The primary objective of Project III is to forge new approaches to the surgical management of cutaneous melanoma, by continuing the clinical and translational studies of lymphatic mapping and sentinel node biopsy (SNB) that were developed and initiated under this Program Project. The focal point of Project III is its two Phase III, internatjonal randomized trials of SNB. The first Multicenter Selective Lymphadenectomy Trial (MSLT-I) examines the accuracy and clinical efficacy of SNB as a staging alternative to complete lymphadenectomy (CLND) in patients with clinical stage I melanoma. MSLT-I has completed accrual of 2001 subjects, who are now being followed to determine the long-term survival benefit of immediate CLND for sentinel node (SN) micrometastses versus delayed CLND for nodal recurrence after wide excision alone. Since most patients with micrometastases have no other tumor-involved nodes, CLND may not be necessary in all patients with tumor-involved SN. We are investigating this hypothesis in a second multicenter randomized trial (MSLT-II). Serum and tisue specimens from both trials will be used to evaluate new molecular biomarkers (with Project II) and to investigate histopathologic markers relating to SN tumor burden, architecture and microenvironment (with Project I). These markers should enable us to determine the likelihood of metastasis beyond the SN and thereby identify candidates for CLND and adjuvant therapy. In related Phase l/II trials with Projects I and II, we will continue to study the, biology and pathophysiology of the regional lymphatics and SN, will examine SN immunosuppression as a predisposing factor for establishment of nodal metastasis, and will assess the prognostic relevance of endogenous immune response as a systemic marker of disease status. Thus, the aims are: 1) continue follow-up of subjects in MSLT-I;2) continue screening, enrollment and randomization in MSLT-II;3) investigate the biology and pathophysiology of the SN;4) develop molecular and immunologic markers for detection of occult systemic metastases;and 5) determine the impact of endogenous immune resonse on prognosis and clinical course.

Public Health Relevance

This project focuses on minimally invasive surgical techniques for staging the regional lymph nodes, highly sensitive immunohistopathologic/molecular techniques for examining these nodes, and serum assays for monitoring tumor markers. Results of this multidisciplinary research will improve outcomes for patients with melanoma and help to establish an internationally standardized approach to early-stage solid malignancy.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Special Emphasis Panel (ZCA1-RPRB-J)
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John Wayne Cancer Institute
Santa Monica
United States
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Wang, Jinhua; Huang, Sharon K; Marzese, Diego M et al. (2015) Epigenetic changes of EGFR have an important role in BRAF inhibitor-resistant cutaneous melanomas. J Invest Dermatol 135:532-41
Lessard, Laurent; Liu, Michelle; Marzese, Diego M et al. (2015) The CASC15 Long Intergenic Noncoding RNA Locus Is Involved in Melanoma Progression and Phenotype Switching. J Invest Dermatol 135:2464-74
Wang, Jinhua; Hua, Wei; Huang, Sharon K et al. (2015) RASSF8 regulates progression of cutaneous melanoma through nuclear factor-κb. Oncotarget 6:30165-77
Deutsch, Gary B; Kirchoff, Daniel D; Faries, Mark B (2015) Metastasectomy for stage IV melanoma. Surg Oncol Clin N Am 24:279-98
Faries, Mark B (2015) From the guest editor: The sentinel node: evolution of the revolution. Introduction. Cancer J 21:1-2
Marzese, Diego M; Hoon, Dave Sb (2015) Emerging technologies for studying DNA methylation for the molecular diagnosis of cancer. Expert Rev Mol Diagn 15:647-64
Faries, M B; Cochran, A J; Elashoff, R M et al. (2015) Multicenter Selective Lymphadenectomy Trial-I confirms the central role of sentinel node biopsy in contemporary melanoma management: response to 'No survival benefit for patients with melanoma undergoing sentinel lymph node biopsy: critical appraisal of t Br J Dermatol 172:571-3
Marzese, Diego M; Liu, Michelle; Huynh, Jamie L et al. (2015) Brain metastasis is predetermined in early stages of cutaneous melanoma by CD44v6 expression through epigenetic regulation of the spliceosome. Pigment Cell Melanoma Res 28:82-93
Ono, Shigeshi; Oyama, Takashi; Lam, Stella et al. (2015) A direct plasma assay of circulating microRNA-210 of hypoxia can identify early systemic metastasis recurrence in melanoma patients. Oncotarget 6:7053-64
Cochran, Alistair J; Huang, Rong-Rong; Su, Albert et al. (2015) Is sentinel node susceptibility to metastases related to nodal immune modulation? Cancer J 21:39-46

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