Melanoma: Urist MM

Coit DG, Andtbacka R, Bichakjian CK, Dilawari RA, Dimaio D, Guild V, Halpern AC, Hodi FS, Kashani-Sabet M, Lange JR, Lind A, Martin L, Martini MC, Pruitt SK, Ross MI, Sener SF, Swetter SM, Tanabe KK, Thompson JA, Trisal V, Urist MM, Weber J, Wong MK, Anonymous00048. · No affiliation provided · J Natl Compr Canc Netw. · Pubmed #19401060 No free full text.

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Houghton AN, Coit DG, Daud A, Dilawari RA, Dimaio D, Gollob JA, Haas NB, Halpern A, Johnson TM, Kashani-Sabet M, Kraybill WG, Lange JR, Martini M, Ross MI, Samlowski WE, Sener SF, Tanabe KK, Thompson JA, Trisal V, Urist MM, Walker MJ, Anonymous00370. · No affiliation provided · J Natl Compr Canc Netw. · Pubmed #16884669 No free full text.

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Balch CM, Soong SJ, Smith T, Ross MI, Urist MM, Karakousis CP, Temple WJ, Mihm MC, Barnhill RL, Jewell WR, Wanebo HJ, Desmond R, Anonymous00101. · Johns Hopkins Medical Center, Baltimore, Maryland, USA. · Ann Surg Oncol. · Pubmed #11258773 No free full text.

Abstract: BACKGROUND: The Intergroup Melanoma Surgical Trial began in 1983 to examine the optimal surgical margins of excision for primary melanomas of intermediate thickness (i.e., 1-4 mm). There is now a median 10-year follow-up. METHODS: There were two cohorts entered into a prospective multi-institutional trial: (1) 468 patients with melanomas on the trunk or proximal extremity who randomly received a 2 cm or 4 cm radial excision margin and (2) 272 patients with melanomas on the head, neck, or distal extremities who received a 2 cm radial excision margin. RESULTS: A local recurrence (LR) was associated with a high mortality rate, with a 5-year survival rate of only 9% (as a first relapse) or 11% (anytime) compared with an 86% survival for those patients who did not have a LR (P < .0001). The 10-year survival for all patients with a LR was 5%. The 10-year survival rates were not significantly different when comparing 2 cm vs. 4 cm margins of excision (70% vs. 77%) or comparing the management of the regional lymph nodes (observation vs. elective node dissection). The incidences of LR were the same for patients having a 2 cm vs. 4 cm excision margin regardless of whether the comparisons were made as first relapse (0.4% vs. 0.9%) or at anytime (2.1% vs. 2.6%). When analyzed by anatomic site, the LR rates were 1.1% for melanomas arising on the proximal extremity, 3.1% for the trunk, 5.3% for the distal extremities, and 9.4% for the head and neck. The most profound influence on LR rates was the presence or absence of ulceration; it was 6.6% vs. 1.1% in the randomized group involving the trunk and proximal extremity and was 16.2% vs. 2.1% in the non-randomized group involving the distal extremity and head and neck (P < .001). A multivariate (Cox) regression analysis showed that ulceration was an adverse and independent factor (P = .0001) as was head and neck melanoma site (P = .01), while the remaining factors were not significant (all with P > .12). CONCLUSION: For this group of melanoma patients, a local recurrence is associated with a high mortality rate, a 2-cm margin of excision is safe and ulceration of the primary melanoma is the most significant prognostic factor heralding an increased risk for a local recurrence.

Balch CM, Soong S, Ross MI, Urist MM, Karakousis CP, Temple WJ, Mihm MC, Barnhill RL, Jewell WR, Wanebo HJ, Harrison R. · · Ann Surg Oncol. · Pubmed #10761786 No free full text.

