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.     

The current management and prognosis of acral lentiginous melanoma.

A computer-aided retrospective analysis was performed on 359 patients with stage I and II melanoma at the time of diagnosis (disease confined to the primary melanoma), at the University of South Florida (Tampa, FL). Eighteen patients were identified with primary melanoma in acral locations, most being acral lentiginous melanoma. A comparison of actuarial survival curves of patients with melanoma in four different locations (acral, head and neck, trunk, and other extremity site) was performed. The patients with melanoma in acral locations did not have a statistically different actuarial survival than those with primary melanoma in other sites. When actuarial disease-free survival curves were constructed, however, acral primary melanoma had a shorter interval to recurrence than those located on the trunk or other extremity sites. Differences between actuarial disease-free survival for the head and neck and for acral primary sites were not significant. To identify prognostic factors responsible for the decreased disease-free survival of the acral lentiginous population, a regression analysis was performed. Three prognostic factors were analyzed for stage I and II melanoma, including Breslow tumor thickness, ulceration of the primary lesion, and primary site location. In the univariate analysis, with each prognostic factor acting independently, tumor thickness (p less than 0.01) and ulceration (p = 0.02) were significant variables influencing the disease-free interval. Primary site did not, however, add prognostic information to the model (p = 0.54). A stepwise multivariate analysis confirmed this finding.     

Thin melanomas: predictive lethal characteristics from a 30-year clinical experience

OBJECTIVE: To guide treatment and clinical follow-up by defining the natural history of thin melanomas and identifying negative prognostic characteristics that may delineate high-risk patients. SUMMARY BACKGROUND DATA: In following > 10,000 patients with cutaneous melanoma over the past 30 years, our institution has observed nodal or metastatic disease in approximately 15% of patients with a thin (<1 mm) primary lesion. METHODS: A database query of patients with cutaneous melanoma returned 1158 patients with primary lesion < or = 1 mm thick and who received their initial treatment at a single institution. Median follow-up was 11 years (range, 1 to 34 years). Patient and melanoma characteristics as well as outcomes were recorded and statistically analyzed. RESULTS: 6.6% of patients had nodal or distant disease at presentation. Over time, an additional 9.4% developed metastases, including nodal and distal recurrences. Overall incidence of advanced disease was 15.3%. Univariate analysis identified male gender (P = 0.01), advanced age (>45 years; P = 0.05), and Breslow thickness (>0.75 mm; P = 0.008) as significant negative prognostic characteristics. Of patients with these 3 high-risk characteristics, 19.7% developed advanced disease (likelihood ratio 6.3; P = 0.007 versus nonhigh-risk patients). This group had more than twice the incidence of nodal recurrences. Patients with recurrence had significantly decreased 10-year survival (82% versus 45%; P < 0.0001). Surprisingly, neither ulceration nor Clark level predicted advanced disease. CONCLUSIONS: Thin melanomas are potentially lethal lesions. Long-term follow-up identified a high-risk population of older males with tumors between 0.75 mm and 1.0 mm whose risk of recurrent disease approaches 20%. Traditionally accepted negative prognostic factors such as ulceration and discordant Clark levels are not predictive for metastasis in this population. Given the poor prognosis associated with recurrent disease, we recommend close clinical evaluation and follow-up to maximize accurate staging and therapeutic options.     

Can Elective Lymph Node Dissection Decrease the Frequency and Mortality Rate of Late Melanoma Recurrences?

