False-negative Sentinel Lymph Node Research Articles

Abstract P2-01-03: Sentinel node procedure before or after neoadjuvant chemotherapy in clinically node negative or positive patients; results from 3 phase III studies of the Dutch breast cancer trialists' group (BOOG)

Abstract Background In breast cancer patients treated with neoadjuvant systemic therapy, the timing of the sentinel node (SN) procedure in patients with clinically node-negative disease (cN0) at diagnosis and the role of the SN procedure after neoadjuvant therapy in patients with initially clinical node-positive disease (cN+) still remains to be elucidated. Methods Between February 2006 and May 2012, 657 patients were enrolled in three clinical trials on neoadjuvant systemic therapy under the auspices of the Dutch Breast Cancer Research Group (BOOG). In the INTENS and NEO-ZOTAC study, patients were treated with TAC or AC-T neo-adjuvant chemotherapy (doxorubicin (A), cyclophosphamide (C) and docetaxel (T)). In the TEAM IIa trial, patients were treated with neoadjuvant endocrine therapy (exemestane for 6 months). Timing of the SN procedure in cN0 disease mainly depends on local policy and period of inclusion. We compared the pN0 rate after SN procedure performed before versus after neoadjuvant systemic therapy, in patients with cN0 disease at initial diagnosis. Further, we assessed the SN negative and the false-negative sentinel node rate in patients with initially cN+ breast cancer and conversion to cN0 when treated with neoadjuvant systemic therapy. The false-negative rate was obtained by dividing the number of patients who were SN-negative but non-SN positive by the number of patients who had a positive SN or a positive non-SN. Results In total, 271 patients (n=93 INTENS, n=107 NEOZOTAC, n= 71 TEAM IIa) underwent a SN procedure (n=233 cN0; n=38 cN+). Of patients with cN0 breast cancer at diagnosis, 131 (56%) underwent the SN procedure before and 102 (44%) after neoadjuvant systemic therapy, with ypN0(sn) or ypN0(i+)(sn) in 90/131 (69%) and 69/102 (68%) patients, respectively. Patients with initially cN+ disease who converted to cN0 disease after systemic therapy had a negative SN in 29% (11/38) of cases. The false-negative rate was 20% (6 of 30). More detailed analyses will be presented at the meeting. Conclusion To our knowledge, this is the first study comparing the impact of the timing of the sentinel procedure in patients with cN0 disease. We showed, that irrespective of the timing of the SN procedure - before or after neoadjuvant systemic therapy - in patients with cN0 breast cancer at diagnosis, two-third of patients had a negative sentinel node. In patients who converted after neoadjuvant chemotherapy from cN+ to cN0 the false negative sentinel node rate was 20%. Citation Format: Vivianne C Tjan-Heijnen, Birgitte E Vriens, Maureen J Aarts, Judith R Kroep, Cock J van de Velde, Gerrit-Jan Liefers, Ayoub Charehbili, Petronella G Peer, Maaike de Boer. Sentinel node procedure before or after neoadjuvant chemotherapy in clinically node negative or positive patients; results from 3 phase III studies of the Dutch breast cancer trialists' group (BOOG) [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 P2-01-03.

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.

Clinicopathologic predictors of survival in patients with desmoplastic melanoma.

Background and ObjectivesDesmoplastic melanoma is a unique subtype of melanoma which typically affects older patients who often have comorbidities that can adversely affect survival. We sought to identify melanoma-specific factors influencing survival in patients with desmoplastic melanoma.MethodsRetrospective review from 1993 to 2011 identified 316 patients with primary desmoplastic melanoma. Clinicopathologic characteristics were correlated with nodal status and outcome.ResultsFifty-five patients (17.4%) had nodal disease: 33 had a positive sentinel lymph node biopsy and 22 developed nodal recurrences (no sentinel lymph node biopsy or false-negative sentinel lymph node biopsy). Nodal disease occurred more often in younger patients and in cases with mixed compared with pure histology (26.7% vs. 14.6%); both of these variables significantly predicted nodal status on multivariable analysis (p<0.05). After a median follow-up of 5.3 years, recurrence developed in 87 patients (27.5%), and 111 deaths occurred. The cause of death was known in 79 cases, with 47 deaths (59.5%) being melanoma-related. On multivariable analysis, Breslow thickness, mitotic rate ≥1/mm2 and nodal status significantly predicted melanoma-specific survival (p<0.05).ConclusionsNodal status predicts melanoma-specific survival in patients with desmoplastic melanoma. However, since patients with desmoplastic melanoma represent an older population, and a considerable proportion of deaths are not melanoma-related (40.5%), comorbidities should be carefully considered in making staging and treatment decisions in this population.

