Dale Han

Clinicopathologic Predictors of Sentinel Lymph Node Metastasis in Thin Melanoma

PURPOSE Indications for sentinel lymph node biopsy (SLNB) for thin melanoma are continually evolving. We present a large multi-institutional study to determine factors predictive of sentinel lymph node (SLN) metastasis in thin melanoma. PATIENTS AND METHODS Retrospective review of the Sentinel Lymph Node Working Group database from 1994 to 2012 identified 1,250 patients who had an SLNB and thin melanomas (≤ 1 mm). Clinicopathologic characteristics were correlated with SLN status and outcome. RESULTS SLN metastases were detected in 65 (5.2%) of 1,250 patients. On univariable analysis, rates of Breslow thickness ≥ 0.75 mm, Clark level ≥ IV, ulceration, and absence of regression differed significantly between positive and negative SLN groups (all P < .05). These four variables and mitotic rate were used in multivariable analysis, which demonstrated that Breslow thickness ≥ 0.75 mm (P = .03), Clark level ≥ IV (P = .05), and ulceration (P = .01) significantly predicted SLN metastasis with 6.3%, 7.0%, and 11.6% of the patients with these respective characteristics having SLN disease. Melanomas < 0.75 mm had positive SLN rates of < 5% regardless of Clark level and ulceration status. Median follow-up was 2.6 years. Melanoma-specific survival was significantly worse for patients with positive versus negative SLNs (P = .001). CONCLUSION Breslow thickness ≥ 0.75 mm, Clark level ≥ IV, and ulceration significantly predict SLN disease in thin melanoma. Most SLN metastases (86.2%) occur in melanomas ≥ 0.75 mm, with 6.3% of these patients having SLN disease, whereas in melanomas < 0.75 mm, SLN metastasis rates are < 5%. By using a 5% metastasis risk threshold, SLNB is indicated for melanomas ≥ 0.75 mm, but further study is needed to define indications for SLNB in melanomas < 0.75 mm.

Radiotherapy influences local control in patients with desmoplastic melanoma

Desmoplastic melanoma may have a high risk of local recurrence after wide excision. The authors hypothesized that adjuvant radiotherapy (RT) would improve local control in patients with desmoplastic melanoma, resulting in at least a 10% absolute decrease in local recurrence rate.

Clinicopathologic Predictors of Survival in Patients with Desmoplastic Melanoma

Background and Objectives Desmoplastic melanoma is a unique subtype of melanoma which typically affects older patients who often have comorbidities that can adversely affect survival. We sought to identify melanoma-specific factors influencing survival in patients with desmoplastic melanoma. Methods Retrospective review from 1993 to 2011 identified 316 patients with primary desmoplastic melanoma. Clinicopathologic characteristics were correlated with nodal status and outcome. Results Fifty-five patients (17.4%) had nodal disease: 33 had a positive sentinel lymph node biopsy and 22 developed nodal recurrences (no sentinel lymph node biopsy or false-negative sentinel lymph node biopsy). Nodal disease occurred more often in younger patients and in cases with mixed compared with pure histology (26.7% vs. 14.6%); both of these variables significantly predicted nodal status on multivariable analysis (p<0.05). After a median follow-up of 5.3 years, recurrence developed in 87 patients (27.5%), and 111 deaths occurred. The cause of death was known in 79 cases, with 47 deaths (59.5%) being melanoma-related. On multivariable analysis, Breslow thickness, mitotic rate ≥1/mm2 and nodal status significantly predicted melanoma-specific survival (p<0.05). Conclusions Nodal status predicts melanoma-specific survival in patients with desmoplastic melanoma. However, since patients with desmoplastic melanoma represent an older population, and a considerable proportion of deaths are not melanoma-related (40.5%), comorbidities should be carefully considered in making staging and treatment decisions in this population.

Minimally invasive intra-arterial regional therapy for metastatic melanoma: isolated limb infusion and percutaneous hepatic perfusion.

Introduction: In-transit melanoma or melanoma presenting as unresectable liver metastases are clinical situations with limited therapeutic options. Regional intra-arterial therapies provide efficacious treatment alternatives for these patients. Through surgical techniques of vascular isolation, regional therapies deliver high-dose chemotherapy to tumor cells while minimizing systemic exposure. However, percutaneous techniques such as isolated limb infusion (ILI) and percutaneous hepatic perfusion (PHP) have been developed, which provide a minimally invasive means of obtaining vascular isolation of target organs. Areas covered: Areas covered in this review include the techniques of ILI and PHP, the chemotherapeutic agents utilized during these regional therapies and the clinical responses seen after ILI and PHP. The pharmacokinetics of regional chemotherapy utilized during ILI and PHP is also reviewed with an additional focus on novel ways to optimize drug delivery to improve response rates and attempts to define the potential systemic manifestations of regional therapeutics. Expert opinion: Unresectable hepatic and limb in-transit metastases from melanoma are very difficult to treat. Systemic chemotherapy has largely been ineffective. Both the minimally invasive, percutaneous techniques of ILI and PHP are excellent methods used to deliver extremely high-dose chemotherapy regionally to patients harboring metastatic melanoma confined to an extremity or liver, respectively. Studies, from prospectively maintained databases as well as Phase II and III trials, have shown the great efficacy of these techniques.