Background: Although more than 90% of the morbidity and mortality from localized cutaneous melanoma occurs in the first decade after initial surgical treatment, melanoma can recur after a 10-year disease-free interval (DFI) with fatal consequences. We reviewed our melanoma data base of more than 8500 prospectively acquired patients to identify clinicopathological factors that affect the type, rate of occurrence, and outcome of disease recurring 10 years or more after surgical treatment of primary cutaneous melanoma.Methods: From 1971 to 1997, 1907 melanoma patients treated at our cancer center reached or presented with a DFI of 10 years or more after surgical treatment of clinically localized melanoma. Of these, 217 (11%) patients had recurrences (mean DFI, 182 months). The sites of recurrence were local/in-transit in 26 (12%) patients, regional lymph nodes in 101 (47%) patients, and distant sites in 90 (41%) patients.Results: Univariate and multivariate analysis, using patient age and sex, type of initial treatment, and the site, Breslow thickness, and Clark level of the initial tumor, showed that the type of treatment for the primary tumor was a significant (P = .0005) prognostic factor in the development of late nodal recurrence. Of the 217 patients who had recurrences, 172 (79%) had undergone wide local excision for their primary melanoma, and 45 (21%) had undergone wide local excision plus elective lymph node dissection (ELND). The rates of nodal recurrence were 53% (92 of 172) and 20% (9 of 45), respectively, a significant (P = .0001) difference. When all patients with a DFI of 10 years or more were stratified by type of initial treatment, the ELND group demonstrated a significant improvement in disease-free survival and overall survival.Conclusions: The risk of late-recurring nodal disease increases and the chance of long-term survival decreases when wide local excision is performed without ELND. With the advent of sentinel lymphadenectomy, ELND can be selectively performed only for those nodal basins with occult tumor cells, thereby decreasing operative morbidity but allowing identification and early removal of nodal micrometastases.Presented at the 52nd Annual Meeting of the Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999.     

Pathologic and clinical features influencing outcome of thin cutaneous melanoma: correlation with newly proposed staging system

The incidence of malignant melanoma is increasing. Because of increased awareness, early recognition of malignant melanoma has become more common. In 1997, a new staging system for cutaneous melanoma was proposed, with reclassification of thin melanoma < 1 mm, with and without ulceration. This report evaluates the pathologic and clinical features of thin melanomas influencing recurrence and survival from a tertiary cancer center in an attempt to correlate findings with the proposed staging system. A review of the Roswell Park Cancer Institute tumor registry identified 352 patients with thin cutaneous melanomas (< 1.0 mm) seen during an 18-year period ending August 30, 1998. Overall survival was 93 and 87 per cent at 5 and 10 years, respectively. Disease-free survival was 94 and 93 per cent at 5 and 10 years, respectively. Local recurrence occurred in 3 per cent of patients, regional recurrence in 3 per cent, and metastatic disease in 3 per cent, for an overall recurrence of 7 per cent, with a median follow-up of 118 months. Only the presence of ulceration was a significant prognostic factor for recurrence by both univariate and multivariate analysis. Failure rates (any recurrence) by Clark levels I, II, and III/IV were 3, 5, and 10 per cent, respectively (P = 0.14). Failure rates by tumor thickness (mm), for 0.0-0.24, 0.25-0.49, 0.50-0.74, and 0.75-0.99 were 3, 4, 7, and 10 per cent, respectively (P = 0.49). Ten-year disease-free survival for ulceration versus no ulceration was 40 and 94 per cent, respectively (P < 0.0001). We conclude that thin cutaneous melanoma carries an excellent prognosis with appropriate treatment. Our findings support inclusion of ulceration in a new staging system. Lesions 0.76 to 0.99 mm and Clark level III and IV may warrant close observation as a separate subgroup.     

