Sentinel Node Negative Patients Research Articles

A prospective audit to assess the feasibility of sentinel lymph node biopsy and/or low axillary sampling in clinicoradiologically node-negative axilla for early breast carcinoma

Background: Sentinel lymph node (SLN) dissection was designed to minimize side effects of lymph node surgery but still offer outcomes of axillary lymph node dissection. Aims and Objectives: Our study is designed to determine whether SLN resection achieves the same therapeutics outcome as complete axillary dissection but with fewer side effects for node-negative axilla in clinicoradiologically operable breast cancer patients. Materials and Methods: Duration-based prospective observational study was carried out at the General Surgery and Surgical Oncology Department at Government Medical College and Hospital, Aurangabad with a duration of 2 ½ years from July 2019 to January 2022. A total of 36 patients of breast cancers with stages T1-T2, N0 with clinically and radiologically negative axilla from July 2019 to January 2022 duration were included in our study. Results: When the histopathological status of axillary lymph nodes was compared to the histopathology of SLNs it was seen that out of 36 patients, the histopathology of sentinel node was positive in 10 patients (10/36) however the rest of the axilla was positive in 6 cases and negative in 4 cases and the histopathology sentinel node was negative in 26 patients out of 36 cases (26/36) however the rest of the axilla was also negative in 24 cases and positive in 2 cases. Conclusion: SLN biopsy using methylene blue dye alone is a highly reliable and predictable technique to stage the axilla in breast cancer patients as this study shown a low false-negative rate (7.69%). This technique may help to avoid complete axillary lymph node dissection in sentinel node-negative patients thereby minimizing the morbidity of axillary lymph node dissection. This study demonstrates that sentinel node localization is possible with methylene blue dye alone.

Can Conization Specimens Predict Sentinel Lymph Node Status in Early-Stage Cervical Cancer? A SENTICOL Group Study.

Simple SummaryLymph node involvement is one of the major prognosis factors for early-stage cervical cancer. Improvement in preoperative identification of node-positive patients may lead to a more accurate triage to primary chemoradiation for these patients instead of radical surgery followed by adjuvant radiotherapy, given the increased morbidity of combined treatment. Several studies have well established risk factors for node involvement, but they are based on final pathologic examination of radical hysterectomy specimens and are usually extrapolated for preoperative risk assessment. Among these risk factors, tumor size, lymphovascular space invasion (LVSI) and depth of stromal invasion might be assessed in conization specimens. Our findings suggest that patients with depth of stromal invasion lower than 10 mm and no LVSI in conization specimens had lower risk of micro- and macrometastatic SLN. In this subpopulation, full node dissection may be questionable in case of SLN unilateral detection.Background: The prognosis of patients with cervical cancer is significantly worsened in case of lymph node involvement. The goal of this study was to determine whether pathologic features in conization specimens can predict the sentinel lymph node (SLN) status in early-stage cervical cancer. Methods: An ancillary analysis of two prospective multicentric database on SLN biopsy for cervical cancer (SENTICOL I and II) was carried out. Patients with IA to IB2 2018 FIGO stage, who underwent preoperative conization before SLN biopsy were included. Results: Between January 2005 and July 2012, 161 patients from 25 French centers fulfilled the inclusion criteria. Macrometastases, micrometastases and Isolated tumor cells (ITCs) were found in 4 (2.5%), 6 (3.7%) and 5 (3.1%) patients respectively. Compared to negative SLN patients, patients with micrometastatic and macrometastatic SLN were more likely to have lymphovascular space invasion (LVSI) (60% vs. 29.5%, p = 0.04) and deep stromal invasion (DSI) ≥ 10 mm (50% vs. 17.8%, p = 0.04). Among the 93 patients with DSI < 10 mm and absence of LVSI on conization specimens, three patients (3.2%) had ITCs and only one (1.1%) had micrometastases. Conclusions: Patients with DSI < 10 mm and no LVSI in conization specimens had lower risk of micro- and macrometastatic SLN. In this subpopulation, full node dissection may be questionable in case of SLN unilateral detection.

