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Melanoma: HELP
Articles from Westmead Hospital
Based on 192 articles published since 2010
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These are the 192 published articles about Melanoma that originated from Westmead Hospital during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8
1 Editorial Is chemotherapy still an option in the treatment of melanoma? 2015

Carlino, M S / Long, G V. ·Melanoma Institute Australia, Sydney The Sydney Medical School, The University of Sydney, Sydney Department of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney. · Melanoma Institute Australia, Sydney The Sydney Medical School, The University of Sydney, Sydney The Mater Hospital, North Sydney, Australia georgina.long@sydney.edu.au. ·Ann Oncol · Pubmed #26374287.

ABSTRACT: -- No abstract --

2 Editorial Molecular biomarkers of prognosis in melanoma: how far are we from the clinic? 2013

Schramm, Sarah-Jane / Menzies, Alexander M / Mann, Graham J. ·aThe University of Sydney at Westmead Millennium Institute for Medical Research bMelanoma Institute Australia, Sydney, New South Wales, Australia. ·Melanoma Res · Pubmed #24165033.

ABSTRACT: -- No abstract --

3 Review Assessment of kidney transplant suitability for patients with prior cancers: is it time for a rethink? 2019

Lim, Wai H / Au, Eric / Krishnan, Anoushka / Wong, Germaine. ·Department of Renal Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia. · School of Medicine, University of Western Australia, Perth, WA, Australia. · Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia. · Centre for Transplant and Renal Research, Westmead Hospital, Sydney, NSW, Australia. · Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, NSW, Australia. ·Transpl Int · Pubmed #31385629.

ABSTRACT: Kidney transplant recipients have up to a 100-fold greater risk of incident cancer compared with the age/sex-matched general population, attributed largely to chronic immunosuppression. In patients with a prior history of treated cancers, the type, stage and the potential for cancer recurrence post-transplant of prior cancers are important factors when determining transplant suitability. Consequently, one of the predicaments facing transplant clinicians is to determine whether patients with prior cancers are eligible for transplantation, balancing between the accelerated risk of death on dialysis, the projected survival benefit and quality of life gains with transplantation, and the premature mortality associated with the potential risk of cancer recurrence post-transplant. The guidelines informing transplant eligibility or screening and preventive strategies against cancer recurrence for patients with prior cancers are inconsistent, underpinned by uncertain evidence on the estimates of the incidence of cancer recurrence and the lack of stage-specific outcomes data, particularly among those with multiple myeloma or immune-driven malignancies such as melanomas. With the advent of newer anti-cancer treatment options, it is unclear whether the current guidelines for those with prior cancers remain appropriate. This review will summarize the uncertainties of evidence informing the current recommendations regarding transplant eligibility of patients with prior cancers.

4 Review The role of radiotherapy in the management of non-melanoma skin cancer. 2019

Garbutcheon-Singh, Kieran B / Veness, Michael J. ·Department of Radiation Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia. · University of Sydney, Sydney, New South Wales, Australia. ·Australas J Dermatol · Pubmed #30931531.

ABSTRACT: The global incidence of non-melanoma skin cancer continues to increase as the global population ages with the highest incidence in the world occurring in Australian and New Zealand patients. There are numerous treatment options available for non-melanoma skin cancer patients of which radiotherapy is an efficacious and versatile tissue preserving non-surgical (or medical) option. In patients where excision may not be an option (medically/technically inoperable) or considered less ideal (e.g. cosmetic outcome), radiotherapy offers an excellent option. Following surgery, adjuvant radiotherapy in patients with unfavourable pathology can decrease the risk of recurrence and associated morbidity. Elderly and co-morbid patients with poor performance status can benefit from short-course hypofractionated radiotherapy in the setting where surgery is not an option. As with any modality, radiotherapy has advantages and disadvantages and it is therefore important for clinicians to appreciate these. We aim to present an update for clinicians that manage patients with non-melanoma skin cancer on the role of radiotherapy.

5 Review Oncogenic signaling in uveal melanoma. 2018

Park, John J / Diefenbach, Russell J / Joshua, Anthony M / Kefford, Richard F / Carlino, Matteo S / Rizos, Helen. ·Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia. · Melanoma Institute Australia, Sydney, New South Wales, Australia. · Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, New South Wales, Australia. · Department of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead and Blacktown Hospitals, Sydney, New South Wales, Australia. ·Pigment Cell Melanoma Res · Pubmed #29738114.

