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Background: The tumor microenvironment after treatment with ipilimumab is not well described. Furthermore, the safety of surgery for patients being treated with ipilimumab for metastatic melanoma has not been well reported. This study analyzed the safety of surgery and the immune phenotype of tumors resected while on ipilimumab., Methods: From our prospective melanoma database, we identified patients undergoing surgery for any indication within 30 days of receiving a dose of induction ipilimumab or while on maintenance ipilimumab therapy. Surgical toxicity was graded 1-5 by the Clavien classification. Tumor-infiltrating lymphocytes were classified by flow cytometry and compared with peripheral blood., Results: 23 patients were identified who underwent 34 operations a median of 27 weeks after initiation of ipilimumab (1-123 weeks). Subcutaneous resections were the most frequent, followed by intra-abdominal and nodal procedures. Grade 1 or 2 wound complications were seen in 22% of patients. No Grade 3-5 complications were seen. Analysis of the T cell infiltrate and matched peripheral blood from ten patients showed an elevated % of CD4+FOXP3+ T-regulatory cells and a 2.8-fold lower ratio of CD8+/CD4+FOXP3+ in the tumor compared with blood (p=0.02). In addition, all CD8+ T cells had a higher expression of PD-1 in the tumor, compared with peripheral blood., Conclusions: Surgery for patients on ipilimumab is safe. This study highlights the immunosuppressive phenotype in tumors not responding to immunotherapy. The high percentage of T-regulatory cells and low T-effector cells in progressive tumors suggests a possible mechanism of immune escape.

While sentinel lymph node biopsy (SLN) is a highly accurate and well-tolerated procedure for patients with cutaneous melanoma, the role of the completion lymph node dissection (CLND) for patients with positive SLN biopsy remains unknown. This study aimed to look at the prognostic value of a positive nonsentinel lymph node (NSLN). A prospectively maintained database identified 222 patients with cutaneous melanoma and a positive SLN biopsy, without evidence of distant disease. All of these patients underwent CLND, and 37 patients (17%) had positive NSLN. With median follow-up of 33 months, patients with negative NSLN had median survival of 104 months, while patients with positive NSLN had median survival of 36 months (p < 0.001). There were no survivors in the patients with positive NSLN beyond 6 years. When patients with an equal number of positive nodes were analyzed, the presence of a positive NSLN was still associated with worse melanoma-specific survival (66 months for NSLN- versus 34 months for NSLN+, p = 0.04). While increasing age, tumor thickness, and male sex were associated with an increased risk of death on multivariate analysis, a positive NSLN was the most important predictor of survival (hazard ratio 2.5). We conclude that positive NSLN is an independent predictor of disease-specific survival in patients with cutaneous melanoma.

Background: Primary vaginal melanoma is a rare and highly malignant disease. The impact of therapy on outcomes is poorly understood., Methods: Records of all patients treated for primary vaginal melanoma at Memorial Sloan-Kettering Cancer Center from 1977 to 2001 were reviewed. Survival analysis was performed based on appropriate patient, tumor, and treatment variables. Pathologic materials were reviewed to confirm the original diagnosis and examine appropriate clinicopathologic features., Results: Thirty-five women were treated for vaginal melanoma; the primary treatment selected was surgical for 69% (24) and radiotherapy for 31% (11) of the patients. Surgical removal of the tumor was achieved in 92% (22) of the 24 patients selected for surgical therapy. At operation, radical excision with en bloc removal of involved pelvic organs was performed in 50% (12) of the 24 patients, a wide excision was performed in 42% (10), and a total vaginectomy was performed in 8% (2). Elective pelvic lymph node dissection was performed in 74% (26) of the 35 cases. Lymph node metastasis was found in only 8% (2) of these 26 patients. The overall median survival was 20 months. Primary surgical therapy was associated with longer overall survival (25 vs. 13 months; P =.039). Recurrence-free survival was not associated with the extent of surgery. None of the examined clinicopathologic features were associated with survival differences., Conclusions: The prognosis is poor for patients with primary vaginal melanoma. Improved clinical outcomes were associated with surgical removal of gross disease whenever possible. Because of the low rate of lymph node metastasis, elective pelvic lymph node dissection is not obligatory. In cases of surgically unresectable disease, primary radiation therapy is indicated.

Background: Although desmoplastic melanoma (DM) often presents at a locally advanced stage, nodal metastases are rare. We describe our experience with lymphatic mapping and sentinel lymph node biopsy (SLNB) in patients with DM to characterize the biological behavior of these tumors., Methods: Twenty-seven patients with cutaneous DM underwent wide excision and attempted SLNB between 1996 and 2001. All pathology was reviewed by a single dermatopathologist (KB). Clinical and histological features were recorded., Results: There were 20 male and 7 female patients. The median age was 64 years (range, 35-83 years). The head and neck was the most commonly involved anatomical region (n = 14). The median Breslow thickness was 2.2 mm. Twenty-four patients underwent successful SLNB. No patient had a positive sentinel node. At a median follow-up of 27 months, five patients recurred (four systemic and one local); all five had undergone successful SLNB. Two of these patients died of disease, two are alive with disease, and one remains alive and disease free. No patient experienced failure in a regional nodal basin., Conclusions: DM is a biologically distinct form of melanoma, with a very low incidence of regional lymph node metastases, either at presentation or in long-term follow-up. This biology should be considered when designing rational treatment strategies for these patients.

Background: The overall prognosis of patients with thick cutaneous melanoma (TCM) is generally thought to be poor. Surgically staging these patients with sentinel lymph node (SLN) biopsy remains controversial. This study was performed to determine whether SLN status improved our ability to predict outcome over other known prognostic factors and to develop a model incorporating independent prognostic factors to estimate the risk of recurrence for an individual patient., Methods: A prospective database identified patients with TCM (>4.0 mm or Clark level V) and clinically negative nodes who underwent SLN biopsy. Univariate and multivariate analyses were performed., Results: From 1991 to 2001, 126 patients were identified; 75 (60%) were male. The median age was 60 years. The median tumor thickness was 5.5 mm, and 43% were ulcerated. Thirty percent of patients had a positive SLN. Recurrence was seen in 50 patients (40%). Median follow-up, relapse-free survival, and overall survival were 25, 50, and 68 months, respectively. Factors independently predictive of recurrence were age >/=60 years, depth >5.5 mm, ulceration, and SLN positivity. SLN status was the most significant prognostic factor (P <.001). The relative risk of recurrence for an individual patient ranged from 1 in patients for whom no adverse factors were present to 29.4 when all factors were present., Conclusions: SLN status was the strongest independent predictor of outcome in patients with TCM. However, patients with TCM are prognostically heterogeneous, and all independently predictive factors should be considered when an individual patient's risk of recurrence is assessed.