Malignant melanoma in children

Background: Cutaneous melanoma is an uncommon malignancy in children and for this reason, there is little information available regarding the timing and patterns of recurrence in children with this disease. This study reviews the experience at a single institution (Duke University Melanoma Clinic) in treating children with malignant melanoma. Methods: Eighty-five patients ≤18 years of age with malignant melanoma have been treated. All but three patients were over the age of 10; 73% of them were >14. As for adults, treatment consisted of wide local excision of all primary lesions with primary closure or split-thickness skin graft, as needed. In addition, 22 patients underwent dissection of regional lymph nodes. Patients whose tumors had aggressive pathologic characteristics were treated with an adjuvant immunotherapy protocol. Patients with recurrence at distant sites were offered combination chemotherapy. Results: Patients and pathologic characteristics of sex, race, primary site, histologic type, tumor thickness, and Clark level were similar to those observed in adults. Actuarial survival rates (79% versus 77% at 5 years) of the pediatric and adult Stage I melanoma patients were also not significantly different. Children had a greater incidence of recurrence after initial treatment, although recurrence tended to happen after a longer disease-free interval than for adults. Half of the 79 children who were first seen with Stage I disease have suffered a relapse, but more than one-third were disease free for ≥5 years after initial treatment. Of the 18 patients who were disease free for ≥7 years, 12 (67%) ultimately had recurrent disease, including five patients who had recurrences >13 years after initial diagnosis. Conclusions: The early age at which malignant melanoma may occur and the significant potential for very late recurrence mandate that pediatricians and other primary care physicians consider the diagnosis of melanoma even in young patients with new skin lesions and that patients treated for melanoma be carefully followed for a lifetime. Presented at the 46th Annual Cancer Symposium of The Society of Surgical Oncology, Los Angeles, California, March 18–21, 1993.     

Prognostic factors in young women with cutaneous melanoma

BackgroundGender is an established prognostic factor in cutaneous melanoma; women as a group have a better overall prognosis than men. However, the investigators hypothesized that melanoma in young women may have distinct clinicopathologic features and biologic behavior compared with melanoma in older women, possibly related to tanning bed use and excessive acute episodes of sun exposure.MethodsA retrospective analysis was performed of a large multicenter study that accrued patients between 1996 and 2003 and included patients aged 18 to 70 years with cutaneous melanoma ≥1 mm Breslow thickness and no evidence of regional or distant metastatic disease. All women with follow-up data were included. Univariate and multivariate analyses as well as Kaplan-Meier (KM) analysis were performed to test for differences in clinicopathologic variables, disease-free survival (DFS), and overall survival (OS) between female patients ≤40 and >40 years of age.ResultsA total of 1,056 female patients were divided into 2 groups: those >40 years of age (n = 757 [71.7%]) and those ≤40 years of age (n = 299 [28.3%]). Overall, there were no differences in Breslow thickness, ulceration, or sentinel lymph node status between groups. Compared with older women, younger women were more likely to have truncal melanomas (39.5% vs 29.5%, P = .0017) and less likely to have regression of the primary tumor (6.4% vs 11.5%, P = .0208). The mean number of sentinel lymph nodes removed was 2.82 for younger women and 2.29 for older women (P < .0001). Multivariate analysis revealed that Breslow thickness, ulceration, and tumor-positive sentinel lymph node were associated with worse DFS in both the younger and older groups; truncal location was associated with worse DFS in the younger group only. The same factors were predictive of OS in both groups, except that ulceration was not significant in the younger patient group. In the younger patient group, the 5-year KM DFS rates were 78.1% for truncal melanomas and 92.5% for nontruncal melanoma locations (P = .0009); the corresponding 5-year KM OS rates were 76.6% and 93.9% (P = .0003). In the older patient group, the 5-year KM DFS rates were 84.1% for truncal and 82.8% for nontruncal melanomas (P = NS), and the corresponding 5-year KM OS rates were 81.6% and 87.5% (P = .0049).ConclusionsAlthough women with cutaneous melanoma tend to have a better prognosis than men, women ≤40 years of age with primary melanoma of the trunk may represent a subgroup at higher risk for disease recurrence and metastasis.     

Sentinel Node Biopsy Improves Prognostic Stratification in Patients with Thin (pT1) Melanomas and an Additional Risk Factor

Background

Sentinel lymph node (SLN) biopsy (SLNB) for pT1 melanomas is not generally recognized as a clinical standard. We studied the value of SLNB for pT1 melanoma patients having at least one additional risk factor.

