: Out of 1152 SLN biopsies performed, 224 were positive for metastatic disease. 203 patients were anaesthetically capable of progressing to CALND. On univariate analysis, involved n-SLN on CALND could not be predicted by age (<50 years; 16/77 vs ≥50 years; 93/125, p=0.272), size of tumour (<50mm; 44/193 and ≥50mm; 4/10, p=0.188), procedure (mastectomy; 24/93, WLE; 24/106, p=0.444), lymphovascular invasion (22/97 vs 26/106, p=0.812), number of positive SLN (≤2; 45/196, >2; 3/7, p=0.213), receptor status; ER (negative; 3/13, positive 45/187, p=0.619), PR (negative; 6/28, positive 41/169, p=0.478), Her2 (negative; 43/175, positive 5/25, p=0.414), triple negative (2/8 vs 46/192, p=0.612). There was a trend toward higher incidence of positive n-SLN with increasing grade (G0-2; 28/139 vs G3; 20/64, p=0.062) and extracapsular spread (14/41 vs 32/149, p=0.073), but these did not reach statistical significance. Positive n-SLN on CALND was however predicted by macrometastases in SLN (macrometastases; 39/141 vs micrometastases; 9/62, p=0.029) and ratio of positive nodes (<0.5; 18/109 vs ≥0.5; 30/94, p=0.008). There were 4/224 recurrences (3 distant metastases and 1 loco-regional), which were not predicted by any of the clinicopathological variables investigated. 3 patients who recurred only had one positive node on SLNB. Conclusion In our series of more than 200 SLNB, a ratio of >0.5 positive SLN yield and presence of macrometastases in positive SLN, were associated with positive n-SLN on CALND. Citation Format: Rajiv V Dave, Muhhamed N Chauhan, Maria Ghaus, Sana Ahmed, Shiv Shapra, Joshua Marriott, Craig Sayers, Zbigniew Kryjak, Deedar Ali. The ratio and size of positive sentinel lymph nodes predicts the involvement of non-sentinel lymph nodes following completion axillary lymph node dissection [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-20.

Abstract P2-01-25: Not all sentinel lymph nodes are equal – A predictive model for axillary burden in early breast cancer

Abstract Introduction The Z11 trial demonstrates that an axillary lymph node dissection (ALND) can be avoided in patients with low axillary burden who undergo breast conserving surgery (BCS), combined with whole-breast radiotherapy and systemic therapy. Our group propose a standardisation of sentinel lymph node biopsy (SLNB), incorporating 2 novel sentinel nodal stations (SNS) which represent sequential echelons of SLN draining the breast – the intercostalbrachial nerve (ICB) and the medial pectoral neurovascular bundle (MP). By increasing the specificity and positive predictive value of SLNB, we aim to identify a subgroup of patients who undergo mastectomy who can be spared from ALND and its associated complications. Materials and Methods 313 female patients who underwent sentinel lymph node biopsy for breast cancer from 2 February 2012 to 19 December 2013 were prospectively studied. 12 patients had bilateral breast cancers, and each laterality was counted as distinct cases, giving a total of 325 cases. 7 had breast surgery performed prior to the SLNB, and the rest had their oncological surgery performed at the same setting of the SLNB. The surgeries were performed by three surgeons in the National Cancer Centre Singapore, using a specific surgical technique to identify SLN at the 2 SNS. Relevant patient demographics, status of SNS and the rates of metastatic non-sentinel lymph nodes were collected and analysed. Results A total of 325 SLNBs using the ICB and MP SNS were identified from 169 simple mastectomies, 35 skin sparing mastectomies, and 129 breast conserving surgeries. The median age was 56 (range 27-89). The ICB SLN and MP SLN were identified in 313 (96.3%) and 258 (79.4%) cases respectively. In 249 (76.6%) cases were both ICB and MP nodes identified, of which 55 (16.9%) had metastatic involvement of the SLN. An axillary clearance was performed if at least one ICB or MP node was positive, and only 27 (49.1%) had further axillary involvement. More than 2 positive SLNs had 100% positive predictive value for further axillary LN metastases. There was a low sensitivity (29.6%) and high false negative rate (70.4%) for positive axillary nodes in patients with ≤2 positive SLNs. MP nodal status, however, was 85.7% specific (p<0.001) and 48.1% sensitive (p=0.649) and a positive predictive value of 76.5% for axillary nodal involvement. Logistic regression also shows that MP node status is significant for predicting axillary nodal status (OR 5.57, p=0.006). Conclusion Our study shows that MP node status is specific, and has a positive predictive value for further axillary LN metastases. Therefore, we propose that in all patients who undergo SLNB with their BCS or mastectomy, an axillary clearance should be performed if the MP node is positive, regardless of the number of positive SLNs. Citation Format: Yirong Sim, Sue Zann Lim, Shaun S Tan, Alvona Z Loh, Cindy Lim, Preetha Madhukumar, Gay H Ho, Veronique KM Tan, Kong Wee Ong. Not all sentinel lymph nodes are equal – A predictive model for axillary burden in early breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-25.