ABSTRACT: Uveal melanoma is the most common primary cancer of the eye, and despite rapidly emerging insights into the molecular profile of this disease, prognosis of patients with metastatic uveal melanoma remains poor with mortality rates unchanged in over 35 years. Early genetic events activate G protein-coupled receptor signaling in nearly all uveal tumors via mutually exclusive mutations in the GNAQ, GNA11, CYSLTR2, or PLCB4 genes. A multitude of signaling cascades downstream of G protein activation, including protein kinase C and mitogen-activated protein kinase activity, are actionable, and many ongoing clinical trials are targeting these pathways. Additional cytogenetic and genetic changes, however, including chromosome 3 monosomy, mutations in the BAP1 tumor suppressor gene, alterations in the splicing factors SRSF2/SF3B1, and mutations in the translation initiation factor EIF1AX, modulate signaling output in uveal tumors and modify the risk of metastases. Here, we review the complex interactions between genetic, molecular signaling, and prognostic profiles in uveal melanoma; the clinical implications of these interactions; and the latest potential targets for rational therapy.

6 Review Metastases to the parotid gland - A review of the clinicopathological evolution, molecular mechanisms and management. 2018

Badlani, James / Gupta, Ruta / Smith, Joel / Ashford, Bruce / Ch'ng, Sydney / Veness, Michael / Clark, Jonathan. ·Sydney Head and Neck Cancer Institute, Department of Head and Neck Surgery, Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia; Department of Oral and Maxillofacial Surgery, Gold Coast University Hospital, Southport, Queensland, Australia. Electronic address: jsbadlani@yahoo.com. · Department of Pathology, Royal Prince Alfred Hospital, New South Wales, Australia; Central Clinical School, University of Sydney, New south Wales, Australia. · Sydney Head and Neck Cancer Institute, Department of Head and Neck Surgery, Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia. · Sydney Head and Neck Cancer Institute, Department of Head and Neck Surgery, Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia; Department of Surgery, Wollongong Hospital, Wollongong, New South Wales, Australia. · Central Clinical School, University of Sydney, New south Wales, Australia; Department of Radiation Oncology, Westmead Hospital, Westmead, New South Wales, Australia. · Sydney Head and Neck Cancer Institute, Department of Head and Neck Surgery, Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia; Central Clinical School, University of Sydney, New south Wales, Australia. ·Surg Oncol · Pubmed #29549903.

ABSTRACT: Metastases to the parotid gland are the commonest cause of parotid malignancies in many regions of the world including Australia. The most common etiology of these metastases is head and neck cutaneous squamous cell carcinoma (HNcSCC) followed by melanoma of the head and neck. This article focuses on the management of the aforementioned pathologies including Merkel cell carcinoma (MCC).

7 Review Efficacy of hypofractionated radiotherapy in patients with non-melanoma skin cancer: Results of a systematic review. 2018

Gunaratne, Dakshika A / Veness, Michael J. ·Department of Otolaryngology, Head and Neck Surgery, Westmead Hospital, Sydney, New South Wales, Australia. · Department of Radiation Oncology, Westmead Hospital, Sydney, New South Wales, Australia. · Department of Radiation Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia. · University of Sydney, Sydney, New South Wales, Australia. ·J Med Imaging Radiat Oncol · Pubmed #29524319.

ABSTRACT: Radiation oncologists are increasingly tasked with the management of elderly patients with non-melanoma skin cancer, unsuitable for surgical intervention due to inoperable lesions and/or poor performance status. In this cohort, hypofractionated radiotherapy, delivered either daily, alternative daily or once weekly is highly effective. A systematic literature search was conducted of PUBMED, MEDLINE and EMBASE databases using the algorithm ('radiotherapy' OR 'radiation therapy' OR 'brachytherapy') AND ('hypofraction' OR 'hypofractionated' OR 'hypofractionation') AND ('skin neoplasms' OR 'carcinoma' OR 'malignancy') AND ('skin' OR 'epidermis' OR 'epidermal' OR 'cutaneous'). Forty relevant publications (1983-2017) encompassing 12,337 irradiated lesions were retrieved. Studies documented a mean age of 71.73 years and male predilection (54.5%). Both external beam radiotherapy and brachytherapy were utilized. Tumour subtype was squamous cell carcinoma (23.5%), basal cell carcinoma (75.2%) or others (1.3%). Irradiated lesions were primary (or denovo) (92.6%), located on the head and neck (95.7%) and received definitive therapy (96.5%). Analysis demonstrated a mean weighted total radiotherapy dose (38.15 Gy), dose per fraction (7.95 Gy) and treatments per week (2.98). Despite significant heterogeneity in the study population, the radiotherapy delivered and follow-up, local recurrence rate (crude or Kaplan-Meier analysis) did not exceed 7.9% in all but three of the 36 publications providing these data. Twenty-nine publications documented local control exceeding 90%. There is a body of evidence documenting the efficacy of hypofractionated radiotherapy as an option that confers no obvious disadvantage in local control when compared to traditional more protracted radiotherapy schedules.

