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Melanoma: HELP
Articles by Jane L. Messina
Based on 70 articles published since 2009
(Why 70 articles?)
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Between 2009 and 2019, J. Messina wrote the following 70 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Editorial Prediction is Difficult, Especially About the Future: Clinical Prognostic Tools in Melanoma. 2016

Sondak, Vernon K / Messina, Jane L. ·Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA. vernon.sondak@moffitt.org. · Department of Oncologic Sciences, University of South Florida Morsani College of Medicine, Tampa, FL, USA. vernon.sondak@moffitt.org. · Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA. · Department of Oncologic Sciences, University of South Florida Morsani College of Medicine, Tampa, FL, USA. · Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL, USA. · Departments of Pathology and Cell Biology, Dermatology and Oncologic Sciences, University of South Florida Morsani College of Medicine, Tampa, FL, USA. ·Ann Surg Oncol · Pubmed #27198510.

ABSTRACT: -- No abstract --

2 Editorial Refining the criteria for sentinel lymph node biopsy in patients with thinner melanoma: a roadmap for the future. 2010

Messina, Jane L / Sondak, Vernon K. · ·Cancer · Pubmed #20091836.

ABSTRACT: -- No abstract --

3 Review Review of diagnostic, prognostic, and predictive biomarkers in melanoma. 2018

Ankeny, Jacob S / Labadie, Brian / Luke, Jason / Hsueh, Eddy / Messina, Jane / Zager, Jonathan S. ·Department of Cutaneous Oncology, Moffitt Cancer Center, 10920 McKinley Dr., MKC 4th 11.4123, Tampa, FL, 33612, USA. · Biological Sciences Division, University of Chicago, 5841 S. Maryland Ave., Chicago, IL, 60637, USA. · Department of Surgical Oncology, St. Louis University, 3655 Vista Ave., 1st Floor, St. Louis, MO, 63110, USA. · Department of Cutaneous Oncology, Moffitt Cancer Center, 10920 McKinley Dr., MKC 4th 11.4123, Tampa, FL, 33612, USA. jonathan.zager@moffitt.org. ·Clin Exp Metastasis · Pubmed #29722000.

ABSTRACT: Melanoma is an aggressive cutaneous malignancy with rapidly rising incidence. Diagnosis of controversial melanocytic lesions, correct prognostication of patients, selection of appropriate adjuvant and systemic therapies, and prediction of response to a given therapy remain very real challenges. Despite these challenges, multiple high throughput, nucleic-acid based biomarkers have been developed that can be assayed from histologic tissue specimens. FISH, CGH, Decision-Dx, and other multi-marker assays have been combined to improve overall predictability. This review discusses some of the most promising nucleic acid based assays that can be obtained from tissue specimens to assist with diagnosis, prognostication, and prediction of treatment response.

4 Review A Comprehensive Approach to Pediatric Atypical Melanocytic Neoplasms with Comment on the Role of Sentinel Lymph Node Biopsy. 2016

Sondak, Vernon K / Reed, Damon / Messina, Jane L. ·Moffitt Cancer Center and University of South Florida Morsani College of Medicine, Tampa, Florida. · Moffitt Cancer Center and University of South Florida Morsani College of Medicine, Tampa, Florida; All Children's Hospital, St. Petersburg, Florida. ·Crit Rev Oncog · Pubmed #27481000.

ABSTRACT: Pediatric melanoma has been rising in incidence in recent years and its management poses challenges that are frequently exacerbated by diagnostic uncertainty about the benign or malignant nature of many pediatric melanocytic neoplasms. Sentinel lymph node biopsy (SLNB), originally described by Dr. Donald L. Morton, has been incorporated selectively into the management of pediatric atypical melanocytic neoplasms (AMNs), but its value and significance in this scenario have been controversial. Herein, we describe a comprehensive approach to the evaluation and management of pediatric AMNs that involves SLNB as a diagnostic, staging, and potentially therapeutic tool. We also describe our approach to educating patients and their families about the inherent uncertainties involved in diagnosing and predicting the ultimate behavior of pediatric melanocytic lesions. In addition, we stress the importance of long-term follow-up, as well as ongoing research to improve our understanding of the prognostic factors and histopathologic characteristics that may one day allow us to minimize or eliminate entirely this diagnostically uncertain category of skin lesions.

5 Review Pediatric Melanoma and Atypical Melanocytic Neoplasms. 2016

Sreeraman Kumar, Radhika / Messina, Jane L / Reed, Damon / Navid, Fariba / Sondak, Vernon K. ·Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA. · Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL, USA. · Department of Cutaneous Oncology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL, 33612, USA. · Department of Pathology and Cell Biology, University of South Florida Morsani College of Medicine, Tampa, FL, USA. · Department of Oncologic Sciences, University of South Florida Morsani College of Medicine, Tampa, FL, USA. · Department of Dermatology, University of South Florida Morsani College of Medicine, Tampa, FL, USA. · Adolescent and Young Adult (AYA) Program, Sarcoma Department, Moffitt Cancer Center, Tampa, FL, USA. · Department of Hematology/Oncology , All Children's Hospital Johns Hopkins Medicine , St. Petersburg, FL, USA. · Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA. · Department of Cutaneous Oncology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL, 33612, USA. vernon.sondak@moffitt.org. · Department of Oncologic Sciences and Surgery, University of South Florida Morsani College of Medicine, Tampa, FL, USA. vernon.sondak@moffitt.org. ·Cancer Treat Res · Pubmed #26601871.

ABSTRACT: Melanoma is uncommon in the pediatric age range, but is increasing in frequency and often presents with atypical features compared to the classic ABCDE criteria common to adult melanoma cases. Moreover, many melanocytic neoplasms in childhood pose diagnostic challenges to the pathologist, and sometimes cannot be unequivocally classified as benign nevi or melanoma. This chapter addresses the evaluation and management of pediatric patients with melanoma and atypical melanocytic neoplasms, including the roles of and unresolved questions surrounding sentinel lymph node biopsy, completion lymphadenectomy, adjuvant therapy, and treatment of advanced disease.