Patients

Among 931 patients with SLNB, 210 had pT1 melanomas. All of the latter showed at least one of the following risk factors: ulceration (4 %) Clark level IV (44 %), nodular growth pattern (11 %), mitoses (59 %), regression (38 %) or age ≤40 years (27 %).

Results

In this selected pT1 population, we observed a surprisingly high SLN positivity rate of 18 %. The melanoma-specific overall survival significantly depended on SLN status. Compared with Clark IV, a lower invasion level (Clark II/III) was associated with a higher proportion of positive SLNs (25 vs. 10 %; p < 0.01). There was a trend towards a higher SLN positivity rate in younger patients (p = 0.06). Breslow, ulceration, mitoses, nodular growth pattern, and sex did not reach significance. Regression was significantly more frequently found in very thin melanomas (≤0.75 mm) and tended to be significant in this subgroup (p = 0.075).

Conclusions

SLNB improves prognostic stratification in patients with thin melanomas having an additional risk factor. Clark level IV most likely does not belong to these risk factors. The impact of regression deserves further consideration. Our data suggest that SLNB should be offered to patients with thin melanomas, if ulceration, nodular growth pattern, mitoses, or regression are present, or if the patient is younger than 40 years of age.     

Factors that predict the presence of sentinel lymph node metastasis in patients with melanoma

BACKGROUND: This analysis was performed to identify prognostic factors that are predictive of sentinel lymph node (SLN) metastasis in melanoma. METHODS: Analysis was performed of a multi-institutional, prospective, randomized trial of SLN biopsy for melanoma. Eligibility criteria included age 18 to 70 years, Breslow thickness of 1.0 mm or more, and clinically negative regional lymph nodes. SLNs were evaluated by serial sectioning and immunohistochemistry for S100. Univariate chi-square and multivariate logistic regression analyses were performed to assess factors predictive of the presence of a positive SLN. Probability values of less than.05 were considered significant. RESULTS: SLNs were identified in 99.7% of patients. A total of 1058 patients were evaluated; 961 patients had complete data and were included in the statistical analysis. SLNs were positive for tumor in 208 of 961 patients (22%). Breslow thickness, Clark level, ulceration, and patient age were factors that were found to be independently predictive of the presence of SLN metastasis. CONCLUSIONS: Increasing Breslow thickness, Clark level of more than III, the presence of ulceration, and patient age of 60 years or less are the most important independent prognostic factors associated with the finding of positive SLN in patients with melanoma.     

Correlation Between Prognostic Factors and Increasing Age in Melanoma

Background: Age of patients with melanoma varies directly with mortality and inversely with the presence of sentinel lymph node (SLN) metastasis. To gain further insight into this apparent paradox, we analyzed the relationship between age and other major prognostic factors.Methods: The Sunbelt Melanoma Trial is a prospective, randomized study with 79 institutions involving SLN biopsy for melanoma. Eligible patients were 18 to 70 years old with melanoma of 1.0-mm Breslow thickness and clinically N0 regional lymph nodes. SLNs were evaluated by serial histological sections and immunohistochemistry for S-100 protein.Results: A total of 3076 patients were enrolled in the study, with a median follow-up of 19 months. Five age groups were examined: 18 to 30, 31 to 40, 41 to 50, 51 to 60, and 61 to 70 years. Trends between age and several key prognostic factors was identified: as age group increased, so did Breslow thickness (analysis of variance; P < .001), the incidence of ulceration and regression, and the proportion of male patients (each variable: ², P < .001). The incidence of SLN metastasis, however, declined with increasing age (²; P < .001).Conclusions: As age increases, so does Breslow thickness, the incidence of ulceration and regression, and the proportion of male patients—all poor prognostic factors. However, the frequency of SLN metastasis declines with increasing age. It is not known whether this represents a decreased sensitivity (higher false-negative rate) of the SLN procedure in older patients or a different biological behavior (hematogenous spread) of melanomas in older patients.     

