Sentinel Lymph Node Involvement Research Articles

Abstract S2-07: Sentinel node detection after neoadjuvant chemotherapy in patient without previous axillary node involvement (GANEA 2 trial): Follow-up of a prospective multi-institutional cohort

Abstract Background Half of the patient treated with neoadjuvant chemotherapy (NAC) for a large operable breast cancer has no axillary lymph node involvement at the time of surgery. Sentinel lymph node detection (SLND), after NAC, is aimed to select patient who should be safely spared of an axillary lymphadenectomy (ALND).GANEA 2 is a French prospective multi institutional trial, aimed to assess SLND after NAC. Objective To assess the risk of relapse for patients without previous axillary node involvement treated with NAC followed with a SLND without a systematic lymphadenectomy. Patients and Method Inclusion: FIGO stage T1-T3 infiltrating breast carcinoma, indication of NAC. Exclusion: inflammatory cancer, local relapse, contra-indication to NAC, NAC interrupted due to progressive disease. Design: indication to plan a NAC, axillary sonography with fine needle cytology before NAC to select patients without lymph node involvement, SLND after NAC. ALND was mandatory in case of SLN involvement (macro or micro-metastasis) or SLND failure. Follow-up was scheduled with a medical visit / 6 months with axillary assessment and a mammography each year. Follow-up results are updated every 6 months. Pathological analysis were carried out according to standard methods and classified according to the last American Joint Committee staging system. Studied parameters were SLND detection rate, pathological results on breast specimen and nodes, rate of relapse (axilla, breast, metastasis), and survival. Results From July 2010 to February 2014, 587 patients were enrolled, from 17 institutions, and experienced breast tumor surgery and a SLND after NAC. Each patient experienced breast surgery. A breast tumour pathological complete response was found in 21.3% (125/587). SLND rate was 97% (570/587), with a median number of 2 sentinel nodes (1-9). Patients with a sentinel detection failure (n=17) experienced a systematic lymphadenectomy, without any involvement (n=13), a micro-metastasis (n=2) and a macro-metastasis (n=2). A total of 140 patients had at least one sentinel node involved: macro-metastasis (n=86), micro-metastasis (n=54). A lymphadenectomy was performed in 128 cases: metastasis free (n=100), macro-metastasis (n=17), micro-metastasis (n=11). A total of 430 patients had a SLN metastasis free (75% ;430/570). A not mandatory lymphadenectomy was performed (n=14): metastasis free (n=11), macro-metastasis (n=2) and micro-metastasis (n=1). 17 patients were lost to follow-up. A total of 399 patients without sentinel node involvement were followed 2.3 years (from 0.5 to 5.6 yrs). At 3 years overall survival was 97.8% [94.9-99.1], disease free survival was 94.8% [91.0-97.1%]. Six patients died. Fifteen patients experienced a relapse: 8 metastasis, 4 homolateral breast, 2 controlateral breast, 1 homolateral axillary relapse. Conclusion This is the most important series of patients followed 2.3 years after SLND without axillary lymphadenectomy after NAC for an advanced breast cancer, showing acceptable results. The current series validate the safety of this conservative strategies avoiding systematic lymphadenectomy to patients without initially involved axillary node treated with NAC. Citation Format: Classe J-M, Loaec C, Alran S, Paillocher N, Tunon-Lara C, Gimbergues P, Faure-Virelizier C, Chauvet M-P, Lasry S, Dupre P-F, Verhaeghe J-L, De Blaye P, Gutowski M, Barranger E, Lecuru F, Lefevre Lacoeuille C, Loussert L, Lambaudie E, Ferron G, Campion L. Sentinel node detection after neoadjuvant chemotherapy in patient without previous axillary node involvement (GANEA 2 trial): Follow-up of a prospective multi-institutional cohort [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr S2-07.

Abstract P2-01-12: Development of prediction model for omission of sentinel lymph node biopsy in T1 breast cancer

Abstract INTRODUCTION Axillary sentinel lymph node (SLN) biopsy is a standard method for axillary nodal staging in the treatment of breast cancer. However, along with the trends to SLN performed only without additional axillary lymph node dissection, it's time to be considered omission of SLN for selective patients. We developed a prediction model to assess the negative probability of sentinel lymph node metastasis, specifically focus on the patients with clinical T1 breast cancer. METHODS and MATERIALS The study group consisted of 513 consecutive patients with clinical T1 breast cancer, who had undergone primary surgery between 2007 and 2012. The clinicopathologic factors and imaging modalities including breast ultrasound (US), magnetic resonance imaging (MRI), chest computed tomography (CT), and positron emission tomography (PET) were evaluated. Patients who fulfilled our inclusion criteria were randomized into experimental and validation set by 3:1 ratio. In the experimental group (n = 256), multivariate logistic regression analysis was used to analyze the association of each variable with the likelihood of SLN metastases. A prediction model was developed based on the patients in the experimental group and was validated with internal patient cohorts. RESULTS Of the 513 patients, 119 (23.1%) were found to have SLN metastases. In univariate analysis, presence of lymphovascular invasion (P < 0.001) and suspicious finding of preoperative image studies (US, PET, and MRI, P < 0.001) were independent positive predictors of SLN metastases. In multivariate analysis of experimental group, estrogen receptor status (P = 0.012), presence of lymphatic invasion (P < 0.001), and suspicious finding of preoperative image studies (US, PET, and MRI, P < 0.001) were each associated with involvement of SLN. A prediction model based on this analysis consists of 9 rows including 6 variables (age, estrogen receptor status, presence of lymphatic invasion, and results of preoperative US, PET or CT, MRI). The sum of assigned points for all six variables made corresponding value of negative probability of SLN metastasis. The accuracy of prediction model applied to the validation group, as measured by the area under the receiver operating curve was 0.789. CONCLUSIONS The prediction model developed here may be a useful tool to assess SLN involvement for clinical T1 breast cancer patients. And prospective study for additional validation of the prediction model is currently in preparation, exploring the possibility of SLN biopsy omission. Citation Format: Cho JN, Song EJ, Lee MH, Jung S-Y, Lee S, Kang H-S, Sim SH, Park IH, Lee KS, Kim YJ, Kim S-K, Kwon Y, Nam B-H, Lee ES. Development of prediction model for omission of sentinel lymph node biopsy in T1 breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-12.