18408 A combined clinicopathologic and gene expression model (CP-GEP) identifies primary cutaneous melanoma patients who can safely forgo sentinel lymph node biopsy

More than 80% of patients undergoing sentinel lymph node (SLN) biopsy have no nodal metastasis, and are unnecessarily exposed to procedure-induced morbidity such as lymphedema. Our objective was to develop a model combining clinicopathologic and gene expression (CP-GEP) to discriminate high-risk patients from patients who can safely forego SLN biopsy, thus reducing procedure-associated morbidity, and prioritizing care for high risk patients. A panel of 108 candidate biomarkers was identified, and the expression of these genes was quantified in FFPE diagnostic biopsy tissue across a cohort of 754 patients; 128/754 (17%) SLN positive patients. All patients underwent SLN biopsy at Mayo Clinic within 90 days of diagnosis between 2004 and 2018. We trained logistic regression models, using a penalized maximum likelihood estimation algorithm, in a repeated cross-validation scheme. The CP-GEP model, combining age and Breslow depth with genes involved in extracellular matrix remodeling (glia-derived nexin, growth differentiation factor 15, integrin β3, interleukin 8, lysyl oxidase homolog 4, TGFβ receptor type 1 and tissue-type plasminogen activator), and melanosome function (antigen recognized by T-cells), outperformed models based on only clinicopathologic variables, or only on gene expression, in discriminating SLN positive and negative patients (AUC, 0.82, 95% CI 0.78-0.86). The CP-GEP model achieved a SLN biopsy reduction rate of 42% at a negative predictive value of 96%. The 5-year relapse-free survival for CP-GEP negative patients was 88% compared with 50% for CP-GEP positive and SLN positive patients, confirming the value of the CP-GEP model as a tool to inform SLN biopsy decisions.

Prognostic Role of Non-Identification of Sentinel Lymph Node in Cutaneous Melanoma Patients: An Observational Retrospective Study.

Simple SummarySentinel lymph node status is the most important prognostic factor for patients with cutaneous melanoma, but occasionally it is not possible to identify the sentinel lymph node. Little is known in cutaneous melanoma literature about the phenomenon of non-identification of sentinel lymph node and its prognostic implications. In this study we observed that not identifying the sentinel lymph node involves a worse nodal disease-free survival, but not a worse melanoma-specific survival than a negative sentinel lymph node. Potentially, patients with non-identified SLN should receive a follow-up schedule like that of patients with positive SLN.Background: Sentinel lymph node (SLN) status is recognized as the most important prognostic factor for patients with cutaneous melanoma. However, sometimes it is not possible to identify SLN. The phenomenon of non-identification of SLN and its prognostic role have not been thoroughly evaluated in melanoma literature. The objective of this study was to identify which patient or tumor variables may be associated to non-identification of SLN and to evaluate the prognostic role of non-identification of SLN. Methods: Observational retrospective study of 834 cutaneous melanoma patients who underwent SLN biopsy at Instituto Valenciano de Oncología. Results: Forty-two patients (5%) presented non-identification of SLN. Patients with age at diagnosis of ≥ 64 years, obesity (BMI ≥ 30), and head and neck localization were at higher risk of non-identification of SLN. Non-identified SLN patients had worse nodal disease-free survival with respect to negative SLN patients, but not worse melanoma-specific survival. Conclusions: Our findings suggest a need to follow-up patients with non-identified SLN in the same way as patients with positive SLN.

Completely resected stage III melanoma controversy - 15 years of national tertiary centre experience.

BackgroundTwo prospective randomized studies analysing cutaneous melanoma (CM) patients with sentinel lymph node (SLN) metastases and rapid development of systemic adjuvant therapy have changed our approach to stage III CM treatment. The aim of this study was to compare results of retrospective survival analysis of stage III CM patients’ treatment from Slovenian national CM register to leading international clinical guidelines.Patients and methodsSince 2000, all Slovenian CM patients with primary tumour ≥ TIb are treated at the Institute of Oncology Ljubljana and data are prospectively collected into a national CM registry. A retrospective analysis of 2426 sentinel lymph node (SLN) biopsies and 789 lymphadenectomies performed until 2015 was conducted using Kaplan-Meier survival curves and log-rank tests.ResultsPositive SLN was found in 519/2426 (21.4%) of patients and completion dissection (CLND) was performed in 455 patients. The 5-year overall survival (OS) of CLND group was 58% vs. 47% of metachronous metastases group (MLNM) (p = 0.003). The 5-year OS of patients with lymph node (LN) metastases and unknown primary site (UPM) was 45% vs. 21% of patients with synchronous LN metastasis. Patients with SLN tumour burden < 0.3 mm had 5-year OS similar to SLN negative patients (86% vs. 85%; p = 0.926). The 5-year OS of patients with burden > 1.0 mm was similar to the MLNM group (49% vs. 47%; p = 0.280).ConclusionsStage III melanoma patients is a heterogeneous group with significant OS differences. CLND after positive SLNB might still remain a method of treatment for selected patients with stage III.