Multiple primary melanomas: Implications for screening and follow-up programs for melanoma

Background: Once individuals are diagnosed with malignant melanoma, they are at an increased risk of developing another melanoma when compared with the normal population. Methods: To determine the impact of an intensive follow-up protocol on the stage of disease at diagnosis of subsequent primary melanomas, a retrospective query was performed of an electronic medical record database of 2,600 consecutively registered melanoma patients. Results: Sixty-seven patients (2.6%) had another melanoma diagnosed at the time of presentation to the clinic or within 2 months (synchronous) and another 44 patients (1.7%) developed a second primary melanoma during the follow-up period (metachronous). For the 44 patients diagnosed with metachronous lesions, the Breslow mean tumor thickness for the first invasive melanoma was 2.27 mm compared with 0.90 mm for the second melanoma. The first melanomas diagnosed are thicker by an average of 3.8 mm (p=0.008). The mean Clark level for the initial melanoma was greater than the mean level for subsequently diagnosed melanomas (p=0.002). Twenty-three percent of the initial melanomas were ulcerated, whereas only one of the second primary lesions showed this adverse prognostic factor (p=0.002). Conclusions: Once individuals are diagnosed with melanoma, they are in a high-risk population for having other primary site melanomas diagnosed and should be placed in an intensive follow-up protocol consisting of a complete skin examination. Presented at the 48th Annual Cancer Symposium of The Society of Surgical Oncology, Boston, Massachusetts, March 23–26, 1995.     

Serum TA90 Antigen-Antibody Complex as a Surrogate Marker for the Efficacy of a Polyvalent Allogeneic Whole-Cell Vaccine (CancerVax) in Melanoma

Introduction: TA90 is a tumor-associated 90-kD glycoprotein antigen expressed on most melanoma cells, including those of CancerVax, a polyvalent allogeneic whole-cell vaccine. Previous studies have shown that a TA90 antigen-antibody immune complex (IC) in the serum of patients with melanoma is a marker of subclinical tumor burden and a strong prognostic factor. We hypothesized that the induction of TA90-IC during postoperative adjuvant CancerVax therapy might indicate vaccine-mediated immune destruction of subclinical melanoma cells with release of TA90, and thereby serve as a surrogate marker of vaccine efficacy.Methods: From 1993 to 1997, 219 melanoma patients were enrolled in a prospective phase II trial of CancerVax plus bacille Calmette-Guerin (BCG) after complete tumor resection. Coded serum samples were prospectively collected and analyzed for TA90-IC before and 2, 4, 8, 12, and 16 weeks after initiation of CancerVax therapy. TA90-IC seroconverters were those patients whose negative TA90-IC values (< .410) became positive ( .410) after initiation of CancerVax treatment.Results: Before CancerVax therapy, 51 patients had positive TA90-IC values and 168 patients had negative TA90-IC values. During CancerVax treatment, all 51 positive patients remained positive, 79 (47%) negative patients seroconverted to positive, and 89 (53%) negative patients remained negative. Seroconverters had higher 2-year rates of disease-free survival (59% vs. 32%; P < .006) and overall survival (78% vs. 63%; P < .02) than did patients whose TA90-IC values remained positive.Conclusions: CancerVax induces TA90-IC in melanoma patients with subclinical disease. TA90-IC seroconverted patients have significantly improved disease-free and overall survival compared with TA90-IC positive patients. TA90-IC is an important prognostic factor that can serve as a surrogate marker for the clinical efficacy of CancerVax.Presented at the Society of Surgical Oncology Annual Meeting, New Orleans, Louisiana, March 16-19, 2010434_2001_Article_198.     

A comparison of prognostic factors and surgical results in 1,786 patients with localized (stage I) melanoma treated in Alabama, USA, and New South Wales, Australia.

