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Melanoma: HELP
Articles by Jonathan S. Zager
Based on 117 articles published since 2010
(Why 117 articles?)
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Between 2010 and 2020, Jonathan Zager wrote the following 117 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5
1 Guideline Sentinel Lymph Node Biopsy and Management of Regional Lymph Nodes in Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Clinical Practice Guideline Update. 2018

Wong, Sandra L / Faries, Mark B / Kennedy, Erin B / Agarwala, Sanjiv S / Akhurst, Timothy J / Ariyan, Charlotte / Balch, Charles M / Berman, Barry S / Cochran, Alistair / Delman, Keith A / Gorman, Mark / Kirkwood, John M / Moncrieff, Marc D / Zager, Jonathan S / Lyman, Gary H. ·Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA. · The Angeles Clinic and Research Institute, Santa Monica, CA, USA. · American Society of Clinical Oncology, Alexandria, VA, USA. guidelines@asco.org. · St Luke's Cancer Center, Easton, PA, USA. · Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. · Memorial Sloan Kettering Cancer Center, New York, NY, USA. · MD Anderson Cancer Center, Houston, TX, USA. · Broward Health, Fort Lauderdale, FL, USA. · Los Angeles Center for Health Services, University of California, Los Angeles, CA, USA. · Emory University, Atlanta, GA, USA. · , Silver Spring, MD, USA. · University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA. · Norfolk and Norwich University Hospital, Norwich, UK. · H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. · Fred Hutchinson Cancer Research Center, Seattle, WA, USA. ·Ann Surg Oncol · Pubmed #29236202.

ABSTRACT: PURPOSE: To update the American Society of Clinical Oncology (ASCO)-Society of Surgical Oncology (SSO) guideline for sentinel lymph node (SLN) biopsy in melanoma. METHODS: An ASCO-SSO panel was formed, and a systematic review of the literature was conducted regarding SLN biopsy and completion lymph node dissection (CLND) after a positive sentinel node in patients with melanoma. RESULTS: Nine new observational studies, two systematic reviews and an updated randomized controlled trial (RCT) of SLN biopsy, as well as two randomized controlled trials of CLND after positive SLN biopsy, were included. RECOMMENDATIONS: Routine SLN biopsy is not recommended for patients with thin melanomas that are T1a (non-ulcerated lesions < 0.8 mm in Breslow thickness). SLN biopsy may be considered for thin melanomas that are T1b (0.8 to 1.0 mm Breslow thickness or <0.8 mm Breslow thickness with ulceration) after a thorough discussion with the patient of the potential benefits and risk of harms associated with the procedure. SLN biopsy is recommended for patients with intermediate-thickness melanomas (T2 or T3; Breslow thickness of >1.0 to 4.0 mm). SLN biopsy may be recommended for patients with thick melanomas (T4; > 4.0 mm in Breslow thickness), after a discussion of the potential benefits and risks of harm. In the case of a positive SLN biopsy, CLND or careful observation are options for patients with low-risk micrometastatic disease, with due consideration of clinicopathological factors. For higher risk patients, careful observation may be considered only after a thorough discussion with patients about the potential risks and benefits of foregoing CLND. Important qualifying statements outlining relevant clinicopathological factors, and details of the reference patient populations are included within the guideline.

2 Guideline Sentinel Lymph Node Biopsy and Management of Regional Lymph Nodes in Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Clinical Practice Guideline Update. 2018

Wong, Sandra L / Faries, Mark B / Kennedy, Erin B / Agarwala, Sanjiv S / Akhurst, Timothy J / Ariyan, Charlotte / Balch, Charles M / Berman, Barry S / Cochran, Alistair / Delman, Keith A / Gorman, Mark / Kirkwood, John M / Moncrieff, Marc D / Zager, Jonathan S / Lyman, Gary H. ·Sandra L. Wong, Dartmouth-Hitchcock Medical Center, Lebanon, NH · Mark B. Faries, The Angeles Clinic and Research Institute, Santa Monica · Alistair Cochran, University of California, Los Angeles Center for Health Services, Los Angeles, CA · Erin B. Kennedy, American Society of Clinical Oncology, Alexandria, VA · Sanjiv S. Agarwala, St Luke's Cancer Center, Easton · John M. Kirkwood, University of Pittsburgh Cancer Institute, Pittsburgh, PA · Timothy J. Akhurst, Peter MacCallum Cancer Centre, Victoria, Australia · Charlotte Ariyan, Memorial Sloan Kettering Cancer Center, New York, NY · Charles M. Balch, MD Anderson Cancer Center, Houston, TX · Barry S. Berman, Broward Health, Fort Lauderdale · Jonathan S. Zager, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL · Keith A. Delman, Emory University, Atlanta, GA · Mark Gorman, Silver Spring, MD · Marc D. Moncrieff, Norfolk and Norwich University Hospital, Norwich, United Kingdom · and Gary H. Lyman, Fred Hutchinson Cancer Research Center, Seattle, WA. ·J Clin Oncol · Pubmed #29232171.