Impact of Tumor-Infiltrating Lymphocytes on Overall Survival in Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine carcinoma of the skin. As the clinical course can be variable, prognostic markers are needed to better stratify patients. Prior literature, composed of small series with limited sample size, has demonstrated that tumor-infiltrating lymphocytes (TILs) are an important prognostic marker in MCC. To validate these findings on a population level, we sought to analyze and report the prognostic value of TILs in a large national data set. A retrospective observational cohort study was conducted of patients with nonmetastatic MCC from 2010 to 2015 using the National Cancer Database. Individual variables trending toward significance using a univariable analysis were included in a multivariable Cox proportional hazards model to assess their independent effect on overall survival (OS). TILs were subclassified into none, nonbrisk, and brisk and the survival analysis was performed. Propensity score-weighted multivariable analysis (PS MVA) was performed to adjust for additional confounding. A total of 2,182 patients met inclusion criteria: 611 (28.0%) were identified as having TILs present, and 1,571 (72.0%) had TILs absent in the tumor. On MVA, subdivision of TIL status into nonbrisk (hazard ratio [HR], 0.750; 95% confidence interval [CI], 0.602-0.933) and brisk (HR, 0.499; 95% CI, 0.338-0.735) was associated with incrementally improved OS compared with no TILs. The association of nonbrisk and brisk TILs with improved OS was retained on PS MVA (Nonbrisk: HR, 0.720; 95% CI, 0.550-0.944; Brisk: HR, 0.483; 95% CI, 0.286-0.814). The presence of nonbrisk and brisk TILs is associated with incrementally improved OS in patients with nonmetastatic MCC in a large national data set. This pathologic feature can aid with risk stratification, estimation of prognosis, and, importantly, decision-making with respect to treatment intensification in high-risk patients. Merkel cell carcinoma (MCC) is an aggressive neuroendocrine cutaneous malignancy with variable clinical course. Prognostic markers are needed to better risk stratify patients. We present the largest retrospective observational cohort study of patients with nonmetastatic MCC using the National Cancer Database. Our analysis demonstrates an association between increasing degrees of tumor-infiltrating lymphocytes and incrementally improved survival. These conclusions improve pathologic risk stratification, and decision-making with respect to treatment intensification. Intensification may include adjuvant radiation therapy to the primary site after wide excision despite small tumor size, to the nodal basin in sentinel lymph node-negative patients, or offering closer follow-up.

Effect of Sentinel Lymph Node Biopsy and LVI on Merkel Cell Carcinoma Prognosis and Treatment.

Prognostic factors and optimal treatment approaches for Merkel cell carcinoma (MCC) remain uncertain. This study evaluated the influences of sentinel lymph node (SLN) biopsy and lymphovascular invasion (LVI) on treatment planning and prognosis. Retrospective cohort study. Stage 1 to 3 MCC patients treated 2005 to 2018. Predictors of nodal radiation were tested using logistic regression. Predictors of recurrence-free, disease-specific, and overall survival were tested in Cox proportional hazard models. Of 122 patients, 99 were without clinically apparent nodal metastases. Of these, 76 (77%) underwent excision and SLN biopsy; 29% had metastasis in SLNs, including 20% of MCCs 1 cm or less. Primary tumor diameter, site, patient age, gender, and immunosuppressed status were not significantly associated with an involved SLN. Among patients who underwent SLN biopsy, 13 of 21 (62%) MCCs with LVI had cancer in SLNs compared with 14 of 44 (25.5%) without LVI (P = .003). Although local radiation was common, nodal radiation was infrequently employed in SLN negative (pathologic N0) patients (21.8% vs. 76.2% for patients with SLN metastases, P = .0001). Survival of patients with positive SLNs was unfavorable, regardless of completion lymphadenectomy and/or adjuvant radiation. After accounting for tumor (T) and node (N) classification, age, immunosuppression, and primary site, a positive SLN and LVI were independently associated with worse survival (LVI/recurrence-free survival [RFS]: hazard ratio [HR] 2.3 (1.04-5, P = .04; LVI/disease-specific survival [DSS]: HR 5.2 (1.8-15, P = .007); N1a vs. pN0/RFS HR 3.6 (1.42-9.3, P = .007); DSS HR5.0 (1.3-19, P = .17). SLN biopsy assists in risk stratification and radiation treatment planning in MCC. LVI and disease in SLNs, independently associated with worse survival, constitute markers of high-risk disease warranting consideration for investigational studies. III Laryngoscope, 131:E828-E835, 2021.

