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10.1245/s10434-006-9319-y
Annals of Surgical Oncology 14:1596-1603 (2007)
© 2007 Society of Surgical Oncology
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Original Article

Regional Nodal Metastatic Disease Is the Strongest Predictor of Survival in Patients with Thin Vertical Growth Phase Melanomas: A Case for SLN Staging Biopsy in These Patients

Giorgos C. Karakousis, MD1, Phyllis A. Gimotty, PhD2,6, Brian J. Czerniecki, MD, PhD1,6, David E. Elder, MB, ChB3,6, Rosalie Elenitsas, MD4,6, Michael E. Ming, MD, MSCE4,6, Douglas L. Fraker, MD1,6, DuPont Guerry, MD5,6 and Francis R. Spitz, MD1,6,7

1 Department of Surgery, Hospital of the University of Pennsylvania, 4th Floor Silverstein Building, 3400 Spruce Street, Philadelphia, PA 19104, USA
2 Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104, USA
3 Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
4 Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
5 Department of Medicine, Division of Hematology and Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
6 Pigmented Lesion Group and Melanoma Program, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA
7 Veterans Administration Hospital, Philadelphia, PA, USA

Correspondence: Address correspondence and reprint requests to: Francis R. Spitz, MD; E-mail: francis.spitz{at}uphs.upenn.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: The benefit of sentinel lymph node (SLN) biopsy for patients with thin (≤ 1.0 mm) melanomas, even for prognostic value, is controversial. This may partly result from the relatively small number and short follow-up of SLN-positive patients in this group. Previously, we have shown that clinical regional nodal metastatic disease (RNMD) serves as a good surrogate for SLN positivity. Here, we use RNMD as a validated surrogate for SLN positivity and examine its prognostic value in a large pre-SLN group of patients with thin vertical growth phase (VGP) lesions who would today commonly be offered SLN biopsy in our practice.

Methods: Between 1972 and 1991, 472 patients with thin VGP melanomas with at least 10 years’ follow-up were eligible for the study. Kaplan-Meier survival curves were computed for patients with and without RNMD. A multivariate Cox model and classification tree analysis were used to evaluate clinical and histopathologic predictors of survival.

Results: Sixty-seven patients (14.2%) developed recurrence, 53.7% of whom developed RNMD. Forty-five patients (9.5%) experienced melanoma-related deaths (MRD). The most statistically significant predictor of MRD was RNMD (hazard ratio [HR] 13.5, P < .0001). Thickness (HR 10.5, P = .004), axial location (HR 4.6, P = .001), and age >60 years (HR 2.7, P = .005) additionally were independently associated with an increased risk of MRD. RNMD patients demonstrated a 44.4% 10-year disease-specific mortality.

Conclusions: RNMD was the most statistically significant factor associated with MRD in patients with thin VGP lesions. This supports the prognostic use of SLN biopsy in this group, recognizing that additional factors, including thickness, axial location, and older age were independently associated with a worse survival outcome.

Key Words: Thin melanomas • Regional nodal disease • SLN biopsy • Predictors of survival


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Since its introduction by Morton and colleagues in the early 1990s,1 lymphatic mapping and sentinel lymph node (LM/SLN) biopsy has played an important role in the early detection of microscopic disease in the regional nodal basins of patients with malignant melanoma. With a false-negative rate reported as low as <1%–2%1 when the combination of lymphoscintigraphy and blue dye is used (which has been validated by several studies2,3), the technique has become firmly established in the management of patients with intermediate thickness melanomas. Despite its high diagnostic accuracy and relatively low morbidity as reported by several investigators (5%–10%),4,5 The wide use of SLN biopsy in patients with melanoma of varying thickness has met with controversy. In particular, its value in the management of patients with lesions ≤ 1.0 mm, which represent nearly 65% of all melanoma lesions,6 has been the subject of ongoing debate.