Abstract P2-01-17: Total tumoral load as a prediction tool of non-sentinel node metastases in patients with early breast cancer and positive sentinel lymph node assesed by OSNA

Abstract Background: Total tumoral load (TTL) in the sentinel lymph nodes (SLN) assessed by the OSNA assay is a new variable that is able to predict the likelihood of more axillary metastasis. Compared with the number of positive SLNs, the TTL is independent of the number of metastatic SLNs and a better predictor of further nodal metastasis. Although establishing specific cutoff-points of the TTL can be questionable because they may change in the future and increasingly become more patient specific, we have seen that TTL <15.000 could be a good cut off by its high negative predictive value (NPV). Changes in practice have been occurred after the ACOSOG Z0011 trial and nowadays, patients with ≤ 2 positive SLNs may spare an axillary lymph node dissection (ALND) with no impact on the oncological outcome. In the Z0011, 27% of patients had additional non-SLN metastasis in the cALND. The objective of this study was to compare two methods of SLN metastatic burden, the TTL and the number of positive SLNs, for predicting non-SLN metastasis in patients with positive SLNs by OSNA. Methods: This is a retrospective cohort study of 145 consecutive patients with cT1-T2 invasive breast cancer with ultrasonographically node-negative treated between April 2010 to April 2013, where there is at least one positive SLN assesed by OSNA. We design a prediction tool based on the TTL results determined by OSNA to calculate the likelihood of not finding more positive non-SLN (http://www.vhebron.net/es/calculadora-risc-metastasi-2). Our group have demonstrated that TTL=15.000 could be a good cut off by its high NPV and sensitivity, 85.5% and 76.7%, respectively. Results: A total 325 SLNs were removed with a mean of 2.24. The type of SLN metastasis were macrometastasis in 85 patients (58.6%) and micrometastasis in 60 patients (41.4%). When considering patients with number of positive SLNs, of 109 patients with ≤2 positives SLNs and an cALND, 17 patients (22%) had non-SLN metastasis; and of 5 patients with ≥3 SLN, four (80%) had non-SLN metastasis. Taking the TTL results, of 51 patients with TTL <15.000 copies/µL with cALND (90.2% with one positive SLN), 7 patients (14%) had non-SLN metastasis, were a media of 2.2 extra non-SLN metastasis. Of 55 patients with TTL ≥15.000 copies/µL (with 1 or 2 positives SLNs) with cALND, 20 patients (36%) had non-SLN metastasis and there were a media of 2.5 non-SLN metastasis (range 1-8). Of 34 patients (62%) with one positive SLN with TTL ≥15.000 copies/µL, 12 patients (35%) had non-SLN metastasis; and of 21 patients with two positive SLN with TTL ≥15.000 copies/µL, eight patients (38%) had non-SLN metastasis. Conclusion: The total tumor load obtained by OSNA predicts non-SLN metastasis independent of the number of positive SLNs. The assess of the TTL in our cohort of patients show that patients with one or two positives SLNs with high TTL had high likelihood of non-SLN metastasis greater than 27% of Z0011 criteria. Prospective studies are needed to determine the clinical impact of this variable in patients outcome in the management of patients with SLN assesed by OSNA. Citation Format: Martin Espinosa-Bravo, Francesc Pérez-Ceresuela, Sebastian Diaz-Botero, Vicente Peg, Isabel T Rubio. Total tumoral load as a prediction tool of non-sentinel node metastases in patients with early breast cancer and positive sentinel lymph node assesed by OSNA [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-17.