ABSTRACT: Purpose To update the American Society of Clinical Oncology (ASCO)-Society of Surgical Oncology (SSO) guideline for sentinel lymph node (SLN) biopsy in melanoma. Methods An ASCO-SSO panel was formed, and a systematic review of the literature was conducted regarding SLN biopsy and completion lymph node dissection (CLND) after a positive sentinel node in patients with melanoma. Results Nine new observational studies, two systematic reviews, and an updated randomized controlled trial of SLN biopsy, as well as two randomized controlled trials of CLND after positive SLN biopsy, were included. Recommendations Routine SLN biopsy is not recommended for patients with thin melanomas that are T1a (nonulcerated lesions < 0.8 mm in Breslow thickness). SLN biopsy may be considered for thin melanomas that are T1b (0.8 to 1.0 mm Breslow thickness or < 0.8 mm Breslow thickness with ulceration) after a thorough discussion with the patient of the potential benefits and risk of harms associated with the procedure. SLN biopsy is recommended for patients with intermediate-thickness melanomas (T2 or T3; Breslow thickness of > 1.0 to 4.0 mm). SLN biopsy may be recommended for patients with thick melanomas (T4; > 4.0 mm in Breslow thickness), after a discussion of the potential benefits and risks of harm. In the case of a positive SLN biopsy, CLND or careful observation are options for patients with low-risk micrometastatic disease, with due consideration of clinicopathological factors. For higher-risk patients, careful observation may be considered only after a thorough discussion with patients about the potential risks and benefits of foregoing CLND. Important qualifying statements outlining relevant clinicopathological factors and details of the reference patient populations are included within the guideline. Additional information is available at www.asco.org/melanoma-guidelines and www.asco.org/guidelineswiki .

3 Editorial Locoregional melanoma: identifying optimal care in a rapidly changing landscape. 2019

Gyorki, David E / Zager, Jonathan S. ·Division of Cancer Surgery, Peter MacCallum Cancer Centre & Department of Surgery, University of Melbourne, Melbourne, VIC, 3000 Australia. · Moffitt Cancer Center, Departments of Cutaneous Oncology & Sarcoma, University of South Florida Morsani School of Medicine, Tampa, FL, 33612 USA. ·Melanoma Manag · Pubmed #31807273.

ABSTRACT: -- No abstract --

4 Editorial Improving clinical outcomes with pembrolizumab in patients with advanced melanoma. 2017

Kim, Dae Won / Zager, Jonathan S / Eroglu, Zeynep. ·Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida, USA. · Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida, USA. Zeynep.Eroglu@moffitt.org. ·Chin Clin Oncol · Pubmed #28285535.

ABSTRACT: -- No abstract --

5 Editorial Recent advances in the treatment of melanoma. 2013

Zager, Jonathan S / Sarnaik, Amod A / Gibney, Geoffrey T / Kudchadkar, Ragini R. ·Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA. Jonathan.Zager@Moffitt.org. ·Cancer Control · Pubmed #24077400.

ABSTRACT: -- No abstract --

6 Editorial What is the significance of the in transit or interval sentinel node in melanoma? 2011

Zager, Jonathan S / Puleo, Christopher A / Sondak, Vernon K. · ·Ann Surg Oncol · Pubmed #21837524.

ABSTRACT: -- No abstract --

7 Editorial Isolated limb infusion for melanoma: a less morbid alternative to hyperthermic isolated limb perfusion in the US. 2010

Santillan, Alfredo A / Zager, Jonathan S. · ·Expert Opin Drug Metab Toxicol · Pubmed #20078252.

ABSTRACT: -- No abstract --

8 Review An evaluation of encorafenib for the treatment of melanoma. 2020

Carr, Michael J / Sun, James / Eroglu, Zeynep / Zager, Jonathan S. ·Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA. ·Expert Opin Pharmacother · Pubmed #31790307.

