Sentinel Lymph Node Biopsy For Cutaneous Melanoma Research Articles

The Use of Indocyanine Green and Near-Infrared Fluorescence Imaging Versus Blue Dye in Sentinel Lymph Node Biopsy in Cutaneous Melanoma: A Retrospective, Cohort Study.

The use of indocyanine green (ICG) and near-infrared fluorescence imaging is a promising option for sentinel lymph node (SLN) mapping in cutaneous melanoma. The study objective was to compare the performance of ICG and blue dye at detecting SLNs with radioisotope nanocolloid (technetium-99). Between April 2018 and June 2022, 293 consecutive patients with cutaneous melanoma (Breslow thickness ≥ 0.8mm) underwent wide local excision and SLN biopsy. Patients were divided into group A (ICG; n = 122) and group B (blue dye; n = 163). All patients underwent SPECT/CT imaging preoperatively. SLN detection parameters and complications were compared between the groups. A total of 285 patients had complete data and were included in the analysis. The median age was 62.0 (range 10-91) years, and 139 (48.8%) were female patients. The mean Breslow thickness was 2.6mm, 89 (31.2%) patients had ulceration, and 179 (62.8%) patients had mitosis ≥ 1mm2. The mean number of SLNs detected per patient in group A was 1.58 and group B was 1.48. In groups A and B, the SLN detection rate was 96.7% versus 89.6% (p = 0.022) and the pathological SLN detection rate was 92.3% versus 97.1% (p = 0.481), respectively. ICG had a higher SLN detection rate and equal pathological SLN detection rate to blue dye. ICG may not be inferior to blue dye and is a useful adjunct to radioisotope in SLN biopsy in cutaneous melanoma.

Use of indocyanine green for sentinel lymph node biopsy in melanoma

Sentinel lymph node (SLN) biopsy for cutaneous melanoma is a critical part of designing therapy for the skin malignancy. A retrospective review of 54 patients with cutaneous melanoma who underwent SLN biopsy guided by both radiotracer injection and indocyanine green (ICG) fluorescent dye compared the accuracy of identifying the SLN using each method. Patients were injected preoperatively with radiotracer at the site of the primary melanoma and intraoperatively with 2.5 mg of ICG. The detection of the SLN was compared between the two methods. Patients were followed to determine local recurrence and survival from 5 months to 4 years. ICG and radiotracer identified the SLN in 52 of 54 patients. In those patients who mapped, 52 of 52 showed mapping to the same node or nodes. The rate of cancer involvement in the identified node was 19.2% for both techniques. There was no difference in recurrence or survival between the two methods of SLN identification in short follow-up. In conclusion, ICG injection and mapping to identify SLN in cutaneous melanoma is confirmatory for radiotracer mapping and in the future may be an accurate and less costly method for SLN biopsy in cutaneous melanoma.

Transcutaneous sentinel lymph node detection in cutaneous melanoma with indocyanine green and near-infrared fluorescence: A diagnostic sensitivity study.

Sentinel lymph node (SLN) biopsy with preoperative radiocolloid-based lymphoscintigraphy and blue dye injection is considered the standard procedure for staging nodal metastases in early-stage cutaneous melanoma patients with clinically uninvolved lymph nodes. While this combination renders good accuracy in SLN detection, radiation exposure and the frequent allergic reactions to the blue dye are considered drawbacks of this technique. Indocyanine green (ICG) is a water-soluble fluorescent dye that can be identified through near-infrared fluorescence imaging (NIRFI). The aim of this prospective diagnostic sensitivity study was to assess the feasibility of ICG and NIRFI to identify SLNs in melanoma transcutaneously ("before skin incision") and to analyze the various factors influencing detection rate, in comparison to lymphoscintigraphy. This study included 93 patients undergoing SLN biopsy for cutaneous melanoma. The region and the number of the SLNs identified with lymphoscintigraphy and with ICG were recorded. Patients' characteristics, as well as tumor details were also recorded preoperatively. One hundred and ninety-four SLNs were identified through lymphoscintigraphy. The sensitivity of ICG for transcutaneous identification of the location of the SLNs was 96.1% overall, while the sensitivity rate for the number of SLNs was 79.4%. Gender and age did not seem to influence detection rate, but a body mass index >30 kg/m2 was associated with a lower identification rate of the number of SLNs (P = .045). Transcutaneous identification of SLNs through ICG and NIRFI technology is a feasible technique that could potentially replace in selected patients the standard SLN detection methodology in cutaneous melanoma.