Reliability of dynamic sentinel node biopsy combined with ultrasound-guided removal of sonographically suspicious lymph nodes as a diagnostic approach in patients with penile cancer with palpable inguinal lymph nodes

Introduction and objectivesDynamic sentinel node biopsy (DSNB) is considered “unsuitable” in patients with penile cancer and palpable inguinal lymph nodes. The aim of this study was to determine the diagnostic reliability of DSNB combined with ultrasound (US)-guided removal of additional suspicious lymph nodes as a minimally invasive diagnostic approach in these patients. Material and methodsA total of 23 consecutive patients with penile cancer and unilaterally or bilaterally palpable inguinal lymph nodes underwent DSNB according to the 2-day protocol. Before the combined staging procedure, the patients underwent preoperative US of both groins. During surgery, sentinel nodes and additional suspicious lymph nodes as determined by the US examination were removed under US guidance. A complete inguinal lymph node dissection was only performed in patients who had tumor-positive nodes. Follow-up consisted of control visits according to the European Association of Urology guidelines, including US investigation of the groins. ResultsThe primary tumors were staged as T1, T2, and T3 carcinomas in 12, 8, and 3 patients, respectively. Grading was good, moderate, and poor in 2, 16, and 4 cases, respectively. Tumor grading could not be determined in 1 patient who underwent surgery of the invasive part of the primary tumor elsewhere. Sentinel nodes or nonsentinel nodes or both were positive in 15 of 36 palpatory-positive groins. DSNB alone showed lymphatic spread in 10 inguinal regions. US-guided removal of suspicious nonsentinel nodes revealed 5 further inguinal basins with metastases, which would have been missed by DSNB owing to rerouting or complete blockage of the lymphotropic tracer. So far, no lymph node relapse has been observed in the 12 patients with node-negative disease by this combined diagnostic approach with a median follow-up of 42 (16–84) months. The morbidity (postoperative bleeding and prolonged lymphorrhea) associated with this procedure was minor (6%). ConclusionsThe results of this study imply that DSNB combined with US-guided removal of suspicious lymph nodes is a reliable diagnostic approach in patients with penile cancer with palpable inguinal lymph nodes. DSNB alone in these patients leads to a significant false-negative rate. These early and promising results have to be confirmed in larger cohort studies.

Predictors of non-sentinel lymph node (non-SLN) metastasis in patients with sentinel lymph node (SLN) metastasis in endometrial cancer

ObjectivesThe aim of this study was to determine the risk of metastasis in the remaining non-SLNs when the SLN is positive and to identify the factors that can predict this risk. MethodsWe reviewed all patients who underwent primary surgery for endometrial carcinoma with lymphadenectomy and SLN mapping (November 2010–November 2013) in our center. SLNs were ultra-staged on final pathology. ResultsA total of 268 patients were included. Overall, 43/268 patients (16%) were found to have SLN metastasis: macro-metastasis in 24 patients, micro-metastasis in 7 and ITC in 12. Non-SLN metastases were found in 15 of the 43 patients (34.8%) with positive SLN. Size of the SLN metastasis was the only factor associated with an increased likelihood of non-SLN metastasis (p=0.005). When the size of the SLN metastasis was ≤2mm, the risk of having another positive lymph node was only 5%, conversely, when the size of the SLN metastasis was >2mm, the risk of having another positive lymph node was 60.8% (p<0.0001). Histologic type, grade, depth of myometrial invasion, LVSI, cervical stromal invasion and CA-125 were not predictive. ConclusionWhen the SLN is positive, the risk of metastasis in the remaining non-SLNs was 34.8%. Size of the metastasis within the SLN was the only factor that could predict the risk of non-SLN metastasis; 2mm seems to be the cutoff size below which the risk of non-SLN metastasis is low.

