Jill S. Frank

Routine restaging PET/CT and detection of initial recurrence in sentinel lymph node positive stage III melanoma

BACKGROUND Follow-up of patients with sentinel lymph node-positive stage III melanoma uses history, physical exam, and cross-sectional imaging. The aim of this study was to evaluate positron emission tomographic (PET)/computed tomographic (CT) scans in the detection of recurrence. METHODS From 2003 to 2009, a single-institution prospective database of all cutaneous melanoma patients was used to identify sentinel lymph node-positive stage III patients with disease-free survival >1 year and 1 restaging PET/CT scan. RESULTS Thirty-eight patients were identified, with a median follow-up period of 27.5 months. Seven (18%) developed recurrence (median time to recurrence, 25 months). Recurrences were detected as follows: 3 by patients, 1 by physician, 1 by PET/CT scan and lactate dehydrogenase, 1 by PET/CT scan, and 1 by brain magnetic resonance imaging. One hundred eight follow-up PET/CT scans were performed. Two of 38 patients had asymptomatic metastases detected by routine restaging PET/CT scan, and there were 9 scans with false-positive results. CONCLUSIONS With short follow-up, the utility of routine PET/CT scans in identifying unsuspected recurrence in patients with sentinel lymph node-positive stage III melanoma appears minimal.

Age and Breslow Depth Are Associated with a Positive Sentinel Lymph Node in Patients with Cutaneous Melanocytic Tumors of Uncertain Malignant Potential

BACKGROUND Atypical melanocytic neoplasms present a therapeutic dilemma. Current consensus is to perform a sentinel lymph node (SLN) biopsy as part of management. However, it is unclear whether this is required in all patients. We present our experience with sentinel lymphadenectomy in these patients and examine the clinical and pathologic variables associated with a positive SLN. STUDY DESIGN A prospectively maintained melanoma database was queried for patients with controversial melanocytic lesions. All patients between January 1997 and January 2009 were included. Demographic and pathologic information was collected and correlated with results of SLN biopsy. RESULTS Thirty-one patients underwent SLN biopsy. Median patient age was 19 years (range 5 to 59 years) and median tumor Breslow depth was 1.35 mm. Five patients (16%) had a positive SLN. Those with a positive SLN were younger (median 11 vs 23.5 years, p = 0.02) and had a greater Breslow depth (median 1.90 vs 1.09; p = 0.03) than those who were SLN negative. Median follow-up was 16 months for patients with at least 6 months of follow-up time and there have been no recurrences identified. CONCLUSIONS We report an SLN positive rate of 16% in patients with atypical melanocytic tumors. Younger age and greater Breslow depth are associated with having a positive SLN. These results confirm earlier work demonstrating the importance of SLN biopsy in this disease and highlight the need to measure Breslow depth in these lesions so that they can be appropriately stratified as to the need for SLN biopsy.

IL2 Inducible T-cell Kinase, a Novel Therapeutic Target in Melanoma.

Purpose: IL2 inducible T-cell kinase (ITK) promoter CpG sites are hypomethylated in melanomas compared with nevi. The expression of ITK in melanomas, however, has not been established and requires elucidation. Experimental Design: An ITK-specific monoclonal antibody was used to probe sections from deidentified, formalin-fixed paraffin-embedded tumor blocks or cell line arrays and ITK was visualized by IHC. Levels of ITK protein differed among melanoma cell lines and representative lines were transduced with four different lentiviral constructs that each contained an shRNA designed to knockdown ITK mRNA levels. The effects of the selective ITK inhibitor BI 10N on cell lines and mouse models were also determined. Results: ITK protein expression increased with nevus to metastatic melanoma progression. In melanoma cell lines, genetic or pharmacologic inhibition of ITK decreased proliferation and migration and increased the percentage of cells in the G0–G1 phase. Treatment of melanoma-bearing mice with BI 10N reduced growth of ITK-expressing xenografts or established autochthonous (Tyr-Cre/Ptennull/BrafV600E) melanomas. Conclusions: We conclude that ITK, formerly considered an immune cell–specific protein, is aberrantly expressed in melanoma and promotes tumor development and progression. Our finding that ITK is aberrantly expressed in most metastatic melanomas suggests that inhibitors of ITK may be efficacious for melanoma treatment. The efficacy of a small-molecule ITK inhibitor in the Tyr-Cre/Ptennull/BrafV600E mouse melanoma model supports this possibility. Clin Cancer Res; 21(9); 2167–76. ©2015 AACR.

Relative value unit impact of complex skin closures to academic surgical melanoma practices

BACKGROUND Melanoma excisions frequently are associated with significant soft-tissue defects, creating the need for complex closures. These closures could be performed by either surgical oncologists or plastic surgeons. We sought to quantify the relative value units (RVUs) and describe the practice patterns of 2 academic surgical subspecialties after a melanoma excision. METHODS After institutional review board approval, a retrospective data analysis of a billing database was conducted on all melanoma patients undergoing an excision and closure by surgical oncology and plastic surgery departments in 2007. Data were obtained using billing records for Current Procedural Terminology diagnosis codes. RVUs were used to quantify the value added to each practice from these closures. The surgical oncologist and patient decided if a plastic surgeon was needed. RESULTS A total of 270 closures were performed, 53 (19.9%) primary and 217 (80.1%) complex. The surgical oncologists performed most complex closures (188; 86.6%), and the plastic surgeons performed the remainder (29; 13.4%), generating a total of 1,921 RVUs (1,630 by the surgical oncologists and 291 by the plastic surgeons). For analysis, complex closures were divided among 4 anatomic sites: trunk, upper extremity, lower extremity, and head and neck. Most closures by the surgical oncologists were adjacent tissue rearrangements (155; 82%) and the remainder were skin grafts (33; 18%). Closures by the plastic surgeons were more likely to be a full-thickness skin graft (P < .0027) in the head and neck region (P < .0001), with a higher associated median RVU/case (10.15 compared with 8.44 for the surgical oncologists; P < .0002). CONCLUSIONS At our institution, the majority of melanoma closures were performed by surgical oncologists. However, plastic surgery often was involved in more complex closures in the head and neck. This data set quantifies the RVUs added and describes the types of closures performed in an academic melanoma practice.