ABSTRACT:

9 Review Management of Locoregionally Advanced Melanoma. 2020

Pointer, David T / Zager, Jonathan S. ·Department of Cutaneous Oncology, Moffitt Cancer Center, 10920 McKinley Drive, Tampa, FL, 33612; Department of Surgery, University of South Florida Morsani College of Medicine, 13220 USF Laurel Dr., Tampa, FL 33612. ·Surg Clin North Am · Pubmed #31753106.

ABSTRACT: Melanoma has a unique propensity for locoregional metastasis secondary to intralymphatic transit not seen in other cutaneous or soft tissue malignancies. Novel intralesional therapies using oncolytic immunotherapy exhibit increasing response rates with observed bystander effect. Intralesional modalities in combination with systemic immunotherapy are the subject of ongoing clinical trials. Regional therapy is used in isolated limb locoregional metastasis whereby chemotherapy is delivered to an isolated limb avoiding systemic side effects. Multimodal treatment strategy is imperative in the treatment of locoregionally advanced melanoma. One must be versed on these quickly evolving therapeutic options.

10 Review The emergence of neoadjuvant therapy in advanced melanoma. 2019

Sun, James / Kirichenko, Dennis A / Zager, Jonathan S / Eroglu, Zeynep. ·Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA. · Univeristy of South Florida, Morsani College of Medicine, Tampa, FL 33612, USA. ·Melanoma Manag · Pubmed #31807278.

ABSTRACT: The discovery of immunotherapy and targeted therapy has introduced new and effective treatment options for advanced melanoma, providing therapeutic options where none existed before. The natural extension of these novel therapies is to identify their role in the neoadjuvant setting. Neoadjuvant therapy for advanced melanoma is still in its infancy, with a wealth of clinical trials underway. Early results are promising, allowing for management of a disease that previously had few options. We review the current literature and interim results from several ongoing investigations to understand the current state of neoadjuvant treatment options and what is to come. These studies pave the way for further advancements in melanoma therapy.

11 Review Neo-DREAM study investigating Daromun for the treatment of clinical stage IIIB/C melanoma. 2019

Miura, John T / Zager, Jonathan S. ·Departments of Cutaneous Oncology & Sarcoma, Moffitt Cancer Center, Tampa, FL 33612, USA. · Department of Surgery, University of South Florida School of Medicine, Tampa FL, USA. ·Future Oncol · Pubmed #31538818.

ABSTRACT: High-risk resectable melanoma poses therapeutic challenges as this subgroup remains most vulnerable for disease recurrence. Immunotherapy has established its efficacy in cases of advanced melanoma, and now is actively being investigated in the multimodal management of resectable disease. Daromun, an intralesional immunocytokine, has emerged as a unique immunotherapy in its ability to preferentially target tumor cells, resulting in direct destruction, while generating a bystander effect that leads to a distant treatment effect. On the basis of its mechanism of action, there is growing interest in delivering immune-based therapies in a neoadjuvant setting. In this review, the neo-DREAM study, a Phase III trial comparing the safety and efficacy of neoadjuvant Daromun for resectable stage IIIB/C melanoma will be described. Clinical Trial Registration Number: NCT03567889.

12 Review Update on BRAF and MEK inhibition for treatment of melanoma in metastatic, unresectable, and adjuvant settings. 2019

Broman, Kristy Kummerow / Dossett, Lesly A / Sun, James / Eroglu, Zeynep / Zager, Jonathan S. ·a Department of Cutaneous Oncology , Moffitt Cancer Center , Tampa , FL , USA. · b Division of Surgical Oncology , University of Michigan , Ann Arbor , MI , USA. ·Expert Opin Drug Saf · Pubmed #30977681.

ABSTRACT: INTRODUCTION: Selective inhibition of the MAPK pathway with BRAF and MEK inhibitors has emerged as a key component of the treatment of BRAF-mutant unresectable/locally advanced metastatic melanoma. AREAS COVERED: Current data are presented on the efficacy and safety of BRAFi + MEKi combination therapy (dabrafenib/trametinib, vemurafenib/cobimetinib, and encorafenib/binimetinib) from phase I, II, and III trials in the unresectable/locally advanced metastatic setting, as well as neoadjuvant and adjuvant applications. The theoretical basis, pre-clinical findings, clinical trial results and current ongoing clinical studies of combined BRAF/MEK inhibition with immunotherapy, also known as 'triplet therapy,' are also explored. EXPERT OPINION: Combination therapy with BRAF and MEK inhibitors dramatically improves response rates, progression-free survival and overall survival in patients with BRAF-mutant metastatic melanoma compared to historical treatments such as chemotherapy. Some serious adverse effects, including cutaneous squamous cell carcinoma, are attenuated with combination therapy, while less severe and reversible effects including pyrexia, left ventricular dysfunction, and ocular events can be more common with combination therapy. Existing data are insufficient to recommend triplet therapy, or a particular treatment sequence, with respect to BRAF and MEK inhibitors and immune therapies, though results from multiple ongoing trials are anticipated.