Abstract P2-01-33: Non-sentinel lymph nodes involvement in early breast cancer patients: Performance of two predictive nomograms integrating the analysis of sentinel nodes by one step nucleic acid amplification in a cohort of 299 patients

Abstract Backgrounds: Sentinel lymph node (SLN) biopsy is a highly accurate predictor of axillary status and has become the surgical axillary standard in breast cancer patients. About 50–70 % of patients with involved SLN have no additional non sentinel node (NSN) involved, suggesting that it be possible to avoid ALND in selected patients. Many tools have been developed to help surgeons in NSLN evaluation but they all need pathological data from tumor and SLN and can't be used during surgery. Developed for intraoperative detection of SLN macro or micrometastasis involvement, the semi-automated molecular one step nucleic acid amplification (OSNA), as accurate as pathology, is available. Two simple nomograms have been developed to predict NSN involvement based on the number of CK19 mRNA copy determined by OSNA: · Nomogram developed by Peg V (Eur J Surg Oncol 2013): based on total tumoral load (TTL). TTL is defined as the addition of CK19 mRNA copies of each positive SLN (copies/μL). A TTL≥1.2 × 10(5) copies/ml (specificity=85.3%, negative predictive value (NPV) = 80%) can predict NSN involvement. · Nomogram developed by Di Filippo F (Journal of Experimental & Clinical Cancer Research 2015): based on the number of CK19 mRNA copies and ultrasound tumor size. These two variables are categorized using quartiles with a score for each and the addition of both corresponds to a probability of NSN involvement (sensitivity = 98.1%, NPV = 92.5 %). Patients and Methods: this is a retrospective study of 299 patients. Each patient had SLN involvement (macro or micrometastasis) and underwent a complementary ALND. The main objective was to evaluate the performance of each nomogram using a discrimination ability model, assessed by ROC analysis. Predictive accuracy was measured by the area under ROC curves (AUC) reported with its 95 % confidence interval. The second objective was to compare the two nomograms using Hanley & McNeil method, to test the statistical significance of the difference between the AUC. Analysis was performed using stata 13.1 SE. Results: The mean age was 59, 1 year. Most patients were treated for an infiltrating ductal carcinoma (80.3%, 240/299). The mean ultrasound tumor size was 13 mm and the mean pathological tumor size was 15 mm. The median number of examined SLN was 2 with a macro-metastasis in 67, 6%, 202/299). 70 patients had involved nodes in ALND (23%). The discrimination of N Peg, quantified with AUC was 0.685 (p<0, 00001). The discrimination of N Di Filippo, quantified with AUC was 0.72 (p<0, 00001). Hanley & McNeil method shows that Di Filippo nomogram is significantly superior to Peg nomogram (p=0,048). Conclusion: The current study shows that these two nomograms are reliable and can be used to predict NSLN involvement. The combination of molecular data and ultrasound tumor size seems to be more efficient than molecular data alone. These results are similar to results of nomogram studies based on pathological analysis but only these nomograms integrating molecular data can be used during the surgery. Citation Format: Bordes V, Campion L, Jezequel P, Lefrancois A, Boiffard F, Brillaud-Meflah V, Dravet F, Jaffre I, Classe J-M. Non-sentinel lymph nodes involvement in early breast cancer patients: Performance of two predictive nomograms integrating the analysis of sentinel nodes by one step nucleic acid amplification in a cohort of 299 patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-33.

Abstract P2-01-20: The non-invasive treatment for sentinel lymph node metastasis by photodynamic therapy using a verteporfin solubilized phospholipid polymer aggregate