6 Review Unusual presentations of melanoma: melanoma of unknown primary site, melanoma arising in childhood, and melanoma arising in the eye and on mucosal surfaces. 2014

Sondak, Vernon K / Messina, Jane L. ·Department of Cutaneous Oncology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA; Department of Oncologic Sciences, USF Morsani College of Medicine, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612, USA; Department of Surgery, USF Morsani College of Medicine, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612, USA. Electronic address: vernon.sondak@moffitt.org. · Department of Cutaneous Oncology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA; Department of Anatomic Pathology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA; Department of Pathology & Cell Biology, USF Morsani College of Medicine, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612, USA; Department of Dermatology, USF Morsani College of Medicine, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612, USA. ·Surg Clin North Am · Pubmed #25245968.

ABSTRACT: Most melanomas present as primary tumors on the skin surface in adults; however, melanomas also arise in the eye and on the mucosal surfaces or present as apparently metastatic disease without any known history of a cutaneous primary. Melanoma is also being diagnosed during childhood more frequently than ever. Surgeons need to be aware of and understand these unusual presentations of melanoma to optimally manage their patients.

7 Review Paradoxical oncogenesis--the long-term effects of BRAF inhibition in melanoma. 2013

Gibney, Geoffrey T / Messina, Jane L / Fedorenko, Inna V / Sondak, Vernon K / Smalley, Keiran S M. ·Department of Cutaneous Oncology, The Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. ·Nat Rev Clin Oncol · Pubmed #23712190.

ABSTRACT: The clinical benefits of BRAF inhibition in patients with advanced-stage BRAF-mutant melanoma are now well established. Although the emergence of cutaneous squamous-cell carcinomas (SCCs) and secondary melanomas in patients on BRAF-inhibitor therapy have been well described, reports are emerging of additional secondary premalignant and malignant events, including RAS-mutant leukaemia, the metastatic recurrence of RAS-mutant colorectal cancer and the development of gastric and colonic polyps. In most cases, paradoxical MAPK activation--resulting from the BRAF-inhibitor-mediated homodimerization and heterodimerization of nonmutant RAF isoforms--seems to underlie the development of these secondary tumours. Although evidence supports that therapy with the simultaneous administration of BRAF and MEK inhibitors abrogates the onset of treatment-induced SCCs, whether combination treatment will limit the emergence of all BRAF-inhibitor-driven pathologies is unclear. In this Review, we describe the clinical and mechanistic manifestations of secondary cancers that have thus far been observed to arise as a consequence of BRAF inhibition. We discuss the concept of pre-existing populations of partly transformed cells with malignant potential that might be present in various organ systems, and the rationale for novel therapeutic strategies for the management of BRAF-inhibitor-induced neoplasia.

8 Review Recent advances in pathologic evaluation and reporting of melanoma. 2012

Mathew, Rahel / Messina, Jane L. ·Department of Pathology and Cell Biology, University of South Florida College of Medicine, H. Lee Moffitt Cancer Center, Tampa, FL, USA. ·Semin Oncol · Pubmed #22484190.

ABSTRACT: Recent changes to the staging of melanoma, coupled with advances in surgical and medical treatment, have resulted in new methods for diagnostic evaluation and reporting of melanocytic lesions by pathologists. This review provides an update on recent changes in evaluation and reporting of primary melanoma, evaluation of regional lymph nodes, especially sentinel nodes, and the workup of distant metastatic melanoma specimens. A brief summary of commercially available molecular diagnostic techniques and their application to practice is included.

9 Review Sentinel lymph node biopsy for melanoma: indications and rationale. 2009

Phan, Giao Q / Messina, Jane L / Sondak, Vernon K / Zager, Jonathan S. ·Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612, USA. ·Cancer Control · Pubmed #19556963.

ABSTRACT: BACKGROUND: The disease status of regional lymph nodes is the most important prognostic indicator for patients with melanoma. Sentinel lymph node biopsy (SLNB) was developed as a technique to surgically assess the regional lymph nodes and spare node-negative patients unnecessary and potentially morbid complete lymphadenectomies. METHODS: We reviewed the literature on SLNB for cutaneous melanoma to provide insight into the rationale for the current widespread use of SLNB. RESULTS: Multiple studies show that the status of the SLN is an important prognostic indicator. Those with positive SLNs have significantly decreased disease-free and melanoma-specific survival compared with those who have negative SLNs. In the Multicenter Selective Lymphadenectomy Trial I (MSLT-I), in which patients with intermediate-thickness melanoma were randomized to SLNB (and immediate completion lymphadenectomy if the SLN was positive) vs observation (and a lymphadenectomy only after presenting with clinically evident recurrence), the 5-year survival rate was 72.3% for patients with positive sentinel nodes and 90.2% for those with negative sentinel nodes (P < .001). Although overall survival was not increased in patients who underwent SLNB compared with those who were randomized to observation, patients who underwent SLNB had a significantly increased 5-year disease-free survival rate compared with those who underwent observation alone (78.3% in the biopsy group and 73.1% in the observation group; P = .009). For those with nodal metastases, patients who underwent SLNB and immediate lymphadenectomy had an increased overall 5-year survival rate compared with those who had lymphadenectomy only after presenting with clinically evident disease (72.3% vs 52.4%; P = .004). Moreover, other studies show that for patients with thin melanomas or= 0.76 mm and increased mitotic rate have been shown to be associated with an increased incidence of SLN metastases. CONCLUSIONS: SLNB provides important prognostic and staging data with minimal morbidity and can be used to identify regional node-negative patients who would not benefit from a complete nodal dissection. In our opinion, SLNB should be performed on most patients (with acceptable surgical and anesthesia risk) who have melanomas with a Breslow depth >or= 0.76 mm.

10 Review Pediatric melanoma: a review. 2009

Mills, Omie / Messina, Jane L. ·University of South Florida College of Medicine, Department of Pathology and Cell Biology, and the H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612, USA. ·Cancer Control · Pubmed #19556962.