Contribution of lymphoscintigraphy to intraoperative sentinel lymph node detection in early cervical cancer: Analysis of the prospective multicenter SENTICOL cohort

PurposeTo evaluate the contribution of preoperative lymphoscintigraphy to intraoperative lymphatic mapping (ILM) in early cervical cancer MethodsWe conducted an ancillary analysis of the multicenter prospective SENTICOL study in early cervical cancer. Radiocolloid was injected intracervically on the day before (long protocol) or morning of (short protocol) surgery, lymphoscintigraphy was performed, and the results of a centralized image review were communicated to the surgeons. ILM was performed on combined radioactivity/patent blue detection. Sentinel lymph nodes (SLNs) were electively sampled before routine bilateral pelvic lymphadenectomy by laparoscopy. ResultsOf 139 patients in the modified intention-to-diagnose analysis, 114 had centrally reviewed lymphoscintigrams, which showed 352 SLNs in 100 patients. Lymphoscintigraphy and ILM detection rates were 87.8% and 97.8%, respectively. Agreement between lymphoscintigraphy and ILM was low for the number of SLNs (κ=0.23; −0.04; 0.49) and bilateral SLNs (κ=0.36; 0.2; 0.52). No patient without SLNs by ILM had SLNs by lymphoscintigraphy. Lymphoscintigraphy identified substantial proportions of unusual drainage pathways. No patients with metastatic nodes had SLNs by lymphoscintigraphy but not by ILM in the relevant territory. In 1 of the 2 patients with false-negative SLN results, SLNs were bilateral by lymphoscintigraphy and unilateral by ILM. ConclusionAlthough the detection rate was lower by lymphoscintigraphy than by ILM, the substantial proportions of SLNs in unusual territories provided valuable guidance for the surgical exploration. Awareness of the limited agreement between lymphoscintigraphic and surgical detection might help surgeons decrease the false-negative rate.

319P - Characteristics of Breast Cancer Patients with False-Negative Sentinel Node Biopsy

ABSTRACT Aim: There are only limited studies that analyzed the clinical significance of false-negative (FN) in sentinel node biopsy (SNB) with sufficient sample size. The aim of this study was to identify the risk factors for FN in SNB and to analyze the clinical significance of that in patients with breast cancer. Methods: Patients with invasive breast cancer who underwent SNB followed by axillary node dissection between 1995 and 2013 were retrospectively identified. We excluded patients with ductal carcinoma in situ or those who had recieved preoperative chemotherapy. A total of 189 patients with FN in SNB were compared to 413 women with true-negative (TN) in SNB. Logistic regression analysis was used to identify risk factors associated with FN result and Cox regression analysis was performed to assess the clinical impact of that. Results: Histologic type, lymphovascular invasion, location of main lesion, tumor size, and administration of adjuvant chemotherapy were associated with FN in SNB. Multivariate analysis showed that ductal carcinoma, tumor located at upper outer quadrant, and larger tumor were significant independent risk factors for FN; adjusted odds ratios representing 2.82 (95% CI: 1.58 to 5.04), 1.74 (95% CI: 1.22 to 2.49), and 1.29 (95% CI: 1.08 to 1.53), respectively. Patients with FN in SNB showed worse disease-free survival (DFS) than those with TN, corresponding to 5-year DFS rates of 86.4% and 94.7%, respectively and an adjusted hazard ratio of 3.87 (95% CI: 1.84 to 8.12; p Conclusions: This study showed that patients with FN in SNB presented worse prognosis than those with TN even with adjuvant treatment. In patients with ductal carcinoma, with larger tumor size, and with tumors located at the upper outer quadrant, it would be necessary to make an effort to find out metastatic non-sentinel nodes with a suspicion after SNB. Disclosure: All authors have declared no conflicts of interest.