Correlation between ferromagnetic and isotopic tracers for sentinel lymph node detection in cutaneous melanoma: IMINEM study.

The usefulness of sentinel lymph node biopsy (SLNB) in staging cutaneous melanoma has been proven. Therefore, different tracers have been used to identify the sentinel lymph nodes (SLNs). The use of isotopic tracers together with radioactivity detectors allowed a much more precise and direct approach to the SLNs. However, not all centres have access to a Nuclear Medicine department hindering sentinel lymph node detection (SLND) and consequently, other markers such as ferromagnetic tracers have been evaluated looking for the same advantages and effectiveness as isotopic tracers. Ferromagnetic tracers have proven their usefulness in other cancer entities such as breast, prostate and thyroid cancer. The objective was to assess the detection and concordance rates between isotopic and ferromagnetic techniques for SLNB in cutaneous melanoma. Isotopic SLNB technique and ferromagnetic tracer were compared for cutaneous melanoma in a non-inferiority multicentre prospective study carried out in six Spanish hospitals. A total of 60 patients were recruited and 133 lymph nodes removed. The detection rate was slightly higher with ferromagnetic tracer in head-neck and trunk melanomas, and with isotopic tracer in limbs. The patients' and nodes' concordance rates between both techniques for ex vivo samples were 95% and 86% for head-neck and trunk tumours and 97% and 93% for limbs tumours, respectively. The concordance rates for involved nodes were 100% and 88.2% for patients and nodes, respectively. The intraoperative detection and biopsy of SLN in cutaneous melanoma using a ferromagnetic was a reliable alternative method to the isotopic technique in cutaneous melanomas.

Mapping sentinel lymph nodes in cutaneous melanoma: a vast array of perioperative imaging modalities.

Sentinel lymph node biopsy (SLNB) is a decisive step in the staging process of melanoma, critically impacting patients' oncological outcome and driving the decision-making process. SLNB limits the extent of the dissection in cases where no metastases are found. Conversely, when metastases are detected, SLNB has the potential to improve regional control of the disease when complete lymphadenectomy or early administration of adjuvant treatment are indicated. Thus, accurately identifying sentinel lymph nodes represents an important prognostic factor. Several strategies have been studied, including novel procedures that are not commonly used in the clinical setting. This review highlights the different tracers, preoperative and intraoperative imaging modalities studied to perform SLNB in cutaneous melanoma. The development of innovative modalities has been fueled by a need to optimize current approaches, offering new alternatives that can overcome some of the limitations of the standard method.

Risk factors for post-operative complications after sentinel lymph node biopsy for cutaneous melanoma: Results from a large cohort study

A sentinel lymph node (SLN) biopsy is a common surgical procedure for cutaneous melanoma. Our aim was to evaluate risk factors for early post-operative complications after SLN biopsy and to examine the impact of complications on health care resource utilisation. We performed a retrospective cohort study including all adult patients who underwent a SLN biopsy for cutaneous melanoma in the Stockholm region from 2006 to 2014. Data of patient and tumour characteristics were collected from medical records, as well as information on complications and outpatient visits within 30 days from surgery. Risk factors were evaluated through logistic regression. Out of 886 patients who underwent SLN biopsy during the study period, 109 (12.3%) had one or several post-operative complications. The most common complication was a wound infection (7.7%), followed by seroma (6.4%). The risk of a post-operative complication was increased in patients with diabetes (odds ratio (OR) = 10.0, 95% confidence interval (CI) 4.0-24.6), who had inguinal location of SLN (OR = 2.7, 95% CI 1.7-4.3), who were male (OR = 1.9, 95% CI 1.2-2.9) and who had ulceration of the primary tumour (OR = 1.6, 95% CI 1.0-2.6). Individuals with post-operative complications had more visits to the outpatient clinic (p < 0.05). Complications after SLN biopsy affect 12.3% of patients. Our results suggest that patients with diabetes, who had inguinal SLN biopsy and who were male have increased risk, and this might warrant more intense post-operative surveillance.