Abstract: BACKGROUND: Ten- to 15-year survival results were analyzed from a prospective multi-institutional randomized surgical trial that involved 740 stages I and II melanoma patients with intermediate thickness melanomas (1.0 to 4.0 mm) and compared elective (immediate) lymph node dissection (ELND) with clinical observation of the lymph nodes as well as prognostic factors that independently predict outcomes. METHODS: Eligible patients were stratified according to tumor thickness, anatomical site, and ulceration, and then prerandomized to either ELND or nodal observation. By using Cox stepwise multivariate regression analysis, the independent predictors of outcome were tumor thickness (P < .001), the presence of tumor ulceration (P < .001), trunk site (P = .003), and patient age more than 60 years (P = .01). RESULTS: Overall 10-year survival was not significantly different for patients who received ELND or nodal observation (77% vs. 73%; P = .12). Among the prospectively stratified subgroups of patients, 10-year survival rates favored those patients with ELND, with a 30% reduction in mortality rate for the 543 patients with nonulcerated melanomas (84% vs. 77%; P = .03), a 30% reduction in mortality rate for the 446 patients with tumor thickness of 1.0 to 2.0 mm (86% vs. 80%; P = .03), and a 27% reduction in mortality rate for 385 patients with limb melanomas (84% vs. 78%; P = .05). Of these subgroups, the presence or absence of ulceration should be the key factor for making treatment recommendations with regard to ELND for patients with intermediate thickness melanomas. CONCLUSIONS: These long-term survival rates from patients treated at 77 institutions demonstrate that ulceration and tumor thickness are dominant predictive factors that should be used in the staging of stages I and II melanomas, and confer a survival advantage for these subgroups of prospectively defined melanoma patients.

Federico AC, Chagpar AB, Ross MI, Martin RC, Noyes RD, Goydos JS, Beitsch PD, Urist MM, Ariyan S, Sussman JJ, McMasters KM, Scoggins CR, Anonymous00302. · Division of Surgical Oncology, Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40292. · Arch Surg. · Pubmed #18645103 links to  free full text

Abstract: HYPOTHESIS: The number of nodal basins draining a primary cutaneous melanoma is not an independent predictor of outcome. DESIGN: Post hoc analysis of patients entered into a randomized, prospective study. SETTING: Multi-institutional academic and community medical centers. PATIENTS: Patients aged 18 to 70 years with melanoma 1.0 mm or greater Breslow thickness. INTERVENTIONS: Wide local excision and sentinel lymph node biopsy were performed on all patients; patients with sentinel lymph node metastases underwent completion lymphadenectomy. Patients with multiple-nodal basin drainage were compared with those with single-nodal basin drainage. MAIN OUTCOME MEASURES: Sentinel lymph node status, locoregional recurrence-free survival, disease-free survival, and overall survival. RESULTS: A total of 2060 patients with single-nodal basin drainage (n = 1709 [83% of cohort]) were included in the analysis, with a median follow-up of 50 months. On univariate analysis, the group with multiple-nodal basin drainage (n = 351) was associated with female sex and primary tumor regression (P < .001). In addition, multiple-nodal basin drainage was associated with truncal primary tumor location (73.2%), while single-nodal basin drainage was more common for extremity tumors (50.9%; P < .001). On multivariate analysis, there were no differences in the rate of sentinel lymph node metastasis, disease-free survival, or overall survival between the groups. Interestingly, locoregional recurrence was significantly worse in the single-nodal basin drainage group (P = .003). CONCLUSIONS: Multiple-nodal basin drainage does not confer a worse prognosis for patients with cutaneous melanoma. In fact, single-nodal basin drainage appears to be associated with a greater risk of locoregional recurrence.

Chagpar RB, Ross MI, Reintgen DS, Edwards MJ, Scoggins CR, Martin RC, Noyes RD, Goydos JS, Beitsch PD, Urist MM, Ariyan S, Davidson BS, Sussman JJ, McMasters KM. · University of Saskatchewan, Saskatoon, Saskatchewan, Canada. · J Surg Res. · Pubmed #17950088 No free full text.