Abstract P4-02-03: Cancer phenotype is the key factor in axillary involvement and distant recurrence in early breast cancer

Abstract BACKGROUND: Factors by which breast cancer cells invade blood and lymphatic capillaries and metastasize regional lymph nodes and distant sites are not well understood. Genetics, molecular subtype, epidemiological, mechanical and pathological factors are being considered. Once breast cancer cells invade lymphatic or blood vessels the route of spread is still unclear. Cells could access the systemic circulation through the sentinel lymph node or directly avoiding the lymph node step. Molecular subtype is one of the most important factors associated with the risk of metastases. Our objective is to determine the influence of immunophenotype and the sentinel lymph node (SLN) status to predict the risk of locoregional relapses and distant metastases in early breast cancer. In our center we are using a molecular technique (OSNA) to ascertain if there is sentinel lymph node involvement, this technique creates a new continuous variable, Total Tumor Load (TTL), defined as the total number of CK19 mRNA copies in all positive SLN (copies/microL), indicating the total tumor volume of axillary tumor involvement. METHODS: Clinicopathological and follow up data were obtained from all patients with early breast cancer treated with Tumorectomy (Tx) and Sentinel Lymph Node (SLN) assessed by OSNA with the decision to proceed to ALND based on Z0011 criteria and systemic therapy between 2011 and 2018 at our center (J Clin Oncol 37, 2019 (suppl; abstr 564)) RESULTS: 304 breast cancer patients underwent Tx and SLN assessed by OSNA followed by systemic therapy with an average follow-up of 64.9 months. SLN was positive in 122 cases and negative in 182. SLN negative patients were Luminal A (LA) 58%, Luminal B (LB) 14%, HER2 10% and Triple-Negative (TN) 7%. SLN positive patients were LA 52%, LB 35%, HER2 7% and TN 5%. Mean TTL was 136,244 copies (see table). As of now, 11 patients have had recurrence (locoregional relapse and distant disease): 6 of them with positive SLN (54,54%) and 5 with negative SLN (45,45%). A total of 4 patients have had locoregional relapse, two of them with negative SLN (50%) both non luminal tumors (1 HER2, 1 TN), and 7 have had distant disease, three of them with negative SLN (43%). Only one patient has died from metastatic breast cancer (HER2 positive, SLN negative). CONCLUSIONS: 1. In our series, almost half of the patients (45%) with recurrence were negative SLN. 2. The probability of recurrence when the sentinel lymph node is negative is higher in HER2 and TN tumors (60%). 3. The probability of recurrence when the SLN is positive is higher in luminal tumors (66,6%). 4. Luminal tumors with positive SLN and large volume axillary involvement (median 1.419.450 copies) have a higher probability of recurrence (statistically significant) than luminal tumors with positive SLN and small volume axillary involvement (median 131.479 copies). PATIENTS AND OUTCOMES VARIABLE N=304Number of cases (n,%)Median age, range (years)LOCOREGIONAL RELAPSEMETASTASIC BREAST CANCEREXITUSMean TTL with NO recurrenceMean TTL with recurrencePOSITIVE SLN122 (40%)59,8 (33-87)2 (1,63%)4 (3,27%)0By ImmunophenotypeLuminal A64 (52,4%)59,3 (36-87)1 (1,5%)2 (3,1%)0371.5592.838.333Luminal B43 (35,2%)59,5 (36-84)1 (2,32%)00258.6221600HER29 (7,3%)61 (33-80)01 (11,1%)021.582640Triple Negative6 (5%)59,6 (50-80)01 (16,6%)0108.181184.000NEGATIVE SLN182 (60%)59,3 (27-89)2 (1,09%)3 (1,64%)1 (0,5%)By ImmunophenotypeLuminal A106 (58%)59,3 (33-82)000Luminal B43 (14,1%)59,5 (36-89)1 (2,32%)1 (2,32%)0HER219 (10,4%)59,3 (40-82)01 (5,2%)1 (5,2%)Triple Negative14 (7,7%)59,4 (27-85)1 (7,14%)1 (7,14%)0 Citation Format: José Enrique Alés-Martínez, Raquel Tur, Juan Parra, Ana De Castro, Jaime Ceballos, Rocío Martín, Rosa Ana Marcos, Paz Blanco, MJose Velasco. Cancer phenotype is the key factor in axillary involvement and distant recurrence in early breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-02-03.