One issue is the relatively low incidence of SLN positivity in this group of patients, ranging from 2% to 5%.7–9 This has led several to question the practicality and cost-effectiveness10 of this approach in this population. This particular concern can perhaps be addressed through the careful selection of a subset of patients with thin melanomas wherein the incidence of SLN positivity is increased. We have previously shown in a group of 181 patients with thin melanomas undergoing SLN biopsy that the incidence of SLN positivity among those with mitogenic lesions ≥ .76 mm was 12.3%.11 Others have also identified mitotic rate12 and/or other clinical and histopathologic factors such as vertical growth phase8,13 (VGP), age,12,14 or tumor thickness12,15,16 to be associated with SLN positivity. These studies offer the prospect of identification of a select group of patients with thin melanomas whose incidence of SLN positivity at least approaches if not compares with that of patients with intermediate thickness lesions for which SLN biopsy is routinely performed.

A second issue which contributes to the controversy of SLN biopsy use in patients with thin melanomas stems from the exceedingly good prognosis of patients in this population. The 5-year survival of patients with thin melanomas treated with wide excision alone has been reported to be upwards of 95%.17 This has led some authors to express uncertainty even as to the prognostic value of this technique for this group of patients.5,18

Although thin melanomas are generally associated with good outcomes, these lesions are not without an appreciable incidence of recurrent disease, reported as high as 6.5% over a 10-year period.19 Clearly, the length of follow-up affects the study results of the natural progression of disease in this patient population where time to recurrence may be on the order of several years. The median time to recurrence among patients with thin melanomas who died from melanoma was reported to be over 4 years from a large database of the New South Wales Central Cancer Registry and the Sidney Melanoma Unit.20 We believe that conclusions drawn from studies of SLN patients concerning the prognostic use of SLN biopsy in patients with thin melanomas may, in part, be statistically limited by relatively small numbers and short follow-up. We have previously demonstrated in a large pre–SLN era population of patients with thin melanomas that regional nodal disease (RNMD) occurred at an incidence similar to that of SLN positivity and that factors predictive of RNMD similarly were predictive of SLN positivity.21 This suggests that RNMD may serve as a valid surrogate marker for microscopic nodal disease. Here we examine the prognostic effect of RNMD, a surrogate for SLN positivity, in a large pre–SLN era cohort of patients with thin VGP lesions who were followed for a minimum of 10 years.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patients
There were 472 patients with ≤ 1.0 mm VGP melanomas who were study eligible in the period between 1972 and 1991. VGP was noted to be present in lesions with aggregates of tumor in the dermis larger than in the epidermis and/or by the presence of any dermal tumor cell mitoses. Patient information was compiled from the Pigmented Lesion Clinic database and clinic charts at the University of Pennsylvania; we followed protocol guidelines approved by that institution’s Institutional Review Board. Specific eligibility criteria for patients have been described in detail elsewhere.19,21 Of note, patients with (n = 22) and without (n = 448) prophylactic lymphadenectomy were included in the analyses. All patients included for study had a minimum of 10 years of follow-up from the time of definitive excision of their primary lesion unless this follow-up period was interrupted by a melanoma-related death.

Prognostic Variables
A total of 10 tumor-specific or patient variables were evaluated for statistical analyses. Specifically, three clinical variables (age, sex, and anatomic location) and six histopathologic variables of the primary lesion (thickness, tumor infiltrating lymphocytes, mitotic rate, Clark’s level, ulceration, regression) were included for purposes of the study. Additionally, the presence or absence of RNMD (diagnosed either pathologically or clinically) was analyzed as a time-dependent prognostic factor. Definitions of these variables were in accordance with those commonly used and have been discussed in detail elsewhere.21 Axial lesions included those of the head and neck, palms and soles, and the trunk, as well as subungual lesions. Mitotic rate (MR) was initially measured in number of mitoses per square millimeter and converted to a binary variable, with categories MR = 0 or MR > 0. All variables were ultimately treated in a binary fashion as listed in Table 1Go, except for tumor thickness, which was considered as a continuous variable (ranging from 0 to 1 mm). RNMD was defined as metastatic disease either pathologically confirmed or clinically evident in the immediate regional nodal basin draining the primary lesion. Most RNMD patients had developed clinically evident disease in the regional nodal basin after wide excision of their melanoma. These patients all underwent regional lymph node dissection. The remainder of RNMD patients fell into one of two categories: those with pathologically detected metastatic disease in the regional nodal basin on prophylactic lymphadenectomy at or around the time of definitive wide excision of their primary (two patients), and those who developed recurrent nonregional disease with concurrent (within a 6-month period) involvement of the regional nodal basin (seven patients).