Abstract: INTRODUCTION: We sought to evaluate the factors that affect sentinel lymph node (SLN) metastasis and survival among young melanoma patients (< or =30 y). METHODS: The Sunbelt Melanoma Trial is a multi-institutional prospective randomized trial of patients aged 18 to 70 y. Statistical analyses were performed to determine if patients < or =30 y of age had a significantly different outcome in terms of SLN metastasis, disease-free survival (DFS), and overall survival (OS) compared to older patients. RESULTS: The median age of the 3031 patients in this study was 50 y (range 18 to 77 y); the 315 patients (10.4%) < or =30 y old were compared with those >30 y old. Of the 1944 patients with follow-up, the median follow-up was 48 mo. On univariate analysis, younger patients were more often female (54.7% versus 40.9%, P < 0.0005), with tumors <4 mm thick (94.9% versus 89.4%, P = 0.001) without ulceration (80.3% versus 70.9%, P < 0.0005) or evidence of regression (93.8% versus 87.8%, P = 0.003), and were less likely to have lentigo maligna (0.0% versus 2.6%) or acral lentiginous (0.4% versus 3.1%, P < 0.0005) subtype. Patient age < or =30 was associated with SLN metastasis on univariate (24.6% versus 19.7%, P = 0.05) and multivariate (OR = 1.77, 95% CI = 1.26-2.49, P = 0.001) analyses. With a median follow-up of 48 mo, younger patients had a significantly improved 5-y DFS (86.2% versus 79.1%, P = 0.036) and OS (89.9% versus 80.1%, P = 0.010). On multivariable Cox regression analysis, however, age group was not a significant independent prognostic factor affecting DFS or OS. CONCLUSION: Despite a higher rate of SLN metastasis, patients < or =30 y old do not have a worse survival attributable to a more favorable clinicopathologic profile.

Scoggins CR, Ross MI, Reintgen DS, Noyes RD, Goydos JS, Beitsch PD, Urist MM, Ariyan S, Davidson BS, Sussman JJ, Edwards MJ, Martin RC, Lewis AM, Stromberg AJ, Conrad AJ, Hagendoorn L, Albrecht J, McMasters KM. · Division of Surgical Oncology, Department of Surgery, University of Louisville, James Graham Brown Cancer Center and Center for Advanced Surgical Technologies (CAST), Louisville, KY 40292, USA. · J Clin Oncol. · Pubmed #16782924 No free full text.

Abstract: PURPOSE: To evaluate the prognostic significance of molecular staging using reverse transcriptase polymerase chain reaction (RT-PCR) in detecting occult melanoma cells in sentinel lymph nodes (SLNs) and circulating bloodstream. PATIENTS AND METHODS: In this multicenter study, eligibility criteria included patient age 18 to 71 years, invasive melanoma > or = 1.0 mm Breslow thickness, and no clinical evidence of metastasis. SLN biopsy and wide excision of the primary tumor were performed. SLNs were examined by serial-section histopathology and S-100 immunohistochemistry. A portion of each SLN was frozen for RT-PCR. In addition, RT-PCR was performed on peripheral-blood mononuclear cells (PBMCs). RT-PCR analysis was performed using four markers: tyrosinase, MART1, MAGE3, and GP-100. Disease-free survival (DFS), distant-DFS (DDFS), and overall survival (OS) were analyzed. RESULTS: A total of 1,446 patients with histologically negative SLNs underwent RT-PCR analysis. At a median follow-up of 30 months, there was no difference in DFS, DDFS, or OS between the RT-PCR-positive (n = 620) and RT-PCR-negative (n = 826) patients. Analysis of PBMC from 820 patients revealed significant differences in DFS and DDFS, but not OS, for patients with detection of more than one RT-PCR marker in peripheral blood. CONCLUSION: In this large, prospective, multi-institutional study, RT-PCR analysis on SLNs and PBMCs provides no additional prognostic information beyond standard histopathologic analysis of SLNs. Detection of more than one marker in PBMC is associated with a worse prognosis. RT-PCR remains investigational and should not be used to direct adjuvant therapy at this time.

