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© 2001 American Society for Clinical Oncology Prognostic Factors Analysis of 17,600 Melanoma Patients: Validation of the American Joint Committee on Cancer Melanoma Staging SystemByFrom the Johns Hopkins Medical Institutions, Baltimore, MD; American Society of Clinical Oncology, Alexandria, VA; University of Alabama at Birmingham, Birmingham, AL; University of Texas, M.D. Anderson Cancer Center, Houston, TX; Sydney Melanoma Unit, University of Sydney, Sydney, New South Wales, Australia; H. Lee Moffit Cancer Center, University of South Florida, Tampa, FL; Istituto Nazionale Tumori, World Health Organization Melanoma Program, Milan, Italy; University of Louisville Medical Center, Louisville, KY; University of Pittsburgh Medical Center, Pittsburgh, PA; Beth Israel Deaconess Medical Center, Boston, MA; University of Washington Medical Center and Fred Hutchinson Cancer Research Center, Seattle, WA; and Memorial Sloan-Kettering Cancer Center, New York, NY. Address reprint requests to Charles M. Balch, MD, American Society of Clinical Oncology, 1900 Duke St, Ste 200, Alexandria, VA 22314; email: balchc{at}asco.org
PURPOSE: The American Joint Committee on Cancer (AJCC) recently proposed major revisions of the tumor-node-metastases (TNM) categories and stage groupings for cutaneous melanoma. Thirteen cancer centers and cancer cooperative groups contributed staging and survival data from a total of 30,450 melanoma patients from their databases in order to validate this staging proposal. PATIENTS AND METHODS: There were 17,600 melanoma patients with complete clinical, pathologic, and follow-up information. Factors predicting melanoma-specific survival rates were analyzed using the Cox proportional hazards regression model. Follow-up survival data for 5 years or longer were available for 73% of the patients.
RESULTS: This analysis demonstrated that (1) in the T category, tumor thickness and ulceration were the most powerful predictors of survival, and the level of invasion had a significant impact only within the subgroup of thin ( CONCLUSION: The results of this evidence-based methodology were incorporated into the AJCC melanoma staging as described in the companion publication.
CLINICAL AND pathologic factors predicting outcome of melanoma patients have been studied for over 30 years. The first multivariate analysis of prognostic factors from a single institution was published in 1978,1,2 and the first multivariate analyses of melanoma from a multi-institutional experience was published in 1981.3 Although a multitude of well-designed single-institution analyses have added to our understanding of prognostic factors in melanoma, few attempts have been made to unify these results into a melanoma staging system to be used in clinical research and clinical practice. In fact, the significant limitations and inaccuracies of the current melanoma staging system have been the subject of recent comprehensive critical evaluations.4-8 Over the past 3 years, the Melanoma Staging Committee of the American Joint Committee on Cancer (AJCC) held a series of meetings to revise the melanoma staging system to incorporate clinical and pathologic factors that more accurately reflected the biology of the disease. This Committee represented the expertise of major melanoma centers in the United States, Europe, and Australia, as well as the major national cancer cooperative groups. The Melanoma Staging Committee used an evidence-based methodology to propose modifications of the tumor-node-metastasis (TNM) criteria and stage groupings, based on their own experience and that published in the medical literature. After three meetings, the Melanoma Committee recommended a major revision of the melanoma staging system, major elements of which have been recently published.9 The proposed melanoma staging system better reflects independent prognostic factors that are used in clinical trials and in reporting the outcomes of various melanoma treatment modalities. Major revisions include (1) melanoma thickness and ulceration to be used in the T category but not the level of invasion (except for T1 melanomas); (2) the number of metastatic lymph nodes to be used in the N category rather than their gross dimensions and the delineation of clinically occult (ie, microscopic) versus clinically apparent (ie, macroscopic) nodal metastases; (3) the site of distant metastases and the presence of elevated serum lactic dehydrogenase (LDH) to be used in the M category; (4) an upstaging of all patients with stage I, II, and III disease when a primary melanoma is ulcerated; (5) a merging of satellite metastases around a primary melanoma and in-transit metastases into a single staging entity that is grouped into stage III disease; and (6) a new convention for defining clinical and pathologic staging so as to take into account the new staging information gained from intraoperative lymphatic mapping and sentinel node biopsy.9,10 In preparation for their final recommendations to the AJCC and International Union Against Cancer TNM committee, members of the Melanoma Staging Committee and additional consultants agreed to an unprecedented collaboration to share prospectively accumulated melanoma outcome data, merged into a single large database for the purpose of validating the proposed revisions to the melanoma staging system. Specifically, we wanted to test (1) that the primary determinants of the TNM categories were those most strongly correlated with melanoma-specific survival rates compared with those known independent prognostic factors published previously and (2) that the proposed stage groupings partitioned patients into cohorts with similar outcome as measured by melanoma-specific survival. The resulting collaborative research project is the largest prognostic factors analysis of melanoma ever conducted. Results from this analysis, as well as input from melanoma clinicians, were used by the AJCC Melanoma Staging Committee to make final adjustments to the melanoma staging system. The final version of the melanoma staging system was formally adopted by both the AJCC Executive Committee and the International Union Against Cancer TNM committee and is described in the companion publication (this issue).10