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  		TABLE 1. Ten-year survival rates by univariate and multivariate Cox modelsa
 
Statistical Methods
Kaplan-Meier analysis was used to estimate all survival curves for the time from definitive surgical treatment to melanoma-specific death. Patients who died of a cause unrelated to melanoma were censored. The log rank test was used to evaluate differences between survival curves for those positive and negative for RNMD, a variable that was assumed to be a surrogate for the outcome of a SLN biopsy, and thus was included as a prognostic factor that was known at the time the tumor was diagnosed. The multivariate Cox regression analyses were used to identify statistically significant associations between the prognostic variables and the time of disease-specific mortality. A reduced multivariate analysis was developed by stepwise successive elimination of variables that were found to be not statistically significant in the full multivariate analysis. A classification tree was developed that used a classification and regression tree analysis (CART) on the basis of a recursive partitioning algorithm (Salford Systems, 1995, San Diego, CA).22 The statistical analyses were performed by SAS/STAT software, version 9.1 (SAS Institute, Cary, NC).15


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Incidence of Metastases and Disease-Specific Mortality
The characteristics of the 472 study patients with thin VGP melanomas are presented in Table 1Go. Twenty-five percent of these patients were American Joint Committee on Cancer (AJCC) stage IB (Clark level IV/V or ulcerated). Of all patients, 67 (14.2%) developed recurrent disease or died of their melanoma; 5 of these 67 patients were among the 22 patients who had a prophylactic lymph node dissection. In addition, included among the 67 patients, there were three local recurrences (.6%). Thirty-six patients (7.6%) had evidence of RNMD which compromised most patients (53.7%) with recurrent disease. There were 45 melanoma-related deaths in the study cohort. Of these patients, 21 (46.7%) had either clinically evident or pathologically confirmed RNMD. The mean and median survival times for those who died of melanoma were 5.2 and 4.8 years respectively; the mean and median follow up times for patients alive at last follow up were 17.4 and 16.7 years respectively (a minimum 10 years follow-up).

Prognostic Variables Associated with Disease-Specific Mortality
Of the 10 clinical and histopathological variables evaluated, RNMD, tumor thickness, anatomic location, and age were statistically significantly associated with disease-specific mortality in the final multivariate model (Table 1Go). Specifically, patients with thicker lesions, those with axial lesions, and those ≥ 60 years of age were found to have a statistically significantly worse survival outcome among patients with thin VGP lesions. The presence of RNMD (hazard ratio [HR] 13.5, P < .0001) had the strongest association with disease-specific mortality. The thinnest lesion with an associated melanoma-related death was .32 mm. There were 12 patients who had melanomas thinner than .32 mm; none of these patients developed metastases or melanoma-related deaths. Although most patients with melanoma-related death had axial lesions (86%), one-third of patients (33%) were ≥ 60 years of age. Nearly half (44.4%) of patients with RNMD had a melanoma-related death within 10 years of diagnosis. Of note, when patients who underwent prophylactic lymphadenectomy were excluded, the variables significantly associated with disease-specific mortality by multivariate analysis remained RNMD (HR = 14.1, P < .001), tumor thickness (HR = 10, P = .007), axial anatomic location (HR = 6.2, P = .001), and patient age ≥ 60 years (HR = 2.8, P < .006).

Survival Outcome of Patients with and without Regional Nodal Disease
The survival distributions of patients with and without RNMD are presented in Fig. 1Go. Patients with RNMD had a statistically significantly worse survival outcome as compared with those without evidence of RNMD (P < .0001). The median survival times for patients in the group of patients who had a metastasis was 6.7 years. For patients with RNMD, the mean and median survival time was 11.6 years.