Abstract Introduction: Sentinel lymph node biopsy (SLNB) has become a standard procedure for axillary lymph node evaluation in clinically node-negative breast cancer patients. Recent trial suggested that patients with 1or 2 sentinel lymph nodes (SLNs) involvement could be treated with SLNB alone. Although SLNB is much less invasive procedure comparing with axillary lymph node dissection (ALND), it is still associated with complications such as lymph edema, numbness and pain. Photodynamic therapy (PDT) against cancer is a non-invasive optical therapeutic method in which the topical or systemic delivery of photosensitizing drugs is followed by its subsequent activation with broadband red light. In this study, the usefulness of PDT for treating SLN metastasis was evaluated in murine model. Materials and Methods: Verteporfin, a hydrophobic photosensitizer (PS) forms a soluble conjugate in aqueous medium with a water-soluble and amphiphilic PMB polymer as a solubilizer. The PMB forms stable and well-dispersed molecular aggregate when its concentration is over 1.0 mg/mL based on the hydrophobic interactions among polymer chains. The verteporfin can form conjugate (PMB-vertepoffin) with hydrophobic domain in the PMB aggregate. The PMB-verteporfin was injected at dorsum manus of BALB/c nude mice. The concentrations of verteporfin in tissues were determined by measuring the fluorescence emitted at 700 nm (with excitation at 430 nm). To develop a murine SLN metastasis model, 5 x 105 human epidermoid carcinoma A431 cells with stable expression of GFP were injected to the forearm of BALB/c nude mice. Seven days after inoculation of cancer cells, 20 μL of PMB-verteporfin was injected at dorsum manus of BALB/c nude mice and 75 J of light energy was delivered using a 640 nm diode laser for a total treatment time of 1 min. Fifty-three mice were randomly assigned to the combination of PMB-verteporfin injection and light exposure (A), light exposure alone (B), PMB-verteporfin injection alone (C), and no treatment (D) groups. Ten days after PDT, brachial lymph nodes, which were considered as SLNs were harvested and evaluated by stereoscopic fluorescence microscope. And, DNA was extracted from harvested lymph node. Human Alu family sequence was detected by 7300 Real Time PCR system (Applied Biosystems, Carlsbad CA USA) to estimate metastatic volume. Results: The concentration of verteporfin in SLN was siginificantly higher than other organs including lung, liver, kidney and brachial skin. The group A significantly reduced the SLN metastasis (13%) comparing with , group B (57%), group C (46%) and group D (52%). The Ct value in a PCR of the combination of group A (Ct=29.17) significantly reduced the SLN metastasis comparing with group B (Ct=22.45, p=0.018), group C (Ct=25.58, p=0.018) and group D (Ct=25.54, p=0.005). Conclusions: These data suggested that PDT using PMB as a nanotransporter of verteporfin could be a minimally invasive treatment of SLN metastasis in breast cancer, and represent a potential alternative procedure to SLNB. Citation Format: Shimada K, Matsuda S, Jinno H, Konno T, Ito A, Arai T, Ishihara K, Kitagawa Y. The non-invasive treatment for sentinel lymph node metastasis by photodynamic therapy using a verteporfin solubilized phospholipid polymer aggregate [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-20.

Abstract P2-01-22: The long term outcomes of Metasin RTqPCR intra-operative sentinel node analysis in early breast cancer

Abstract Background: Axillary lymph node involvement is a prognostic factor in breast cancer and it is used to guide adjuvant therapy. Axillary clearance remains the standard of care in lymph node positive disease in most parts of the world. Usually this is performed as second procedure but immediate intra-operative node analysis allows clearance to be performed as part of the initial procedure where necessary. The Metasin assay targets the breast epithelial cell markers CK19 and mammaglobin mRNA and detects the presence of breast tissue (metastatic disease) in the sentinel nodes. Evidence shows the Metasin assay to be fast (average assay time 41.2min) and accurate with a discordance rate below 4% compared with histology. The cost effectiveness of the assay has been reported in our previous studies. Aim: The aim of this study is to assess the risk of axillary recurrence following the use of the Metasin assay to guide axillary management. Method: This is a single centre retrospective study which included all patients presenting to a district general hospital with early clinically node negative breast cancer undergoing sentinel node biopsy between Oct 2011 and Dec 2014. Alternate 2 mm slices of the node were examined intraoperatively using the Metasin assay and the remainder sent for histological examination. The results of the Metasin assay and histology were compared. The risk of axillary recurrence using the Metasin test to select patients for immediate axillary clearance was assessed. Results: 1073 sentinel nodes from 545 patients were analysed during this three-year period. 2 patients were lost to follow up. 94 patients were node positive and underwent axillary clearance as part of their primary surgery. 449 patients had sentinel node biopsy with no further axillary procedure. There were 36 nodes (3.34%) with discordant results. Median follow up was 32 months (range 18 to 55 months). Fourteen patients presented with recurrences (2.56%). The mean event free interval was 15 months. Of the 14 patients, 5 patients tested with Metasin had macrometastases and underwent immediate axillary clearance during the primary surgery. 7 patients were node negative and 2 patients were shown to have micrometastases. 11 patients recurred with distant metastases, 3 patients with local recurrence and 2 patients (0.36%) with axillary recurrences. The two axillary recurrences occurred at 3 and 5 months after primary surgery. Both patients underwent Metasin intraoperative analyses of sentinel nodes which were negative. Subsequent histological examination confirmed no metastatic node involvement in one patient but micro-metastases in the other. Both of these patients had aggressive disease with local, axillary and distant metastasis and subsequently died of their disease. Conclusions: The Metasin assay is a reliable intraoperative test for sentinel node involvement and when used to guide surgical axillary management is associated with very low axillary recurrences (0.36% with a median follow up of 32 months). Citation Format: Udayasankar S, Ashley E, Jenkins KS, Huws A, Sharaiha Y, Sai-Giridhar P, Thomas D, Munir A, Holt S, Khawaja S. The long term outcomes of Metasin RTqPCR intra-operative sentinel node analysis in early breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-22.

One-step nucleic acid amplification analysis of sentinel lymph nodes in papillary thyroid cancer patients.