Intra-nodal nevi in sentinel node-negative patients with cutaneous melanoma does not influence survival.

BackgroundMelanoma patients with intra‐nodal nevi (INN) and without melanoma metastasis in the sentinel lymph node biopsy (SLNB) are generally treated as patients with negative SLNB. However, diagnosis of INN may be difficult and nodal melanoma metastases may falsely be regarded as INN.ObjectivesOur aim was to evaluate the clinical significance of INN in the SLNB in patients with primary cutaneous melanoma on a nationwide level in The Netherlands by comparing survival between three groups: patients with INN and without nodal melanoma metastasis (INN group), patients without INN and without nodal melanoma metastasis (negative SLNB group) and patients with nodal melanoma metastasis irrespective of INN (positive SLNB group).MethodsData were obtained from ‘PALGA’, the Dutch Nationwide Network and Registry of Histopathology and Cytopathology, yielding a cohort of adults with histologically proven, primary, invasive cutaneous melanoma patients in The Netherlands diagnosed between 2000 and 2014 who underwent SLNB. Clinical and pathological variables were extracted from the pathology text files. Differences between patients with INN, negative SLNB and positive SLNB were analysed using Kaplan–Meier analysis.ResultsA total of 11 274 patients were eligible for inclusion. The prevalence of INN in the SLNB was 5.0%. Melanomas with INN had similar median Breslow thickness compared to melanomas with negative SLNB and were more frequently located on trunk and upper limbs and observed in younger patients compared to melanomas with negative and positive SLNB. Overall survival of patients with INN showed no significant difference compared with negative SLNB (median follow‐up of 5.7 years of all patients).ConclusionsAs there seems to be no difference in overall survival between patients with INN and negative SLNB, the diagnosis of INN seems to be reliable. Current practice to treat patients with INN as patients with negative SLNB appears to be appropriate.

Axillary dissection versus non dissection in negative sentinel node biopsy patients

Background: The goal of this series was to compare performing axillary clearance versus none performing in patients with node biopsy negative.Methods: This study included 114 patients had breast cancer , presented with breast mass no enlarged axillary node either clinically or radiologically and all patients had negative sentinel lymph node intraoperatively those patients presented to Sohag Cancer Center and General Surgery Department Sohag, Egypt during the period of May 2018 to May 2019. Analysis of the clinical presentation, grade of breast cancer and radiological findings was done. All patients with above mentioned criteria were fitted for the study.Results: A total of 114 patients, all of them had sentinel lymph node negative, axillary dissection done in 55 patients of them while 59 patients had no dissection. We divided the patients in our series into group A (with axillary dissection) and group B with non-dissection; in group A 27 (49.1%) patients had lymphoedema on post-operative follow up while in group B none of patients complained from lymphoedema. Numbness was found in 11 (20%) patients among group A patients, while in group B none of patients complained from numbness. On follow up of seroma we discovered that in group A all the patients had seroma while in group B only 9 (15.3%) patients had seroma. None of our 114 patients either with or without dissection had recurrence on follow up period.Conclusions: Clearance of the axilla in sentinel node negative patients has no significant difference in overall survival but also increased rates of lymphoedema, seroma and haematoma.

Long-term morbidity after a negative sentinel node in breast cancer patients.

Morbidity after sentinel lymph node biopsy is often underestimated. The aim of this study was to inventory arm and shoulder complaints in sentinel node-negative breast cancer patients post-surgery after long-term follow-up. Sentinel node-negative breast cancer patients with at least 2years of follow-up after surgery were included in this study. Self-reported arm and shoulder morbidities were assessed using a survey. Patients (n=126) were asked if they ever developed complaints, if these complaints were still present and whether they were ever treated for these complaints. After a mean follow-up of 55.5months (range 25-86months), the prevalence of the self-reported arm and shoulder complaints was 25.8% for pain, 12.0% for numbness, 6.4% for paraesthesias, 7.1% for lymphedema, 8.0% for axillary web syndrome, 26.2% for loss of strength and 19.5% for limitations in range of motion. About 38.1% of the patients were treated by a physical therapist concerning the experienced complaints after SLNB. Up to 7years post-surgery a considerable amount of sentinel node-negative patients still suffer from arm and shoulder complaints. These complaints affect the activities of daily living. Therefore, more research is needed regarding the value of early detection and treatment of these complaints.