8 Review Liquid biomarkers in melanoma: detection and discovery. 2018

Lim, Su Yin / Lee, Jenny H / Diefenbach, Russell J / Kefford, Richard F / Rizos, Helen. ·Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia. · Melanoma Institute Australia, Sydney, NSW, Australia. · Department of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead and Blacktown Hospitals, Sydney, NSW, Australia. · Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia. Helen.rizos@mq.edu.au. · Melanoma Institute Australia, Sydney, NSW, Australia. Helen.rizos@mq.edu.au. · Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, 2 Technology Place, Sydney, NSW, 2109, Australia. Helen.rizos@mq.edu.au. ·Mol Cancer · Pubmed #29343260.

ABSTRACT: A vast array of tumor-derived genetic, proteomic and cellular components are constantly released into the circulation of cancer patients. These molecules including circulating tumor DNA and RNA, proteins, tumor and immune cells are emerging as convenient and accurate liquid biomarkers of cancer. Circulating cancer biomarkers provide invaluable information on cancer detection and diagnosis, prognosticate patient outcomes, and predict treatment response. In this era of effective molecular targeted treatments and immunotherapies, there is now an urgent need to implement use of these circulating biomarkers in the clinic to facilitate personalized therapy. In this review, we present recent findings in circulating melanoma biomarkers, examine the challenges and promise of evolving technologies used for liquid biomarker discovery, and discuss future directions and perspectives in melanoma biomarker research.

9 Review Management of the cutaneous adverse effects of antimelanoma therapy. 2017

Liu, Rose Congwei / Consuegra, Germana / Fernández-Peñas, Pablo. ·Department of Dermatology, Westmead Hospital, Sydney 2145, Australia. · Westmead Clinical School, University of Sydney Medical School, Sydney 2145, Australia. ·Melanoma Manag · Pubmed #30190925.

ABSTRACT: The advent of targeted therapy and immunotherapy has revolutionized the management of advanced melanoma. However, these novel therapies are associated with adverse effects (AEs), of which cutaneous toxicities are the most frequently observed. These cutaneous AEs can exert significant morbidity and impact on patient quality of life, hence the recognition and management of AEs is fundamental in preventing interruption or cessation of survival-prolonging treatments. Additionally, knowledge of these AEs are necessary in order for healthcare professionals to counsel patients when starting treatment and in the initiation of AE prophylaxis. The incidence and clinical presentation of the cutaneous toxicities of novel melanoma therapies will be discussed, and treatment guidelines provided.

10 Review Cutaneous Adverse Events of New Anti-melanoma Therapies: Classification and Management. 2017

Hwang, S J E / Anforth, R / Carlos, G / Fernandez-Peñas, P. ·Department of Dermatology, Westmead Hospital, Westmead, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia. ·Actas Dermosifiliogr · Pubmed #27642030.

ABSTRACT: Over the past decade, targeted therapies such as BRAF inhibitors, MEK inhibitors and immunotherapies such as anti-CTLA4 and anti-PD1 antibodies have emerged as novel treatments of advanced melanoma. Along with increased use of these therapies, a range of cutaneous adverse events have also emerged, varying from more serious and frequent cutaneous squamous cell carcinoma to mere cosmetic changes such as curly hair or rare severe toxic epidermal necrolysis. Early detection and management of these cutaneous adverse events will aid patients to receive accurate treatment, avoid unnecessary discontinuation of anti-tumour treatment and improve the patient's overall quality of life. This review will describe various cutaneous adverse events of anti-melanoma therapies and its management.