Figure 1
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  		FIG. 1. Survival distribution of patients with and without regional nodal metastatic disease (RNMD). Deaths reflect disease-specific mortality.

 
Classification and Regression Tree Analysis
Patients were further stratified into prognostic risk groups for 10-year disease-specific mortality by CART analysis (Fig. 2Go). The first partition selected by the computer algorithm was on the basis of the presence or absence of RNMD. Although patients with evidence of RNMD displayed a 44.4% 10-year disease-specific mortality, those without RNMD had a less than 5% incidence of melanoma-related deaths (MRD). Interestingly, among patients without RNMD, those with mitogenic lesions had a 10-year MRD rate of 9.1%. This rate increased to 14.8% for non-RNMD patients with mitogenic lesions that were axial in location. In contrast, the incidence of MRD was exceedingly small in non-RNMD patients with nonmitogenic lesions (.8%).


Figure 2
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  		FIG. 2. Classification and regression tree (CART) analysis for the development of risk groups for 10-year disease-specific mortality in patients with thin vertical growth phase (VGP) melanomas. RNMD, regional nodal metastatic disease.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
An estimated nearly 60,000 cases of melanoma were diagnosed in the United States last year;23 most were lesions ≤ 1.0 mm in size. Despite an increasing frequency of these lesions, there is still considerable discord in the staging work-up of these patients. Specifically, which, if any, patients with thin melanomas should undergo SLN biopsy is a matter of debate. Two questions which immediately arise are: Is there a subset of these patients in which the incidence of SLN positivity is high enough to justify this relatively low morbidity, but not benign procedure? And what, if any, is the prognostic or therapeutic benefit of this procedure in this group?

Several investigators have shown associations between various clinical or histopathological factors and SLN positivity. These variables have included age,12,14,24 Clark’s level14 and ulceration,14,24 mitotic rate,12 and VGP,8 to list a few. By using these variables in CART analysis, one can theoretically generate prognostic risk groups to identify patients with increased likelihood of SLN positivity. The response to the first question above seems, then, to be yes. We have demonstrated by CART analysis an incidence (12.3%) of SLN positivity among a group of patients with thin melanomas,11 a rate that has been observed by others in a series of patients with 1–2-mm intermediate thickness lesions (12.9%).12 However, the identification of statistically significant independent clinical and/or histopathologic variables predictive of SLN positivity in patients with thin melanomas has not been universally demonstrated. In a study of 223 patients with thin melanoma who underwent SLN biopsy at Memorial Sloan-Kettering Cancer Center,18 investigation of at least 10 prognostic factors failed to reveal any independent predictor of SLN positivity. The large variability in these studies results can at least partly be attributed to the statistical limitations imposed by the fairly small number of patients with thin melanoma who are SLN positive. In reviewing several studies in the literature, the absolute number of SLN positive patients with thin melanomas ranges from 4 to 14.7,11,12,18,25,26

The relatively small patient numbers, compounded by relatively short follow-up periods, likely contributes to the statistically significant amount of variability that exists in the findings of studies examining the prognostic significance of SLN positivity in patients with thin melanomas. Although the presence of microscopic metastatic disease in lymph nodes was deemed a strong predictor of disease-specific mortality in the 2002 AJCC staging system, which evaluated data from 17,600 patients,27 it has not been consistently shown to be a statistically significant predictor of survival in studies with patients with thin melanomas. With a median follow-up of 25 and 45 months for SLN-positive and SLN-negative patients, respectively, with primary lesions ≤ 1.5 mm, Bleicher et al.7 reported a statistically significantly decreased disease-free survival in patients in the SLN-positive group of patients as compared with those in the latter. This result was corroborated by Ranieri et al.28 who demonstrated that SLN positivity was associated with poorer survival outcome in a series of 184 patients (12 SLN-positive patients) with thin melanomas who underwent SLN biopsy. However, these findings were not demonstrated by Agnese et al.,10 who showed a slight, but not statistically significant, survival advantage of SLN-positive patients over SLN-negative patients in lesions <1 mm. Likewise, Wong et al.18 demonstrated no consistent association in patients with lesions ≤ 1.0 mm between SLN positivity and recurrent disease or disease-specific mortality. Of 223 patients with thin melanoma in their series, 6 patients developed recurrent disease with a median follow-up of 25 months; 1 of these 6 had a positive SLN, and none of the 3 with melanoma related death was SLN positive. In a study of 60 patients with a mean follow-up of 32 months, Blumenthal et al.5 reported a slight but not statistically significant survival advantage of stage IB and II patients who were SLN negative (90%) as compared with those who were SLN positive (82%).