Scoggins CR, Ross MI, Reintgen DS, Noyes RD, Goydos JS, Beitsch PD, Urist MM, Ariyan S, Sussman JJ, Edwards MJ, Chagpar AB, Martin RC, Stromberg AJ, Hagendoorn L, McMasters KM, Anonymous00327. · Division of Surgical Oncology, Department of Surgery, University of Louisville, KY 40292, USA. · Ann Surg. · Pubmed #16633005 links to  free full text

Abstract: OBJECTIVE: To better understand the factors associated with the well-established gender difference in survival for patients with melanoma. SUMMARY BACKGROUND DATA: Gender is an important factor in patients with cutaneous melanoma. Male patients have a worse outcome when compared with females. The reasons for this difference are poorly understood. METHODS: This prospective multi-institutional study included patients aged 18 to 70 years with melanomas > or =1.0 mm Breslow thickness. Wide excision and sentinel lymph node (SLN) biopsy was performed in all patients. Clinicopathologic factors, including gender, were assessed and correlated with disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). RESULTS: A total of 3324 patients were included in the covariate analyses; 1829 patients had follow-up data available and were included in the survival analyses. Median follow-up was 30 months. On univariate analysis, men (n = 1906) were more likely than women to be older than 60 years (P < 0.0001), have thicker melanomas (P < 0.0001), have primary tumor regression (P = 0.0054), ulceration (P < 0.0001), and axial primary tumor location (P < 0.0001). On multivariate analysis, age (P = 0.0002), thickness (P < 0.0001), ulceration (P = 0.015), and location (P < 0.0001) remained significant in the model. There was no difference in the rate of SLN metastasis between men and women (P = 0.37) on multivariate analysis. When factors affecting survival were considered, the prognosis was worse for men as validated by lower DFS (P = 0.0005), DDFS (P < 0.0001), and OS (P < 0.0001). CONCLUSIONS: Male gender is associated with a greater incidence of unfavorable primary tumor characteristics without an increased risk for nodal metastasis. Nonetheless, gender is an independent factor affecting survival.

Urist MM. · Department of Surgery, University of Alabama at Birmingham, USA. · Curr Surg. · Pubmed #15214316 No free full text.

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Medina-Franco H, Beenken SW, Heslin MJ, Urist MM. · Department of Surgery, The University of Alabama at Birmingham, USA. · Ann Surg Oncol. · Pubmed #11597012 No free full text.

Abstract: BACKGROUND: Selective sentinel lymphadenectomy has gained widespread acceptance for staging of melanomas arising in the trunk and extremities, but the complex lymphatic drainage of the head and neck area has limited its application in this area. METHODS: We performed a retrospective analysis of patients who underwent selective sentinel lymphadenectomy for cutaneous melanoma of the head and neck at the University of Alabama at Birmingham from 1997 through 2000, by using a standard technique of preoperative lymphoscintigram and biopsy guided with blue dye injection and a handheld gamma probe. Complete lymph node dissection was recommended only for tumor-positive sentinel lymph nodes (SLNs). Survival curves were constructed with the Kaplan-Meier method. Fisher's exact test was used for comparisons. Significance was defined as P < .05. RESULTS: Thirty-eight patients underwent selective sentinel lymphadenectomy with the standard technique during the study period. A majority (82%) of patients were men with a median age of 55 years. The most common site of the primary tumor was the face (44%), followed by the scalp (24%). Mean tumor thickness was 2.5 mm. The sentinel node was identified during surgery in 35 patients (92%). Before the use of the handheld gamma probe, the identification rate of the SLN was only 56%. A single SLN was identified in 53% of cases. The incidence of metastases in SLN was 11.4%. With a mean follow-up of 17 months, the actuarial 3-year overall survival was 92%. The accuracy of the selective sentinel lymphadenectomy in this series was 80%. CONCLUSIONS: Selective sentinel lymphadenectomy in the head and neck region is a technically demanding procedure, but the combined use of blue dye and gamma-probe radiolocalization can be a reliable method of staging regional lymph nodes and determining the need for elective lymphadenectomy.