IntroductionIt is essential to look for methods to define the need for central lymphadenectomy for papillary thyroid cancer patients. The aim is to determine the efficacy of one-step nucleic acid amplification (OSNA) and sentinel lymph node (SLN) biopsy in the intraoperative detection of nodal involvement.Material and methodsThis prospective, experimental study enrolled 49 patients with clinically negative lymph nodes. Intraoperatively, 1% Patent Blue dye was injected intratumorally. Lymph nodes that stained blue were defined as SLNs. They were directly cut into blocks at 2-mm intervals. Nonadjacent blocks were subjected to either the OSNA assay or histological examination.ResultsSixty-five SLNs were found in 43 (87.8%) patients. There were 20 (30.8%) histopathologically positive SLNs. According to the OSNA, 22 (33.8%) SLNs were positive. The OSNA results were different from histopathology in 8 (12.3%) SLNs. The OSNA gave a positive result in 5 (7.7%) SLNs, while they were not involved according to the histopathology. However, OSNA upstaged N status from N0 to N1 only in 2 (3.1%) patients. Inverse results (histopathology +, OSNA–) were obtained in 3 (4.6%) SLNs. Positive and negative predictive values (PPV and NPV) for OSNA were 0.77 and 0.93, respectively. The concordance rate between examinations was 85.5%.ConclusionsIn some patients with clinically negative lymph nodes, OSNA and SLN biopsy may prevent unnecessary central lymphadenectomy. On the other hand, the sentinel lymph node biopsy may reveal the presence of potentially involved sentinel lymph nodes outside the central compartment. These SLNs can also be assessed by means of OSNA.

Efficacy of Sentinel Lymph Node Biopsy in Detecting Axillary Metastasis in Breast Cancer Using Methylene Blue.

Breast cancer is the leading malignancy and the second leading cause of cancer-related deaths. Axillary lymph node status is a very important prognostic factor in breast cancer patients; nodal evaluation is therefore a critical part of breast cancer management. Axillary lymph node dissection results in significant morbidity. Sentinel lymph node biopsy (SLNB) is being used in many centers to stage the axilla in planning axillary dissection management of patients and hence plays an important part in reducing morbidity among patients with carcinoma breast. The objectives of this paper is to study the (1) efficacy of sentinel lymph node biopsy in detecting axillary metastasis, (2) location of sentinel lymph node in the axilla, (3) rate of involvement of sentinel lymph nodes, and (4) incidence of skip metastasis. Thirty-five patients with breast cancer with clinically node-negative axilla were selected for the study. Methylene blue dye was injected intralesional and perilesional 20min prior to surgery. All patients underwent modified radical mastectomy with sentinel lymph node biopsy and axillary dissection and after pathological examination diagnostic statics, namely sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were computed. Sentinel lymph node was identified in all of these patients. Sixty percent patients had pathologically positive lymph nodes in the axilla. 90.48% patients of these had sentinel lymph nodes positive for malignant cells. Incidence of skip metastasis is 9.52%. 88.57% patients had sentinel lymph node mapped to level I lymph nodes. Sensitivity of SLNB is 90.48%, specificity is 85.71%, PPV of is 90.48%, NPV is 85.71%, and accuracy is 88.57%. Sentinel lymph node biopsy is an effective method of staging the axilla and deciding on axillary clearance in patients of carcinoma breast. Unnecessary axillary dissection and associated complications can be prevented in most of patients due to sentinel lymph node biopsy.

Validation and Enhancement of the Clinicopathological Melanoma Nomogram via Incorporation of a Molecular Marker in the Primary Tumor.

To validate the melanoma nomogram and improve its function in prediction of nodal dissemination by incorporating a molecular marker in the model. Microphthalmia transcription factor (MITF) is an important regulator of melanocyte homeostasis and differentiation. We have shown that the grade of MITF expression in primary melanoma cells can serve as a predictor of nodal status. Many efforts to identify the nodal spread in cutaneous melanoma using non-invasive means have been recently undertaken. A nomogram was developed by Memorial Sloan Kettering Cancer Center (MSKCC) based on clinicopathological features of the primary melanoma to predict the nodal status. In this study, we applied the same nomogram for external validation. Then, we added MITF as an independent predictive factor, and assessed its impact on the nomogram's accuracy in prediction of the nodal spread. We included 171 patients with melanoma with available tumor specimens, and used MITF staining grade of ≥50% as a pathological characteristic of the primary tumor in addition to age, location, thickness, Clark level, and ulceration, as reported by MSKCC. Upon comparison of receiver operating curves, we confirmed the external validation of the melanoma nomogram, in accordance with the MSKCC curves [area under the curve (AUC) 0.742 vs. 0.650]. Addition of MITF ≥50% as an independent factor in the analysis improved the model fit significantly (AUC=0.825 vs. 0.742; p<0.0001). The nomogram described by MSKCC is a valuable tool in predicting sentinel lymph node involvement in primary cutaneous melanoma. Addition of MITF≥50% into the logistic regression analysis significantly improves the accuracy of the melanoma nomogram in prediction of regional nodal spread.

Laparoscopic Sentinel Node Mapping in Endometrial Cancer After Hysteroscopic Injection of Indocyanine Green