Surgeon bias in sentinel lymph node dissection: Do tumor characteristics influence decision making?

BackgroundDetermining sentinel lymph nodes (SLNs) in breast cancer staging involves subjective interpretation by the surgeon. We hypothesized patient and tumor characteristics influence number of SLNs harvested. MethodsA single-institution, prospectively collected database was queried for breast cancer patients undergoing SLN surgery (2002–2013) and mean SLN counts were compared. ResultsThere were 2394 SLN biopsies. Mean number of SLNs per patient for the entire cohort was 2.6. Mean number of SLNs removed was greater for patients ≤50 years (2.9 versus 2.6; p < 0.0001). Fewer SLNs were removed with tumors ≤1 cm (2.5 versus 2.6; p = 0.002). Patients with grades 2 or 3 tumors had more SLNs removed than grade 1 (2.6 versus 2.5; p = 0.03). Receipt of neoadjuvant therapy was associated with more SLNs removed (3.0 versus 2.6; p = 0.005). ConclusionNumber of SLNs removed varies based on risk factors for SLN metastasis or false-negative SLN biopsy.

The value of intraoperative frozen section analysis for margin status in breast conservation surgery in a nontertiary institution.

Introduction. Breast conservation treatment (BCT) for early-stage breast malignancies requires negative margins and good cosmesis. Reoperations may be needed to achieve negative margins, which can have an adverse impact on outcomes. This study was performed to evaluate the efficacy of intraoperative frozen section analysis (IFSA) for margin assessment to reduce excision rates. Methods. All patients treated at the authors' private healthcare facility between 2009 and 2011 for breast cancer were included in the study. Those for whom BCT was intended underwent wide excision with IFSA. Six margins of the excised tissue, and the sentinel lymph node (SLN), where appropriate, were submitted for IFSA. Patient demographics, tumour characteristics, number of operations performed, and outcomes were analysed. Results. Of the 161 patients analysed, 138 (85.7%) had successful breast conservation. Four patients required a reoperation for incomplete surgical extirpation. One had a false negative SLN assessment on IFSA, and was returned to the operating room for an axillary dissection. Three patients required reoperations for inadvertently missed multicentric disease. None had false negative margin evaluation with IFSA necessitating reexcision. Conclusion. The use of IFSA allows low rates of reoperation with BCT. Further research is needed to establish consistency in low reexcision rates for cost-effectiveness and optimum resource allocation.

False-negative sentinel node biopsy in breast cancer with positive intraoperative palpable axillary nodes: Case report and review of literature

Sentinel lymph node (SLN) biopsy has become increasingly accepted as a minimally invasive alternative to level I/II axillary dissection for the staging of breast cancer. We present a case of a patient with breast cancer with clinically negative axillary node and histologically negative sentinel biopsy. Intraoperatively, she had highly suspicious palpable level I and II axillary nodes though the sentinel biopsy wound, of which 9 out of 11 nodes removed were positive for malignancy.

Is Atypical Metastasis Obstructive to Sentinel Node Navigation Surgery in Early Gastric Cancer Patients?