Thirteen institutions and cooperative study groups agreed to contribute prospectively accumulated melanoma patient data to validate the proposed staging system. A subcommittee of six experienced clinical statisticians participated in this analysis. The data were merged from 13 prospective databases, all of which had quality control measures in place regarding data entry, pathology, and surgery. The data items requested from each participating institution or study group were those known to be independent prognostic factors, were generally available in the prospective databases, and were relevant to validating the proposed staging system. To facilitate the uniformity of data submission, the Statistical Subcommittee of the Melanoma Staging Committee developed a list of required data items and a standardized coding format. Each institution/group submitted its data electronically to the Biostatistics Unit of the Comprehensive Cancer Center at the University of Alabama at Birmingham. The Biostatistics Unit converted the data file from each institution/group into an SAS (Statistical Analysis System Institute, Cary, NC) data set. After quality control checks, all data sets were integrated into a single large AJCC Melanoma Database for statistical analysis and report generation. The AJCC Melanoma Database consisted of a total of 30,450 melanoma patients, of whom 17,600 patients (58%) had information available for all of the factors required for the proposed TNM classification and stage grouping. A breakdown of the various cohorts according to clinical status and initial surgical management is shown in Fig 1. Of the 17,600 patients included in this analysis, 12,837 (73%) had at least 5 years of follow-up information, 8,633 (49%) had at least 10 years of follow-up, and 2,485 (14%) had at least 20 years of follow-up.
We analyzed the baseline characteristics of the entire study population, comparing those patients with complete data, who were included in the final data analysis, with those who were missing some data covariates. The distribution of data covariates was essentially the same for both groups (data not shown), so there was no systematic bias due to incomplete data. Nevertheless, it should be noted that varying referral patterns and clinical trial entry criteria to these tertiary medical institutions and cooperative groups might have skewed the patient distribution overall compared with the general melanoma population. In those circumstances where a smaller number of patients were used in a Cox multivariate analysis because of missing data covariates, the actual sample size used is specifically stated.
Statistical analyses of the AJCC Melanoma Database were based primarily on the methods of survival data analysis. Survival times were calculated from onset of primary melanoma diagnosis and considered censored for patients who were alive at the last follow-up or who died without evidence of melanoma. The survival rates were obtained based on Kaplan-Meier estimates, and the standard errors were calculated using Greenwood’s formula. Melanoma-specific survival curves were generated according to the Kaplan-Meier product-limit method and were compared using the log-rank test. Multivariate analyses of prognostic factors were based on the Cox proportional hazards model. The relative importance of prognostic factors was measured by the
Prognostic factors included in the multivariate analysis of the primary melanoma characteristics were the following: age (coded as deciles 1, 10 to 19 years; 2, 20 to 29 years;. . . 8,
Because it is well-established that tumor thickness is the single most important prognostic feature of primary melanoma, a mathematical model of f(t) = 1 - a·ebt + ct2 was developed to fit the data to describe the relationship between tumor thickness (t) and the 10-year mortality rates (f [t]) for melanoma patients. The coefficients a, b, and c in the model are the parameters to be estimated from the data. Other prognostic factors may have varying degrees of prognostic value within tumor thickness levels in the primary melanoma category. Therefore, further multivariate analysis was performed within each of the following four subgroups of tumor thickness: Tumor burden was defined as whether the nodal metastases were clinically occult (ie, not palpable) and detected by sentinel or elective node dissection (designated operationally as micrometastases) or clinically apparent (ie, palpable) metastases and confirmed by therapeutic lymphadenectomy (designated operationally as macrometastases). Information about the number of distant metastases, any elevations of serum LDH, and the presence or absence of intralymphatic (ie, satellites and in transit) metastases was not available consistently enough to include them in the prognostics factors analysis. Therefore, in patients with distant metastases, only the site of distant metastases was analyzed, along with the same clinical and pathologic features used for patients with stages I, II, and III.