Study ObjectiveTo report the detection rate (DR) of sentinel lymph nodes (SLNs) in endometrial cancer (EC) patients after hysteroscopic injection of indocyanine green (ICG) and laparoscopic near-infrared (L-NIR) fluorescence mapping. DesignProspectively collected data (Canadian Task Force classification II-2). SettingGynecologic oncology referral center. PatientsConsecutive patients with apparent early-stage endometrioid EC scheduled for surgical treatment: total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, SLN mapping. InterventionsThe mapping technique consisted in an intraoperative hysteroscopic peritumoral injection of 5 mg ICG followed by L-NIR fluorescence mapping. Evaluations of the SLN DR and sites of mapping were performed. Measurements and Main ResultsA total of 57 procedures was performed. Patient mean age was 60 years (range, 28–80) and mean body mass index was 28.2 kg/m2 (range, 19–43). At least 1 SLN was detected in 89.5% of the whole population (51/57). After the first 16 cases, L-NIR camera technical improvement led to a 95% DR (39/41). The mean number of harvested SLNs was 4.1 (range. 1–8), and in 47% of cases SLNs mapped to aortic nodes (24/51). Bilateral pelvic mapping was found in 74.5% of cases (38/51). Three patients had SLN metastases: 1 in the pelvic area only, 1 both in the pelvic and aortic area, and 1 presented with 2 metastatic aortic SLNs with negative pelvic SLNs. Overall, 2 of 3 node-positive patients (67%) had aortic SLN involvement. No adverse events were reported. ConclusionsLaparoscopic SLN mapping after the hysteroscopic injection of ICG has comparable DRs with both radioactive tracer series and ICG series with cervical injection, overcoming the need for radioactive substances. Hysteroscopic injection leads to a higher mapping in the aortic area compared with cervical injection. Further investigation is warranted on this topic.

Lymphatic mapping and sentinel node biopsy in ovarian tumors: a study using intra-operative Tc-99m-Phytate and lymphoscintigraphy imaging

BackgroundExperience on sentinel node mapping in ovarian tumors is very limited. We evaluated the sentinel node concept in ovarian tumors using intra-operativeTc-99m-Phytate injection and lymphoscintigraphy imaging.MethodsThirty-five patients with a pelvic mass due to an ovarian pathology were included in the study. The radiotracer was injected just after laparotomy and before removal of the tumor either beneath the normal cortex (10 patients) or in the utero-ovarian and suspensory ligaments of the ovary just beneath the peritoneum two injections of the radiotracer (25 patients). For malignant masses, the sentinel nodes were identified using a hand held gamma probe. Then standard pelvic and para-aortic lymphadenectomy was performed. In case of benign pathologies or borderline ovarian tumors on frozen section, lymphadenectomy was not performed. The morning after surgery, all patients were sent for lymphoscintigraphy imaging of the abdomen and pelvis.ResultsSentinel node was identified only in 4 patients of the cortical injection group. At least one sentinel node could be identified in 21 patients of the sub-peritoneal group. Sentinel nodes were identified only in the para-aortic area in 21, pelvic/para-aortic areas in 2, and pelvic only area in 2 patients. Three patients had lymph node involvement and all had involved sentinel nodes (no false negative case).ConclusionSentinel node mapping using intra-operative injection of the radiotracer (in the utero-ovarian and suspensory ligaments of the ovary just beneath the peritoneum) is feasible in ovarian tumors. Technical aspects of this method should be explored in larger multicenter studies in the future.

The Combination of Preoperative Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography and Sentinel Lymph Node Mapping in the Surgical Management of Endometrioid Endometrial Cancer.

The goal of this study was to evaluate the combination of sentinel lymph node (SLN) mapping and F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scan in detection of lymph node involvement in patients with endometrioid endometrial cancer (EEC). Ninety-five patients with EEC who had preoperative PET/CT imaging and underwent SLN mapping were retrospectively analyzed. Methylene blue dye was used and injected to the cervix at 3- and 9-o'clock positions (a total of 4 mL). Pelvic lymphadenectomy was performed on all of the patients after SLN mapping. If the SLN was negative in the initial hematoxylin and eosin staining, an ultrastaging study was performed for the SLNs. Sentinel lymph nodes were detected in 77 (81.1%) of 95 patients, with a mean of 2.95 SLNs. There was only 1 case (1.4%) with a positive SLN in the intraoperative frozen section examination in those patients with negative PET/CT findings and in whom SLNs were detected (n = 70). Among the remaining 69 patients with negative preoperative PET/CT findings and negative frozen section results for the SLNs, there were 2 patients with SLN involvement in the final ultrastaging pathology. In the patient-based analyses, the sensitivity, specificity, and positive and negative predictive values of the PET/CT and SLN frozen section were 33%, 100%, 100%, and 97.1%, respectively. As no metastases in the nonsentinel pelvic lymph nodes were found in patients with EEC who had both negative PET/CT findings and frozen section results of the SLNs in both hemipelvises, we suggest using both methods to reduce the incidence of unnecessary systematic lymphadenectomy.

Sentinel Lymph Nodes for Breast Carcinoma: A Paradigm Shift.

-Sentinel lymph node biopsy has been established as the new standard of care for axillary staging in most patients with invasive breast carcinoma. Historically, all patients with a positive sentinel lymph node biopsy result underwent axillary lymph node dissection. Recent trials show that axillary lymph node dissection can be safely omitted in women with clinically node negative, T1 or T2 invasive breast cancer treated with breast-conserving surgery and whole-breast radiotherapy. This change in practice also has implications on the pathologic examination and reporting of sentinel lymph nodes. -To review recent clinical and pathologic studies of sentinel lymph nodes and explore how these findings influence the pathologic evaluation of sentinel lymph nodes. -Sources were published articles from peer-reviewed journals in PubMed (US National Library of Medicine) and published guidelines from the American Joint Committee on Cancer, the Union for International Cancer Control, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network. -The main goal of sentinel lymph node examination should be to detect all macrometastases (>2 mm). Grossly sectioning sentinel lymph nodes at 2-mm intervals and evaluation of one hematoxylin-eosin-stained section from each block is the preferred method of pathologic evaluation. Axillary lymph node dissection can be safely omitted in clinically node-negative patients with negative sentinel lymph nodes, as well as in a selected group of patients with limited sentinel lymph node involvement. The pathologic features of the primary carcinoma and its sentinel lymph node metastases contribute to estimate the extent of non-sentinel lymph node involvement. This information is important to decide on further axillary treatment.