Predictors of Metastasis and Outcome Following True Negative Sentinel Node Biopsy

Up to 30% of sentinel node-negative patients develop metastases during follow-up. Negative sentinel node biopsies (SNB) can be classified to false (FN) and true negative (TN) categories. Little attention has been paid to the characteristics and outcomes of patients who experience direct distant metastasis following TN-SNB. In this retrospective study of a melanoma database at Tampere university hospital we analyzed characteristics and outcome following metastases after TN-SNB. A total of 506 patients underwent SNB between 2006 and 2016. After review, SNBs were classified FN, TN and true positive (TP). Follow-up was performed until 30.4.2019.

Predictors of Metastasis and Outcome Following True Negative Sentinel Node Biopsy

Up to 30% of sentinel node-negative patients develop metastases during follow-up. Negative sentinel node biopsies (SNB) can be classified to false (FN) and true negative (TN) categories. Little attention has been paid to the characteristics and outcomes of patients who experience direct distant metastasis following TN-SNB. In this retrospective study of a melanoma database at Tampere university hospital we analyzed characteristics and outcome following metastases after TN-SNB. A total of 506 patients underwent SNB between 2006 and 2016. After review, SNBs were classified FN, TN and true positive (TP). Follow-up was performed until 30.4.2019. Of SN-negative patients, 74 of 396 (19%) developed recurrence, including 17 (4%) local, 22 (6%) regional lymph node (FN) and 35 (9%) direct distant metastases (TN-D). False negative rate was 16% and negative predictive value 93.8%. Locoregional recurrences occurred earlier compared to distal metastases (median of 2.14 /2.93 years). Compared to patients without recurrence, thickness ≥ 2 mm (univariable p<0.001), male gender (p=0.021), nodular melanoma (p=0.001), ulceration (p<0.001) and location in upper limb region (p=0.062) were predictors of TN-D. The 5-year melanoma specific survival in TN-D patients did not differ significantly from TP patients (2.36 /2.26 years). TN-D is associated with nodular melanomas in upper limb region, male gender, cervical SNBs and ulcerated tumors with Breslow thickness ≥ 2 mm. These patients should be considered at high-risk relapse and mortality. Surveillance imaging to detect distant metastases is mandatory regardless of SNB status. In future, inclusion criteria for therapy trials for high-risk SNB-negative patients might also be worth considering.

Surgical Management of the Axilla in Breast Cancer Patients with Negative Sentinel Lymph Node: A Method to Reduce False-Negative Rate.

False-negative rate (FNR) of sentinel lymph node dissection (SLND) has not been eliminated. The study was conducted to optimize the surgical resection of axilla in patients with negative sentinel lymph node (SLN) for the purpose of eradicating false-negative (FN) events of SLND. A total of 312 clinically node-negative patients without neoadjuvant therapy underwent SLND with indocyanine green (ICG), methylene blue and the combination of ICG and methylene blue. Axillary dissection was performed subsequently regardless of the status of SLN. Lymph nodes were sent for pathological examination separately by serial resection every 0.5cm away from marginally visualized SLNs. SLND was successfully conducted in 98.1% (306/312) of patients using methylene blue, ICG, and its combination. Further examination revealed 97 true-positive, 189 true-negative, and 13 FN results. The overall FNR was 11.8% (13/110). A horizontal line 1.5cm away from the superior vSLN and a vertical line 1.5cm away from the medial vSLN formed a zone of lower outer quadrant (LOQ) in axilla. Surgical resection of LOQ 'en bloc' showed a FNR of zero. The surgical management of axilla may benefit negative SLN patients with potential nodal involvement, reducing the FNR of SLND to zero. This study was registered with the Chinese Clinical Trial Registry (ChiCTR1800014247).

Risk Factors for Regional and Systemic Metastases in Patients with Sentinel Lymph Node-negative Melanoma.