11 Review Biology and treatment of BRAF mutant metastatic melanoma. 2016

Kong, Benjamin Y / Carlino, Matteo S / Menzies, Alexander M. ·Crown Princess Mary Cancer Care Centre, Westmead, Sydney, NSW 2145, Australia. · Melanoma Institute Australia, North Sydney, NSW 2060, Australia. · Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia. · Royal North Shore Hospital, Sydney, NSW 2065, Australia. ·Melanoma Manag · Pubmed #30190871.

ABSTRACT: BRAF inhibitors were among the first systemic therapies to show clinical benefit in metastatic melanoma. Here, we review the spectrum of BRAF mutations in melanoma, their role in oncogenesis, clinicopathological associations and response to treatment. The differing biology and clinical features of V600E- and V600K-mutated melanoma are outlined. The molecular changes associated with

12 Review Ipilimumab Combined with Nivolumab: A Standard of Care for the Treatment of Advanced Melanoma? 2016

Carlino, Matteo S / Long, Georgina V. ·Melanoma Institute Australia, The University of Sydney, and Crown Princess Mary Cancer Centre, Westmead and Blacktown Hospitals, Sydney, Australia. · Melanoma Institute Australia, The University of Sydney, and Royal North Shore and Mater Hospitals, Sydney, Australia. georgina.long@sydney.edu.au. ·Clin Cancer Res · Pubmed #27340279.

ABSTRACT: Ipilimumab, an inhibitor of CTLA-4 on T cells, was the first drug to improve overall survival in patients with advanced melanoma. Subsequently, inhibitors of PD-1, including nivolumab and pembrolizumab, were shown to be superior to ipilimumab with a more favorable safety profile. The combination of ipilimumab and nivolumab is associated with a further improvement in response rate and progression-free survival; however, the combination is associated with an increased rate of immune-related toxicities. In 2015, the FDA approved the combination for the treatment of BRAF wild-type advanced melanoma. This review examines the preclinical rationale for the combination of ipilimumab and nivolumab as well as the efficacy and toxicity data from clinical trials in patients with advanced melanoma. Finally, alternative treatment options are discussed with a focus on patient selection. Clin Cancer Res; 22(16); 3992-8. ©2016 AACR.

13 Review PD-1 and PD-L1 inhibitors in melanoma treatment: past success, present application and future challenges. 2016

Lee, Jenny / Kefford, Richard / Carlino, Matteo. ·Crown Princess Mary Cancer Centre, Westmead hospital, Westmead, NSW 2145, Australia. · Departments of Clinical Medicine and Biomedical Sciences, Macquarie University, NSW 2109, Australia. · Melanoma Institute Australia, North Sydney, NSW, Australia. · University of Sydney, Sydney, NSW, Australia. ·Immunotherapy · Pubmed #27197541.

ABSTRACT: Anti-programmed death (PD)-1 antibodies have now become the standard of care for advanced melanoma, with two drugs gaining US FDA approval in recent years: nivolumab and pembrolizumab. Both have demonstrated significant activity and durable response with a manageable toxicity profile. Despite initial success, ongoing challenges include patient selection and predictors of response, innate resistance and optimizing combination strategies. In this overview, we take a closer look at the history and development of therapeutic targets to the PD-1/PD-ligand (L)1 pathway, clinical evidence, availability of biomarkers and their limitations in clinical practice and future strategies to improve treatment outcomes.

14 Review Identification, Review, and Systematic Cross-Validation of microRNA Prognostic Signatures in Metastatic Melanoma. 2016

Jayawardana, Kaushala / Schramm, Sarah-Jane / Tembe, Varsha / Mueller, Samuel / Thompson, John F / Scolyer, Richard A / Mann, Graham J / Yang, Jean. ·School of Mathematics and Statistics, The University of Sydney, Sydney, NSW, Australia. · The Westmead Millennium Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia; Melanoma Institute Australia, Sydney, NSW, Australia. Electronic address: sarah-jane.schramm@sydney.edu.au. · The Westmead Millennium Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia; Melanoma Institute Australia, Sydney, NSW, Australia. · Melanoma Institute Australia, Sydney, NSW, Australia; Discipline of Surgery, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia. · Melanoma Institute Australia, Sydney, NSW, Australia; Discipline of Pathology, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia. ·J Invest Dermatol · Pubmed #26763444.