Ultrasound of the sentinel node in melanoma patients: echo-free island is a discriminatory morphologic feature for node positivity.

Unlike breast and thyroid cancer, the use of ultrasound (US)-guided fine needle aspiration cytology (FNAC) for preoperative staging is limited in melanoma. New US morphology criteria have shown that US-FNAC can correctly identify 50% of all involved sentinel nodes (SN) in melanoma patients before surgical excision. The aim of this study was to examine a new criterion: the echo-free island (EFI). A total of 1000 consecutively staged melanoma patients (Breslow thickness>1 or<1 mm, but ulcerated, Clark IV/V or regressed) scheduled for SN staging underwent preoperative US. US morphology items were assessed: peripheral perfusion, loss of central echoes, balloon shape, and EFI. FNAC was performed in case of suspicious and malignant US patterns. All patients proceeded to undergo an SN biopsy or direct completion lymph node dissection (CLND) (in the case of positive FNAC). In all, 57% of the patients were men. The mean/median Breslow thickness was 2.58/1.57 mm. The mean/median follow-up was 56/53 months. SN was positive in 21%. EFI information was available in 95.3%. EFI was seen in 40 patients (4%). EFI sensitivity was 10.8%, specificity was 97.6%, positive predictive value was 50%, and negative predictive value was 80.2%. EFI was significantly correlated to peripheral perfusion (67.5%). There was no correlation to balloon shape or loss of central echoes. Five-year melanoma-specific survival of patients with EFI was significantly worse: 80% versus 92% when absent. The EFI can be useful in the early detection of SN melanoma metastasis. It is an early sign of involvement and thus associated with a decreased survival.

Practice Patterns of Radiation Field Design for Sentinel Lymph Node-Positive Early-Stage Breast Cancer

BackgroundRecent randomized trials have led to decreased use of completion axillary lymph node dissection (ALND) in early-stage breast cancer patients with a positive sentinel lymph node (SLN), causing controversy surrounding radiotherapy coverage of the axilla. We investigated the practice variation among radiation oncologists for regional nodal coverage for clinicopathologic scenarios and evaluated axillary field design decision-making processes. Materials and MethodsA customized, web-based questionnaire was e-mailed to 983 community (n = 617) and academic (n = 366) radiation oncologists with a breast cancer subspecialty practicing in the United States. The survey consisted of 18 multiple-choice questions evaluating general clinical preferences surrounding radiation therapy (RT) field design for patients with early-stage breast cancer and a positive SLN. Seven case scenarios were developed to investigate the field design in the setting of specific clinical and pathologic risk factors. Nodal coverage was classified as standard tangents (STs), high tangents (HTs), STs and a supraclavicular field (SCF), or STs and full axillary coverage (AX). ResultsA total of 145 evaluable responses were collected, with a response rate of 15.0%. Of the respondents, 12 (8.3%) reported using completion ALND for patients with 1 to 3 positive SLNs without extracapsular extension (ECE) and 66 (45.5%) performed ALND with 1 to 3 positive SLNs with ECE. For micrometastatic SLNs, with no lymphovascular system invasion, 115 (87.1%) used STs or HTs. The use of neoadjuvant chemotherapy (NAC) influenced RT field design for patients with a positive SLN without ECE, with 64 (48.5%) using STs and SCF or STs and AX treatment without NAC and 94 (70.7%) using SCF and AX after NAC. With macrometastatic SLN involvement, most respondents preferred SCF (45.27%) and AX (45.66%). In contrast, for micrometastatic involvement, HTs (43.61%) were frequently chosen. Forty (27.8%) reported using online predictive nomograms to predict further axillary involvement, with no difference between the academic and community radiation oncologists (P = .11). ConclusionIn SLN biopsy-positive early-stage breast cancer with omission of completion ALND, axillary RT is increasing used to cover the undissected axilla. Most respondents use SCF or AX for patients with low to intermediate pathologic features. Online prediction nomograms are used by a few practitioners to assist in clinical decision-making in this setting.

Sentinel Node Lymphoscintigraphy in High-risk Cutaneous Squamous Cell Carcinoma

BackgroundHigh-risk cutaneous squamous cell carcinoma includes recurrent disease, a tumor diameter > 2 cm, T4 stage, perineural or lymphovascular invasion, tumor depth of ≥ 4 mm, and high-grade histologic features. All have been implicated in an increased risk of occult regional lymph node involvement. Patients and MethodsAmong a large group of patients with nonmucosal, cutaneous squamous cell carcinoma seen at our center, 30 patients with high-risk inclusion criteria were prospectively evaluated to undergo wide local excision and sentinel lymph node mapping. ResultsWith a median follow-up period of 56 months, 4 patients (13%) had regional lymph nodal involvement. The patients identified with lymph node-positive disease underwent adjuvant therapy. Five patients (17%), none of whom had nodal disease at diagnosis, developed locally recurrent disease requiring additional therapy. On multivariate analysis, a statistically significant correlation was found between the depth of tumor invasion and occult sentinel lymph node involvement. ConclusionIn the present prospective analysis, sentinel lymph node mapping resulted in upstaging in 13% of the patients. The tumor depth was independently associated with an increased risk of nodal involvement. Given the association between a depth of tumor invasion of ≥ 4 mm and occult nodal disease in cutaneous squamous cell carcinoma, sentinel lymph node mapping could be considered an integral part of surgical staging for patients with high-risk features.