Sentinel lymph node status is a strong prognostic factor in melanoma. However, up to 21% of sentinel lymph node-negative patients develop locoregional and distant metastases during follow-up. To analyze risk factors for locoregional and distant metastasis in patients with sentinel lymph node-negative melanoma. A total of 545 patients underwent sentinel lymph node biopsy (SNB) between 2005 and 2013 at our hospital. Data for 449 patients with a negative SNB were analyzed regarding risk factors and development of metastases. Follow-up was performed until 2016. A total of 72 SNB-negative patients developed metastases, including 25 (34.7%) distant and 47 (63.3%) locoregional metastases. Locoregional metastases occurred earlier compared to distant metastases (with a mean of 24.2 and 23.5 months for regional lymph node and cutaneous metastases, respectively, vs. 31.4 months for distant metastases). Patients with metastases despite negative SNB had a greater tumor thickness (p=0.001), a higher rate of nodular melanoma (p=0.001), ulceration (p<0.001), and were older (p=0.05) compared to SNB-negative patients without subsequent metastases. Out of SNB-negative patients, 16% developed metastases. Close clinical follow-up including sonography of the draining lymph node region is mandatory for melanoma patients regardless of SNB status.

Sentinel Lymph Node Status is a Main Prognostic Parameter Needful for the Correct Staging of Patients with Melanoma Thicker than 4 mm: Single-Institution Experience and Literature Meta-Analysis

ABSTRACTPurpose of the study: The usefulness of sentinel lymph node biopsy in thick melanomas is debated. The aim of this study was to evaluate the possible prognostic significance of sentinel lymph node biopsy in T4 melanoma patients and to verify whether this was a homogeneous group of patients with similar poor behavior.Materials and Methods: A retrospective observational study was performed. Data were extracted from the Tuscan Regional Referral Center database. The outcome of sentinel lymph node-negative and sentinel lymph node-positive T4 melanomas were compared. A systematic review of published series on this issue and a meta-analysis were performed.Results: Among 125 T4 melanoma patients, 53 patients (42.4%) were sentinel lymph node-positive and 72 (57.6%) patients were sentinel lymph node-negative. The 5-year and the 10-year melanoma specific survival were 81.9% and 72.3% for sentinel lymph node-negative patients and 42.4% and 17.9% (P < 0.001) for sentinel lymph node-positive patients. A positive sentinel lymph node showed an HR of 3.08. The meta-analysis confirmed that there was a significantly greater risk of death for patients with thick melanoma and positive sentinel lymph node (RR 1.75).Conclusions: The results of the study point out that the sentinel lymph node biopsy is required for the correct staging of patients with melanoma thicker than 4 mm and that the status of sentinel lymph node is a significant predictor of melanoma specific survival. This knowledge allows early surgical and adjuvant treatment as well as appropriate trial enrollment and tailored follow-up.

Sentinel node biopsy in ductal carcinoma in situ of the breast: Never justified?

Sentinel lymph node biopsy for ductal carcinoma in situ (DCIS) of the breast is not standard of care. However, nodal involvement for DCIS patients is reported. Aim of our study was to identify preoperative features predictive of nodal involvement in DCIS patients. We have retrospectively reviewed 175 patients with a preoperative diagnosis of DCIS following a vacuum-assisted breast biopsy, and undergoing surgery with sentinel node biopsy. Variables distribution was compared between patients upstaged to invasive cancer at final pathology and patients with a confirmed DCIS, and between positive vs negative sentinel node patients. Univariate and multivariate analyses were performed for risk of a positive node. Lymph node biopsy was positive in 13 (7.4%) patients, with 8 (61.5%) macrometastases and 5 (38.5%) micrometastases. In these patients, Breast Imaging Reporting and Data System (BI-RADS) index >4 (OR 4.69, 95% CI 1.282-17.224, P = .02), lesion extension ≥20 mm (OR 4.25, 95% CI 1.255-14.447, P = .02), multifocal disease (OR 4.12, 95% CI 0.987-17.174, P = .05), comedo type (OR 3.54, 95% CI 1.044-11.969, P = .04), and upstaging (OR 4.56, 95% CI 1.080-19.249, P = .04) were all predictive of nodal involvement, although upstaging could not be predicted preoperatively. By multivariate analysis, the only independent factor predictive for positive sentinel node was multifocal disease (OR 5.14, 95% CI 1.015-26.066, P < .05). A preoperative diagnosis of DCIS, also including advanced biopsy systems such as vacuum-assisted breast biopsy, may be not always sufficient to exclude patients from sentinel node biopsy. DCIS patients with associated BI-RADS >4, lesion extension ≥20 mm, comedo type, and above all multifocal disease should be considered for axillary evaluation.

Metastatic Melanoma in Sentinel Node-Negative Patients: The Ottawa Experience.