ABSTRACT: In metastatic melanoma, it is vital to identify and validate biomarkers of prognosis. Previous studies have systematically evaluated protein biomarkers or mRNA-based expression signatures. No such analyses have been applied to microRNA (miRNA)-based prognostic signatures. As a first step, we identified two prognostic miRNA signatures from publicly available data sets (Gene Expression Omnibus/The Cancer Genome Atlas) of global miRNA expression profiling information. A 12-miRNA signature predicted longer survival after surgery for resection of American Joint Committee on Cancer stage III disease (>4 years, no sign of relapse) and outperformed American Joint Committee on Cancer standard-of-care prognostic markers in leave-one-out cross-validation analysis (error rates 34% and 38%, respectively). A similar 15-miRNA biomarker derived from The Cancer Genome Atlas miRNA-seq data performed slightly worse (39%) than these current biomarkers. Both signatures were then assessed for replication in two independent data sets and subjected to systematic cross-validation together with the three other miRNA-based prognostic signatures proposed in the literature to date. Five miRNAs (miR-142-5p, miR-150-5p, miR-342-3p, miR-155-5p, and miR-146b-5p) were reproducibly associated with patient outcome and have the greatest potential for application in the clinic. Our extensive validation approach highlighted among multiple independent cohorts the translational potential and limitations of miRNA signatures, and pointed to future directions in the analysis of this emerging class of markers.

15 Review Immune checkpoint inhibitors in melanoma. 2015

Cooper, Adam J / Carlino, Matteo S / Kefford, Richard F. ·Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, NSW, Australia. · School of Medicine, The University of Sydney, Sydney, NSW, Australia. · Melanoma Institute Australia, Sydney, NSW, Australia. · Westmead Institute for Cancer Research, University of Sydney at the Westmead Millennium Institute, Westmead, NSW, Australia. · Department of Clinical Medicine, Macquarie University, Sydney, NSW, Australia. ·Melanoma Manag · Pubmed #30190854.

ABSTRACT: The potential to harness the power of the immune system and effectively treat patients with metastatic melanoma is finally being realized with the advent of immune checkpoint inhibitors. These new therapies herald a new era in the treatment of melanoma with the potential to produce very durable responses and possible cure for a subset of patients, though bring with them challenges including novel toxicities and nonconventional response patterns. This article reviews the currently available immune checkpoint inhibitors, potential biomarkers to predict response and promising investigational approaches including combination therapies.

16 Review Targeting oncogenic BRAF and aberrant MAPK activation in the treatment of cutaneous melanoma. 2015

Carlino, Matteo S / Long, Georgina V / Kefford, Richard F / Rizos, Helen. ·Departments of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia; Centre for Cancer Research, Westmead Millennium Institute, Westmead, New South Wales, Australia; Melanoma Institute Australia, Sydney, New South Wales, Australia; The Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia. Electronic address: matteo.carlino@sydney.edu.au. · Melanoma Institute Australia, Sydney, New South Wales, Australia; The Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia; The Mater Hospital, North Sydney, New South Wales, Australia. · Departments of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia; Centre for Cancer Research, Westmead Millennium Institute, Westmead, New South Wales, Australia; Melanoma Institute Australia, Sydney, New South Wales, Australia; Faculty of Medicine and Health Science, Macquarie University, New South Wales, Australia. · Centre for Cancer Research, Westmead Millennium Institute, Westmead, New South Wales, Australia; Melanoma Institute Australia, Sydney, New South Wales, Australia; Faculty of Medicine and Health Science, Macquarie University, New South Wales, Australia. ·Crit Rev Oncol Hematol · Pubmed #26358420.

ABSTRACT: BRAF and MEK inhibitors, alone or in combination, are highly active in the 40% of patients with BRAF mutant metastatic melanoma. Despite this activity resistance often develops in patients treated with these agents. This review summarises the biology of the mitogen activated protein kinase (MAPK) pathway, with particular reference to the effects of BRAF and MEK inhibitors in BRAF mutant melanoma. The clinical and molecular predictors of response and mechanisms of resistance are discussed in detail along with the biological rationale and evidence for future treatment strategies in both MAPK inhibitor naïve and resistant BRAF mutant melanoma.