Twelve clinical and pathologic parameters were compared in two series of Stage I melanoma patients treated at the University of Alabama in Birmingham, USA (676 patients) and at the University of Sydney in New South Wales, Australia (1,110 patients). Actuarial survival rates were virtually the same at the two institutions over a 25-year follow-up period. The incidence of thin melanomas (less than 0.76 mm) was also similar at both geographic locations (25% vs. 26%). Other similarities of these two patient populations included the following: 1) tumor thickness (Breslow Microstaging). 2) level of invasion (Clark Microstaging), 3) surgical results, 4) sex distribution, and 5) age distribution. The greatest differences between the two patient populations were their 1) anatomic distribution, 2) growth pattern, and 3) incidence of ulceration. The trunk was the most common site of melanoma, and occurred more frequently among Australian patients (37% vs. 28%). A multifactorial analysis (Cox's regression model) was then performed that included a comparison of the two institutions as a variable (Alabama vs. Australia). The dominant prognostic factors (p less than 0.0001) were 1) ulceration, 2) tumor thickness, 3) initial surgical management (wide excision +/- node dissection), 4) anatomic location, 5) pathologic stage (I vs. II), and 6) level of invasion. The benefit of elective lymph node dissection was demonstrated in both series for patients with intermediate thickness melanoma (0.76 to 3.99 mm.) For melanomas ranging from 0.76 to 1.5 mm in thickness, the benefit of node dissection was primarily in male patients. Survival rates for melanoma at the two institutions were not significantly different in the multifactorial analysis, even after adjusting for all other variable. Thus, the biologic behavior of melanoma in these two different parts of the world was virtually the same, with only minor differences that did not significantly influence survival rates. Long-term follow-up exceeding eight to ten years after surgery is critical in the interpretation of these prognostic factors and the surgical results.     

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.     

Treatment Outcomes of Advanced Stage Malignant Melanoma in Hand and Foot after Amputation in Korean Patients

Background

A retrospective study was conducted to review the overall survival and treatment outcomes of high grade melanoma in the extremity to explore the clinical features of malignant melanoma of the hand and foot, and the therapeutic efficacies and survival rate after amputation.

Methods

The clinical data of 30 patients with malignant melanoma of the hand and foot (confirmed by pathological examination), who were admitted and treated in our hospital between 2001 and 2010, were analyzed retrospectively. We analyzed variables affecting overall and disease-free survival.

Results

Thirty patients (18 men and 12 women) treated with an amputation procedure for malignant melanoma in the hand or foot constituted the study cohort. The average age of the patients at the time of diagnosis was 58.7 years. Univariate analysis for overall melanoma survival revealed that diagnosis at over 70 years of age, postoperative lymph node metastasis, and location of the tumor were significant prognostic factors. And on the Kaplan-Meier survival curve, old age, American Joint Committee on Cancer stage and postoperative lymph node metastasis showed statistically significant differences in the 5-year survival rate. Also, amputation with aggressive lymph node dissection showed improved long term survival in advanced stage melanoma.

Conclusions

In Korean melanoma patients, for the treatment of high grade melanomas in the extremities after amputation, early diagnosis and postoperative follow-up for evaluation of lymph node metastasis are critical factors for long-term survival. And by performing lymph node dissection during amputation, we may improve the survival rate in advanced stage melanoma patients.     

Significance of Plasma Cytokine Levels in Melanoma Patients With Histologically Negative Sentinel Lymph Nodes