Primary Melanoma Prognostic Features: T Category In a multivariate analysis of 13,581 patients with localized melanoma (either clinically or pathologically), the two most powerful independent characteristics of the primary melanoma among all the prognostic variables analyzed were tumor thickness and ulceration (Table 1). These two factors remained the most significant predictors of outcome even after adjustment in the model for the individual centers contributing the data. Other statistically significant prognostic factors were patient age, site of the primary melanoma, level of invasion, and sex (Table 1).
The multivariate analysis was repeated for the cohort of 4,750 pathologically staged patients without clinical evidence of nodal metastases preoperatively and pathologically staged after sentinel or elective lymphadenectomy. The adjusted risk ratios as well as the ranking of factors by  2 values were similar to those for the combined group of clinically and pathologically staged patients (Table 2). There were the following two major differences: (1) nodal status (ie, presence or absence of metastases) was the most significant predictor, which could not be accounted for in the clinically staged patients; and (2) level of invasion and patient sex were no longer independent predictors of outcome (Table 2).
A nonlinear model was fit to the data to describe the relationship between tumor thickness and mortality. Increasing melanoma thickness was highly correlated with 10-year melanoma-specific mortality (P < .00001) (Fig 2). This model demonstrated no naturally occurring breakpoints that delineated different biologic risks for melanoma-specific mortality. Subsequent analysis of thickness cohorts used the four categories of tumor thickness previously selected by the AJCC Melanoma Staging Committee for clinical convenience and ease of use in the TNM staging system.
The presence or absence of primary tumor ulceration (as documented on histologic sections of each melanoma) was the second most powerful predictor of survival among those independent prognostic factors analyzed. The estimated hazard for those patients with ulceration was two-fold higher than those without ulceration. Although this was clearly a predictive feature independent of tumor thickness, the incidence of melanoma ulceration increased with increasing tumor thickness, ranging from 6% for thin (  1.0 mm) melanomas to 63% for thick (> 4.0 mm) lesions (Fig 3). It was remarkable that the survival for patients with ulcerated melanomas diminished to a level equivalent to that for thicker melanomas that were not ulcerated (Fig 4). In every instance, the survival rate for ulcerated melanomas was virtually the same as for nonulcerated melanomas of the next greater thickness category (Fig 4).
Interaction Among Tumor Thickness, Ulceration, and Level of Invasion One of the controversies that could be addressed with this large database was the interactions among melanoma thickness, level of invasion, and ulceration. This was particularly important for thin melanomas, for which published data had suggested that deeper levels were associated with a poor outcome.4,12-16 To determine the relative predictive strength of these prognostic features within cohorts of tumor thickness, the Cox regression analysis was performed within each of the major thickness subgroups used in the melanoma T categories (Table 3). When comparing level of invasion and ulceration within thickness subgroups, there was a hierarchy of relative predictive strength for thin melanomas that was different from all other thickness groups. Thus, for this specific subgroup of patients, level of invasion was more predictive of survival outcome than tumor ulceration. The opposite was true for all melanomas thicker than 1.0 mm, in which ulceration was clearly the most predictive factor, and the level of invasion ranked below that of patient age and anatomic site of the primary melanoma (Table 3).
The incidence of ulceration was quite low overall for patients with thin melanomas (6%) and was slightly greater for deeper levels of invasion (Table 4). In this patient series, 10-year survival rates for the 5,480 patients with thin melanomas diminished with increasing level of invasion or the presence of ulceration (Table 4). Overall, the 10-year survival rate was significantly lower for thin melanomas with ulceration compared with those without ulceration (76% v 86%; P < .0001). Only 16% of thin melanomas had level IV invasion (< 0.01% with level V); only 8% of these level IV thin melanomas were ulcerated.