13 Review Chemoprevention agents for melanoma: A path forward into phase 3 clinical trials. 2019

Jeter, Joanne M / Bowles, Tawnya L / Curiel-Lewandrowski, Clara / Swetter, Susan M / Filipp, Fabian V / Abdel-Malek, Zalfa A / Geskin, Larisa J / Brewer, Jerry D / Arbiser, Jack L / Gershenwald, Jeffrey E / Chu, Emily Y / Kirkwood, John M / Box, Neil F / Funchain, Pauline / Fisher, David E / Kendra, Kari L / Marghoob, Ashfaq A / Chen, Suephy C / Ming, Michael E / Albertini, Mark R / Vetto, John T / Margolin, Kim A / Pagoto, Sherry L / Hay, Jennifer L / Grossman, Douglas / Ellis, Darrel L / Kashani-Sabet, Mohammed / Mangold, Aaron R / Markovic, Svetomir N / Meyskens, Frank L / Nelson, Kelly C / Powers, Jennifer G / Robinson, June K / Sahni, Debjani / Sekulic, Aleksandar / Sondak, Vernon K / Wei, Maria L / Zager, Jonathan S / Dellavalle, Robert P / Thompson, John A / Weinstock, Martin A / Leachman, Sancy A / Cassidy, Pamela B. ·Department of Medicine, Divisions of Genetics and Oncology, The Ohio State University, Columbus, Ohio. · Department of Surgery, Intermountain Health Care, Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah. · Department of Medicine, The University of Arizona Cancer Center, Tucson, Arizona. · Department of Dermatology, Pigmented Lesion and Melanoma Program, Stanford University Medical Center Cancer Institute, Veterans Affairs Palo Alto Health Care System, Palo Alto, California. · Systems Biology and Cancer Metabolism, Program for Quantitative Systems Biology, University of California Merced, Merced, California. · Department of Dermatology, University of Cincinnati, Cincinnati, Ohio. · Department of Dermatology, Cutaneous Oncology Center, Columbia University Medical Center, New York, New York. · Department of Dermatologic Surgery, Mayo Clinic Minnesota, Rochester, Minnesota. · Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia. · Division of Dermatology, Veterans Affairs Medical Center, Atlanta, Georgia. · Departments of Surgical Oncology and Cancer Biology, Melanoma and Skin Cancer Center, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. · Melanoma and Skin Cancer Program, Department of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. · Department of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. · Dermatology Service, U.S. Department of Veterans Affairs, Eastern Colorado Health Care System, Denver, Colorado. · Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado. · Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio. · Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts. · Department of Internal Medicine, Medical Oncology Division, The Ohio State University, Columbus, Ohio. · Memorial Sloan Kettering Skin Cancer Center and Department of Dermatology, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Medicine, University of Wisconsin, School of Medicine and Public Health, University of Wisconsin Carbone Cancer Center, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin. · Division of Surgical Oncology, Oregon Health & Science University, Portland, Oregon. · Department of Medical Oncology, City of Hope National Medical Center, Duarte, California. · Department of Allied Health Sciences, UConn Institute for Collaboration in Health, Interventions, and Policy, University of Connecticut, Storrs, Connecticut. · Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, New York. · Departments of Dermatology and Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah. · Department of Dermatology, Vanderbilt University Medical Center and Division of Dermatology, Vanderbilt Ingram Cancer Center, Nashville, Tennessee. · Department of Medicine, Tennessee Valley Healthcare System, Nashville Veterans Affairs Medical Center, Nashville, Tennessee. · Center for Melanoma Research and Treatment, California Pacific Medical Center, San Francisco, California. · Department of Dermatology, Mayo Clinic, Scottsdale, Arizona. · Department of Hematology and Oncology, Mayo Clinic, Rochester, Minnesota. · Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Dermatology, University of Iowa, Iowa City, Iowa. · Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. · Department of Dermatology, Boston Medical Center, Boston, Massachusetts. · Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida. · Departments of Oncologic Sciences and Surgery, University of South Florida Morsani College of Medicine, Tampa, Florida. · Department of Dermatology, University of California, San Francisco, San Francisco, California. · Dermatology Service, San Francisco Veterans Affairs Medical Center, San Francisco, California. · Department of Sarcoma, H. Lee Moffitt Cancer Center, Tampa, Florida. · Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington. · Center for Dermatoepidemiology, Veterans Affairs Medical Center, Providence, Rhode Island. · Department of Dermatology, Brown University, Providence, Rhode Island. · Department of Epidemiology, Brown University, Providence, Rhode Island. · Department of Dermatology, Rhode Island Hospital, Providence, Rhode Island. · Department of Dermatology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon. ·Cancer · Pubmed #30281145.