The role of cytoreductive surgery for recurrent endometrial cancer

Objectives: To determine the rate and performance of sentinel lymph node (SLN) mapping among women with high-risk endometrial cancers. Methods: Patients diagnosed between 2012 and 2014 with uterine cancer of grade 3 endometrioid, clear cell, serous, or carcinosarcoma histology who underwent SLN mapping before full lymph node dissection were included. Patients underwent either methylene blue or indocyanine green injection for laparoscopic (n = 15) or roboticassisted laparoscopic staging (n = 12). Outcomes examined included rates of SLN mapping using each surgical approach, SLN and non-SLN positive rates, false-negative SLN rate, and the negative predictive value of SLN. Ultrastaging of SLN was not routinely performed during the study period. Fisher's exact test was used to compare mapping and node positivity rates. Results: A total of 10/27 (37%) patients with high-risk uterine cancer had at least one positive lymph node identified. Twelve patients (44%) mapped bilaterally, 10 (37%) mapped unilaterally, and 5 (18%) did not map. Thirty-four of 54 sides (63%) mapped successfully. Successful SLN mapping rates by side were: 19/30 sides (63%) for the laparoscopic and 15/24 sides (66%) for the robotic approach (P=0.53). Among 20 sides that failed to map, 4 (26%) had findings of grossly enlarged nodes, 7 (35%) had reportable adhesions, 6 (30%) had fibroids, and 4 (20%) were morbidly obese, making node visualization difficult. Nine of 75 (12%) sentinel nodes and 8/513 (2%) nonsentinel nodes were positive (P = 0.0009). Eight of nine (89%) positive SLNs were the only positive lymph nodes identified on that side. The false-negative SLN rate (negative SLN but other malignant lymph nodes identified on the same side) was 1/20 (5%); the negative predictive value of SLN was 95%. Conclusions: In this series of women with high-risk uterine cancer, SLNs had a significantly higher rate of metastasis than nonsentinel lymph nodes. However, successful mapping rates may be slightly lower than historical controls among high-risk histology cancers. The 95% negative predictive value of SLN is consistent with larger subsets of lower risk endometrial cancers.

Predictors of non-sentinel lymph node metastasis in patients with positive sentinel lymph node (SLN) in endometrial cancer

histology (Grade 3, Type I vs. Type II), depth of invasion, and lymphovascular space invasion. Group B cases were older (65.5 ± 9.2 vs. 63.0 ± 10.9 years, P= 0.02) and had more pelvic LNs harvested (26.4 ± 10.5 vs. 18.8 ± 8.5, P b 0.0001). Aortic LN yields were identical (9.0 ± 5.6 vs. 9.0 ± 6.0). More pelvic LN metastases were detected in Group B (30.3% vs. 13.6%, P b 0.0001). Group B had more Stage IIIC1 cases (19.3% vs. 6.0%, P b 0.0001), fewer Stage IIIA cases (0.8% vs. 6.6%, P b 0.01), more GOG high-risk cases (32.8% vs. 19.8%, P b 0.01), fewer low-risk cases (21.8% vs. 36.3%, P b 0.01), and more patients receiving combination chemotherapy + radiation (28.6% vs. 16.3%, P b 0.003). A total of 18/36 (50%) Group B cases with LNmetastases were isolated to the SLN, and 12/18 (66.7%) of these were micrometastases or isolated tumor cells that were missed on hematoxylin-and-eosin pathology. These 12 upstaged cases would have been considered GOG low-risk (n= 4), low-intermediate risk (n= 2), and high-intermediate risk (n= 6) without SLN mapping. Conclusions: This study suggests that compared to traditional pelvic lymphadenectomy, the addition of SLN mapping identifies more pelvic lymph node metastases and shifts GOG lowand intermediate-risk cases to high-risk cases, possibly resulting in administration of more postoperative chemotherapy and radiation therapy.

Sentinel node biopsy in vulvar cancer: Implications for staging

In 2008, the first Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V) showed that omission of inguinofemoral lymphadenectomy is safe in patients with early-stage vulvar cancer and a negative sentinel node and it simultaneously decreases treatment-related morbidity. An important part of the sentinel node procedure is pathologic ultrastaging of the removed sentinel nodes. Subsequently, since the introduction of this procedure in the standard care of patients with early-stage vulvar cancer, more and smaller inguinofemoral lymph node metastases have been diagnosed. The clinical consequences of these micrometastases are not clear yet. With increasing size of the sentinel node metastasis, chances of non-sentinel node metastases increase and those of survival decrease. The size of lymph node metastases is included in the latest staging system for vulvar cancer, however at this moment without clinical implications. Furthermore, a separate category for micrometastases is not incorporated yet. More research is needed to determine the clinical consequences of the size of (sentinel) lymph node metastases.