17 Review Treatment algorithms in stage IV melanoma. 2015

Espinosa, Enrique / Grob, Jean-Jacques / Dummer, Reinhard / Rutkowski, Piotr / Robert, Caroline / Gogas, Helen / Kefford, Richard / Eggermont, Alexander M M / Martin Algarra, Salvador / Hauschild, Axel / Schadendorf, Dirk. ·1Service of Oncology, Hospital La Paz, Madrid, Spain · 2Department of Dermatology, Hopital Ste Marguerite, Marseille, France · 3Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland · 4Department of Sarcoma and Melanoma, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland · 5Department of Dermatology (CR), and General Director (AE), Institute Gustave Roussy, Villejuif Cedex, France · 6First Department of Medicine, University of Athens Medical School, Athens, Greece · 7Department of Oncology, Westmead Hospital and Melanoma Institute Australia, University of Sydney, Sydney, Australia · 8Service of Oncology, Clinica Universitaria de Navarra, Pamplona, Spain · 9Department of Dermatology, University of Kiel, Kiel, Germany · and 10Department of Dermatology, University Hospital Essen, Essen, Germany. ·Am J Ther · Pubmed #24413374.

ABSTRACT: The molecular classification of melanoma and the advent of new drugs are changing the paradigm of therapy for advanced melanoma. A review of the recent key studies was performed, followed by a discussion in an expert forum. The aim of this review was to generate a therapeutic algorithm for stage IV melanoma. Tumor genotyping for BRAF and/or KIT should be performed before selection of therapy. For most BRAF-mutated melanoma patients and particularly those with a high tumor load, vemurafenib or other BRAF inhibitors such as dabrafenib are the treatment of choice. KIT inhibitors can be effective in KIT-mutant tumors, especially in those patients with mutations at exons 11 and 13. Ipilimumab is a good option for patients with nontargetable or nondetected mutations and those who progress under therapy with vemurafenib or a KIT inhibitor. There is still a role for conventional chemotherapy either as first-line treatment in BRAF wild-type patients or as salvage therapy in second or third line, or after other treatment modalities. Participation in clinical trials is strongly encouraged, either in first or in subsequent lines. New therapeutic options for advanced melanoma are guided by tumor genotyping. The current therapeutic algorithm includes kinase inhibitors, anti-CTLA4 therapy, immunotherapy, and chemotherapy, depending on the tumor genotype and response to previous treatments. Participation in clinical trials should always be encouraged because the treatment goal is long-term survival and potential cure in a subset of patients.

18 Review Hepatic resection for metastatic melanoma: a systematic review. 2014

Hameed, Ahmer M / Ng, E-Ern I / Johnston, Emma / Hollands, Michael J / Richardson, Arthur J / Pleass, Henry C / Lam, Vincent W T. ·aDepartment of Surgery, Westmead Hospital bDiscipline of Surgery, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia. ·Melanoma Res · Pubmed #24300091.

ABSTRACT: Melanoma metastatic to the liver has a very poor prognosis, and has traditionally been treated using systemic chemotherapy with limited efficacy. Surgery is increasingly being explored as a therapeutic option for melanoma liver metastases, with varying levels of success. A systematic review was undertaken to explore the short-term and long-term outcomes associated with hepatectomy for melanoma metastases, in addition to identifying prognostic factors favouring increased survival. All eligible studies were identified through an electronic search of Medline and Embase (January 1990-March 2013). Each study was independently analysed by two reviewers, with relevant data extracted and tabulated according to predetermined criteria. Thirteen studies were selected that fulfilled the selection criteria, with a total of 551 patients undergoing hepatic resection for melanoma metastases. Metastases to the liver occurred at a median interval of 54 months. The median perioperative morbidity and mortality were 10% (range 0-28.6%) and 0% (range 0-7.1%), respectively. The median overall survival for operative patients was 24 months, with median survival being greater in the R0 resection group (25 months; range 9.5-65.6 months) compared with the R1/2 resection group (16 months; range 11.7-29 months). Overall median 1-, 3- and 5-year survival rates were 70% (range 39-100%), 36% (range 10.2-53%) and 24% (range 3-53%), respectively. Positive prognostic factors may include single hepatic metastases, a longer time to development of hepatic metastases and R0 resection. Hepatic resection for metastatic melanoma might confer a distinct survival benefit in a select group of patients, although disease recurrence is the norm.

19 Review Cutaneous toxicities of RAF inhibitors. 2013

Anforth, Rachael / Fernandez-Peñas, Pablo / Long, Georgina V. ·Department of Dermatology, Westmead Hospital, Sydney, NSW, Australia. ·Lancet Oncol · Pubmed #23276366.