Sentinel node navigation surgery (SNNS) is defined as novel, minimally invasive surgery which can avoid unnecessary lymph node dissection based on sentinel node (SN) biopsy and diagnosis for nodal metastasis targeting SN. In the past 10 years, several studies supporting the validity of the SN concept for early-stage gastric cancer have been reported. Single-institutional results of SN mapping for early gastric cancer are being increasingly considered acceptable in terms of detection rate and accuracy of predicting regional lymph node status. We recently conducted a multicenter, prospective trial of SN mapping for early gastric cancer using a dual-tracer method with a radioactive colloid and blue dye. In the trial, SN mapping was performed for 397 patients who had a single tumor (cT1N0M0 or cT2N0M0) with a primary lesion having a diameter of less than 4 cm and not undergone any previous treatments. As a result, the SN detection rate was 98 %, and the accuracy of nodal evaluation for metastasis was 99 %. The results of that clinical trial are expected to provide us with a perspective on the future of SNNS for early gastric cancer. A recent article by Lee et al. reported on the pattern of lymphatic drainage in gastric cancer patients. They retrospectively evaluated the distribution of metastatic lymph nodes according to the longitudinal and circumferential location of tumors in 462 pT1 or pT2 gastric cancer patients with metastasis to 1–3 lymph nodes. A considerable number of atypical metastases (skip or transversal metastasis) were observed, regardless of tumor location. In particular, tumors in the lower third of the stomach and/or lesser curvature side had a significant propensity to exhibit atypical metastasis. They concluded that when applying SNNS in gastric cancer patients, care should be taken with tumors at these locations to prevent false-negative results when applying SNNS in gastric cancer patients. Although this finding should be interpreted with caution as Lee et al. did not attempt SN mapping in their study, they have provided a valuable reference for the clinical application of SNNS in early gastric cancer patients. In fact, the pattern of lymph node metastasis, including atypical metastasis, in their study was remarkably similar to the distribution of SN in our previous multicenter trial. For instance, in our trial, the tumors in the lower third of the stomach had SNs at #8a (in the second compartment) with relatively high probability. This result is in agreement with that obtained by Lee et al. Thus, the similarity of these two results suggests that most of atypical metastasis in their study may not represent false-negative SNs but ‘typical and true’ metastasis to SNs via aberrant lymphatic vessels from the primary tumor. We believe that most false-negative SNs may be owing to technical issues of SN biopsy rather than atypical metastasis. Meanwhile, in our previous trial, SNs were located out of the area of D2 lymph node dissection in 1 % of cases with primary tumors in the upper third, 3 % in the middle third, and 6 % in the lower third of the stomach, respectively. Therefore, caution needs to be taken regarding the application of D2 lymph node dissection even for early gastric cancer. In future studies, appropriate indications for functionpreserving gastrectomy, including proximal gastrectomy, segmental gastrectomy, pylorus-preserving gastrectomy, and partial resection for cT1N0 gastric cancer, should be individually determined on the basis of SN mapping. Various types of laparoscopic function-preserving surgeries can be performed in gastric cancer patients with no metastatic SNs. Previous reports on SN biopsy have Society of Surgical Oncology 2013

Accuracy and prognostic value of sentinel lymph node biopsy in head and neck melanomas

BackgroundDebate remains around the accuracy and prognostic implications of sentinel lymph node biopsy (SLNB) for melanoma arising in the head and neck (HN) areas because several analyses have shown discordances between clinically predicted lymphatic drainage pathways and those identified by lymphoscintigraphy. This study assesses the accuracy and prognostic value of SLNB in this critical anatomic region. MethodsRetrospective review of a prospectively collected melanoma database identified 331 patients with HN melanomas from January 2000 to December 2012. Primary end points included SLNB result, time to recurrence, site of recurrence, and survival. Multivariate models were constructed for analyses. ResultsA sentinel lymph node (SLN) was identified in all 331 patients. There were 59 patients with a positive SLN (17.8%) with a recurrence rate of 88.1% compared with 22.4% in SLN-negative patients (P < 0.0001). The 5-y overall survival was 91.2% for SLN-negative patients and 48.7% for SLN-positive patients (P < 0.0001). Patients with scalp melanoma had thicker lesions and an elevated risk of SLN positivity, recurrence, and death compared with those with other sites. Among the 272 SLN-negative patients, four patients developed regional nodal disease in the same basin and had undergone a previous SLNB procedure for a false-omission rate of 1.45%. Risks for false-negative SLN occurrences included thick and scalp melanomas. Multivariate analysis on prognostic factors affecting relapse-free survival showed positive SLNB status to be the most prognostic clinicopathologic predictor of recurrence (hazard ratio, 20.56; P < 0.0001). ConclusionsSLNB for patients with HN melanomas is an accurate procedure and has prognostic value.

