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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Ozao-Choy, Junko; Lee, Delphine J; Faries, Mark B (2014) Melanoma vaccines: mixed past, promising future. Surg Clin North Am 94:1017-30, viii
Chiu, Connie G; Nakamura, Yoshitaka; Chong, Kelly K et al. (2014) Genome-wide characterization of circulating tumor cells identifies novel prognostic genomic alterations in systemic melanoma metastasis. Clin Chem 60:873-85
Marzese, Diego M; Scolyer, Richard A; Roqué, Maria et al. (2014) DNA methylation and gene deletion analysis of brain metastases in melanoma patients identifies mutually exclusive molecular alterations. Neuro Oncol 16:1499-509
Greenberg, Edward S; Chong, Kelly K; Huynh, Kelly T et al. (2014) Epigenetic biomarkers in skin cancer. Cancer Lett 342:170-7
Tanaka, Ryo; Donovan, Nicholas C; Yu, Qiang et al. (2014) Tumor necrosis factor-* and apoptosis induction in melanoma cells through histone modification by 3-deazaneplanocin A. J Invest Dermatol 134:1470-2
Yang, James C; Sherry, Richard M (2014) MSLT-I-response of clinical trial investigators. Nat Rev Clin Oncol 11:
Nelson, Michael D; Rader, Florian; Tang, Xiu et al. (2014) PDE5 inhibition alleviates functional muscle ischemia in boys with Duchenne muscular dystrophy. Neurology 82:2085-91
Marzese, Diego M; Scolyer, Richard A; Huynh, Jamie L et al. (2014) Epigenome-wide DNA methylation landscape of melanoma progression to brain metastasis reveals aberrations on homeobox D cluster associated with prognosis. Hum Mol Genet 23:226-38
Morton, Donald L; Thompson, John F; Cochran, Alistair J et al. (2014) Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med 370:599-609
Marzese, Diego M; Hirose, Hajime; Hoon, Dave S B (2013) Diagnostic and prognostic value of circulating tumor-related DNA in cancer patients. Expert Rev Mol Diagn 13:827-44

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