ABSTRACT: BACKGROUND: Malignant melanoma is a rare neoplasm in the pediatric population, but its incidence has risen in recent years. METHODS: The literature was reviewed to define the current clinical and pathologic features of pediatric melanoma, highlighting the similarities and differences between adult and pediatric melanoma. RESULTS: Distinctive features of this disease, including frequency and type of genetic abnormalities, predisposing conditions, clinical presentation, stage at diagnosis, prognostic features, and frequency of sentinel lymph node positivity are emphasized. Treatment strategies, extrapolated from adult melanoma trials, are also discussed. CONCLUSIONS: Despite the differences between pediatric and adult melanoma, survival rates are similar and are improving in both populations. Further studies will help delineate the pathogenesis of both adult and pediatric melanoma, with the goal of contributing to early detection and improved survival.

11 Clinical Trial Combined analysis of phase III trials evaluating [⁹⁹mTc]tilmanocept and vital blue dye for identification of sentinel lymph nodes in clinically node-negative cutaneous melanoma. 2013

Sondak, Vernon K / King, Dennis W / Zager, Jonathan S / Schneebaum, Schlomo / Kim, Julian / Leong, Stanley P L / Faries, Mark B / Averbook, Bruce J / Martinez, Steve R / Puleo, Christopher A / Messina, Jane L / Christman, Lori / Wallace, Anne M. ·H. Lee Moffitt Cancer Center, Tampa, FL, USA. vernon.sondak@moffitt.org ·Ann Surg Oncol · Pubmed #23054107.

ABSTRACT: BACKGROUND: [(99m)Tc]Tilmanocept is a CD206 receptor-targeted radiopharmaceutical designed for sentinel lymph node (SLN) identification. Two nearly identical nonrandomized phase III trials compared [(99m)Tc]tilmanocept to vital blue dye. METHODS: Patients received [(99m)Tc]tilmanocept and blue dye. SLNs identified intraoperatively as radioactive and/or blue were excised and histologically examined. The primary end point, concordance, was the proportion of blue nodes detected by [(99m)Tc]tilmanocept; 90 % concordance was the prespecified minimum concordance level. Reverse concordance, the proportion of radioactive nodes detected by blue dye, was also calculated. The prospective statistical plan combined the data from both trials. RESULTS: Fifteen centers contributed 154 melanoma patients who were injected with both agents and were intraoperatively evaluated. Intraoperatively, 232 of 235 blue nodes were detected by [(99m)Tc]tilmanocept, for 98.7 % concordance (p < 0.001). [(99m)Tc]Tilmanocept detected 364 nodes, for 63.7 % reverse concordance (232 of 364 nodes). [(99m)Tc]Tilmanocept detected at least one node in more patients (n = 150) than blue dye (n = 138, p = 0.002). In 135 of 138 patients with at least one blue node, all blue nodes were radioactive. Melanoma was identified in the SLNs of 22.1 % of patients; all 45 melanoma-positive SLNs were detected by [(99m)Tc]tilmanocept, whereas blue dye detected only 36 (80 %) of 45 (p = 0.004). No positive SLNs were detected exclusively by blue dye. Four of 34 node-positive patients were identified only by [(99m)Tc]tilmanocept, so 4 (2.6 %) of 154 patients were correctly staged only by [(99m)Tc]tilmanocept. No serious adverse events were attributed to [(99m)Tc]tilmanocept. CONCLUSIONS: [(99m)Tc]Tilmanocept met the prespecified concordance primary end point, identifying 98.7 % of blue nodes. It identified more SLNs in more patients, and identified more melanoma-containing nodes than blue dye.

12 Clinical Trial The unique clinical characteristics of melanoma diagnosed in children. 2012

Han, Dale / Zager, Jonathan S / Han, Gang / Marzban, Suroosh S / Puleo, Christopher A / Sarnaik, Amod A / Reed, Damon / Messina, Jane L / Sondak, Vernon K. ·Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA. ·Ann Surg Oncol · Pubmed #22864798.

ABSTRACT: BACKGROUND: Studies have demonstrated a higher rate of nodal metastases in melanoma of childhood, but there is controversy about the overall prognosis relative to adults. We describe a large single-institution experience with pediatric melanoma and assess prognostic characteristics. METHODS: Retrospective review identified 126 patients diagnosed with melanoma at <21 years of age and referred for treatment from 1986 to 2011. Atypical lesions were excluded. Clinicopathologic characteristics were correlated with sentinel lymph node (SLN) status and outcomes. RESULTS: SLN biopsy was positive in 18 of 62 cases (29 %). Increasing Breslow thickness correlated with a positive SLN (p < 0.05). After a median follow-up of 5 years, there were 27 recurrences and 20 deaths. Positive SLN patients had significantly worse recurrence-free survival (RFS, p < 0.05) and significantly worse melanoma-specific survival (MSS, p = 0.05) compared with negative SLN patients. The 5-year RFS and MSS for positive SLN patients were 59.5 and 77.8 %, compared with 93.7 and 96.8 % for negative SLN patients. Recurrences and melanoma-related deaths were often seen beyond 5 years. No deaths have occurred in patients <12 years, but 9.1 % of patients 12-17 years and 17.2 % of patients 18-20 years died from melanoma (p = 0.291). CONCLUSIONS: Children with melanoma have higher rates of SLN metastases (29 %) than adults with comparable melanomas. Despite the higher incidence of nodal metastases, survival is equal to or better than what is reported for adults. However, long-term follow-up is necessary in this population since recurrences and deaths are often seen beyond 5 years.

13 Clinical Trial Sentinel node biopsy in atypical melanocytic neoplasms in childhood: a single institution experience in 24 patients. 2012

Mills, Omie L / Marzban, Suroosh / Zager, Jonathan S / Sondak, Vernon K / Messina, Jane L. ·Department of Pathology and Cell Biology, College of Medicine, University of South Florida, Tampa, FL 33612, USA. ·J Cutan Pathol · Pubmed #22335592.