Patient Age, Sex, and Anatomic Site of Primary Melanoma Increasing patient age was also an independent prognostic factor with respect to the overall survival rate (Tables 1 and 2) and within each of the thickness subgroups (Table 3). There was a significant and consistent step-down of survival based on increasing decades of life (Table 5). In addition to the patient’s age, sex (males with poorer prognosis than females) and the anatomic site (trunk and head and neck sites with poorer prognosis than extremities) of their primary melanoma correlated significantly with survival, although their 2 values were much lower compared with those for melanoma thickness and ulceration (Tables 1 to 3).
Nodal Metastases Prognostic Features: N Category Complete clinical and histopathologic data were available for 1,201 patients with lymph node metastases. A Cox multivariate analysis demonstrated that the following three factors were most significant (P < .0001): (1) the number of metastatic nodes, (2) the tumor burden at the time of staging (ie, microscopic v macroscopic), and (3) the presence or absence of ulceration of the primary melanoma (Table 6). These three factors remained the most significant predictors of outcome even after adjustment in the model for the individual centers contributing the data. The site of the primary melanoma and the patient’s age had a somewhat lower but statistically significant correlation with survival rates (Table 6).
Number of Metastatic Nodes The actual number of nodal metastases was the most significant predictor of outcome in these patients (Table 6). Melanoma-specific survival (calculated from the onset of primary melanoma diagnosis) decreased significantly with increasing nodal involvement (P < .0001) (Fig 5). The best grouping for the number of metastatic nodes that correlated with 5-year survival rates was one versus two to three versus  four metastatic nodes. All other statistical groupings, including one combining two to four metastatic nodes, did not delineate any greater survival differences among the cohorts analyzed.
Regional Lymph Node Tumor Burden The next most significant prognostic factor was the tumor burden of nodal metastases (microscopic or clinically occult v macroscopic or clinically apparent). The definitions of microscopic and macroscopic used here are proffered as operational definitions; microscopic tumor burden is defined as nodal metastases not detectable by clinical examination but pathologically detected, whereas macroscopic tumor burden refers to clinically evident and pathologically confirmed metastatic deposits. There was a significantly lower survival (calculated from the onset of primary melanoma diagnosis) for those patients who presented with macroscopic (ie, palpable) nodal metastases compared with those with microscopic (ie, nonpalpable) nodal metastases, even after accounting for lead-time bias (P < .0001) (Fig 6). Diminishing 5-year survival rates with increasing tumor burden based on increasing number of metastatic nodes present was observed for all subgroups (P < .0001) (Table 7).
Impact of Primary Tumor Ulceration on Stage III Outcome Ulceration of a primary melanoma was the only primary tumor feature that predicted an adverse outcome in stage III disease (Table 6). This was true even within each of the stage III subgroups examined, including a two-way survival comparison correlating presence or absence of ulceration with the number of metastatic lymph nodes (P < .0001) (Table 8), or a three-way comparison that integrated subgroups according to all three of the most important prognostic factors, ulceration of the primary melanoma, nodal tumor burden, and the number of metastatic nodes (Table 9). Overall, only 49% of all patients with nodal metastases survived 5 years (37% at 10 years), but the range of melanoma-specific survival was large, ranging from 13% at 5 years for patients with the highest risk combination of factors to 69% at 5 years for the lowest risk combination of predictive factors (Table 9).
Distant Metastases Prognostic Features: M Category The prognostic influence of different distant metastatic sites was analyzed in 1,158 stage IV patients using various combinations of sites of metastases. The most significant differences were noted when visceral versus nonvisceral sites (ie, skin, subcutaneous, and distant lymph nodes) were compared. Although significant 1-year survival differences were observed when patients with lung metastases were compared with those patients with metastases in other visceral sites (P < .0001), no differences were noted when 2-year survival data were compared (Fig 7).