Introduction:Although sentinel lymph node (SLN) status is the most powerful predictor of prognosis in patients with clinically localized melanoma, a proportion of melanoma patients with histologically negative SLNs will still recur. It is hypothesized that tumor response may be altered or mediated by specific cytokines. We therefore investigated whether levels of IL-4, IL-6, IL-10, TNF-, or IFN- would predict disease recurrence in melanoma patients with histologically negative SLNs.Methods:This prospective cohort study involved 218 patients with clinically localized melanoma who underwent a histologically negative SLN biopsy. Preoperative plasma cytokine levels were determined by enzyme-linked immunosorbent assay on these patients, as well as on 90 healthy controls. Kaplan-Meier life tables were constructed, and Cox proportional hazards analyses were performed to assess predictors of disease-free survival (DFS).Results:At a median follow-up of 43 months, 33 of 218 patients (15%) had suffered disease recurrence. Melanoma patients had significant elevations of IL-4, IL-6, and IL-10 compared to healthy controls; levels of IFN- were less elevated in melanoma patients compared to controls. Despite this, melanoma patients with detectable IFN- levels were at significantly higher risk for recurrence compared to patients with undetectable levels (5-year DFS 70% vs. 86%, P = .03). On multivariate analysis including standard melanoma prognostic factors, only tumor thickness (P = .004) and the presence of detectable IFN- levels (P = .05) were significant independent prognostic factors for disease-free survival.Conclusions:Among melanoma patients with clinically localized disease who have undergone a histologically negative SLN biopsy, presence of a detectable plasma level of IFN- is an independent predictor of disease recurrence. Elevated levels of IFN- may identify a group of early-stage melanoma patients who are more likely to have recurrence of disease and who may benefit from adjuvant therapies, including immunotherapies.Presented at the 52nd Annual Meeting of the Society of Surgical Oncology, New Orleans, Louisiana, March 17, 2000     

Risk Factors and Predictors of Survival Among Patients with Amelanotic Melanoma Compared to Melanotic Melanoma in the National Cancer Database

BackgroundAmelanotic melanoma (AM) is a rare form of melanoma lacking pigment. Data on AM risk factors and factors predicting survival are limited.ObjectivesWe sought to identify predictors of AM, survival differences in AM and melanotic melanoma, and AM-specific survival rates.MethodsUsing 2004 through 2015 National Cancer Database data, we compared 358,543 melanoma cases to 1,384 AM cases. Multivariable logistic regression identified AM risk factors, and AM survival was explored using Kaplan-Meier and multivariable Cox regression.ResultsIncreased age; tumor location on the face, scalp, and neck; increased Breslow thickness; metastatic disease; ulceration; and higher mitotic rate were associated with AM. Five- and ten-year survival rates were higher for patients with MM (melanotic melanoma) than AM tumors (75.4% vs. 58.8% and 62.4% vs 45.1%; log-rank P<0.0001). No survival difference was seen after adjusting for staging factors. Among patients with AM, more recent diagnosis was associated with improved survival. Increased age, T4 tumor size, higher N-stage, metastasis, and ulceration predicted poorer survival. No survival advantage was seen for chemotherapy, immunotherapy, or radiation therapy, likely due to confounding.ConclusionAM is more common in older patients on sun-exposed skin and is diagnosed at later stages. Advanced staging at diagnosis explains the survival differences. In patients with AM, regional and metastatic disease were the primary contributors of poorer outcomes. In at-risk patients, the threshold to biopsy should be lower for suspicious nonpigmented lesions.     

Sentinel lymph node biopsy in thick malignant melanoma: A 10-year single unit experience

Between the years 2000-2010, 195 patients were diagnosed with ≥4?mm Breslow thickness malignant melanoma in our unit. Median follow-up was 36.8 months. 49% of patients were male and 51% were female. Median age was 74 years. The commonest melanoma type was nodular (55%). The commonest tumour location was on the extremity (45%). 64% of tumours were ulcerated. Median mitotic rate was 9. Median Breslow thickness was 7?mm 66 patients underwent sentinel lymph node biopsy. 44 (67%) patients had negative results and the remaining 22 (33%) patients were positive for metastatic melanoma. There was no statistically significant correlation between any of the patient or tumour variables (age, sex, melanoma type, melanoma site, Clark level, Breslow thickness, mitotic rate, ulceration) and sentinel lymph node status. Patients with Breslow thickness melanoma of <6?mm had a significantly better 5-year disease free and overall survival compared with those patients with >6?mm Breslow thickness melanoma (63.5% vs. 32.9%; P?=?0.004 and 73.9% vs. 54.7%; P?=?0.02 respectively). Recurrence rate was 50% in those with positive sentinel lymph node biopsy compared to 23% in those with negative results. Distant recurrence was the commonest in both groups. 5-year disease free survival was 64.1% in the SLNB -ve group and 35.4% in the SLNB +ve group (P?=?0.01). There was no significant difference in overall survival between the SLNB -ve and SLNB +ve groups (70.3% vs. 63.7% respectively; P?=?0.66). We conclude that sentinel lymph node biopsy in our unit has provided no survival benefit in those with thick melanoma over the past 10 years but is an important predictor of recurrence free survival. Breslow thickness remains an important predictor of disease free and overall survival in thick melanoma.     