Clinical utilities and biological characteristics of melanoma sentinel lymph nodes

An estimated 73870 people will be diagnosed with melanoma in the United States in 2015, resulting in 9940 deaths. The majority of patients with cutaneous melanomas are cured with wide local excision. However, current evidence supports the use of sentinel lymph node biopsy (SLNB) given the 15%-20% of patients who harbor regional node metastasis. More importantly, the presence or absence of nodal micrometastases has been found to be the most important prognostic factor in early-stage melanoma, particularly in intermediate thickness melanoma. This review examines the development of SLNB for melanoma as a means to determine a patients nodal status, the efficacy of SLNB in patients with melanoma, and the biology of melanoma metastatic to sentinel lymph nodes. Prospective randomized trials have guided the development of practice guidelines for use of SLNB for melanoma and have shown the prognostic value of SLNB. Given the rapidly advancing molecular and surgical technologies, the technical aspects of diagnosis, identification, and management of regional lymph nodes in melanoma continues to evolve and to improve. Additionally, there is ongoing research examining both the role of SLNB for specific clinical scenarios and the ways to identify patients who may benefit from completion lymphadenectomy for a positive SLN. Until further data provides sufficient evidence to alter national consensus-based guidelines, SLNB with completion lymphadenectomy remains the standard of care for clinically node-negative patients found to have a positive SLN.

Current and planned multicenter trials for patients with primary or metastatic melanoma

Multicenter clinical trials have established new standards of care in the surgical and medical management of malignant melanoma. They have led to the testing of new therapies and improved outcomes for patients with loco‐regional and distant disease. Many pressing questions remain, however, and additional multicenter trials are currently underway to address them. The purpose of this review is to summarize relevant ongoing and planned multicenter trials that have and continue to define current melanoma management. J. Surg. Oncol. 2011; 104:430–437.

Prognostic factors and immunobiologic insights into Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine cancer that has a propensity for local recurrence and nodal and distant metastasis. For patients with MCC, reported 5-year overall survival (OS) rates vary widely and range from 40% to 62%, whereas the 5-year disease-specific survival (DSS) rate is approximately 65%. Because of its rarity, much of the published literature on MCC reports relatively low numbers of patients and various prognostic features. The small patient numbers and inconsistent reporting endpoints have challenged the identification of clinicopathologic prognostic factors, and predictive factors for therapeutic intervention have not emerged. The lack of consensus on prognostic markers is exemplified by the fact that before 2010, 5 different staging systems for MCC were described in the literature. In 2010, for the first time, the American Joint Committee on Cancer (AJCC) published a separate staging system for MCC. Several studies report that the 7th edition of the AJCC staging system for MCC predicts survival and outcome; however, the validity of this staging system has been questioned because it is primarily based on an analysis of the National Cancer Data Base (NCDB) using OS as the primary outcome measure. Some authors have argued that analyses using large registries such as the NCDB have significant limitations and do not provide comprehensive data that allow an accurate prognostic analysis. These limitations also include the fact that these large registries do not capture data on causes of death or patterns of recurrence and often lack consistent and complete pathology data, particularly for lymph nodes. Other authors have suggested that OS is a poor outcome marker for MCC patients because of the older age of this population and because a considerable proportion of deaths are not due to MCC, as exemplified by Smith et al, who report that 55% of deaths were due to non-MCC causes. Within this setting, questions have arisen about whether other clinicopathologic factors should be considered as prognostic markers for MCC. For instance, the tumor growth pattern has been reported to predict outcomes for MCC patients. Mott et al showed that a diffuse growth pattern was correlated with metastatic disease or death from MCC (P 5 .04). Andea et al reported that a nodular growth pattern was significantly correlated with improved survival in a multivariate analysis. Another promising factor reported to predict survival for MCC patients is lymphovascular invasion (LVI). Fields et al published the largest single-institution study on MCC and evaluated 500 patients from 1969 to 2010. They reported that 49% of cases had LVI and that LVI significantly predicted OS and disease-specific mortality. Lim et al reported a similar LVI rate (40%) but, in contrast, did not show a significant correlation with DSS or disease-free survival (DFS) in a multivariate analysis after adjusting for tumor thickness. Notably, the NCDB study did not present data on LVI for MCC. Similarly, Smith et al were unable to assess LVI as a predictive marker because of incomplete data. Instead, Smith et al evaluated the prognostic significance of tumor thickness in MCC. Although MCC size has been correlated with survival, the prognostic value of tumor thickness remains undefined. There are data suggesting that MCC thickness can be correlated with outcome. In 2004, Mott et al reported that patients with tumors invading subcutaneous fat had significantly worse outcomes (metastatic disease or death from MCC). This study did not specifically analyze tumor thickness, but tumor depth was the best predictor of outcomes among the histologic characteristics analyzed. Several subsequent studies specifically reported on the prognostic value of tumor thickness in MCC. Lim et al showed that a tumor thickness> 10 mm was significantly correlated with worse DSS and DFS, whereas Andea et al reported that tumor thickness was significantly prognostic for survival. Smith et al also report that tumor thickness significantly