Unique Genes in Tumor-Positive Sentinel Lymph Nodes Associated with Nonsentinel Lymph Node Metastases in Melanoma.

Current risk assessment tools to estimate the risk of nonsentinel lymph node metastases after completion lymphadenectomy for a positive sentinel lymph node (SLN) biopsy in cutaneous melanoma are based on clinical and pathologic factors. We identified a novel genetic signature that can predict non-SLN metastases in patients with cutaneous melanoma staged with a SLN biopsy. RNA was collected for tumor-positive SLNs in patients staged by SLN biopsy for cutaneous melanoma. All patients with a tumor-positive SLN biopsy underwent completion lymphadenectomy. A 1:10 case:control series of positive and negative non-SLN patients was analyzed by microarray and quantitative RT-PCR. Candidate differentially expressed genes were validated in a 1:3 case:control separate cohort of positive and negative non-SLN patients. The 1:10 case:control discovery set consisted of 7 positive non-SLN cases matched to 70 negative non-SLN controls. The cases and controls were similar with regards to important clinicopathologic factors, such as gender, primary tumor site, age, ulceration, and thickness. Microarray and RT-PCR identified six potential differentially expressed genes for validation. In the 40-patient separate validation set, 10 positive non-SLN patients were matched to 30 negative non-SLN controls based on gender, ulceration, age, and thickness. Five of the six genes were differentially expressed. The five gene panel identified patients at low (7.1%) and high risk (66.7%) for non-SLN metastases. A novel, non-SLN gene score based on differential expressed genes in a tumor-positive SLN can identify patients at high and low risk for non-SLN metastases.

SPECT/CT Improves Detection of Metastatic Sentinel Lymph Nodes in Patients with Head and Neck Melanoma.

A positive sentinel lymph node (SLN) is the most important prognostic factor for predicting survival in cutaneous melanoma. This study aimed to evaluate how the addition of single-photon emission computed tomography (SPECT) and computed tomography (CT) to planar lymphoscintigraphy (PL) alters SLN identification, yield, and localization of metastatic nodes in head and neck melanoma. This retrospective review examined patients undergoing SLN biopsy for cutaneous melanoma of the head and neck between July 2003 and December 2015. Patient demographics and pathologic outcomes were compared for patients undergoing SPECT-CT versus PL. A multivariable logistic regression analysis was used to identify factors associated with the identification of a positive SLN. Among 176 patients undergoing SLN biopsy, 91 underwent PL and 85 underwent SPECT-CT and PL. The patients in the SPECT-CT group were older than the PL patients (p=0.050) but the groups did not differ in gender (p=0.447), Breslow thickness (p=0.744), or total number of SLNs identified (p=0.633). As shown by the multivariate regression analysis, only Breslow thickness [odds ratio (OR) 1.47; 95% confidence interval (CI) 1.17-1.84] and SPECT-CT (OR 3.58; 95% CI 1.24-10.4) were associated with a positive SLN. The use of SPECT-CT for patients with head and neck cutaneous melanoma significantly increases the likelihood of retrieving a positive SLN. Long-term follow-up evaluation is needed for further definition of the impact that SPECT-CT has on recurrence and survival.

Prognostic factors in melanoma patients with tumor-negative sentinel lymph nodes

Sentinel lymph node (SLN) biopsy for melanoma results in accurate nodal staging, which guides treatment decisions. Patients with a negative SLN biopsy in general have a favorable prognosis, but certain subsets are at increased risk for recurrence and death. This study aimed to identify risk factors predictive of prognosis in patients with a tumor-negative SLN biopsy for cutaneous melanoma. In this post-hoc analysis of data from a multicenter prospective randomized trial, clinicopathologic data of patients with cutaneous melanoma ≥1.0 mm Breslow thickness and tumor-negative SLN were analyzed. Disease-free survival, overall survival (OS), and local and in-transit recurrence-free survival were compared by Kaplan-Meier analysis. Risk factors for worse survival were identified with Cox proportional hazard models. This analysis included 1,998 patients with tumor-negative SLN with a median follow-up of 70 months. Ulceration, Breslow thickness, nonextremity tumor location, and age ≥45 years were independent risk factors for worse disease-free survival and OS. Breslow thickness and ulceration were the only factors on multivariate analysis that predicted local and in-transit recurrence-free survival. Estimated 5-year OS rates ranged from 55.5 to 95.4% on the basis of the defined risk factors. There is a wide range of prognosis among patients with tumor-negative SLN. Breslow thickness, ulceration, age, and anatomic location of the primary melanoma are important independent factors predicting survival and recurrence among such patients. These factors can be used to stratify prognosis among patients with tumor-negative SLN to formulate rational long-term follow-up strategies as well as identify high-risk, SLN-negative patients for clinical trials of adjuvant therapy.

Association of sentinel lymph node diameter with melanoma metastasis

BackgroundLymph nodes are an important part of the immune system and the size of the lymph node reflects local immunologic activity. The purpose of this study was to examine the association between sentinel lymph node (SLN) size and the presence of nodal metastasis in patients with melanoma. MethodsRetrospective review of a prospectively maintained database of patients undergoing SLN biopsy for cutaneous melanoma between February 1995 and January 2013. The maximum pathologic diameter and the volume of the largest node was used. A nodal diameter of 1.5 cm, included in 2 interquartile ranges of both positive and negative SLNs, was used as the cutoff for multivariate regression. ResultsOf 1,017 SLN biopsies, 826 (81%) had complete size measurements and were included in the analysis. Patients with a positive SLN were younger (median 50 vs 53 years, P = .032), had deeper primary lesions (2 vs 1.4 mm, P < .001), and had larger SLN volume (.8 vs .6 cc, P = .009) or maximum diameter (1.9 vs. 1.6 cm, P = .03). Sex, pathologic ulceration, mitosis, and the type or location of the primary was not statistically different. On multivariate analysis; age, depth of primary, and both SLN volume and maximum diameter remained significant. An SLN greater than 1.5 cm in maximum diameter has a 60% increased odds ratio of being positive after adjusting for age, sex, and depth of primary lesion (P = .046). ConclusionsLarger SLN maximum diameter is associated with nodal positivity independent of age, sex, depth of primary lesion, and location of SLN biopsy. The etiology and significance of larger SLNs warrant further analysis.

False‐Negative Sentinel Lymph Node Biopsy in Head and Neck Melanoma

The results of sentinel lymph node biopsy (SLNB) can be useful for staging and deciding on adjuvant treatment for patients with head and neck melanoma. False-negative SLNB can result in treatment delay. This study aimed to evaluate the characteristics and outcome of patients with false-negative SLNB in cutaneous melanoma of the head and neck. Longitudinal cohort study using a prospective institutional tumor registry. Academic health center. Data from 153 patients who underwent SLNB for melanoma of the head and neck were analyzed. False-negative biopsy was defined as recurrence of tumor in a previously identified negative nodal basin. Statistical analysis was performed on registry data. Positive sentinel lymph nodes were identified in 19 (12.4%) patients. False-negative SLNB was noted in 9 (5.9%) patients, with a false-negative SLNB rate of 32.1%. Using multivariate regression analysis, only examination of a single sentinel lymph node was a significant predictor of false-negative SLNB (P = .01). The mean treatment delay for the false-negative SLNB group was 470 days compared with 23 days in the positive SLNB group (P < .001). The 2-year overall survival of patients with false-negative SLNB was 75% compared with 84% and 98% in positive and negative SLNB groups, respectively (P = .02). False-negative SLNB is more likely to occur when a single sentinel lymph node is harvested. There is significant treatment delay in patients with false-negative SLNB. False-negative SLNB is associated with poor outcome in patients with melanoma of the head and neck.