ABSTRACT: Recent progress in the treatment of advanced melanoma has led to unprecedented improvements in overall survival and, as these new melanoma treatments have been developed and deployed in the clinic, much has been learned about the natural history of the disease. Now is the time to apply that knowledge toward the design and clinical evaluation of new chemoprevention agents. Melanoma chemoprevention has the potential to reduce dramatically both the morbidity and the high costs associated with treating patients who have metastatic disease. In this work, scientific and clinical melanoma experts from the national Melanoma Prevention Working Group, composed of National Cancer Trials Network investigators, discuss research aimed at discovering and developing (or repurposing) drugs and natural products for the prevention of melanoma and propose an updated pipeline for translating the most promising agents into the clinic. The mechanism of action, preclinical data, epidemiological evidence, and results from available clinical trials are discussed for each class of compounds. Selected keratinocyte carcinoma chemoprevention studies also are considered, and a rationale for their inclusion is presented. These data are summarized in a table that lists the type and level of evidence available for each class of agents. Also included in the discussion is an assessment of additional research necessary and the likelihood that a given compound may be a suitable candidate for a phase 3 clinical trial within the next 5 years.

14 Review Encorafenib/binimetinib for the treatment of BRAF-mutant advanced, unresectable, or metastatic melanoma: design, development, and potential place in therapy. 2018

Sun, James / Zager, Jonathan S / Eroglu, Zeynep. ·Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA, zeynep.eroglu@moffitt.org. ·Onco Targets Ther · Pubmed #30588020.

ABSTRACT: Major advances in the understanding of the pathophysiology of melanoma have led to a new era of melanoma treatment with targeted therapy and immunotherapies. Since 2011, four new classes of medications with unique mechanisms of action have been approved, which allow melanoma to be treated at many different stages in its development. These include the checkpoint inhibitors anti-PD1/PDL-1 and anti-CTLA4, as well as BRAF inhibitors and MEK inhibitors. The latter two were developed to directly inhibit key components in the MAP kinase pathway with significant breakthrough in the treatment of metastatic and unresectable melanoma. In this review, we discuss the development of targeted therapy of melanoma up to the latest agents encorafenib and binimetinib, including mechanisms of action, adverse effects, and the latest data on treatment response. Current ongoing trials will continue to elucidate these medications and their ultimate impact on melanoma therapy.

15 Review Engineered oncolytic viruses to treat melanoma: where are we now and what comes next? 2018

Rothermel, Luke D / Zager, Jonathan S. ·a Surgical Oncology , Moffitt Cancer Center , Tampa , FL , USA. · b Department of Cutaneous Oncology and Sarcoma , Moffitt Cancer Center , Tampa , FL , USA. ·Expert Opin Biol Ther · Pubmed #30392405.

ABSTRACT: INTRODUCTION: Melanoma treatments have evolved rapidly in the past decade and have included the use of intratumoral injections of engineered oncolytic viruses. One such oncolytic virus is talimogene laherparepvec (T-VEC), which is the first approved therapy of its kind for use in recurrent, unresectable stage IIIB-IVM1a melanoma. Additional oncolytic viruses and their uses in combination with other interventions are currently under investigation. AREAS COVERED: Oncolytic viruses are being evaluated as immunotherapies for a variety of advanced malignancies. In this article, we review T-VEC, the only FDA-approved engineered oncolytic virus, in addition to ongoing research regarding other oncolytic viruses for the treatment of advanced melanomas. Finally, we discuss opportunities to improve these therapies through viral, host, and tumor-related modifications. EXPERT OPINION: Engineered and naturally oncolytic viruses have demonstrable local and systemic efficacy as immunotherapies in cancer. T-VEC leads the way with improved survival outcomes for unresectable, stage IIIB-IVM1a melanoma as a monotherapy, and is demonstrating superior results in combination with systemic checkpoint inhibitors. Additional viral vectors show acceptable safety profiles and varying degrees of efficacy in targeting melanoma. The indications for use of oncolytic viruses will expand as their efficacy and appropriate usage is better understood in coming years.