ABSTRACT: The RAF inhibitors vemurafenib and dabrafenib are emerging as the standard of care for Val600 BRAF-mutant metastatic melanoma. These drugs have shown clinical benefit over the standard care (dacarbazine); however, they are associated with frequent cutaneous adverse events, which can be concerning to the patient and their physician. Herein, we review the range of cutaneous disorders that seem to be induced by RAF inhibitors, including cutaneous squamous-cell carcinoma, hyperkeratotic lesions, Grover's disease, keratosis pilaris-like reactions, and photosensitivity. These disorders often affect patients' quality of life; therefore, dermatological assessment and timely management is essential to ensure that patients continue to use RAF inhibitors.

20 Review Treatment of melanoma brain metastases: a new paradigm. 2012

Carlino, Matteo S / Fogarty, Gerald B / Long, Georgina V. ·Westmead Institute for Cancer Research, Westmead Millennium Institute, Sydney, Australia. ·Cancer J · Pubmed #22453023.

ABSTRACT: Brain metastases occur commonly in patients with metastatic melanoma, are associated with a poor prognosis, and cause significant morbidity. Both surgery and stereotactic radiosurgery are used to control brain metastases and, in selected patients, improve survival. In those with extensive brain involvement, whole-brain radiotherapy can alleviate symptoms. Historically, systemic therapy has had little role to play in the management of melanoma brain metastases; however, early clinical trials of BRAF inhibitors have shown promising activity. This review examines the evidence for local and systemic treatments in the management of patients with melanoma brain metastases. We present a new treatment algorithm for melanoma patients with brain metastases, which integrates the evolving evidence for the use of BRAF inhibitors.

21 Review Review and cross-validation of gene expression signatures and melanoma prognosis. 2012

Schramm, Sarah-Jane / Campain, Anna E / Scolyer, Richard A / Yang, Yee Hwa / Mann, Graham J. ·Sydney Medical School, The University of Sydney at Westmead Millennium Institute, Sydney, New South Wales, Australia. graham.mann@sydney.edu.au ·J Invest Dermatol · Pubmed #21956122.

ABSTRACT: In melanoma, there is an urgent need to identify novel biomarkers with prognostic performance superior to traditional clinical and histological parameters. Gene expression-based prognostic signatures offer promise, but studies have been challenged by sample scarcity, cohort heterogeneity, and doubts about the efficacy of such signatures relative to current clinical practices. Motivated by new studies that have begun to address these challenges, we reviewed prognostic signatures derived from gene expression microarray analysis of human melanoma tissue. We used REMARK-based criteria to select the most relevant studies and directly compared their signature gene lists. Through functional ontology enrichment analysis, we observed that these independent data sets converge in part upon immune response processes and the G-protein signaling NRAS-regulation pathway, both important in melanoma development and progression. The signatures correctly predicted patient outcome in independent gene expression data sets with some notably low misclassification rates, particularly among studies involving more advanced-stage tumors. This successful cross-validation indicates that gene expression analysis-based signatures are becoming translationally relevant to care of melanoma patients, as well as improving understanding of the aspects of melanoma biology that determine patient outcome.

22 Review Melanoma prognosis: a REMARK-based systematic review and bioinformatic analysis of immunohistochemical and gene microarray studies. 2011

Schramm, Sarah-Jane / Mann, Graham J. ·Melanoma Genomics and Genetic Epidemiology Research Group, The University of Sydney at Westmead Millennium Institute, Westmead, NSW, Australia. ·Mol Cancer Ther · Pubmed #21659462.

ABSTRACT: Despite intensive research efforts, within-stage survival rates for melanoma vary widely. Pursuit of molecular biomarkers with improved prognostic significance over clinicohistological measures has produced extensive literature. Reviews have synthesized these data, but none have systematically partitioned high-quality studies from the remainder across different molecular methods nor examined system properties of that output. Databases were searched for studies analyzing protein expression by immunohistochemistry (n = 617, extending the only systematic review to date by 102 studies) or for gene expression microarray studies (n = 45) in melanoma in relation to outcome. REMARK-derived criteria were applied to identify high-quality studies. Biomarkers and pathways were functionally assessed by using gene ontology software. Most manuscripts did not meet REMARK-based criteria, an ongoing trend that can impede translational research. Across REMARK-compliant literature, 41 proteins were significantly associated with outcome. Multimarker tests consistently emerged among the most promising potential biomarkers, indicating a need to continue assessing candidates in that composite setting. Twenty-one canonical pathways were populated by outcome-related proteins but not by those that failed to show such an association; we propose that this set of pathways warrants closer investigation to understand drivers of poor outcome in melanoma. Two-gene expression microarray studies met REMARK-based criteria reflecting a genuine paucity of literature in the area. The 254 outcome-related genes were examined for correspondences with the systematically identified protein signature. This analysis highlighted proliferating cell nuclear antigen and survivin as priorities for further examination as biomarkers in melanoma prognosis, and illustrated ongoing need to integrate alternative approaches to biomarker discovery in melanoma translational research.