The results of these analyses showed (1) tumor thickness and ulceration were the most powerful predictors of survival in patients with localized melanomas (stages I and II), whereas level of invasion had a significant impact only within the subgroup of thin melanomas; (2) the number of metastatic nodes, tumor burden (microscopic v macroscopic), and presence or absence of melanoma ulceration were the most powerful predictors of survival in patients with nodal metastases (stage III); and (3) the anatomic site of distant metastases was the most significant predictor of survival in patients with distant metastases (stage IV). The prognostic factors compared in this analysis were not intended to include all putative prognostic features of melanoma but were limited to those known from previous studies to be the most significant and reproducible, and were amenable to be used in a staging system. We did not have sufficiently available data to include two factors that were included in the proposed melanoma staging criteria: intralymphatic (ie, in-transit and satellite) metastases and the serum LDH levels (normal or elevated). The measured tumor thickness was the single most powerful of all prognostic features in patients with localized melanoma, both in this analysis as well as in those previously published.1,3,17-31 Because there were no discernable thresholds or breakpoints as tumor thickness increased, the Melanoma Committee’s recommendations to use even integers of melanoma thickness for the T category is justified. The level of invasion does not reflect prognosis as accurately as tumor thickness for reasons that have been discussed in previous publications.1,6,9,32-35 Nevertheless, level of invasion does provide additional prognostic discrimination in the specific subgroup of thin (ie, T1) melanomas.4,12-16,36 Melanoma ulceration was identified in this analysis as the single most important feature of a primary melanoma (from among those studied) that influenced mortality rates in both localized and regional disease, as previous studies have shown.1,5,13,18,21,26,29,31,37-47 The only exception to this observation was for the thin melanomas, in which the incidence of ulceration was low overall (6%) even for deeper levels of invasion. The multivariate analysis thus demonstrated that a deep level of invasion (ie, IV or V) is not a surrogate for ulceration but an independent factor that eclipses the predictive value for ulceration in this specific subgroup of patients. This relationship was not true for all melanomas thicker than 1.0 mm, because the level of invasion was no longer a significant predictor of survival outcome relative to ulceration (presence or absence), increasing age, or the anatomic site of the primary melanoma (trunk, head and neck v extremity). From a staging perspective, the interpretation of melanoma ulceration is one of the most reproducible of all the major histopathologic features.35,48-50 Most ulcerated melanomas do not have any ulcer crater per se but rather an absent epidermis above the tumor. The biologic events associated with invasion of a primary melanoma through the overlying epidermis rather than simply displacing it upward is clearly associated with a greater capacity to metastasize, compared with its nonulcerated counterpart of equivalent thickness. The metastatic capacity of an ulcerated melanoma is thus similar to that of cancers categorized as poorly differentiated or locally advanced primary tumors. Indeed, the survival rates for thick, ulcerated melanomas (ie, T4b) without nodal metastases are actually worse than those for some substages of nodal metastases.10 Melanoma ulceration correlates with increased mitotic rate within a primary melanoma, more evidence that this factor is associated with increased metastatic behavior.51 The patient’s age is confirmed as an independent prognostic variable, perhaps representing a surrogate for declining host defense mechanism associated with advancing age. Even though older patients have thicker melanomas and a higher incidence of ulcerated melanomas, their age is an independent adverse prognostic factor even after adjusting for these other factors in multivariate analyses.5,17,31,40,52,53 In this study, there was a consistent and incremental decline in both 5- and 10-year survival rates with each 10-year increase of age (Table 5). Numerous other studies have demonstrated that older melanoma patients have a lower survival rate, especially those over 60 years of age.5,17,31,40,46,53-56 This has included a number of multi-institutional clinical trials involving various stages of melanoma, age groups, and treatment effects.31,40,57-59 Indeed, national cancer statistics demonstrate that melanoma had the second highest mortality rate increases among Americans 65 years of age or older (from 1973 to 1997), especially for men.60 The number of metastatic nodes (independent of tumor burden or size) was the most significant risk factor of stage III patients from among those analyzed. These findings are consistent with much of the published experience, especially the correlation of decreasing survival with increasing number of metastatic nodes.6,61-70 The second most significant risk factor was tumor burden, as reflected by whether the nodal metastases were clinically occult (and identified by either sentinel or elective node dissection for clinical N0 patients) or clinically palpable nodal metastases (ie, clinical N+ disease). The third most significant feature is the presence or absence of melanoma ulceration, implying that nodal metastases arising from an ulcerated primary melanoma are associated with a greater capacity to metastasize to distant sites