In the absence of data from large prospective multicenter trials currently underway, addressing the prognostic value of SLN biopsy in patients with thin melanomas is challenging. The relatively recent application of LM/SLN to patients with thin lesions poses limitations on retrospective studies with regards to sample size and longitudinal follow-up. Thin melanomas have been well recognized to have a seemingly indolent course, with median time to recurrence being reported as high as 49.8 months and median time to death as high as 65.9 months.20 The long disease free-survival period in patients with thin melanomas poses potential limitations on SLN studies with relatively short follow-up. Moreover, determination of any prognostic use of SLN biopsy in this population is confounded by uncertainty as to how, if at all, this technique affects the natural progression of disease.

In this study, we investigate the prognostic role of RNMD, used as a surrogate for SLN biopsy outcome, in a large cohort of patients with thin VGP melanomas in the pre–SLN era. We have previously reported on this population,21 demonstrating that RNMD seems to be a good surrogate marker for SLN positivity, having a similar incidence and association with similar prognostic factors to the latter. Study of this pre-SLN patient population offers several potential advantages. It affords the possibility of long term longitudinal follow-up on a relatively large number of patients. Additionally, evaluation of RNMD in all patients with thin melanomas theoretically avoids the potential selection bias that may occur by study of a select group of patients thin melanomas undergoing SLN biopsy. Finally, in addressing the prognostic value of micrometastatic disease in patients with thin melanomas, study of RNMD as a surrogate avoids the potential and uncertain effect that SLN biopsy itself may have on the therapeutic aspect of the disease process.

In the present study, we found RNMD to be have the highest association with disease-specific mortality in patients with thin VGP lesions. Patients with RNMD had a statistically significantly worse survival outcome compared with those without RNMD. Interestingly, in the group of patients without evidence of RNMD, there were still some subgroups with a high incidence of disease-specific mortality. In particular, non-RNMD patients with mitogenic axial lesions who were 60 years or older had a 10-year disease-specific mortality of 37.5% (data not presented). This 10-year survival rate is close to the rate observed in the RNMD group. If one considers non-RNMD patients to likely have been SLN-negative should these patients have undergone SLN biopsy, this suggests that there may be small subgroups of SLN-negative patients with high risk for disease-specific mortality. These subgroups may potentially contribute to the challenges in detecting differences in survival outcome between SLN-positive and SLN-negative patients if they are selected for in nonrandomized studies. Moreover, the unclear therapeutic benefit of the SLN biopsy technique itself and specifically whether there is an asymmetric effect on survival between the SLN-positive and SLN-negative populations, make the results of studies questioning the prognostic value of the technique more difficult to interpret. Our study theoretically affords one a window to investigate a prognostic role for SLN biopsy without necessarily addressing the question of a therapeutic role in this population.

In our study, we did not find Clark’s level or ulceration to be independently predictive of a poor survival outcome as was noted in the validation study for the 2002 AJCC staging system.29 In fact, the rates of melanoma related death among our patients with level II/III lesions was 5.1% and 44% for those without and with RNMD respectively, which were almost the same rates as those with level IV lesions. Our lack of identifying ulceration to be statistically significant by multivariate analysis may be the result of the relatively small number of patients with this histopathologic feature (n = 12, 2.5%). Additionally, our study only considered patients with VGP lesions (in whom the metastasis rate was 14.2%) rather than all patients with thin lesions. In congruence with the study by Leiter et al.,30 which also considered data from all patients with thin melanomas from the German-based Central Malignant Melanoma Registry, we found in a multivariable analysis increasing tumor thickness, axial location, and older age to be independently predictive of disease specific mortality in patients with thin melanomas. Additionally, in a CART analysis, we found mitogenicity (i.e., the presence of any mitoses in the dermal component of the melanoma) to be also predictive of mortality in patients without RNMD.