ABSTRACT: INTRODUCTION: Sentinel lymph node biopsy (SLNB) is a controversial but frequently used adjunct to wide excision of difficult-to-diagnose melanocytic proliferations of childhood. We herein report our institutional experience with SLNB in pediatric patients with these lesions, hereafter referred to as 'atypical melanocytic proliferations'. METHODS: Our prospectively collected melanoma database was queried for patients ≤21 years of age status post-SLNB for a diagnosis of atypical melanocytic proliferation in which the diagnosis of melanoma ≥1 mm in depth was considered in the differential diagnosis by one or more expert dermatopathologists and for which no diagnostic consensus could be reached. RESULTS: Of 24 patients identified over 17 years, 7 patients (29%) had a positive sentinel lymph node (SLN). Six SLN-positive patients underwent complete lymph node dissection, with one (14%) having additional nodal involvement identified. With a median follow-up of 4.1 years (range < 0.1 to 14.8 years), all patients showed no evidence of disease. CONCLUSIONS: Despite a significant rate of identification of melanocytes in SLNs of children with atypical melanocytic proliferations, survival appears favorable and controversy surrounding the significance of nodal involvement remains. Further studies with larger numbers of patients and long-term follow-up are needed before the true prognostic value of SLNB in this setting can be determined.

14 Clinical Trial Phase I clinical trial of the Src inhibitor dasatinib with dacarbazine in metastatic melanoma. 2012

Algazi, A P / Weber, J S / Andrews, S C / Urbas, P / Munster, P N / DeConti, R C / Hwang, J / Sondak, V K / Messina, J L / McCalmont, T / Daud, A I. ·University of California, San Francisco, MTZ-A741, 1600 Divisadero Street, San Francisco, CA 94143, USA. ·Br J Cancer · Pubmed #22127285.

ABSTRACT: BACKGROUND: Src inhibitors sensitise melanoma cells to chemotherapy in preclinical models. The combination of dasatinib and dacarbazine was tested in a phase I trial in melanoma. METHODS: Patients had ECOG performance status 0-2 and normal organ function. Dacarbazine was administered on day 1 and dasatinib on day 2 through 19 of each 21-day cycle. Both were escalated from 50 mg b.i.d. of dasatinib and 800 mg m(-2) of dacarbazine. Available pre-treatment biopsies were sequenced for BRAF, NRAS, and C-Kit mutations. RESULTS: Dose-limiting toxicity was reached at dasatinib 70 mg b.i.d./dacarbazine 1000 mg m(-2), and was predominantly haematological. In 29 patients receiving dasatinib 70 mg b.i.d., the objective response rate (ORR) was 13.8%, the clinical benefit rate (ORR+SD) was 72.4%, the 6-month progression-free survival (PFS) was 20.7%, and the 12-month overall survival (OS) was 34.5%. Two out of three patients who were wild type for BRAF, NRAS, and c-KIT mutations had confirmed partial responses, and one had a minor response. CONCLUSION: The recommended phase II dose is dasatinib 70 mg b.i.d with dacarbazine 800 mg m(-2). PFS and OS data for dasatinib at 70 mg b.i.d. with dacarbazine compared favourably with historical controls. Preliminary data support evaluating tumour mutation status further as a biomarker of response.

15 Article Completion lymphadenectomy for a positive sentinel node biopsy in melanoma patients is not associated with a survival benefit. 2019

Klemen, Nicholas D / Han, Gang / Leong, Stanley P / Kashani-Sabet, Mohammed / Vetto, John / White, Richard / Schneebaum, Schlomo / Pockaj, Barbara / Mozzillo, Nicola / Charney, Kim / Hoekstra, Harald / Sondak, Vernon K / Messina, Jane L / Zager, Jonathan S / Han, Dale. ·Section of Surgical Oncology, Yale School of Medicine, New Haven, Connecticut. · Department of Epidemiology and Biostatistics, School of Public Health, Texas A&M University, College Station, Texas. · California Pacific Medical Center and Research Institute, San Francisco, California. · Division of Surgical Oncology, Oregon Health & Science University, Portland, Oregon. · Levine Cancer Institute, Carolinas Medical Center, Charlotte, North Carolina. · Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. · Mayo Clinic, Phoenix, Arizona. · Instituto Tumori Napoli Fondazione G. Pascale, Napoli, Italy. · St. Joseph Hospital of Orange, Orange, California. · University of Groningen, Groningen, Netherlands. · Moffitt Cancer Center, Tampa, Florida. ·J Surg Oncol · Pubmed #30883771.

ABSTRACT: BACKGROUND: Completion lymph node dissection (CLND) for sentinel lymph node (SLN) disease in melanoma patients is debated. We evaluated the impact of CLND on survival and assessed for predictors of nonsentinel node metastasis (positive CLND). METHODS: Positive SLN melanoma patients were retrospectively identified in the Sentinel Lymph Node Working Group database. Clinicopathological factors were correlated with CLND status, overall survival (OS), and melanoma-specific survival (MSS). RESULTS: There were 953 positive SLN patients of whom 831 (87%) had CLND. Positive CLND was seen in 141 (17%) cases and was associated with worse OS and MSS (both P < 0.001). CLND was not performed (No-CLND) in 122 of 953 positive SLN cases (13%), of whom 100 had follow-up and 18 (18%) developed a nodal recurrence (NR). No significant differences in OS and MSS were seen comparing CLND with No-CLND (P = 0.084, P = 0.161, respectively) and comparing positive CLND with No-CLND NR patients (P = 0.565, P = 0.998, respectively). Gender, primary site, ulceration, and number of positive SLNs were correlated with nonsentinel node metastasis. CONCLUSIONS: Performance of CLND provides prognostic information but is not associated with a survival benefit. Clinical variables can predict a positive CLND in patients who may be at high risk of recurrence.