Cellular Blue Nevomelanocytic Lesions: Analysis of Clinical, Histological, and Outcome Data in 37 Cases

Cellular blue nevomelanocytic lesions (CBNLs) frequently pose diagnostic problems to pathologists, and their biological potential may be difficult to establish. In this study, the authors have analyzed the clinical, histological, and outcome data of 37 cellular blue nevomelanocytic lesions and the molecular characteristics of 4 lesions. The cohort of cases comprised 8 cellular blue nevi (CBNs), 17 atypical cellular blue nevi (ACBNs), and 12 blue-nevus-like melanomas (BNLMs) with a mean follow-up of 5 years. The average age at diagnosis was 25.9 years for patients with ACBN, versus 30.4 years for CBN, and 44.6 years for BNLM. Both CBN and ACBN occurred most frequently on the trunk or extremities, whereas BNLM primarily involved the scalp. Histologically, CBN and ACBN were characterized by a mean diameter of <1 cm, absence of necrosis, low mitotic rate (mean: 1-2 mitotic figures/mm), little or no infiltrative properties, and usually low-grade cytologic atypia. In contrast, BNLM had a mean diameter of 1.6 cm, necrosis, tissue infiltration, greater mitotic activity (mean: 6 mitotic figures/mm), and high-grade cytologic atypia. ACBNs often were larger, more densely cellular, exhibited higher mitotic counts, and were cytologically more atypical than CBN. Seven CBN cases with follow-up had a benign clinical course (average follow-up of 4.7 years). Among 6 patients with ACBN who underwent sentinel lymph node (SLN) biopsy, 3 were positive, and a single additional case had 1 positive non-SLN (this patient did not have a SLN biopsy performed). All 14 cases of ACBN with follow-up were alive and without recurrence with mean follow-up of 5 years. Of the 9 melanoma cases with follow-up, 3 patients with SLN and non-SLN involvement died from their disease (average follow-up of 4.8 years). Array comparative genomic hybridization was performed on 2 ACBNs and 1 BNLM: One of the 2 ACBNs showed chromosomal aberrations and 1 BNLM showed multiple chromosomal gains and losses. Multiplex polymerase chain reaction was performed on 1 ACBN, and no mutations were found. From these results, the authors conclude that ACBN occupy an intermediate position within the spectrum of CBN and BNLM, yet many lesions cannot be reliably distinguished from either CBN or BNLM because of overlapping histologic features. However, in general, ACBNs seem to aggregate more closely with CBN in terms of clinical, histological, molecular profile (limited data), and biological behavior.

Excision margins and sentinel lymph node status as prognostic factors in thick melanoma of the head and neck: A retrospective analysis.

Recommended margins for thick cutaneous melanoma (Breslow thickness >4 mm; T4) have decreased over recent decades. Optimal margins and the role of sentinel node biopsy (SNB) in thick head and neck melanoma remain controversial. A single-center review was conducted of patients treated between 2002 and 2012 assessing the impact of excision margins and sentinel lymph node status on locoregional recurrence and melanoma-specific survival (MSS). One hundred eight patients were identified. Median age was 71.1 years and median Breslow thickness was 6.0 mm. Median follow-up was 40 months. Locoregional recurrence occurred in 27% and there was no significant reduction in recurrence with margins ≥2 cm (p = .17). Increasing margins did not improve survival (p = .58). Fifty-nine patients (55%) underwent SNB, of which 27% were positive. There was a trend toward longer survival for patients who were sentinel lymph node-negative (p = .097). Wider margins do not significantly improve locoregional recurrence or MSS. Sentinel lymph node involvement reflects a poor prognosis. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1373-1379, 2016.

Abstract P3-01-14: A nomogram to predict the likelihood of axillary non-sentinel lymph node metastases in sentinel lymph node positive primary breast cancer patients

Abstract Background: Completion of axillary lymph node dissection (ALND) was long lasting standard in patients with non-metastatic primary breast cancer (PBC) and axillary sentinel lymph node (SLN) involvement. However, this approach is currently questioned since recent prospective trials have found that some SLN-positive women with PBC might not benefit from subsequent ALND. Nomograms that estimate the probability of further non-sentinel lymph node (NSLN) metastases could guide clinical decisions. Methods: We compared the predictability of three different nomograms (MSKCC, Stanford University, Cambridge) on the NSLN status with an own logistic regression model in a training and validation set. SLN-positive women who underwent primary surgery including ALND at Tuebingen University, Germany, between 06/2005 - 12/2009 (training set) and 01/2010 - 02/2012 (validation set) were available for this analysis. The area under the receiver operating characteristics (ROC) curve was calculated for each nomogram. Results: 295 and 175 patients were included into the training and validation set, respectively. Of these 118 (40%) and 57 (33%) patients were NSLN-positive. Variables within our model were tumor size, proportion of positive SLNs, size of SLN metastases, lymphangiosis carcinomatosa, multicentricity and extracapsular invasion. The respective area under the ROC curve values for the MSKCC / Stanford University / Cambridge / own regression model were 0.73 / 0.70 / 0.63 / 0.75 in the training set and 0.73 / 0.66 / 0.52 / 0.73 in the validation set. Conclusion: The predictability of our logistic regression model was comparable to the MSKCC nomogram and superior to the Stanford University and Cambridge nomogram. Although a training and a validation set was used, further testing on an independent patient population is warranted. Citation Format: Hartkopf AD, Brucker SY, Helms G, Henzel M, Hahn M, Wallwiener M, Schoenfisch B, Taran F-A, Fehm TN. A nomogram to predict the likelihood of axillary non-sentinel lymph node metastases in sentinel lymph node positive primary breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-01-14.