16 Review Regional therapies for locoregionally advanced and unresectable melanoma. 2018

Weitman, Evan S / Zager, Jonathan S. ·Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL, 33612, USA. · Department of Cutaneous Oncology, Moffitt Cancer Center, 10920 McKinley Dr., MKC 4123, Tampa, FL, 33612, USA. jonathan.zager@moffitt.org. ·Clin Exp Metastasis · Pubmed #29736626.

ABSTRACT: Locoregionally advanced and unresectable disease can be seen in up to 10% of melanoma patients. Treatment options for these patients have been evolving most notably over the past few decades and have demonstrated efficacy through multiple intra-arterial as well as intralesional therapies. Isolated limb perfusions and isolated limb infusions have been utilized to treat locoregionally advanced melanoma of the extremity with overall response rates up to 90% in some reports. Intralesional therapies, for in transit metastatic melanoma, such as Bacille Calmette-Guerin, talimogene laherparepvec, and PV-10 (Rose Bengal) have all demonstrated efficacy in the treatment of unresectable cutaneous melanoma. The treatment effect due to intralesional injection has been identified in directly injected lesions as well as in distant uninjected "bystander lesions" with some injectables. This bystander effect is likely an immunologic reaction due to tumor antigen release, antigen-presenting cell uptake, T cell activation and subsequent bystander tumor destruction in uninjected lesions. Treatment options for unresectable melanoma metastases limited to the liver include isolated hepatic perfusion, which can now be performed through a minimally invasive approach known as percutaneous hepatic perfusion. These intra-arterial and intralesional regional therapies offer a variety of effective treatment modalities for unresectable disease and may potentially be combined with systemic treatments, such as immunotherapy, in the future treatment of locoregionally advanced melanoma.

17 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.

18 Review Pharmacokinetic drug evaluation of talimogene laherparepvec for the treatment of advanced melanoma. 2018

Burke, Erin E / Zager, Jonathan S. ·a Moffitt Cancer Center , Tampa , FL , USA. · b Department of Cutaneous Oncology , Moffitt Cancer Center , Tampa , FL , USA. ·Expert Opin Drug Metab Toxicol · Pubmed #29557682.

ABSTRACT: INTRODUCTION: Current treatment of advanced melanoma is rapidly changing with the introduction of new and effective therapies including systemic as well as locoregional therapies. An example of one such locoregional therapy is intralesional injection with talimogene laherparepvec (T-VEC). Areas covered: T-VEC has been shown in a number of studies to be an effective treatment for patients with stage IIIB, IIIC and IVM1a melanoma. In this article the effectiveness, pharmacokinetics and safety profile of T-VEC is reviewed. Additionally, new research looking at combinations of T-VEC and systemic immunotherapies is reviewed. Expert opinion: Overall, T-VEC is an easily administered, safe, well tolerated and effective oncolytic viral therapy for the treatment of stage IIIB, IIIC, IVM1a unresectable and injectable metastatic melanoma. Recently published studies are showing promising results when T-VEC is combined with systemic therapy and this may be the way of the not too distant future in how we treat metastatic melanoma. Continued work regarding the use of T-VEC with other systemic agents will provide new and more effective treatment strategies for advanced melanoma.

19 Review Intralesional therapy as a treatment for locoregionally metastatic melanoma. 2018

Miura, John T / Zager, Jonathan S. ·a Departments of Cutaneous Oncology and Sarcoma, Moffitt Cancer Center , University of South Florida School of Medicine , Tampa , FL , USA. ·Expert Rev Anticancer Ther · Pubmed #29466885.