Lymph node involvement is a major independent prognostic factor for survival in patients with malignant melanoma. Sentinel lymph node biopsy (SLNB) detection of microscopic nodal melanoma has been shown to improve both 5-year survival and 5-year disease-free survival. To determine the rate of metastatic melanoma in SLNB-negative patients at long-term follow-up. Study subjects include all 152 patients who had a negative SLNB and were followed at the Ottawa Regional Cancer Centre (ORCC) between 1999 and 2004. Patients with a follow-up period less than 6 months, more than 1 primary melanoma, and metastatic melanoma at diagnosis were excluded. Age at diagnosis, sex, Breslow thickness, ulceration, mitoses, regression, Clark level, anatomical location, development of metastatic melanoma, time to detection of metastatic disease, and time to death from melanoma were studied. In this retrospective study at the ORCC, 40 of 140 (28.6%) patients with a single primary melanoma developed metastatic melanoma following negative SLNB at a mean follow-up of 63 months. The rate of metastatic melanoma following negative SLNB at long-term follow-up at the ORCC is higher than the upper limit of rates reported in the literature (6%-24%). The reason for this is multifactorial, and the long follow-up period of 5 years allowed for detection of metastatic disease at a mean of 3.9 years. Long-term prognosis may be guarded in node-negative patients with a primary cutaneous melanoma, and surveillance by a multidisciplinary team is crucial.

Nodular Histologic Subtype and Ulceration are Tumor Factors Associated with High Risk of Recurrence in Sentinel Node-Negative Melanoma Patients

BackgroundSince its introduction, the sentinel lymph node biopsy (SLNB) has become the standard staging procedure in clinical node-negative melanoma patients. A negative SLNB, however, does not guarantee a recurrence-free survival. Insight into metastatic patterns and risk factors for recurrence in SLNB negative melanoma patients can provide patient tailored guidelines.MethodsData concerning melanoma patients who underwent SLNB between 1996 and 2015 in a single center were prospectively collected. Cox regression analyses were used to determine variables associated with overall recurrence and distant first site of recurrence in SLNB-negative patients.ResultsIn 668 patients, SLNBs were performed between 1996 and 2015. Of these patients, 50.4 % were male and 49.6 % female with a median age of 55.2 (range 5.7–88.8) years. Median Breslow thickness was 2.2 (range 0.3–20) mm. The SLNB was positive in 27.8 % of patients. Recurrence rates were 53.2 % in SLNB-positive and 17.9 % in SLNB-negative patients (p < 0.001). For SLNB-negative patients, the site of first recurrence was distant in 58.5 %. Melanoma located in the head and neck region (hazard ratio 4.88, p = 0.003) and increasing Breslow thickness (hazard ratio 1.15, p = 0.013) were predictive for distant first site of recurrence in SLNB-negative patients. SLNB-negative patients with a nodular melanoma and ulceration had a recurrence rate of 43.1 %; the site of recurrence was distant in 64 % of these patients.ConclusionsThe recurrence rates of SLNB-negative nodular ulcerative melanoma patients approach those of SLNB-positive patients. Stringent follow-up is recommended in this subset of patients.

105. A negative sentinel node in melanoma patients; no need to worry?

Background: Since its introduction, the outcome of the SLNB is one of the most important prognostic factors in melanoma patients. A negative sentinel node however, does not guarantee a recurrence-free follow-up. This study was performed to determine risk factors of regional or systemic disease recurrence in node negative melanoma patients. Material and methods: Data concerning patients treated between 1996 and 2014 in the University Medical Center Groningen were prospectively collected. The database contained patient and tumor characteristics, follow-up, recurrence and survival data. Cox regression analyses were used to determine variables associated with systemic first site of recurrence in sentinel node negative patients. Results: A total of 668 SLNB's were performed between 1996 and 2014. The SLNB was positive in 27.8% of the patients and negative in 68.6% of the patients. Recurrence rates were 53.2% in the SLNB positive group and 17.9% in the SLNB negative group. Thirty and a half percent of all patients recurred (204/668), 77% of these patients progressed to stage IV during the course of their disease. Multivariate cox regression analysis of factors associated with immediate stage IV recurrence in sentinel node negative patients revealed melanoma located on the head/neck (HR 3.09, p: 0.035) and the presence of ulceration (HR 2.31, p: 0.035) as significant factors. In sentinel node negative patients with a nodular melanoma the ever recurrence rate was 38/128 (29.7%), if ulceration was present the recurrence rate was 43.1%, the first site of recurrence was systemic in 64% of these patients. Analysis of ever stage IV recurrence in all patients revealed SLNB positive results of strong predictive value (HR 3.00, P: