Use of oncogene expression as an independent prognostic marker for primary melanoma

For 25 years, the Breslow depth of primary tumors has remained the most accurate prognostic test of survival for primary melanoma. However a number of studies have indicated that outcome for intermediate-thickness melanomas (0.75-2.49 mm) is often at variance with that predicted by the Breslow depth. This study investigated c-myc oncogene expression in 92 primary tumors of intermediate thickness using flow cytometry. Oncoprotein expression was detected in 87 tumors (95%) with a median positivity of 48% (range, 0%-96%). Survival analysis performed using the Kaplan-Meier method revealed a significant association between oncoprotein positivity and clinical outcome (p < 0.01, log-rank test). Multifactorial analysis of survival using Cox's proportional hazards model revealed c-myc oncoprotein to be an independent prognostic marker more accurate than all other clinicopathological parameters including the Breslow depth (chi(2) = 9.68, p< 0.01). Estimation of c-myc oncoprotein is therefore recommended as a powerful prognostic marker for intermediate-thickness primary melanoma.     

Surgical margins and prognostic factors in patients with thick (>4 mm) primary melanoma

Background: Randomized trials have demonstrated the efficacy of 1- and 2-cm excision margins for thin and intermediate-thickness melanomas, respectively. The optimal margin of excision for thick melanomas is still unknown, however. We evaluated whether the margins used for intermediate-thickness melanomas can be applied safely to thicker lesions. Methods: The charts of 278 patients with thick primary melanomas treated between 1985 and 1996 were retrospectively reviewed. Patients with distant metastases at presentation or with follow-up less than 6 months were excluded. Median follow-up was 27 months. Known melanoma prognostic factors and excision margins were evaluated for their impact on local recurrence (LR), disease-free survival (DFS), and overall survival (OS). Results: Median tumor thickness was 6.0 mm, and 57% were ulcerated. At presentation, 201 patients (72%) were node negative and 77 (28%) were node positive (palpable or occult). The 5-year OS and DFS rates were 55% and 30%, respectively. The LR rate for all patients was 12%. Although nodal status, thickness, and ulceration were significantly associated with OS by multivariate analysis, neither LR nor excisional margin (<2 cm vs. >2 cm) significantly affected DFS or OS in these patients. Conclusions: Because margins of excision greater than 2 cm do not improve LR, DFS, or OS compared to a margin of 2 cm or less, a 2-cm margin of excision is adequate for patients with thick melanoma. Because nodal status is a significant prognostic factor in these patients, staging by sentinel node biopsy should be considered in patients with thick melanomas and clinically negative nodal basins to allow proper entry and stratification in adjuvant therapy trials. Presented at the 50th Annual Cancer Symposium of The Society of Surgical Oncology, Chicago, IL, March 20–23, 1997.     

Efficacy of Lymphatic Mapping, Sentinel Lymphadenectomy, and Selective Complete Lymph Node Dissection as a Therapeutic Procedure for Early-Stage Melanoma

Background: Lymphatic mapping, sentinel lymphadenectomy, and selective complete lymph node dissection (LM/SL/SCLND) is an increasingly popular alternative to elective lymphadenectomy (ELND) for patients with early-stage melanoma. Although several reports have demonstrated the accuracy of the LM/SL technique, there are no data on its therapeutic value.Methods: We performed a matched-pair statistical analysis of 534 patients with clinical stage I melanoma; one half of the patients were treated with LM/SL and the other half were treated with ELND. Patients in the two treatment groups were matched for age (54% were 50 years of age), gender (63% were male patients), site of the primary melanoma (49% were on the extremities, 36% on the trunk, and 15% on the head and neck), and thickness of the primary melanoma (7% were <0.75 mm, 42% between 0.75 and 1.5 mm, 43% between 1.51 and 4.0 mm, and 8% >4 mm). Patients in the LM/SL group underwent complete regional lymphadenectomy (SCLND) only if the LM/SL specimen contained metastatic melanoma.Results: The overall incidences of nodal metastases were no different (P = .18) between LM/SL (15.7%) and ELND (12%) groups, but the incidence of occult nodal disease was significantly (P = .025) higher among patients with intermediate-thickness (1.51–4.0-mm) primary tumors who underwent LM/SL (23.7%) instead of ELND (12.2%). Survival data were compared by the log-rank score test. LM/SL/SCLND and ELND resulted in equivalent 5-year rates of disease-free survival (79 ± 3.3% and 84 ± 2.2%, respectively; P = .25) and overall survival (88 ± 3.0% and 86 ± 2.1%, respectively; P = .98). The LM/SL and ELND groups also exhibited similar incidences of same-basin recurrences (4.8% vs. 2.1%, P = .10, respectively) and in-transit metastases (2.6% vs. 3.8%, P = .48) after tumor-negative dissections. Patients who underwent ELND showed a higher incidence of distant recurrences (8.9% vs. 4.0%, P = .03), but this may be related to the longer follow-up period for these patients (median, 169 months), compared with the LM/SL-treated patients (45 months). Among patients with tumor-positive nodal dissections, the 5-year overall survival rates were higher, and approached significance (P = .077) for patients treated by LM/SL/SCLND (64 ± 12%) compared with ELND (45 ± 10%).Conclusions: These findings suggest that LM/SL/SCLND is therapeutically equivalent to ELND but may be more effective for identifying nodal metastases in patients with intermediate-thickness primary tumors.Supported by National Institutes of Health Grants CA12582 and CA29605 and by funding from the Wrather Family Foundation (Los Angeles, CA). Richard Essner, MD, is the recipient of an American Cancer Society Career Development Award.Presented at the 51st Annual Cancer Symposium of The Society of Surgical Oncology, San Diego, California, March 26–29, 1998.     

Local recurrence in malignant melanoma: Long-term results of the multiinstitutional randomized surgical trial

Background: In the past, radical margins of excision were prescribed for cutaneous melanoma based on preconceived notions rather than on hard clinical evidence. Methods: In a prospective study of 742 patients with intermediate-thickness melanoma (1–4 mm), 470 patients with trunk or proximal extremity lesions were randomized into a 2-or 4-cm margin. Patients with distal extremity or head and neck lesions (n=272) received uniformly a 2-cm margin. Results: The overall rate of local recurrence was 3.8%. This rate in the randomized portion (n=470) was 2.1% for the 2-cm margin and 2.6% for the 4-cm margin (p=0.72). A progressive increase in local recurrence rates was observed with thickness: 2.3% for lesions 1.0–2.0 mm, 4.2% for those 2.01–3.0 mm, and 11.7% for those 3.01–4.0 mm thick (p=0.001). Local recurrence occurred in 1.5% of those without ulceration and in 10.6% of those with ulceration of the primary lesion (p=0.001). The local recurrence rate was not significantly affected by the margin of resection even among the thicker or ulcerated lesions. It also was not affected significantly by the method of closure of the primary site or management of the regional nodes, or the age or gender of the patients. Conclusions: A 2-cm margin is as effective as a 4-cm margin in local control and survival of intermediate-thickness melanomas. The local recurrence rate is significantly affected by the thickness of the primary lesion and the presence or not of ulceration. Presented at the 48th Annual Cancer Symposium of The Society of Surgical Oncology, Boston, Massachusetts, March 23–26, 1996.     

Efficacy of an elective regional lymph node dissection of 1 to 4 mm thick melanomas for patients 60 years of age and younger.

OBJECTIVE: A prospective multi-institutional randomized surgical trial involving 740 stage I and II melanoma patients was conducted by the Intergroup Melanoma Surgical Program to determine whether elective (immediate) lymph node dissection (ELND) for intermediate-thickness melanoma (1-4 mm) improves survival rates compared with clinical observation of the lymph nodes. A second objective was to define subgroups of melanoma patients who would have a higher survival with ELND. METHODS: The eligible patients were stratified according to tumor thickness, anatomic site, and ulceration, and then were prerandomized to either ELND or nodal observation. Femoral, axillary, or modified neck dissections were performed using standardized surgical guidelines. RESULTS: The median follow-up was 7.4 years. A multifactorial (Cox regression) analysis showed that the following factors independently influenced survival: tumor ulceration, trunk site, tumor thickness, and patient age. Surgical treatment results were first compared based on randomized intent. Overall 5-year survival was not significantly different for patients who received ELND or nodal observation. However, the 552 patients 60 years of age or younger (75% of total group) with ELND has a significantly better 5-year survival. Among these patients, 5-year survival was better with ELND versus nodal observation for the 335 patients with tumors 1 to 2 mm thick, the 403 patients without tumor ulceration, and the 284 patients with tumors 1 to 2 mm thick and no ulceration. In contrast, patients older than 60 years of age who had ELND actually had a lower survival trend than those who had nodal observation. When survival rates were compared based on treatment actually received (i.e., including crossover patients), the patients with significantly improved 5-year survival rates after ELND included those with tumors 1 to 2 mm thick, those without tumor ulceration, and those 60 years of age or younger with tumors 1 to 2 mm thick or without ulceration. CONCLUSION: This is the first randomized study to prove the value of surgical treatment for clinically occult regional metastases. Patients 60 years or age or younger with intermediate-thickness melanomas, especially with nonulcerative melanoma and those with tumors 1 to 2 mm thick, may benefit from ELND. However, because some patients still are developing distant disease, these results should be considered an interim analysis.     

Results of Sentinel Lymph Node Biopsy in Patients With Thin Melanoma

Background Sentinel lymph node (SLN) biopsy has been shown to be a highly accurate method of staging nodal basins in melanoma patients. Although this technique is widely accepted in patients with intermediate-thickness tumors, it is unclear what the indications are for thin (≤1 mm) melanoma. Methods From May 1991 to October 2004, 223 patients with thin melanoma underwent SLN biopsy at Memorial Sloan-Kettering Cancer Center. Most patients with thin melanoma were selected for the procedure because of high-risk clinicopathologic features. Results Nodal metastases were found in eight patients (3.6%) who underwent SLN biopsy. All positive SLNs were found in patients with ≥.75 mm-thick and Clark level IV melanoma (8 of 114; 7%). Age, sex, tumor location, thickness, Clark level, ulceration, regression, tumor-infiltrating lymphocytes, mitotic rate, and number of mapped nodal basins were not predictive of positive SLNs (χ²; P = not significant). With a median follow-up of 25 months, there have been no recurrences or deaths in patients with melanoma <.75 mm. Six patients have had regional and/or systemic recurrences (2.7%), only one of whom had a positive SLN. Three patients have died of melanoma; all had negative SLNs. Conclusions Nodal metastasis in thin melanoma is uncommon, especially in patients with <.75 mm and Clark level II or III melanoma. In our experience, no single clinicopathologic factor was predictive of nodal metastases. The prognostic implications of positive SLNs in thin melanoma remain undefined.     

Metastasis of primary melanoma to two separate lymph node basins: Prognostic significance

Background and Methods: Depending on the location of the primary lesion, melanoma patients may develop metastases in more than one regional lymph node basin. To determine whether this is prognostically significant, we reviewed our experience with melanoma patients who had undergone regional lymphadenectomy (RLND) in two separate basins. Results: Of 3,603 patients who underwent RLND between April 1971 and January 1993, 406 underwent procedures in two separate basins; of these, 120 (30%) had metastases in both basins and 124 (30%) had metastases in one basin. When calculated from the first positive RLND, 1-year, 3-year, and 5-year survival rates were 82%, 48%, and 33%, respectively, for patients with dual-basin involvement and 88%, 59%, and 48%, respectively, for patients with single-basin involvement (p=0.0173). Median survival from the first positive RLND was 33.5 months for dual-basin involvement and 56.6 months for single-basin involvement. Univariate analysis demonstrated that Breslow thickness of the primary melanoma, clinical status of the regional lymph nodes, number of positive RLNDs, and tumor burden (total number of positive lymph nodes) were significant indicators of survival. The patient's age and gender, the anatomic location and Clark level of the primary melanoma, the disease-free interval before regional metastasis, and the site and timing of RLNDs were not significant by univariate analysis. Multivariate analysis demonstrated significance for Breslow thickness, number of positive RLNDs, and tumor burden. Conclusions: The survival rate of melanoma patients with regional metastases in two lymph node basins is lower than that of patients with an equal tumor burden confined to a single basin. This suggests that primary melanomas metastasizing to more than one lymph node basin may have a higher metastatic potential, or that dual-basin involvement may increase the risk of systemic spread. We advocate lymphatic mapping, sentinel node biopsy, and selective lymphadenectomy as a cost-effective technique with little morbidity to identify and manage occult metastases in patients who have two lymph basins at risk. Presented at the 47th Annual Cancer Symposium of The Society of Surgical Oncology, Houston, Texas, March 17–20, 1994.     

Predictors for Use of Sentinel Node Biopsy and the Association with Improved Survival in Melanoma Patients Who Have Nodal Staging

Background

It is unknown how many patients with localized melanoma undergo sentinel lymph node biopsy (SLNB) or if there is a therapeutic effect from performing nodal staging. We evaluated predictors for SLNB use and assessed if there was an association with improved survival in melanoma patients who had SLNB.

Methods

The Surveillance, Epidemiology, and End Results database was queried for clinically node-negative melanoma cases ≥ 0.75 mm in thickness treated from 2010 to 2012. Clinicopathologic factors were correlated with SLNB use, overall survival (OS), and melanoma-specific survival (MSS).

Results

Overall, 13,703 cases were included. SLNB was performed in 1479 of 3439 thin cases (43.0%), 5810 of 8522 intermediate-thickness cases (68.2%), and 916 of 1742 thick cases (52.6%). On multivariable analysis, age ≥ 70 years, thickness < 1 or > 4 mm, head/neck or trunk tumor location, being unmarried, African American race, and residing in a county with a lower level of education were significantly associated with a lower likelihood of performing SLNB (p < 0.05). Patients with intermediate-thickness or thick melanoma who had a SLNB had significantly improved OS and MSS compared with patients who did not have a SLNB (p < 0.05). On multivariable analysis, SLNB use significantly predicted for improved OS and MSS (p < 0.01).

Conclusions

Only 68.2% of intermediate-thickness and 52.6% of thick melanomas are treated with SLNB. Age, thickness, tumor location, race, marital status, and socioeconomic factors appear to influence the performance of SLNB. This data becomes more relevant with the finding that SLNB use is potentially associated with improved survival.

     

Intermediate-thickness melanoma: A population-based study of surgical quality metrics

BackgroundVariability in guideline compliance for melanoma lymph node surgery is partially attributable to controversy about patient selection. Prior data has indicated suboptimal practice of sentinel lymph node biopsy and undertreatment of clinically node-positive disease, predating Multicenter Selective Lymphadenectomy Trial II publication. To minimize bias, we studied compliance with lymph node surgery guidelines in T2/T3 (intermediate-thickness) melanoma patients, where the greatest agreement exists.MethodsT2/T3 and metastasis 0 melanoma cases were identified from 2004 to 2018 Surveillance, Epidemiology, and End Results data. Analysis used Cochran-Armitage test for trends, multivariable logistic regression, and Kaplan-Meier survival estimates.ResultsOf 66,319 eligible T2/T3 patients, 57,211 were clinically node negative; 2,191 were clinically node positive; 6,197 were clinical node unreported; and 19,044/66,319 (28.8%) had no lymph node surgery. Among clinically node-negative patients, 36,433 (63.7%) underwent sentinel lymph node biopsy and 31,026 (85.2%) were pathologically node negative; 1,499 clinically node-positive patients (68.4%) had a lymph node dissection. Lymph node dissection rates declined from 2004 to 2018, 79.8% to 32.0% for clinically node-negative/pathologically node-positive patients and 80.4% to 61.2% for clinically node-positive/pathologically node-positive patients (both P < .0001). For clinically node-negative patients, lymph node surgery compliance improved from 63.7% (2004) to 70.4% (2018) (P < .0001). Compliance correlated with younger age, male sex, tumor mitotic rate, and site (extremity > trunk/head/neck) in multivariable analysis and improved 5-year cancer-specific survival (90.0% vs 83.4%) (all P < .0001).ConclusionsDespite clear guidelines, one-third of intermediate-thickness melanoma patients in a recent cohort did not have recommended lymph node surgery. Lymph node status is a key determinant of the relative benefit of adjuvant systemic therapy and the need for active surveillance of pathologically node-positive/clinically node-negative patients. These data highlighted a clinical care gap. Efforts to improve guideline compliance are a logical strategy to improve cancer outcomes for intermediate-thickness melanoma patients.     

Role for Lymphatic Mapping and Sentinel Lymph Node Biopsy in Patients With Thick (≥4 mm) Primary Melanoma

Background: Historically, patients with thick (4 mm) primary melanoma have not been considered candidates for elective lymph node dissection, because their risk for occult distant disease is significant. Sentinel lymph node (SLN) biopsy offers an alternative approach to assess disease in the regional nodal basin, but no studies have specifically addressed the role for this technique in patients with thick melanoma. Although adjuvant therapy benefits patients who develop nodal metastases, data that supports its routine use in all patients with thick melanoma is both limited and controversial. This study was performed to determine whether pathological status of the SLN is an important risk factor in this heterogeneous group and, thus, provides a rationale for SLN biopsy.Methods: The records of 131 patients with primary cutaneous melanoma whose primary tumors were at least 4 mm thick and who underwent lymphatic mapping and SLN biopsy were reviewed. Several known prognostic factors, i.e., tumor thickness, ulceration, Clark level, location, sex, as well as SLN pathological status were analyzed with respect to disease-free and overall survival.Results: Lymphatic mapping and SLN biopsy was successful in 126 (96%) of 131 patients who underwent the procedure. In 49 patients (39%), the SLN biopsy was positive by conventional histology, although it was negative in 77 patients (61%). The median follow-up was 3 years. Although presence of ulceration and SLN status were independent prognostic factors with respect to disease-free and overall survival, SLN status was the most powerful predictor of overall survival by univariate and multivariate analyses.Conclusions: Lymphatic mapping and SLN biopsy is a highly accurate method of staging lymph node basins at risk for regional metastases in patients with thick melanoma and identifies those patients who may benefit from earlier lymphadenectomy as well as patients with a more favorable prognosis. Pathological status of the SLN in these patients with clinically negative nodes is the most important prognostic factor for survival and is essential to establish stratification criteria for future adjuvant trials in this high-risk group.Presented at the 52nd Annual Meeting of the Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999.     

Are Locoregional Cutaneous Metastases in Melanoma Predictable?

Background: In-transit metastases and satellite lesions are manifestations of locoregional cutaneous recurrence that are characteristic of malignant melanoma. They are the result of tumor cell emboli entrapped in the dermal lymphatics between the primary tumor and the regional lymph node basin. Histopathological features of lymphatic invasion were investigated to determine the possibility of predicting locoregional cutaneous metastases in melanoma patients.Methods: In a prospective study, 258 patients with clinical stage I melanoma underwent wide local excision and sentinel node biopsy. Nodal metastases were found in 53 (21%) patients. Of 29 patients (11.2%) who had developed recurrences to date, 17 (6.6%) had locoregional cutaneous metastases. All surgical specimens were examined with particular attention to histopathological signs of lymphatic vascular invasion or microscopic satellites.Results: Unequivocal signs of lymphatic invasion were observed in 14 of 258 patients (5.4%), and 13 (93%) of these patients subsequently developed in-transit metastases, after a median interval of 10 months. The primary melanoma was located on the extremities in seven patients. The median Breslow thickness was 2.5 mm, and 5 showed ulceration. In 244 of 258 patients (94.6%), there were no signs of lymphatic invasion. To date, only four patients (1.6%) have had a locoregional cutaneous recurrence, occurring after a median interval of 29 months. All four of these patients had ulcerative melanomas on an extremity, with a median thickness of 4.0 mm. The presence of lymphatic invasion was significantly related to early locoregional cutaneous relapse (P _ .0001).Conclusions: Locoregional cutaneous recurrence appears to be highly predictable in the presence of histopathological signs of lymphatic invasion. Lymphatic invasion is an important prognostic parameter and should be included as a stratification criterion when selecting patients for adjuvant (locoregional) therapy. Presented at the 51st Annual Cancer Symposium of The Society of Surgical Oncology, San Diego, California, March 26–29, 1998.     

Clinical node-negative thick melanoma

BACKGROUND: Patients with T4 N0 M0 melanoma are considered at high risk for having occult metastases, and adjuvant therapy is usually recommended. HYPOTHESIS: Long-term survival in patients with thick melanoma is not universally poor. DESIGN: A retrospective study. SETTING: University teaching hospital. PATIENTS: We evaluated clinical node-negative thick (> or = l4.0 mm) melanoma in 151 patients who received their primary definitive surgical treatment in our department. None of these patients received any adjuvant therapy. RESULTS: Median follow-up was 44 months; median thickness, 5.5 mm. Median overall (OS) and disease-free survivals (DFS) were 70 (5-year survival, 52%) and 51 months (5-year survival, 47%), respectively. Patients with node-positive disease faired significantly worse than did those with node-negative disease. Median OS and DFS for patients with node-positive disease were 49 and 32 months (5-year survival, 35%), respectively, compared with 209 (5-year survival, 61%) and 165 months (5-year survival, 56%), respectively, for patients with node-negative disease. Similarly, OS and DFS were significantly lower when the primary tumor had at least 5 mitoses/mm(2) or was located in the head and neck region. After multivariate analysis, status of the lymph nodes was the most predictive variable for OS and DFS. CONCLUSIONS: The thickness of melanoma, by itself, should not be used as a criterion for adjuvant therapy. Other prognostic factors should be considered.     

Revised American Joint Committee on Cancer Staging Criteria Accurately Predict Sentinel Lymph Node Positivity in Clinically Node-Negative Melanoma Patients

Background: The American Joint Committee on Cancer (AJCC) has recently modified staging criteria for primary melanoma patients and recommends sentinel lymph node (SLN) biopsy in many because microscopic nodal metastasis represents the most important factor predicting survival. The purpose of this study was to correlate the incidence of SLN metastasis with revised AJCC staging.Methods: The records of 1375 melanoma patients undergoing SLN biopsy were reviewed. Univariate and multivariate analyses were performed to identify predictors of a positive SLN. Patients were stratified by using revised AJCC criteria to determine whether such groups also predicted positive SLNs.Results: A positive SLN was found in 16.9% of patients. By multivariate analysis, tumor thickness (relative risk [RR], 3.4) and ulceration (RR, 2.2) were dominant independent predictors of SLN metastases; age 50 years (RR, 1.8) and axial tumor location (RR, 1.5) were also significant. When patients were stratified by AJCC staging criteria, a significant increase in SLN metastases between successive stages was demonstrated.Conclusions: Stratification of patients by using AJCC classification reveals an increasing risk of SLN metastases with successive stage groups. Given the significant association of SLN status and survival, the ability of the revised AJCC staging system to predict survival is likely due to its ability to predict the risk of occult nodal disease.Presented at the Society of Surgical Oncology Annual Meeting, Denver, Colorado, March 14–17, 2002.     

Surgical management of regional lymph nodes in patients with melanoma. Experience with 4682 patients.

OBJECTIVE: The purpose of this study was to evaluate a large number of patients with cutaneous melanoma who had or who were at risk for lymph node metastases to contribute to the understanding of the behavior of and appropriate management of draining nodes. A major goal of the study was to reassess the clinical impact of elective lymph node dissections (ELND) in a large patient population. SUMMARY BACKGROUND DATA: Large retrospective studies suggest that ELND may improve the prognosis of patients with intermediate thickness melanomas; however, that improvement has not been observed in two randomized prospective controlled trials. METHODS: The charts of 4682 patients treated at a single institution for localized or regional disease were reviewed individually. The median follow-up was 4.7 years, with 814 patients followed more than 10 years. The data were tabulated and evaluated with the aid of a computer data base system. RESULTS: Among patients with nodal metastases, 10% of nodal metastases were to contralateral nodes, and 6% were to nodal basins that would not be predicted by classic models of lymphatic drainage; in 13% of patients, nodal metastases occurred to greater than one nodal basin (3% of the entire study group). For all thickness ranges, the incidence of nodal metastases was comparable to the incidence of distant metastases; intermediate-thickness lesions had no relative predilection for nodal metastases. At the initial evaluation, regional nodal basins were clinically negative in 3550 patients, of whom 911 (25.7%) underwent ELND. Stratified into five thickness groups (< 0.76 mm, 0.76 to 1.5 mm, 1.5 to 2.5 mm, 2.5 to 4 mm, and > 4 mm), pathologically positive nodes were identified in 0%, 5%, 16%, 24%, and 36%, respectively (16% overall). Among the 911 patients who underwent ELND, 214 (23%) had nodal metastases, 143 at the time of ELND and 71 at a later date. Of these 71 patients, 31 (44%) had nodal metastases in a previously dissected nodal basin, and 40 (56%) had them in basins not previously dissected. The survival of patients with clinically negative nodes treated with and without ELND were compared. The two groups were well matched for major prognostic factors. Stratified by Breslow thickness and primary site, no significant improvement in survival was observed with ELND. CONCLUSIONS: Because of the significant incidence of metastases to contralateral and atypical nodal basins, lymphoscintigraphy may be justified for the preoperative evaluation of patients for ELND. However, the therapeutic value of ELND is questionable as a result of (1) the finding that the risk of nodal metastases is not relatively more common than is that of distant metastases among patients with intermediate-thickness melanomas, (2) the fact that only 16% of ELND were positive, (3) the finding that ELND may not prevent recurrent nodal disease in the dissected basin, and (4) the absence of any apparent impact on survival among patients who underwent ELND.     

Review and Evaluation of Sentinel Node Procedures in 250 Melanoma Patients With a Median Follow-Up of 6 Years

Background: The aim of this study was to evaluate the results of sentinel node biopsy in cutaneous melanoma at our institute.Methods: A total of 250 patients with cutaneous melanoma were studied prospectively. Preoperative lymphoscintigraphy was performed after injection of ^99mTc-nanocolloid intradermally around the primary tumor or biopsy site (.32 mL, 65.5 MBq [1.8 mCi]). The sentinel node was surgically identified with the aid of patent blue dye and a gamma ray detection probe. The median follow-up was 72 months.Results: Lymphoscintigraphic visualization was 100%, and surgical identification was 99.6%. In 60 patients (24%), 1 or more sentinel nodes were tumor positive at initial pathology evaluation. Late complications after sentinel node biopsy of the remaining 190 patients were seen in 35 patients (18%). The false-negative rate was 9%. In-transit metastases were seen in 7% of sentinel node–negative and 23% of sentinel node–positive patients. The estimated 5-year overall survival rates were 89% and 64%, respectively (P < .001).Conclusions: This study confirms that the status of the sentinel node is a strong independent prognostic factor. The false-negative rate and the incidence of in-transit metastases in sentinel node–positive patients are high and have to be weighed against the possible survival benefit of early removal of nodal metastases.     

Epidemiology,management and survival outcomes of primary cutaneous melanoma: a ten-year overview

Background: Malignant melanoma (MM) is the most aggressive type of skin cancer, accounting for 90% of all the skin cancer mortality. The objective of this study was providing an overview of current patient- and tumour characteristics, treatment strategies, complications and survival in patients with MM over the past ten years. Hereby, an up-to-date view of every day clinical practice is obtained.

Methods: Files of patients treated for primary cutaneous melanoma (n?=?686) in the VieCuri Medical Centre in the Netherlands between January 2002 and December 2013 were retrospectively reviewed. Relevant patient features, tumour characteristics, and (surgical) outcomes were evaluated.

Results: The majority of all the patients presented thin tumours (59.1% stage 1A/in situ melanoma). Men showed more ulceration (17.7% vs. 8.4%, p?p?p?n?=?3).

Conclusions: Patients generally presented with thin melanomas. Lymph node disease and distant metastases remained infrequently observed during following years, and general 1- and 5-year overall disease-specific survival rates exceeded 85%. Small numbers of rescue surgery and palliative medical treatment warrant further centralisation and investigation.     

Total Sentinel Lymph Node Tumor Size Predicts Nonsentinel Node Metastasis and Survival in Patients with Melanoma

Introduction  

In patients with a primary melanoma ≥1.0mm in Breslow thickness, the rate of metastasis to regional lymph nodes, as determined by sentinel node biopsy (SLNB), is approximately 20%. Among the patients with a positive SLNB result, however, only approximately 20% have tumor identified in additional non-SLNs. Therefore, many melanoma patients are still subjected to the morbidity of a complete lymph node dissection (CLND) without obvious benefit. In the current study, we analyzed the clinical and pathologic features of melanoma patients with positive SLNBs treated at the Melanoma Institute Australia. The aim was to correlate clinical and pathologic features of both the primary melanoma and the SLN metastases, including total SLN metastasis, with non-SN metastasis and (disease specific and overall) survival.     

Influence of the tumor site and histopathology after resection for non-colorectal non-neuroendocrine liver metastases. A single center experience

IntroductionIt remains unclear whether liver resection is justified in patients with non-colorectal non-neuroendocrine liver metastases (NCNNLM). A single-center study was conducted to analyse overall survival (OS), disease-free survival (DFS), and potential prognostic factors in patients with different types of NCNNLM.MethodA retrospective analysis of all patients who underwent liver resection of NCNNLM from January 2006 to July 2019 was performed.ResultsA total of 62 patients were analyzed. 82.3% presented metachronous metastases and 74.2% were unilobar. The most frequent primary tumor site (PTS) were breast (24.2%), urinary tract (19.4%), melanoma (12.9%), and pancreas (9.7%). The most frequent primary tumor pathologies were breast carcinoma (24.2%), non-breast adenocarcinoma (21%), melanoma (12.9%) and sarcoma (12.9%). The most frequent surgical procedure performed was minor hepatectomy (72.6%). R0 resection was achieved in 79.5% of cases. The major complications’ rate was 9.7% with a 90-day mortality rate of 1.6%. The 1, 3 and 5-year OS/DFS rate were 65%/28%, 45%/36% and 46%/28%, respectively. We identified the response to neoadjuvant therapy and PTS as possible prognostic factors for OS (P =0.06) and DFS (P =0.06) respectively.ConclusionBased on the results of our series, NCNNLM resection produces beneficial outcomes in terms of OS and DFS. PTS and the response to neoadjuvant therapy could be the main prognostic factors after resection.     

Indications for Lymphatic Mapping and Sentinel Lymphadenectomy in Patients with Thin Melanoma (Breslow Thickness ≤1.0 mm)

Background: Patients with thin (Breslow thickness 1.0 mm) melanoma have a good prognosis (5-year survival >90%). Consequently, the added benefit of lymphatic mapping and sentinel lymphadenectomy (LM/SL) in these patients is controversial. We hypothesize that LM/SL with a focused examination of the sentinel node (SN) will detect a significant number of SN metastases in patients with thin melanoma and that certain clinical or histopathologic factors may serve as predictors of SN tumor involvement.Methods: Over 6 years, 349 patients with melanoma underwent LM/SL and were prospectively entered into an institutional review board (IRB)-approved database. LM/SL was performed with a combined radiotracer and blue dye technique. SNs were serially sectioned, and each section was examined by a dermatopathologist at multiple levels with hematoxylin and eosin as well as immunohistochemical stains.Results: One hundred forty-six patients (42%) had a melanoma with Breslow thickness 1.0 mm; six (4%) of these 146 patients had a tumor-involved SN. On multivariate analysis, none of the clinical or histopathologic factors examined were significantly associated with SN tumor involvement in patients with thin melanoma. Completion lymphadenectomy was performed on all patients with a tumor-involved SN. None of the patients had non-SN tumor involvement.Conclusions: The incidence of SN tumor involvement in patients with thin melanoma is considerable. Although we were unable to identify predictors of SN tumor involvement in patients with thin melanoma, efforts to identify predictors of SN tumor involvement should continue. Until better predictors are identified, we continue to advocate offering LM/SL to patients with thin melanomas who demonstrate clinical or histopathologic characteristics that have historically been associated with an increased risk of recurrence and mortality.     

Does complete resection of melanoma metastatic to solid intra-abdominal organs improve survival?

Background:Patients with distant melanoma metastases have median survivals of 4 to 8 months. Previous studies have demonstrated improved survival after complete resection of pulmonary and hollow viscus gastrointestinal metastases. We hypothesized that patients with metastatic disease to intra-abdominal solid organs might also benefit from complete surgical resection.Methods:A prospectively acquired database identified patients treated for melanoma metastatic to the liver, pancreas, spleen, adrenal glands, or a combination of these from 1971 to 2010434_2001_Article_658. The primary intervention was complete or incomplete surgical resection of intra-abdominal solid-organ metastases, and the main outcome measure was postoperative overall survival (OS). Disease-free survival (DFS) was a secondary outcome measure.Results:Sixty patients underwent adrenalectomy, hepatectomy, splenectomy, or pancreatectomy. Median OS was significantly improved after complete versus incomplete resections, but median OS after complete resection was not significantly different for single-site versus synchronous multisite metastases. The 5-year survival in the group after complete resection was 24%, whereas in the incomplete resection group, there were no 5-year survivors. Median DFS after complete resection was 15 months. Of note, the 2-year DFS after complete resection was 53% for synchronous multi-site metastases versus 26% for single-site metastases.Conclusions:In highly selected patients with melanoma metastatic to intra-abdominal solid organs, aggressive attempts at complete surgical resection may improve OS. It is important that the number of metastatic sites does not seem to affect the OS after complete resection.