Abstract CS1-2: Optimal management of the axilla: A look at the evidence

Abstract The surgical management of the axilla has undergone significant evolution during the past 20 years. The inception of the sentinel lymph node (SLN) concept and the clinical validation of lymphatic mapping and SLN biopsy (SLNB) starting in the 1990s, challenged the century-old primacy of axillary lymph node dissection (ALND) as the procedure of choice for staging the axilla and ushered us into a new era of axillary surgical management. Randomized clinical trials, evaluating SLNB with or without completion ALND in patients with operable breast cancer and negative SLN(s), established SLNB alone as the standard of care for staging the axilla in this setting. These trials established the performance characteristics of SLNB and factors that affect identification and false-negative rate and led to the refinement of the original SLN node concept. More importantly, the results from these trials provided the launching pad for the conduct of additional randomized trials evaluating SLNB alone vs. SLNB with completion ALND in patients with operable breast cancer and limited SLN involvement (micrometastases in IBCSG 23-01 or macrometastases in 1 or 2 SLNs in ACOSOG Z0011). These trials demonstrated no disease-free or overall survival advantage with completion ALND, thus expanding the use of SLNB alone in patients with limited SLN involvement. Another clinical trial (AMAROS) compared the effect of axillary radiotherapy vs. completion ALND in patients with positive SLN(s) and demonstrated equivalent oncologic outcomes between the two approaches but with less morbidity in favor of axillary radiotherapy. Thus, for patients who meet the criteria for inclusion in the ACOSOG Z11 and the IBCSG 23-01 trials, SLNB alone without completion ALND is adequate for staging the axilla. For patients who meet the criteria for inclusion in the AMAROS trial, axillary radiotherapy appears to represent a better option than completion ALND. Lastly, the increasing use of neoadjuvant chemotherapy in appropriately-selected patients with large operable breast cancer and the resulting axillary nodal down-staging in a considerable proportion of patients with axillary lymph node involvement at presentation, has led to an increased interest in the evaluation of SLNB in this setting. After a decade-old debate, the prevailing approach for patients who present with clinically negative axilla and are considered for neoadjuvant chemotherapy, is to perform SLNB after neoadjuvant chemotherapy. This approach has now also been expanded to include patients who present with clinically (or biopsy proven) involvement of the axillary nodes, become clinically node-negative after neoadjuvant chemotherapy and have negative SLNB. Several prospective trials (ACOSOG Z1071, SENTINA, SN FNAC) have recently demonstrated the feasibility and accuracy of SLNB alone in this setting. Provided that certain procedures are followed (removal of 3 or more SLNs, dual-agent lymphatic mapping, localization and removal of previously biopsied positive nodes and even the use of immunohistochemistry in the SLN evaluation), the false-negative rate of SLNB drops to below 10%. Adoption of this approach has the potential to further decrease the use of ALND in patients who present with documented axillary lymph node involvement. Citation Format: Mamounas EP. Optimal management of the axilla: A look at the evidence. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr CS1-2.

Histological pattern of Merkel cell carcinoma sentinel lymph node metastasis improves stratification of Stage III patients

Sentinel lymph node biopsy is used to stage Merkel cell carcinoma, but its prognostic value has been questioned. Furthermore, predictors of outcome in sentinel lymph node positive Merkel cell carcinoma patients are poorly defined. In breast carcinoma, isolated immunohistochemically positive tumor cells have no impact, but in melanoma they are considered significant. The significance of sentinel lymph node metastasis tumor burden (including isolated tumor cells) and pattern of involvement in Merkel cell carcinoma are unknown. In this study, 64 Merkel cell carcinomas involving sentinel lymph nodes and corresponding immunohistochemical stains were reviewed and clinicopathological predictors of outcome were sought. Five metastatic patterns were identified: (1) sheet-like (n=38, 59%); (2) non-solid parafollicular (n=4, 6%); (3) sinusoidal, (n=11, 17%); (4) perivascular hilar (n=1, 2%); and (5) rare scattered parenchymal cells (n=10, 16%). At the time of follow-up, 30/63 (48%) patients had died with 21 (33%) attributable to Merkel cell carcinoma. Patients with pattern 1 metastases had poorer overall survival compared with patients with patterns 2–5 metastases (P=0.03), with 22/30 (73%) deaths occurring in pattern 1 patients. Three (10%) deaths occurred in patients showing pattern 5, all of whom were immunosuppressed. Four (13%) deaths occurred in pattern 3 patients and 1 (3%) death occurred in a pattern 2 patient. In multivariable analysis, the number of positive sentinel lymph nodes (1 or 2 versus >2, P<0.0001), age (<70 versus ≥70, P=0.01), sentinel lymph node metastasis pattern (patterns 2–5 versus 1, P=0.02), and immune status (immunocompetent versus suppressed, P=0.03) were independent predictors of outcome, and could be used to stratify Stage III patients into three groups with markedly different outcomes. In Merkel cell carcinoma, the pattern of sentinel lymph node involvement provides important prognostic information and utilizing this data with other clinicopathological features facilitates risk stratification of Merkel cell carcinoma patients who may have management implications.