ABSTRACT: INTRODUCTION: The emergence of novel intralesional therapies have dramatically changed the treatment landscape for melanoma. The heterogeneous presentation of melanoma continues to pose challenges for clinicians, especially when dealing with advanced locoregional disease. Intralesional therapies have the benefit of causing local tumor destruction, while minimizing systemic toxicity. Moreover, the integration of immunotherapeutic agents into intralesional compounds has resulted in the additional benefit of a bystander effect, whereby untreated distant lesions also derive a benefit from treatment. Intralesional therapy has assumed an important role in the management of unresectable, locoregional disease for melanoma. Areas covered: Multiple intralesional agents have been studied over the years, with only a few demonstrating promising results. This review will provide an overview of the different intralesional agents for melanoma. Mechanisms of action, clinical efficacy, and side effects will be the primary focus. Expert commentary: Treatment options for advanced melanoma continue to evolve. Attractive new therapies delivered by an intralesional route has demonstrated promising results, with minimal side effects. The ideal treatment strategy for melanoma will remain a multimodal approach; intralesional therapy provides an additional tool in the treatment armamentarium for melanoma.

20 Review Current standards of surgical management in primary melanoma. 2018

Perez, Matthew C / Orcutt, Sonia T / Zager, Jonathan S. ·Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA. · Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA - Jonathan.zager@moffitt.org. ·G Ital Dermatol Venereol · Pubmed #28895666.

ABSTRACT: Melanoma accounts for the majority of skin cancer-related deaths, and its incidence continues to rise worldwide. While advanced disease has historically been associated with poor long-term survival, early-stage disease has a favorable prognosis and therefore, early diagnosis is paramount. Resection of primary melanoma requires a balance of maximizing oncological outcome while minimizing morbidity. Wide excision with 1-2 cm margins, depending on depth of the tumor, is the standard of care for surgical treatment of primary, invasive melanoma. Sentinel lymph node biopsy is indicated for patients with clinically node-negative, intermediate-thickness primary melanomas but should also be considered in selected patients with thin and thick primaries. In this article, historical perspectives and key clinical trials regarding the current guidelines for the surgical management of primary melanoma are discussed.

21 Review Chemosaturation With Percutaneous Hepatic Perfusion in Unresectable Hepatic Metastases. 2017

Glazer, Evan S / Zager, Jonathan S. ·Division of Surgical Oncology, Department of Surgery, University of Tennessee Health Sciences Center, Memphis,TN. · Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL. Jonathan.Zager@Moffitt.org. ·Cancer Control · Pubmed #28178721.

ABSTRACT: BACKGROUND: In patients with hepatic metastases from solid-organ malignancies, surgical resection may be a potentially curative option, but it is not possible in most cases. Chemosaturation with percutaneous hepatic perfusion was developed for the management of unresectable metastases to the liver. METHODS: Relevant medical literature was summarized with regard to the outcomes and limitations of chemosaturation with percutaneous hepatic perfusion. RESULTS: Six articles were identified that contained data on 91 individuals who received chemosaturation with percutaneous hepatic perfusion. More than 60% of these study patients were diagnosed with ocular melanoma. The overall response rate was 48% and the rate of disease control was 90%. Chemosaturation with percutaneous hepatic perfusion improved the rates of overall and hepatic progression-free survival (PFS). The data are limited but suggest that the rate of PFS was improved in study patients with isolated melanoma hepatic metastases who received chemosaturation with percutaneous hepatic perfusion compared with those assigned to standard care. CONCLUSIONS: Our results suggest that chemosaturation with percutaneous hepatic perfusion produces favorable tumor response rates in select individuals with unresectable hepatic metastases from multiple primary cancers, particularly ocular and cutaneous melanomas. Data from a single randomized clinical trial have also shown that chemosaturation with percutaneous hepatic perfusion can affect hepatic PFS in certain patients.

22 Review The safety of talimogene laherparepvec for the treatment of advanced melanoma. 2017

Gangi, Alexandra / Zager, Jonathan S. ·a Department of Cutaneous Oncology , Moffitt Cancer Center , Tampa , FL , USA. ·Expert Opin Drug Saf · Pubmed #27989216.

ABSTRACT: INTRODUCTION: Talimogene laherparepvec (T-VEC, IMLYGIC) is an oncolytic herpes virus type I used as intralesional therapy for the treatment of unresectable metastatic melanoma in a cutaneous, subcutaneous, or nodal location. Talimogene laherparepvec selectively replicates within and lyses tumor cells while producing granulocyte macrophage colony-stimulating factor (GM-CSF), which may promote an immune mediated antitumor response. Areas covered: The US Food and Drug Administration approved Talimogene laherparepvec in late 2015 following the completion of phase I, II and III trials that demonstrated safety and efficacy. Current NCCN practice guidelines have added Talimogene laherparepvec as a primary treatment for stage IIIB/C and stage IVM1a melanoma patients with evidence of good durable response rates, and this article sets out to review the use and safety and efficacy of T-VEC Expert opinion: Treatment options for locally advanced and metastatic melanoma are expanding with new developments in immunotherapy and immune checkpoint inhibitors. The ideal treatment of metastatic melanoma continues to be multimodal, combining systemic treatments, intralesional and regional therapies, surgery and radiotherapy to achieve optimal outcomes. Use of talimogene laherparepvec as intrelsional therapy has demonstrated promising effects in select patients with advanced melanoma. Future directions for Talimogene laherparepvec include combination therapies with other systemic immunotherapies such as anti-CTLA-4 antibody and anti-PD-1 drugs.