16 Article BRAF Targeting Sensitizes Resistant Melanoma to Cytotoxic T Cells. 2019

Atay, Cigdem / Kwak, Taekyoung / Lavilla-Alonso, Sergio / Donthireddy, Laxminarasimha / Richards, Allison / Moberg, Valerie / Pilon-Thomas, Shari / Schell, Michael / Messina, Jane L / Rebecca, Vito W / Xiao, Min / Tan, Jiufeng / Zhang, Gao / Weber, Jeffrey S / Herlyn, Meenhard / Sarnaik, Amod A / Gabrilovich, Dmitry I. ·The Wistar Institute, Philadelphia, Philadelphia. · H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. · Perlmutter Cancer Center, New York University Langone Health, New York, New York. · The Wistar Institute, Philadelphia, Philadelphia. dgabrilovich@wistar.org. ·Clin Cancer Res · Pubmed #30765391.

ABSTRACT: PURPOSE: BRAF and MEK inhibitors (BRAFi and MEKi) are actively used for the treatment of metastatic melanoma in patients with BRAF EXPERIMENTAL DESIGN: Investigations were performed RESULTS: Herein we report that in human melanoma cell lines, senstitive and resistant to BRAFi and in PDX from patients who progressed on BRAFi and MEKi therapy, BRAFi caused transient upregulation of mannose-6-phosphate receptor (M6PR). This sensitized tumor cells to CTLs via uptake of granzyme B, a main component of the cytotoxic activity of CTLs. Treatment of mice bearing resistant tumors with BRAFi enhanced the antitumor effect of patients' TILs. A pilot clinical trial of 16 patients with metastatic melanoma who were treated with the BRAFi vemurafenib followed by therapy with TILs demonstrated a significant increase of M6PR expression on tumors during vemurafenib treatment. CONCLUSIONS: BRAF-targeted therapy sensitized resistant melanoma cells to CTLs, which opens new therapeutic opportunities for the treatment of patients with BRAF-resistant disease.

17 Article Management of intussusception in patients with melanoma. 2019

Perez, Matthew C / Sun, James / Farley, Clara / Han, Dale / Sun, Alexander H / Narayan, Deepak / Lowe, Michael / Delman, Keith A / Messina, Jane L / Gonzalez, Ricardo J / Sondak, Vernon K / Khushalani, Nikhil I / Zager, Jonathan S. ·Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida. · Division of Surgical Oncology, Emory University, Atlanta, Georgia. · Division of Surgical Oncology, Department of Surgery, Oregon Health and Science University, Portland, Oregon. · Department of Plastic and Reconstructive Surgery, Johns Hopkins University, Baltimore, Maryland. · Division of Plastic Surgery, Department of Surgery, Yale University, New Haven, Connecticut. ·J Surg Oncol · Pubmed #30734297.

ABSTRACT: BACKGROUND: Increased cross-sectional imaging for surveillance of metastatic melanoma has led to more diagnoses of asymptomatic intussusception. METHODS: We performed a multi-institutional retrospective review of patient records with a history of metastatic melanoma and a diagnosis of intussusception. Patients were divided into three groups: 1) asymptomatic patients without current evidence of melanoma (no evidence of disease [NED]); 2) asymptomatic intussusception and known active metastatic melanoma; 3) symptomatic intussusception and known active metastatic melanoma; the number of patients requiring surgery and intraoperative findings were recorded. RESULTS: We reviewed 73 patients diagnosed with intussusception from 2004 to 2017. Among asymptomatic patients with NED (n = 16), 14 spontaneously resolved and 2 underwent pre-emptive surgery without abnormal intraoperative findings. Of asymptomatic patients with active metastatic disease (n = 32), 25 were initially observed and 7 underwent pre-emptive surgery and 9 of the 25 initially observed patients required surgery for development of symptoms. In this group, all 16 patients undergoing surgery (50% of the group) had intraoperative findings of intussusception and/or metastatic intestinal melanoma.. All symptomatic patients with metastatic melanoma (n = 25) underwent surgery; all had intraoperative findings of intussusception and/or metastatic melanoma except 1 (Meckel's diverticulum). CONCLUSION: Asymptomatic patients with NED do not require surgery and intussusception will likely resolve spontaneously. Asymptomatic patients with known metastatic melanoma may be initially observed, but a low threshold for surgery should be maintained. Symptomatic patients with known metastases should undergo surgery.

18 Article Microsatellitosis in Patients with Melanoma. 2019

Karakousis, Giorgos C / Gimotty, Phyllis A / Leong, Stanley P / Pockaj, Barbara A / White, Richard L / O'Donoghue, Cristina / Sinnamon, Andrew J / Bartlett, Edmund K / Dueck, Amylou C / Gould Rothberg, Bonnie E / Messina, Jane L / Vetto, John T / Sondak, Vernon K / Schneebaum, Schlomo / Kashani-Sabet, Mohammed / Han, Dale / Faries, Mark B / Zager, Jonathan S / Anonymous2571200. ·Hospital of the University of Pennsylvania, Philadelphia, PA, USA. giorgos.karakousis@uphs.upenn.edu. · Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA. · California Pacific Medical Center and Research Institute, San Francisco, CA, USA. · Mayo Clinic, Phoenix, AZ, USA. · Carolinas Medical Center, Charlotte, NC, USA. · Department of Surgery, Rush Medical College, Chicago, IL, USA. · Hospital of the University of Pennsylvania, Philadelphia, PA, USA. · Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Yale University School of Medicine, New Haven, CT, USA. · Moffitt Cancer Center, Tampa, FL, USA. · Oregon Health and Science University, Portland, OR, USA. · Ichilov Hospital, Tel Aviv, Israel. · Angeles Clinic and Research Institute, Los Angeles, CA, USA. ·Ann Surg Oncol · Pubmed #30421045.