Regression does not predict nodal metastasis or survival in patients with cutaneous melanoma

Controversy exists regarding the prognostic implications of regression in patients with cutaneous melanoma. Some consider regression to be an indication for sentinel lymph node (SLN) biopsy because regression may result in underestimation of the true Breslow thickness. Other data support regression as a favorable prognostic indicator, representing immune system recognition of the primary tumor. This analysis was performed to determine whether regression predicts nodal metastasis, disease-free survival (DFS), or overall survival (OS). Post hoc analysis was performed of a multicenter prospective randomized trial that included patients aged 18 to 70 years with cutaneous melanomas 1 mm or greater Breslow thickness. All patients underwent SLN biopsy; those with tumor-positive SLN underwent completion lymphadenectomy. Kaplan-Meier analysis of survival, univariate analysis, and multivariate analysis were performed. A total of 2220 patients (261 with regression; 1959 without regression) were included in this analysis with a median follow-up of 68 months. Patients with regression were more likely to be male, older than 50 years old, and have lower median Breslow thickness, superficial spreading histologic subtype, and a nonextremity anatomic location (P < 0.05 in all cases). Regression was not significantly associated with Clark level, ulceration, lymphovascular invasion, number of SLNs removed, or SLN metastasis. On multivariate analysis, factors independently predictive of DFS included Breslow thickness, ulceration, and SLN status (P < 0.05 in all cases); the same factors along with age, gender, and anatomic tumor location were significantly associated with OS (P < 0.05 in all cases). Regression was not significantly associated with DFS (risk ratio [RR], 0.94; 95% confidence interval [CI], 0.67-1.27; P = 0.68) or OS (RR, 1.01; 95% CI, 0.76-1.32; P = 0.93). These data suggest that regression is not a significant prognostic factor for patients with cutaneous melanoma and should not be used to guide clinical decision-making for such patients.     

Sentinel Lymph Node Biopsy for Head and Neck Melanomas

Background: Sentinel lymph node (SLN) biopsy for head and neck (H&&N) melanomas may be more technically challenging compared with other locations because of complex lymphatic drainage patterns. This analysis was performed to compare the results of SLN biopsy for H&&N, truncal, and extremity melanomas.Methods: The Sunbelt Melanoma Trial includes patients aged 18 to 70 with melanomas 1.0 mm thick. Statistical comparison was performed by ² or analysis of variance test.Results: A total of 2610 patients were evaluated with a median follow-up of 18 months. The mean number of SLN per nodal basin was 2.8, 2.7, and 2.1 for H&&N, truncal, and extremity melanomas, respectively. Median Clark level, Breslow thickness, and percentage of ulceration were similar between the groups. Peri-parotid SLN was identified in 25% of cases; there were no facial nerve injuries. SLN biopsy for H&&N melanoma had higher false-negative rates at 1.5% (vs. 0.5% for trunk or extremity) but less histologically positive SLN at 15% (vs. 23.4%, and 19.5%; P &< .001) compared with truncal and extremity melanoma. Blue dye was visualized less frequently in SLN of H&&N melanoma patients compared with those with trunk or extremity melanomas.Conclusions: Preoperative lymphoscintigraphy and meticulous intraoperative search for blue/radioactive nodes may improve results in H&&N melanomas.Presented at the Society of Surgical Oncology Annual Meeting, Denver, CO, March 14–17, 2002.