Most patients (53.7%) with thin VGP lesions who developed metastases developed disease in a regional nodal basin. RNMD had the strongest association with melanoma-related death in this population, with patients in this group displaying a 46.7% disease-specific mortality in the study period. Thickness, axial location, and older age, in order of decreasing hazard ratio, were also found to be statistically significant independent prognostic factors of disease-related mortality. We have previously shown RNMD to be a good surrogate marker for SLN positivity in patients with thin melanomas. In this context, our data support the prognostic value of RNMD and therefore potentially SLN positivity in patients with thin VGP lesions.


   ACKNOWLEDGMENTS
 
Supported in part by the SPORE on Skin Cancer (CA-093372, M. Herlyn, PI). We thank all of the patients who have been seen at the Pigmented Lesion Clinic (PLC) and who have given their consent for use of their data for research studies, and we also thank the investigators (Drs. W. H. Clark Jr. [deceased], E. E. Bondi, L. P. Bucky, L. S. Callans, B. Chang, K. T. Flaherty, A. C. Halpern, R. Hamilton, D. Hershock, D. D. Larossa, S. R. Lessin, D. Low, P. Van Belle, and J. Wolfe) and staff (R. Holmes, S. Hotz, N. Lowden, I. Matozzo, M. Price, M. Synnestvedt, and J. Thompson) of the PLC for their contributions over the last three decades to the Melanoma Core Database, on which this report is based.