ABSTRACT: BACKGROUND: Microsatellitosis (mS) in melanoma has been considered a marker of unfavorable tumor biology, leading to the current American Joint Committee on Cancer staging of IIIB/C/D disease, despite few investigative studies of this entity limited by the small sample sizes and incomplete nodal microstaging. We sought to better characterize outcomes and prognostic factors in a multi-institutional cohort of patients with mS and nodal microstaging. METHODS: The Sentinel Lymph Node Working Group cohort included 414 mS patients who underwent sentinel lymph node (SLN) biopsy. Cox regression analysis was used to evaluate the prognostic significance of established clinicopathologic characteristics. Melanoma-specific survival (MSS) of patients with mS was compared with 3002 similarly staged patients from the Surveillance, Epidemiology, and End Results (SEER) Program registry. RESULTS: The median age of the mS cohort was 64.9 years; 39.6% were female. Median thickness was 3 mm, 40.6% of cases were ulcerated, and the SLN positivity rate was 46.7%. Increasing thickness, male sex, and SLN positivity were significantly associated with poorer MSS. Stage IIIB/C/D 5-year MSS rates were 86.3% (95% confidence interval [CI] 79.4-93.3%), 54.1% (95% CI 45.4-59.7%), and 44.2% (95% CI 25.4-63.0%), respectively. MSS survival for the stage IIIB mS cohort was significantly better than a similarly staged SEER cohort (5-year MSS of 70.1%, 95% CI 66.0-74.2%), while no significant difference was observed for the stage IIIC or D cohorts. CONCLUSIONS: SLN metastases are common and are a significant prognostic factor in patients with mS. Survival in stage IIIB patients with mS was considerably more favorable than their stage would otherwise suggest, which has important implications for decisions regarding adjuvant therapy for patients with mS.

19 Article Female genitourinary tract melanoma: mutation analysis with clinicopathologic correlation: a single-institution experience. 2018

Saglam, Ozlen / Naqvi, Syeda M H / Zhang, Yonghong / Mesa, Tania / Teer, Jamie K / Yoder, Sean / Lee, Jae / Messina, Jane. ·Departments of Anatomic Pathology. · Biostatistics and Bioinformatics. · Cancer Informatics Core. · Molecular Genomics Core, Moffitt Cancer Center, Tampa, Florida, USA. ·Melanoma Res · Pubmed #30028779.

ABSTRACT: Female genitourinary tract melanoma (FGTM) is a rare and often-fatal form of mucosal melanoma. We describe our institutional experience with 55 cases of FGTM, 16 of which were evaluated with next-generation sequencing targeting 151 cancer-associated genes. Tumors tended to be thicker than conventional melanoma at presentation (median: 3.2 mm), were frequently ulcerated (50%), and characterized by incomplete initial resections. Regional lymph nodes showed tumor involvement at presentation in 28% of cases. With a median follow-up of 23.6 months, the median recurrence free survival was 14.5 months and the median overall survival was 29.6 months. Genomic analysis revealed mutually exclusive mutations in TP53 and KIT in 25%, while 19% of cases showed BRAF mutation. NRAS mutation was found in 13% of cases. Mutation in ATRX, previously undescribed in mucosal melanoma, was seen in three (10%) of 16 patients. Only invasive melanoma cases were included in statistical analyses. Patients with three or more mutations had marginally worse overall survival rates than those with two or less (P=0.07). Further studies are required for potential adjuvant treatment modalities to improve survival outcomes of FGTM.

20 Article Stratifying SLN incidence in intermediate thickness melanoma patients. 2018

Chang, James M / Kosiorek, Heidi E / Dueck, Amylou C / Leong, Stanley P L / Vetto, John T / White, Richard L / Avisar, Eli / Sondak, Vernon K / Messina, Jane L / Zager, Jonathan S / Garberoglio, Carlos / Kashani-Sabet, Mohammed / Pockaj, Barbara A. ·Department of Surgery, Mayo Clinic Arizona, Phoenix, AZ, USA. · Section of Biostatistics, Mayo Clinic Arizona, Phoenix, AZ, USA. · Center for Melanoma Research and Treatment, Department of Surgery, California Pacific Medical Center, San Francisco, CA, USA. · Department of Surgery, Oregon Health & Science University, Portland, OR, USA. · Department of Surgery, Levine Cancer Institute, Carolinas Medical Center, Charlotte, NC, USA. · Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA. · Departments of Cutaneous Oncology and Sarcoma, Moffitt Cancer Center, Tampa, FL, USA. · Department of Surgery, Loma Linda University School of Medicine, Loma Linda, CA, USA. · Department of Surgery, Mayo Clinic Arizona, Phoenix, AZ, USA. Electronic address: pockaj.barbara@mayo.edu. ·Am J Surg · Pubmed #29502857.

ABSTRACT: BACKGROUND: Guidelines for melanoma recommend sentinel lymph node biopsy (SLNB) in patients with melanomas ≥1 mm thickness. Recent single institution studies have found tumors <1.5 mm a low-risk group for positive SLNB. METHODS: A retrospective review of the Sentinel Lymph Node Working Group multicenter database identified patients with intermediate thickness melanoma (1.01-4.00 mm) who had SLNB, and assessed predictors for positive SLNB. RESULTS: 3460 patients were analyzed, 584 (17%) had a positive SLNB. Univariate factors associated with a positive SLNB included age <60 (p < .001), tumor on the trunk/lower extremity (p < .001), Breslow depth ≥2 mm (p < .001), ulceration (p < .001), mitotic rate ≥1/mm CONCLUSIONS: Intermediate thickness melanoma has significant heterogeneity of SLNB positivity. Low-risk subgroups can be found among older patients in the absence of high-risk features.