Sentinel Lymph Node Biopsy for Cutaneous Melanoma

To review sentinel lymph node (SLN) data from Stanford University Medical Center from January 1, 1997, to January 1, 2004, including rates of SLN positivity according to 2002 American Joint Committee on Cancer (AJCC) tumor classification, relation to other clinical and pathologic prognostic factors, and rates and sites of melanoma recurrence. Retrospective case series. Stanford University Medical Center and Stanford melanoma clinics. A total of 274 consecutive patients with primary melanoma who underwent SLN biopsy (SLNB) between January 1, 1997, and January 1, 2004, or who were referred to the Stanford melanoma clinics after SLNB and were followed up through March 2005. All patients underwent standard wide local excision of their primary tumors and SLNB with intradermal injection of isosulfan blue dye and/or technetium sulfur colloid. Rates of SLN positivity per 2002 AJCC tumor classification, relation to other clinical and pathologic prognostic factors, and rates and sites of melanoma recurrence in node-negative and node-positive patients. Positive SLNs were detected in 39 (15%) of 260 cases, including 0 (0%) of 45 for cutaneous melanomas 1.0 mm thick or less (T1), 21 (18%) of 115 for melanomas 1.01 to 2.0 mm thick (T2), 12 (19%) of 64 for melanomas 2.01 to 4.0 mm thick (T3), and 5 (16%) of 32 for melanomas thicker than 4.0 mm (T4). Median Breslow depths were 1.89 mm for SLN-positive biopsy specimens and 1.50 mm for SLN-negative biopsy specimens (P = .07). The recurrence rate was 46% among SLN-positive patients, with a median time to recurrence of 8 months. Bivariate analysis revealed SLN positivity to be associated with AJCC tumor classification (P = .02), location on the trunk (P = .03), and presence of ulceration (P = .03). By multivariate logistic regression, ulceration (P = .01) was predictive of SLN positivity, whereas SLN status (P< .001), ulceration (P = .02), and location (P = .03) were predictive of recurrent disease. Data from the past 8 years confirm the accuracy and prognostic value of SLNB in cutaneous melanoma and the low rate of regional nodal recurrence for SLN-negative patients.

Predictors of Nonsentinel Lymph Node Positivity in Patients with a Positive Sentinel Node for Melanoma

Patients found to harbor melanoma micrometastases in the sentinel lymph node (SLN) are recommended to proceed to complete lymph node dissection (CLND), although the majority of patients will have no additional disease identified in the nonsentinel lymph nodes (NSLNs). We sought to assess predictive factors associated with finding positive NSLNs, and identify a subset of patients with low likelihood of finding additional disease on CLND. We queried our prospective melanoma database for patients from January 1996 to August 2003 with a positive SLN. Univariable logistic regression models were fit for multiple factors and a positive NSLN. To derive a probabilistic model for occurrence of one or more positive NSLN(s), a multivariable logistic model was fit using a stepwise variable selection method. Of 980 patients who underwent SLN biopsy for cutaneous melanoma, 232 (24%) had a positive SLN; 221 (23%) followed by CLND. Of these patients, 34 (15%) had one or more positive NSLN(s). In multivariable analysis, male gender (odds ratio [OR] 3.6 [95% CI 1.33, 9.71]; p = 0.01), Breslow thickness (OR 4.58 [95% CI 1.28, 16.36]; p = 0.019), extranodal extension (OR 3.2 [95% CI 1.0, 10.5]; p = 0.05), and three or more positive sentinel nodes (OR 65.81 [95% CI 5.2, 825.7]; p = 0.001) were all associated with the likelihood of finding additional positive nodes on CLND. Of 47 patients with minimal tumor burden in the SLN, only 1 (2%) had additional disease in the NSLN. These results provide additional data to plan clinical trials to answer the question of who can safely avoid CLND after a positive SLN. Patients with minimal tumor burden in the SLN might be the most likely group, although defining "minimal tumor burden" must be standardized. Serial sectioning and immunohistochemistry on the NSLN in any "low-risk" group must be performed in a clinical trial to confirm that residual disease is unlikely before avoiding CLND can be recommended.