Received for publication June 27, 2006. Accepted for publication November 15, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Morton DL, Wen DR, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 1992; 127:392–9.[Abstract/Free Full Text]
  2. Reintgen D, Cruse CW, Wells K, et al. The orderly progression of melanoma nodal metastases. Ann Surg 1994; 220:759–67.[Medline]
  3. Thompson JF, McCarthy WH, Bosch CM, et al. Sentinel lymph node status as an indicator of the presence of metastatic melanoma in regional lymph nodes. Melanoma Res 1995; 5:255–60.[Medline]
  4. Morton DL, Cochran AJ, Thompson JF, et al. Sentinel node biopsy for early-stage melanoma: accuracy and morbidity in MSLT-I, an international multicenter trial. Ann Surg 2005; 242:302–11; discussion 311–3.[Medline]
  5. Blumenthal R, Banic A, Brand CU, et al. Morbidity and outcome after sentinel lymph node dissection in patients with early-stage malignant cutaneous melanoma. Swiss Surg 2002; 8:209–14.[CrossRef][Medline]
  6. Surveillance Epidemiology and End Results (SEER) Program. SEER 1973–2000 Public-Use Data. Available at: http://www.seer.cancer.gov/publicdata/. Accessed December 18, 2006.
  7. Bleicher RJ, Essner R, Foshag LJ, et al. Role of sentinel lymphadenectomy in thin invasive cutaneous melanomas. J Clin Oncol 2003; 21:1326–31.[Abstract/Free Full Text]
  8. Bedrosian I, Faries MB, Guerry D, et al. Incidence of sentinel node metastasis in patients with thin primary melanoma (< or = 1 mm) with vertical growth phase. Ann Surg Oncol 2000; 7:262–7.[Abstract]
  9. Gershenwald JE, Thompson W, Mansfield PF, et al. Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 612 stage I or II melanoma patients. J Clin Oncol 1999; 17:976–83.[Abstract/Free Full Text]
  10. Agnese DM, Abdessalam SF, Burak WE Jr, et al. Cost-effectiveness of sentinel lymph node biopsy in thin melanomas. Surgery 2003; 134:542–7; discussion 547–8.[CrossRef][Medline]
  11. Kesmodel SB, Karakousis GC, Botbyl JD, et al. Mitotic rate as a predictor of sentinel lymph node positivity in patients with thin melanomas. Ann Surg Oncol 2005; 12:449–58.[Abstract/Free Full Text]
  12. Sondak VK, Taylor JM, Sabel MS, et al. Mitotic rate and younger age are predictors of sentinel lymph node positivity: lessons learned from the generation of a probabilistic model. Ann Surg Oncol 2004; 11:247–58.[Abstract/Free Full Text]
  13. Oliveira Filho RS, Ferreira LM, Biasi LJ, et al. Vertical growth phase and positive sentinel node in thin melanoma. Braz J Med Biol Res 2003; 36:347–50.[Medline]
  14. McMasters KM, Wong SL, Edwards MJ, et al. Factors that predict the presence of sentinel lymph node metastasis in patients with melanoma. Surgery 2001; 130:151–6.[CrossRef][Medline]
  15. Wagner JD, Gordon MS, Chuang TY, et al. Predicting sentinel and residual lymph node basin disease after sentinel lymph node biopsy for melanoma. Cancer 2000; 89:453–62.[CrossRef][Medline]
  16. Nguyen CL, McClay EF, Cole DJ, et al. Melanoma thickness and histology predict sentinel lymph node status. Am J Surg 2001; 181:8–11.[CrossRef][Medline]
  17. Reintgen D, Balch CM, Kirkwood J, Ross M. Recent advances in the care of the patient with malignant melanoma. Ann Surg 1997; 225:1–14.[CrossRef][Medline]
  18. Wong SL, Brady MS, Busam KJ, Coit DG. Results of sentinel lymph node biopsy in patients with thin melanoma. Ann Surg Oncol 2006; 13:302–9.[Abstract/Free Full Text]
  19. Gimotty PA, Guerry D, Ming ME, et al. Thin primary cutaneous malignant melanoma: a prognostic tree for 10-year metastasis is more accurate than American Joint Committee on Cancer staging. J Clin Oncol 2004; 22:3668–76.[Abstract/Free Full Text]
  20. McKinnon JG, Yu XQ, McCarthy WH, Thompson JF. Prognosis for patients with thin cutaneous melanoma: long-term survival data from New South Wales Central Cancer Registry and the Sydney Melanoma Unit. Cancer 2003; 98:1223–31.[CrossRef][Medline]
  21. Karakousis GC, Gimotty PA, Botbyl JD, et al. Predictors of regional nodal disease in patients with thin melanomas. Ann Surg Oncol 2006; 13:533–41.[Abstract/Free Full Text]
  22. CP SD CART: Tree-Structured Non-Parametric Data Analysis San Diego: Salford Systems; 1995.
  23. Jemal A, Murray T, Ward E, et al. Cancer statistics, 2005. CA Cancer J Clin 2005; 55:10–30.[Abstract/Free Full Text]
  24. Rousseau DL Jr, Ross MI, Johnson MM, et al. Revised American Joint Committee on Cancer staging criteria accurately predict sentinel lymph node positivity in clinically node-negative melanoma patients. Ann Surg Oncol 2003; 10:569–74.[Abstract/Free Full Text]
  25. Stitzenberg KB, Groben PA, Stern SL, et al. Indications for lymphatic mapping and sentinel lymphadenectomy in patients with thin melanoma (Breslow thickness < or = 1.0 mm). Ann Surg Oncol 2004; 11:900–6.[Abstract/Free Full Text]
  26. Olah J, Gyulai R, Korom I, et al. Tumour regression predicts higher risk of sentinel node involvement in thin cutaneous melanomas. Br J Dermatol 2003; 149:662–3.[CrossRef][Medline]
  27. Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 2001; 19:3635–48.[Abstract/Free Full Text]
  28. Ranieri JM, Wagner JD, Wenck S, et al. The prognostic importance of sentinel lymph node biopsy in thin melanoma. Ann Surg Oncol 2006.
  29. Balch CM, Soong SJ, Gershenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol 2001; 19:3622–34.[Abstract/Free Full Text]
  30. Leiter U, Buettner PG, Eigentler TK, Garbe C. Prognostic factors of thin cutaneous melanoma: an analysis of the central malignant melanoma registry of the German dermatological society. J Clin Oncol 2004; 22:3660–7.[Abstract/Free Full Text]



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