Multidisciplinary Care for Melanoma of Unknown Primary: Experience in the Era of Molecular Profiling
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ORIGINAL ARTICLE – MELANOMA
Multidisciplinary Care for Melanoma of Unknown Primary: Experience in the Era of Molecular Profiling James P. De Andrade, MD1, Paul Wong, BS1, Michael P. O’Leary, MD1, Vishwas Parekh, MD2, Arya Amini, MD3, Hans F. Schoellhammer, MD1, Kim A. Margolin, MD4, Michelle Afkhami, MD2, and Laleh G. Melstrom, MD, MS1 1
Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Duarte, CA; 2Department of Pathology, City of Hope National Medical Center, Duarte, CA; 3Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA; 4Division of Medical Oncology, Department of Medicine, City of Hope National Medical Center, Duarte, CA
ABSTRACT Background. Melanoma of unknown primary (MUP) accounts for approximately 3% of melanoma diagnoses. This study sought to evaluate treatment and outcomes for a modern MUP cohort. Methods. A retrospective review of MUP was performed at a tertiary referral cancer center. Results. Of 815 melanoma patients, 67 (8.2%) had MUP. Men were more likely to have MUP than women (67% vs. 55%; p = 0.04). The most common sites of MUP were lymph nodes (28%), visceral solid organs (25%), brain (16%), and skin/subcutaneous tissues (10%). Of the patients who underwent tumor genomic profiling, 52% harbored pathogenic BRAF mutations. Of the 24 patients who underwent multi-gene panel testing, all had pathogenic mutations and 21 (88%) had mutations in addition to or exclusive of BRAF, including 11 patients (46%) with telomerase reverse transcriptase promoter mutations. Checkpoint inhibitors (39%) and BRAF-MEK inhibitors (7%) were the most common first-line treatments. Upfront surgical resection was used for 25% of the MUP patients, and 12 of these resections were for curative intent. During a median follow-up period of 22.1 months, the median overall survival (OS) was not met for the patients with
Ó Society of Surgical Oncology 2020 First Received: 13 July 2020 Accepted: 14 August 2020 L. G. Melstrom, MD, MS e-mail: [email protected]
MUP isolated to lymph nodes. At 56.8 months, 75% of these patients were alive. The median OS was 37.4 months for skin/soft tissue MUP, 33.3 months for single solid organ viscera MUP, and 29.8 months for metastatic brain MUP. Conclusion. Multigene panel testing identified pathogenic mutations in all tested MUP patients and frequently identified targets outside BRAF. Despite advanced stage, aggressive multimodal therapy for MUP can be associated with 5-year OS and should be pursued for appropriate candidates.
In 2020, melanoma is expected to be diagnosed for more than 100,000 patients, and 6850 will die of this disease.1 Of the newly diagnosed melanomas, approximately 3% are characterized as melanoma of unknown primary (MUP).2 Specifically, MUP is the presentation of in-transit, regional, or distant melanoma metastasis without a known primary lesion. Most commonly, the sites of metastatic disease in patients with MUP are a single regional lymph node basin, subcutaneous tissue, and solid organ viscera. G
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