A Nomogram That Predicts the Presence of Sentinel Node Metastasis in Melanoma With Better Discrimination Than the American Joint Committee on CancerStaging System

The threshold and indications for sentinel lymph node (SLN) biopsy in patients with melanoma remain somewhat arbitrary. Many variables associated with SLN positivity have previously been identified, including a significant association between the American Joint Committee on Cancer (AJCC) staging system and SLN status. We developed a user-friendly nomogram that takes several characteristics into account simultaneously to more accurately predict the presence of SLN metastasis for an individual patient. A total of 979 patients who underwent successful SLN biopsy for cutaneous melanoma at a single institution between February 1991 and November 2003 were included in the analysis. Predictors were used to develop a nomogram, based on logistic regression analysis, to predict the probability of SLN positivity. A large multi-institutional trial with 3108 patients was used to validate the predictive accuracy of the nomogram compared with the AJCC staging system. The nomogram was developed and found to be accurate and discriminating. The concordance index of the nomogram, a measure of predictive ability, was .694 when evaluated with the validation dataset. In contrast, the concordance index of the AJCC staging system was lower (.663; P < .001). Using commonly available clinicopathologic information, we developed a nomogram to accurately predict the probability of a positive SLN in patients with melanoma. This tool takes several characteristics into account simultaneously. This model should enable improved patient counseling and treatment selection.

Patterns of recurrence after sentinel lymph node biopsy for cutaneous melanoma

Background Previous sentinel lymph node (SLN) studies for cutaneous melanoma have shown that the SLN accurately reflects the nodal status of the corresponding nodal basin. However, there are few long-term studies that describe recurrence site patterns, predictors for recurrence, and overall survival and disease-free survival after SLN biopsy. Methods A retrospective review of patients over a 6-year period was performed to determine patient outcomes and the patterns of recurrence. In all cases, Tc-99 sulfur colloid along with isosulfan blue dye was injected at the primary melanoma site. After resection, the SLN was serially sectioned and evaluated by hematoxylin and eosin staining and immunohistochemistry. Results One hundred ninety-eight patients were identified who underwent SLN biopsy for cutaneous melanoma including T1 (n = 21), T2 (n = 88), T3 (n = 75), and T4 (n = 14) primary tumors. Of these patients, 38 had a positive SLN. Of the 38 patients with a positive SLN (mean follow-up 38 months), recurrent disease was identified in 10 (26.3%) at a mean interval of 14.2 months. The site of first recurrence was distant (n = 4) and local (n = 6). Regional lymphatic basin recurrence was not identified. Of the 160 patients with a negative SLN (mean follow-up 50 months), recurrent disease was identified in 16 (10.0%) at a mean interval of 31.3 months. The site of first recurrence was systemic (n = 11), local (n = 4), and nodal (n = 1). Overall survival and disease-free survival for patients with a positive SLN at 55 months was 53.3% and 47.7% respectively, while overall survival and disease-free survival for patients with a negative SLN at 53 months was 92.2% and 87.7% respectively ( P <0.01). Univariate and multivariate analysis of the entire cohort (n = 198) identified primary tumor depth and positive SLN status as significant predictors of recurrence. Conclusions The incidence of nodal basin recurrence after SLN biopsy was found to be 0.6%. Primary tumor depth and pathological status of the SLN are significant predictors of local and systemic recurrence. Long-term follow-up indicates that patients with a positive SLN clearly recur sooner and have decreased overall survival than those with a negative SLN.