OSNA for detection of sentinel lymph node metastasis.

74 Background: SLN (sentinel lymph node) biopsy is a common procedure in surgical treatment of clinically node-negative breast cancer. OSNA (One-step nucleic acid amplification) is a semi-automated examination using molecular biological technique, and OSNA allows straightforward diagnosis of SLN metastasis without a pathologist by quantitative evaluation of CK19 m-RNA. The objective of this study was to confirm the reliability of OSNA for detection of sentinel Lymph node metastasis, and OSNA is also useful even in neoadjuvant chemotherapy (NAC) patients. Methods: Surgically obtained 159 SLNs from 106 breast cancer patients were evaluated and compared. The SLNs were sectioned into three pieces along the major axis. The central piece was sent to pathologists in an outside laboratory for postoperative histological investigation to diagnose metastasis. The other two pieces were examined with the OSNA to detecting metastasis during an operation. The OSNA analysis and the histological investigation were compared. Then, the patients were divided into two groups, one group was the patients with NAC (22 SLNs from 13 patients), and another group was the patients without NAC (137 SLNs from 93 patients). It was examined whether those concordance rates were similar. Results: 151 SLNs were same diagnosis using both methods. 4 SLNs were negative on OSNA but positive on histology, and these 4 SLNs contained only micrometastasis lesion. Other 4 SLNs were positive on OSNA but negative on histology. The concordance rate was 95.0%. In the patients with NAC, 20 SLNs were same diagnosis. Two SLNs were negative on OSNA but positive on histology, and these 2 SLNs were micrometastasis. The concordance rate was 90.9%. In the patients without NAC, 131 SLNs were same diagnosis. 2 SLNs were positive on OSNA but negative on history, and these 2 SLNs were micrometastasis. 4 SLNs were positive on OSNA but negative on history. The concordance rate was 95.6%. Conclusions: The concordance rate in patients with NAC was as high level as the rate in patients without NAC. The false negative SLNs were all micrometastasis. These results suggest that OSNA is very useful for detecting SLN metastasis and it is clinically acceptable in NAC patients.

Sentinel Node Mapping for Gastric Cancer: A Prospective Multicenter Trial in Japan

Complicated gastric lymphatic drainage potentially undermines the utility of sentinel node (SN) biopsy in patients with gastric cancer. Encouraged by several favorable single-institution reports, we conducted a multicenter, single-arm, phase II study of SN mapping that used a standardized dual tracer endoscopic injection technique. Patients with previously untreated cT1 or cT2 gastric adenocarcinomas < 4 cm in gross diameter were eligible for inclusion in this study. SN mapping was performed by using a standardized dual tracer endoscopic injection technique. Following biopsy of the identified SNs, mandatory comprehensive D2 or modified D2 gastrectomy was performed according to current Japanese Gastric Cancer Association guidelines. Among 433 patients who gave preoperative consent, 397 were deemed eligible on the basis of surgical findings. SN biopsy was performed in all patients, and the SN detection rate was 97.5% (387 of 397). Of 57 patients with lymph node metastasis by conventional hematoxylin and eosin staining, 93% (53 of 57) had positive SNs, and the accuracy of nodal evaluation for metastasis was 99% (383 of 387). Only four false-negative SN biopsies were observed, and pathologic analysis revealed that three of those biopsies were pT2 or tumors > 4 cm. We observed no serious adverse effects related to endoscopic tracer injection or the SN mapping procedure. The endoscopic dual tracer method for SN biopsy was confirmed as safe and effective when applied to the superficial, relatively small gastric adenocarcinomas included in this study.

Authors' reply: Causes of false-negative sentinel node biopsy in patients with breast cancer (Br J Surg 2013; 100: 775–783)

Authors' reply: Causes of false-negative sentinel node biopsy in patients with breast cancer (<i>Br J Surg</i> 2013; 100: 775–783)

Causes of false-negative sentinel node biopsy in patients with breast cancer (Br J Surg 2013; 100: 775–783)

Causes of false-negative sentinel node biopsy in patients with breast cancer (<i>Br J Surg</i> 2013; 100: 775–783)

Diagnostic value of intraoperative histopathological examination of the sentinel nodes in breast cancer and skin melanoma—Preliminary results of single centre retrospective study

ObjectiveIntraoperative histopatological examination of the sentinel nodes enables selection of patients who need dissection of the regional lymphatic system during the same operation. The aim of this study is to evaluate the diagnostic value of intraoperative histopathological examination of the sentinel nodes in breast cancer and skin melanoma. Intraoperative histopathology of the sentinel nodes as a diagnostic method is used in patients with melanoma and breast cancer. Recent studies have proved it to be an effective method for evaluating the nodes in the final histopathology. Intraoperative histopathological examination of the sentinel nodes is not performed routinely and there is no clear position on this issue. In this paper we try to prove that intraoperative test gives patients the simultaneous benefits of removal of regional lymph nodes metastases and earlier initiation of adjuvant therapy. MethodsThe study comprises 137 patients with breast cancer and 35 patients with malignant skin melanoma. Sentinel nodes were intraoperatively sectioned and examined by means of the imprint method and frozen section evaluation. The patients with positive sentinel nodes underwent immediate dissection of regional lymph nodes. Those with negative sentinel nodes diagnosed in the intraoperative examination, but positive in final pathologic results, underwent subsequent dissection of regional lymph nodes. Results60 sentinel lymph nodes were found in 35 patients with skin melanoma. In 3 patients, 3 sentinel lymph nodes were false negative in the intraoperative histopathological examination. No false positive sentinel lymph nodes were found. 249 sentinel lymph nodes were found in the intraoperative histopathological examination in 137 patients with breast cancer. There were no false positive sentinel nodes, but there were 7 false negative sentinel nodes. In this study, only 5 (3.6%) patients with breast cancer and 3 (8.5%) patients with skin melanoma required another regional operation. ConclusionThe method of intraoperative histopathological evaluation of the sentinel nodes enables identification of metastases in these lymph nodes and gives a possibility to carry out a one-step regional lymphadenectomy and start the adjuvant therapy earlier.

Causes of false-negative sentinel node biopsy in patients with breast cancer

Sentinel lymph node (SLN) biopsy has replaced axillary lymph node dissection as the routine staging procedure in clinically node-negative breast cancer. False-negative SLN biopsy results in misclassification and may cause undertreatment of the disease. The aim of this study was to investigate whether serial sectioning of SLNs reveals metastases more frequently in patients with false-negative SLNs than in patients with true-negative SLNs. This was a case-control study. Tissue blocks from patients with false-negative SLNs, defined as tumour-positive lymph nodes excised at completion axillary dissection or a subsequent axillary tumour recurrence, were reassessed by serial sectioning and immunohistochemical staining. For each false-negative node, two true-negative SLN biopsies were analysed. Tumour and node characteristics in patients with false-negative SLNs were compared with those in patients with a positive SLN by univariable and multivariable regression analysis. Undiagnosed SLN metastases were discovered in nine (18 per cent) of 50 patients in the false-negative group and in 12 (11.2 per cent) of 107 patients in the true-negative group (P = 0.245). The metastases were represented by isolated tumour cells in 14 of these 21 patients. The risk of a false-negative SLN was higher in patients with hormone receptor-negative (odds ratio (OR) 2.50, 95 per cent confidence interval 1.17 to 5.33) or multifocal tumours (OR 3.39, 1.71 to 6.71), or if only one SLN was identified (OR 3.57, 1.98 to 6.45). SLN serial sectioning contributes to a higher rate of detection of SLN metastasis. The rate of upstaging of the tumour is similar in false- and true-negative groups of patients.

Abstract P1-01-21: Sentinel Lymph Node detection after previous breast tumour surgical resection: identification rate and false negative rate through a prospective multi institutional study.

Abstract Background: Large multi institutional studies have pointed that previous surgical resection of breast tumours before axillary sentinel node detection (ASLND) was the main criteria of failure of this technique. Screening campaigns provide small tumours and despite efforts to obtain a diagnosis of early breast cancer, this is not always obtained, due to small tumours or false negative results of micro biopsies. The aim of our series was to assess identification rates and false negative rates of ASLND after previous surgical resection of breast tumours. Material and Methods: In a prospective multi institutional setting (14 multidisciplinary teams), we have included patients with a previous breast tumour surgical resection for the diagnosis of infiltrative breast adenocarcinoma. Patients with only a core biopsy and no surgical removal of the tumor before axillary surgery were not included. Each patient underwent a secondary surgical procedure for ASLND and axillary lymphadenectomy, and sometimes a breast secondary surgical procedure for margins. ASLND was performed with the combined method, with blue dye and technetium. Pathology was performed with serial sectioning, eosin safron and immune histo chemistry (IHC). Results: From July 2006 to November 2011, 138 patients where included. The median tumor size was 9mm. Identification rate was 86% (118/138). A macrometastasis was found in 11 cases, in a sentinel node (9), or in a non sentinel node(2). False negative rate was 9% (1 false negative sentinel node with macrometastasis in non sentinel node from lymphadenectomy/11 cases with a macrometastasis in either a sentinel node or a non sentinel node). In 1 case a micrometastasis was found in a sentinel node through IHC, with a macrometastasis in a non sentinel node from lymphadenectomy. Without IHC or without the decision of performing a complementary lymphadenectomy in the case of micrometastasis, the false negative rate would have been 18%. Conclusions: After previous surgical resection of early breast cancer, ASLND remains feasible with a low identification rate of 86%, despite the use of the combined method. The False negative rate is acceptable with the use of IHC. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-21.

Abstract S2-1: The role of sentinel lymph node surgery in patients presenting with node positive breast cancer (T0-T4, N1-2) who receive neoadjuvant chemotherapy – results from the ACOSOG Z1071 trial

Abstract Background: The utility of sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) in patients presenting with node-positive breast cancer has not been determined. The American College of Surgeons Oncology Group (ACOSOG) Z0171 trial was designed to evaluate SLN surgery after NAC in women presenting with node positive disease. Methods: ACOSOG Z1071 enrolled women with clinical T0-4, N1-2, M0 breast cancer receiving NAC. At the time of surgery, all patients were to undergo SLN surgery followed by axillary lymph node dissection (ALND). The primary endpoint was false negative rate (FNR) in women with cN1 disease with 2 or more SLNs reviewed. Positive SLNs were defined as metastases &amp;gt;0.2mm on H&amp;E. The protocol encouraged dual tracer technique. A Bayesian study design with a non-informative prior was chosen to assess whether the probability that the SLN surgery FNR is greater than 10%. Results: From July 2009 to July 2011, 756 patients were enrolled from 136 institutions. Fifteen women were ineligible and 33 withdrew. Of 708 evaluable pts (668 cN1, 40 cN2), 643 had a SLN identified and an ALND (607 cN1, with indeterminate SLN results in 2); 52 pts (48 cN1) had no SLN identified and had ALND; 11 underwent ALND only (all cN1), and 2 pts had SLN only (both cN1). In patients with SLN and ALND, the SLN identification rate was 92.5% (92.7% in cN1, 90% in cN2). SLN correctly identified nodal status in 84% of the 695 pts [258 of pathologically node negative and 327 of pathologically node positive; cN1: 83.8% (549/655), cN2: 90.0% (36/40)]. Of the 643 pts with a SLN identified there was a complete pathologic response in 40.3% (40.3 % for cN1 and 50% for cN2). Of the pts with a positive SLN, the SLN was the only site of disease in 40%. For pts with cN1 disease with 2+ SLNs identified with residual nodal disease, the SLN FNR was 12.8%. In pts with dual tracer technique the FNR was 11.1%. There were no FN results among pts with cN2 disease with 2+ SLNs reviewed. Of the 40 pts with a false negative SLN of the 528 cN1 patients with 2+ SLNs examined, the number of positive nodes at ALND was 1 (50.0%); 2 (25%); 3 (10.0%) and 4–9 (15.0%). Conclusions: NAC resulted in eradication of lymph node disease in 40% of node positive breast cancer patients. SLN surgery after NAC in node positive breast cancer pts correctly identified nodal status in 84% of all patients and was associated with a FNR of 12.8%. The FNR of SLN is higher than the prespecified study endpoint of 10%. Further analysis of factors associated with FNR such as clinical response, histological findings and axillary ultrasound findings is warranted prior to widespread use of SLN in these patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr S2-1.