compared with nodal metastases arising from nonulcerated melanomas. The integration of these three factors in survival analysis reveals a marked diversity in the natural history of stage III melanoma. This is demonstrated by the more than five-fold difference in 5-year survival rates for defined substages that ranged from 69% for patients with nonulcerated melanomas (regardless of thickness) who had a single clinically occult nodal metastasis (detected by sentinel or elective lymphadenectomy) to a low of 13% for patients with ulcerated melanomas (regardless of thickness) with four or more clinically apparent nodal metastases (detected by therapeutic lymphadenectomy). It is sometimes assumed that stage III patients are at a particularly high risk for distant metastases and, therefore, may be offered intensive forms of systemic therapy (eg, biochemotherapy). However, this analysis, as well as previously published experiences, clearly demonstrated that stage III melanoma patients are a heterogeneous group with respect to their risk for distant metastases and melanoma-specific mortality.14,57,58,61-67,69,71-73 Understanding these differences in clinical outcome is important not only in the design and analysis of melanoma clinical trials but also in calibrating therapeutic intensity to metastatic risk. Once a patient had progressed to stage IV disease, survival rates were measured in months rather than in years. Indeed, there were no prognostic features in this analysis that substantially separated survival rates by more than a few months. The only significant prognostic feature identified in this analysis was the site of distant metastasis. Others have reported similar results with only a minority of stage IV patients living beyond 1 year.59,74-78 As in previous publications, the greatest difference in survival exists between patients with melanoma metastases in visceral sites compared with those with metastases in nonvisceral sites (ie, skin, subcutaneous, and distant lymph nodes). An analysis of various combinations of visceral sites showed only that patients with the lung as the only site of visceral metastasis had a better survival time compared with other visceral sites, but this effect was transient, being significantly different when comparing 1-year survival rates but not significant beyond that timeframe. Some institutions and cooperative groups have also reported that patients with lung metastases have a somewhat better prognosis compared with those with metastases to other visceral sites.59,74,78 This analysis did not have access to accurate or complete information about the number of metastases (which would depend on the type of diagnostic tests performed) or the levels of LDH. These features have been shown to have independent significance in other series of stage IV melanoma patients.75,76,79-81 This collaborative prognostic factors analysis demonstrates that database integration can assimilate large and complex data sets to examine prognosis and survival outcome. It should be noted, however, as a result of varying referral patterns and patient entry criteria for melanoma clinical trials the survival rates of the patients in this study might not exactly reflect those of the general melanoma population. Nevertheless, the major prognostic factors identified and their rankings were consistent among institutions and cooperative groups even though there were slight differences among the contributing centers of survival rates within some cohorts (data not shown). These prognostic factors can, therefore, identify distinct subgroups of melanoma patients with respect to metastatic risk and survival rates. This prognostic factors analysis, the largest ever conducted, was invaluable to the AJCC Melanoma Staging Committee. A preliminary version of this analysis helped determine the initial TNM classifications and stage grouping as previously published,9 while the final data analysis was the focal point of an evidence-based decision-making process used to complete the revised melanoma-staging product described in the companion publication.10
The following institutions, organizations, and cancer cooperative groups generously contributed their patient database for the purposes of validating the melanoma staging proposal. John F. Thompson, MD, Marjorie Colman, BSc, Sydney Melanoma Unit, Royal Prince Alfred Hospital, Sydney, Australia; Jeffrey E. Gershenwald, MD, Merrick I. Ross, MD, University of Texas, M.D. Anderson Cancer Center, Houston, TX; Daniel G. Coit, MD, Memorial Sloan-Kettering Cancer Center, New York, NY; Marshall Urist, MD, Seng-Jaw Soong, PhD, Rene Desmond, PhD, University of Alabama at Birmingham Cancer Center, Birmingham, AL; Douglas S. Reintgen, MD, Gary Lyman, MD, University of South Florida, Moffitt Cancer Center, Tampa, FL; Natale Cascinelli, MD, Aberto Morabito, PhD, National Tumor Institute, Milan, Italy; David Byrd, MD, University of Washington Cancer Center, Seattle, WA; John M. Kirkwood, MD, Michael B. Atkins, MD, Eastern Cooperative Oncology Group, Pittsburgh, PA, and Boston, MA; John A. Thompson, MD, Ping-Yu Liu, PhD, Southwest Oncology Group, Seattle, WA; Charles M. Balch, MD, Seng-Jaw Soong, PhD, Renee Desmond, PhD, Intergroup Melanoma Surgical Trial, Birmingham, AL, and Baltimore, MD; Natale Cascinelli, MD, Aberto Morabito, PhD, World Health Organization Melanoma Program, Milan, Italy; Kelly M. McMasters, MD, Patricia B. Cerrito, PhD, Sunbelt Melanoma Group, Louisville, KY.
Supported in part by an unrestricted educational grant from Schering Pharmaceutical, Kenilworth, NJ
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Copyright © 2001 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