21 Article Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. 2018

Zager, Jonathan S / Gastman, Brian R / Leachman, Sancy / Gonzalez, Rene C / Fleming, Martin D / Ferris, Laura K / Ho, Jonhan / Miller, Alexander R / Cook, Robert W / Covington, Kyle R / Meldi-Plasseraud, Kristen / Middlebrook, Brooke / Kaminester, Lewis H / Greisinger, Anthony / Estrada, Sarah I / Pariser, David M / Cranmer, Lee D / Messina, Jane L / Vetto, John T / Wayne, Jeffrey D / Delman, Keith A / Lawson, David H / Gerami, Pedram. ·Department of Cutaneous Oncology, Moffitt Cancer Center, 10920 N. McKinley Drive room 4123, Tampa, FL, 33612, USA. · Department of Plastic Surgery, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH, 44195, USA. · Department of Dermatology, Knight Cancer Institute, Oregon Health & Science University, 3303 S.W. Bond Avenue, Portland, OR, 97239, USA. · Department of Medical Oncology, University of Colorado School of Medicine, 12801 E. 17th Avenue, Aurora, CO, 80045, USA. · Department of Surgical Oncology, The University of Tennessee Health Science Center, 910 Madison, Suite 303, Memphis, TN, 38163, USA. · Department of Dermatology, University of Pittsburgh Medical Center, 3601 Fifth Avenue, Pittsburgh, PA, 15213, USA. · Department of Pathology, University of Pittsburgh Medical Center, 3708 Fifth Avenue, Suite 500.94, Pittsburgh, PA, 15213, USA. · START Center for Cancer Care, 4383 Medical Drive, San Antonio, TX, 78229, USA. · Castle Biosciences, Inc., 820 S. Friendswood Drive, Suite 201, Friendswood, TX, 77546, USA. · Dermatology North Palm Beach, 840 U.S. Highway Number One, North Palm Beach, FL, 33408, USA. · Research & Development, Kelsey Research Foundation, 5615 Kirby Drive, Suite 660, Houston, TX, 77005, USA. · Affiliated Dermatology, 20401 North 73rd Street, Suite 230, Scottsdale, AZ, 85255, USA. · Pariser Dermatology Specialists, Virginia Clinical Research, Inc., 6160 Kempsville Circle, Suite 200A, Norfolk, VA, 23502, USA. · Eastern Virginia Medical School, P.O. Box 1980, Norfolk, VA, 23501-1980, USA. · Department of Sarcoma Medical Oncology, Seattle Cancer Care Alliance, 825 Eastlake Avenue E, Seattle, WA, 98109, USA. · Department of Anatomic Pathology, Moffitt Cancer Center, 10920 N. McKinley Drive, Tampa, FL, 33612, USA. · Division of Surgical Oncology, Knight Cancer Institute, Oregon Health & Science University, 3303 S.W. Bond Avenue, Portland, OR, 97239, USA. · Department of Surgical Oncology, Northwestern University Feinberg School of Medicine, 251 East Huron Street, Chicago, IL, 60611, USA. · Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 North St. Clair Street, Suite 1600, Chicago, IL, 60611, USA. · Skin Cancer Institute, Northwestern University, Lurie Comprehensive Cancer Center, 420 East Superior Street, Chicago, IL, 60611, USA. · Department of Surgery, Emory University Winship Cancer Institute, 1364 Clifton Road NE, Atlanta, GA, 30322, USA. · Department of Hematology and Medical Oncology, Emory University Winship Cancer Institute, 550 Peachtree Street NE, Atlanta, GA, 30308, USA. · Skin Cancer Institute, Northwestern University, Lurie Comprehensive Cancer Center, 420 East Superior Street, Chicago, IL, 60611, USA. pgerami1@nm.org. · Departments of Dermatology and Pathology, Northwestern University Feinberg School of Medicine, 676 North St. Clair Street, Arkes 1600, Chicago, IL, 60611, USA. pgerami1@nm.org. ·BMC Cancer · Pubmed #29402264.

ABSTRACT: BACKGROUND: The heterogeneous behavior of patients with melanoma makes prognostication challenging. To address this, a gene expression profile (GEP) test to predict metastatic risk was previously developed. This study evaluates the GEP's prognostic accuracy in an independent cohort of cutaneous melanoma patients. METHODS: This multi-center study analyzed primary melanoma tumors from 523 patients, using the GEP to classify patients as Class 1 (low risk) and Class 2 (high risk). Molecular classification was correlated to clinical outcome and assessed along with AJCC v7 staging criteria. Primary endpoints were recurrence-free (RFS) and distant metastasis-free (DMFS) survival. RESULTS: The 5-year RFS rates for Class 1 and Class 2 were 88% and 52%, respectively, and DMFS rates were 93% versus 60%, respectively (P < 0.001). The GEP was a significant predictor of RFS and DMFS in univariate analysis (hazard ratio [HR] = 5.4 and 6.6, respectively, P < 0.001 for each), along with Breslow thickness, ulceration, mitotic rate, and sentinel lymph node (SLN) status (P < 0.001 for each). GEP, tumor thickness and SLN status were significant predictors of RFS and DMFS in a multivariate model that also included ulceration and mitotic rate (RFS HR = 2.1, 1.2, and 2.5, respectively, P < 0.001 for each; and DMFS HR = 2.7, 1.3 and 3.0, respectively, P < 0.01 for each). CONCLUSIONS: The GEP test is an objective predictor of metastatic risk and provides additional independent prognostic information to traditional staging to help estimate an individual's risk for recurrence. The assay identified 70% of stage I and II patients who ultimately developed distant metastasis. Its role in consideration of patients for adjuvant therapy should be examined prospectively.