Bilateral ultrastaging of sentinel lymph node in cervical cancer: Lowering the false-negative rate and improving the detection of micrometastasis

ObjectiveTo evaluate the sensitivity of sentinel node (SN) ultrastaging and to define parameters that may reduce the overall false-negative rate in women with early-stage cervical cancer. MethodsWe analyzed data from a large retrospective multicenter cohort group with FIGO stages IA–IIB cervical cancer in whom at least one SN was identified and systematic pelvic lymphadenectomy was uniformly performed. All who were SN negative by initial evaluation were subjected to ultrastaging. ResultsIn all, 645 patients were evaluable. SN were detected bilaterally in 72% of cases and unilaterally in 28%. Patients with optimal bilateral SN detection were significantly more likely to have any metastasis detected (33.3% vs. 19.2%; P<0.001) as well as micrometastasis detected in their SN (39.6% vs. 11.4%). SN ultrastaging resulted in a low overall false-negative rate of 2.8% (whole group) and an even lower false-negative rate of 1.3% for patients with optimal bilateral mapping. Patients with false-negative SN after ultrastaging had a higher prevalence of LVSI and more frequent unilateral SN detection. Sensitivity of SN ultrastaging was 91% (95% CI: 86%–95%) for the whole group and 97% (95% CI: 91%–99%) in the subgroup with bilateral SN detection. ConclusionThese data confirm previous observations that optimal bilateral SN detection substantially decreases the false negative rate of SN ultrastaging and increases detection of micrometastasis. In patients with bilateral SN detection, the sensitivity of SN ultrastaging is not reduced in more advanced stages of the disease. SN mapping and ultrastaging should become standard practice in the surgical management of early-stage cervical cancer.

Analysis of regional recurrence after negative sentinel lymph node biopsy for head and neck melanoma

The head and neck have a rich lymphatic drainage and complex anatomy, which complicate sentinel lymph node (SLN) biopsy for melanoma. The incidence of regional recurrence after a negative SLN biopsy has been shown to be higher than that at other sites. Compounding factors in this scenario were analyzed to determine their impact on both SLN status and survival. A retrospective review of a prospective database of 315 patients who underwent SLN biopsy for head and neck melanoma from 1994 to 2009 was performed. A false-negative SLN biopsy was defined as a regional recurrence in a previously mapped nodal basin. In all, 267 patients (84.8%) were SLN negative (SLN-) and 48 patients (15.2%) were SLN positive (SLN+). The false-negative SLN biopsy occurred in 17 patients (6.4%). The mean follow-up was 37.6 months (3-152 months). The false-negative SLN and SLN+ patients were similar with respect to patient age and sex and primary melanoma tumor thickness and ulceration. The site of the primary melanoma and the lymphatic drainage patterns did not influence the false-negative biopsy rate. The mean survival was SLN- 119.3 months (95% confidence interval [CI], 106.1-132.5, p < .001), SLN+ 73.4 months (95% CI, 52.3-94.4), and the false-negative SLN 70.7 months (95% CI, 54.2-87.1). The risk of a false-negative SLN biopsy in head and neck melanoma is independent of primary site and lymphatic drainage pattern. Patients with head and neck melanoma who have a regional recurrence after a negative SLN biopsy do not have a worse survival than that of patients who are initially SLN positive.