23 Review Talimogene laherparepvec: overview, combination therapy and current practices. 2016

O'Donoghue, Cristina / Doepker, Matthew P / Zager, Jonathan S. ·Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, 33647 USA. ·Melanoma Manag · Pubmed #30190898.

ABSTRACT: Talimogene laherparepvec (T-VEC, Imlygic

24 Review Intralesional and systemic immunotherapy for metastatic melanoma. 2016

Luu, Carrie / Khushalani, Nikhil I / Zager, Jonathan S. ·a Department of Cutaneous Oncology , H. Lee Moffitt Cancer Center , Tampa , FL , USA. · b Department of Cutaneous Oncology , Director of Regional Therapies Moffitt Cancer Center , Tampa , FL , USA. ·Expert Opin Biol Ther · Pubmed #27602429.

ABSTRACT: INTRODUCTION: Immunotherapy has revolutionized the treatment of metastatic melanoma and dramatically improved patient outcomes. Ipilimumab, an inhibitor of cytotoxic T-lymphocyte antigen-4 (CTLA-4), was the first immunotherapeutic agent to demonstrate improved survival in advanced melanoma. More recently, other immune checkpoint inhibitors, including the programmed death-1 (PD-1) inhibitors pembrolizumab and nivolumab, have demonstrated efficacy in locally advanced unresectable and metastatic melanoma. In addition to systemically delivered immunotherapies, intralesional therapies such as talimogene laherparepvec (TVEC) play an important role in the treatment of locoregionally advanced and metastatic melanoma. Areas covered: This review provides an overview of the mechanisms behind immune checkpoint inhibitors. Clinical evidence of their efficacy is presented and discussion of new patterns of response and associated immune related adverse events associated with immunotherapy are provided. Expert opinion: Treatment options for locally advanced and metastatic melanoma are expanding with new developments in immunotherapy and immune checkpoint inhibitors. The utility of these novel therapies in the adjuvant setting is currently being explored. The ideal treatment of metastatic melanoma continues to be multimodal, combining systemic treatments, intralesional and regional therapies, surgery and radiotherapy to achieve optimal outcomes.

25 Review Clinical utilities and biological characteristics of melanoma sentinel lymph nodes. 2016

Han, Dale / Thomas, Daniel C / Zager, Jonathan S / Pockaj, Barbara / White, Richard L / Leong, Stanley Pl. ·Dale Han, Daniel C Thomas, Department of Surgery, Yale University School of Medicine, New Haven, CT 06520, United States. ·World J Clin Oncol · Pubmed #27081640.

ABSTRACT: An estimated 73870 people will be diagnosed with melanoma in the United States in 2015, resulting in 9940 deaths. The majority of patients with cutaneous melanomas are cured with wide local excision. However, current evidence supports the use of sentinel lymph node biopsy (SLNB) given the 15%-20% of patients who harbor regional node metastasis. More importantly, the presence or absence of nodal micrometastases has been found to be the most important prognostic factor in early-stage melanoma, particularly in intermediate thickness melanoma. This review examines the development of SLNB for melanoma as a means to determine a patient's nodal status, the efficacy of SLNB in patients with melanoma, and the biology of melanoma metastatic to sentinel lymph nodes. Prospective randomized trials have guided the development of practice guidelines for use of SLNB for melanoma and have shown the prognostic value of SLNB. Given the rapidly advancing molecular and surgical technologies, the technical aspects of diagnosis, identification, and management of regional lymph nodes in melanoma continues to evolve and to improve. Additionally, there is ongoing research examining both the role of SLNB for specific clinical scenarios and the ways to identify patients who may benefit from completion lymphadenectomy for a positive SLN. Until further data provides sufficient evidence to alter national consensus-based guidelines, SLNB with completion lymphadenectomy remains the standard of care for clinically node-negative patients found to have a positive SLN.

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