22 Article High response rate to PD-1 blockade in desmoplastic melanomas. 2018

Eroglu, Zeynep / Zaretsky, Jesse M / Hu-Lieskovan, Siwen / Kim, Dae Won / Algazi, Alain / Johnson, Douglas B / Liniker, Elizabeth / Ben Kong, ? / Munhoz, Rodrigo / Rapisuwon, Suthee / Gherardini, Pier Federico / Chmielowski, Bartosz / Wang, Xiaoyan / Shintaku, I Peter / Wei, Cody / Sosman, Jeffrey A / Joseph, Richard W / Postow, Michael A / Carlino, Matteo S / Hwu, Wen-Jen / Scolyer, Richard A / Messina, Jane / Cochran, Alistair J / Long, Georgina V / Ribas, Antoni. ·University of California Los Angeles, Los Angeles, California, USA. · Moffitt Cancer Center and University of South Florida, Tampa, Florida, USA. · The University of Texas-MD Anderson Cancer Center, Houston, Texas, USA. · University of California San Francisco, San Francisco, California, USA. · Vanderbilt Ingram Cancer Center, Nashville, Tennessee, USA. · Melanoma Institute Australia, Sydney, New South Wales, Australia. · Westmead Hospital, Sydney, New South Wales, Australia. · Memorial Sloan Kettering Cancer Center, New York, New York, USA. · Weill Cornell Medical College, New York, New York, USA. · Georgetown Lombardi Cancer Center, Washington DC, USA. · Parker Institute for Cancer Immunotherapy, San Francisco, California, USA. · Mayo Clinic, Jacksonville, Florida, USA. · The University of Sydney, Sydney, New South Wales, Australia. · Royal Prince Alfred Hospital, Sydney, New South Wales, Australia. · Royal North Shore Hospital, Sydney, New South Wales, Australia. ·Nature · Pubmed #29320474.

ABSTRACT: Desmoplastic melanoma is a rare subtype of melanoma characterized by dense fibrous stroma, resistance to chemotherapy and a lack of actionable driver mutations, and is highly associated with ultraviolet light-induced DNA damage. We analysed sixty patients with advanced desmoplastic melanoma who had been treated with antibodies to block programmed cell death 1 (PD-1) or PD-1 ligand (PD-L1). Objective tumour responses were observed in forty-two of the sixty patients (70%; 95% confidence interval 57-81%), including nineteen patients (32%) with a complete response. Whole-exome sequencing revealed a high mutational load and frequent NF1 mutations (fourteen out of seventeen cases) in these tumours. Immunohistochemistry analysis from nineteen desmoplastic melanomas and thirteen non-desmoplastic melanomas revealed a higher percentage of PD-L1-positive cells in the tumour parenchyma in desmoplastic melanomas (P = 0.04); these cells were highly associated with increased CD8 density and PD-L1 expression in the tumour invasive margin. Therefore, patients with advanced desmoplastic melanoma derive substantial clinical benefit from PD-1 or PD-L1 immune checkpoint blockade therapy, even though desmoplastic melanoma is defined by its dense desmoplastic fibrous stroma. The benefit is likely to result from the high mutational burden and a frequent pre-existing adaptive immune response limited by PD-L1 expression.

23 Article Selecting Patients With Thin Melanoma for Sentinel Lymph Node Biopsy-This Time It's Personal. 2017

Sondak, Vernon K / Messina, Jane L / Zager, Jonathan S. ·Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida. · Department of Oncologic Sciences, University of South Florida Morsani College of Medicine, Tampa. · Department of Surgery, University of South Florida Morsani College of Medicine, Tampa. · Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, Florida. · Department of Pathology & Cell Biology, University of South Florida Morsani College of Medicine, Tampa. · Department of Dermatology, University of South Florida Morsani College of Medicine, Tampa. ·JAMA Dermatol · Pubmed #28724141.

ABSTRACT: -- No abstract --

24 Article Regional Radiation Therapy Impacts Outcome for Node-Positive Cutaneous Melanoma. 2017

Strom, Tobin / Torres-Roca, Javier F / Parekh, Akash / Naghavi, Arash O / Caudell, Jimmy J / Oliver, Daniel E / Messina, Jane L / Khushalani, Nikhil I / Zager, Jonathan S / Sarnaik, Amod / Mulé, James J / Trotti, Andy M / Eschrich, Steven A / Sondak, Vernon K / Harrison, Louis B. ·Department of Radiation Oncology, Moffitt Cancer Center and Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas · Department of Oncologic Sciences, University of South Florida Morsani College of Medicine · Department of Cutaneous Oncology, Moffitt Cancer Center · Department of Pathology & Cell Biology and Dermatology, University of South Florida Morsani College of Medicine · Center for Translational Research, Moffitt Cancer Center · Department of Biomedical Informatics, Moffitt Cancer Center, Tampa, Florida ·J Natl Compr Canc Netw · Pubmed #28404758.

ABSTRACT:

25 Article Treatment of Head and Neck Melanoma In Situ With Staged Contoured Marginal Excisions. 2017

Glazer, Evan S / Porubsky, Caitlin F / Francis, Jeffrey D / Ibanez, Jamie / Castner, Nicholas / Messina, Jane L / Sarnaik, Amod A / Harrington, Michael A / Cruse, C Wayne / Sondak, Vernon K / Zager, Jonathan S. ·From the *Department of Cutaneous Oncology, Moffitt Cancer Center; †Department of Oncologic Sciences, University of South Florida Morsani College of Medicine; ‡Department of Anatomic Pathology, Moffitt Cancer Center, and Departments of Pathology & Cell Biology, and Dermatology, and §Division of Plastic Surgery, Department of Surgery, University of South Florida Morsani College of Medicine, Tampa, FL. ·Ann Plast Surg · Pubmed #27984218.

ABSTRACT: Staged marginal evaluation of melanoma in situ (MIS) is performed to avoid reconstruction on positive margins. Contoured marginal excision (CME) is an excision of a 2-mm wide strip of normal-appearing skin taken approximately 5 mm from the visible tumor periphery. If positive, a new CME is excised; the tumor is resected once negative margins are confirmed. The purpose of this study is to report our experience using this technique for the treatment of head/neck MIS. Clinicopathological data were abstracted for all patients who underwent staged CME followed by central tumor resection for head/neck MIS; patients with invasive melanoma were excluded. Statistical analyses included χ test and t test. Overall, 127 patients with MIS were identified. Fifty-six percent were men; the average age was 68 years. The median number of CME procedures per patient was 1 (range, 1-4). Twenty-three percent of patients required more than 1 CME procedure to achieve negative margins. Local recurrence occurred in 3 of 127 patients after a median follow-up of 5 months. Patients requiring multiple CME procedures were more likely to experience local recurrence (P < 0.001). In conclusion, this technique is an effective method to avoid reconstruction on positive MIS margins with high local disease control rates.

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