23 Clinical Trial Combined BRAF and MEK inhibition with PD-1 blockade immunotherapy in BRAF-mutant melanoma. 2019

Ribas, Antoni / Lawrence, Donald / Atkinson, Victoria / Agarwal, Sachin / Miller, Wilson H / Carlino, Matteo S / Fisher, Rosalie / Long, Georgina V / Hodi, F Stephen / Tsoi, Jennifer / Grasso, Catherine S / Mookerjee, Bijoyesh / Zhao, Qing / Ghori, Razi / Moreno, Blanca Homet / Ibrahim, Nageatte / Hamid, Omid. ·University of California, Los Angeles, Los Angeles, CA, USA. aribas@mednet.ucla.edu. · Massachusetts General Hospital, Boston, MA, USA. · Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Greenslopes, Queensland, Australia. · Indiana University Health Goshen Center for Cancer Care, Goshen, IN, USA. · Segal Cancer Centre, Montreal, Quebec, Canada. · Jewish General Hospital, Montreal, Quebec, Canada. · McGill University, Montreal, Quebec, Canada. · Westmead Hospital, Sydney, New South Wales, Australia. · Blacktown Hospital, Sydney, New South Wales, Australia. · The University of Sydney, Sydney, New South Wales, Australia. · Melanoma Institute Australia, Sydney, New South Wales, Australia. · Auckland District Health Board, Auckland, New Zealand. · Royal North Shore Hospital, Sydney, New South Wales, Australia. · Mater Hospital, Sydney, New South Wales, Australia. · Dana-Farber Cancer Institute, Boston, MA, USA. · University of California, Los Angeles, Los Angeles, CA, USA. · Novartis, East Hanover, NJ, USA. · Merck & Co., Inc., Kenilworth, NJ, USA. · The Angeles Clinic and Research Institute, Los Angeles, CA, USA. ·Nat Med · Pubmed #31171879.

ABSTRACT: Oncogene-targeted therapy with B-Raf proto-oncogene (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitors induces a high initial response rate in patients with BRAF

24 Clinical Trial Outcomes by line of therapy and programmed death ligand 1 expression in patients with advanced melanoma treated with pembrolizumab or ipilimumab in KEYNOTE-006: A randomised clinical trial. 2018

Carlino, Matteo S / Long, Georgina V / Schadendorf, Dirk / Robert, Caroline / Ribas, Antoni / Richtig, Erika / Nyakas, Marta / Caglevic, Christian / Tarhini, Ahmed / Blank, Christian / Hoeller, Christoph / Bar-Sela, Gil / Barrow, Catherine / Wolter, Pascal / Zhou, Honghong / Emancipator, Kenneth / Jensen, Erin H / Ebbinghaus, Scot / Ibrahim, Nageatte / Daud, Adil. ·Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, NSW, Australia; Blacktown Hospital, Blacktown, NSW, Australia; Melanoma Institute Australia, Sydney, NSW, Australia; School of Medicine, University of Sydney, Sydney, NSW, Australia. Electronic address: Matteo.carlino@sydney.edu.au. · Melanoma Institute Australia, Sydney, NSW, Australia; Department of Medical Oncology and Translational Research, University of Sydney, Sydney, NSW, Australia; Royal North Shore Hospital, Sydney, NSW, Australia; Mater Hospital, Sydney, NSW, Australia. Electronic address: georgina.long@sydney.edu.au. · Department of Dermatology, University Hospital Essen, Essen, Germany; German Cancer Consortium, Heidelberg, Germany. Electronic address: Dirk.Schadendorf@uk-essen.de. · Department of Oncology, Gustave Roussy, Villejuif, France; Paris-Sud University, Orsay, France. Electronic address: Caroline.Robert@igr.fr. · Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: aribas@mednet.ucla.edu. · Department of Dermatology, Medical University of Graz, Graz, Austria. Electronic address: erika.richtig@medunigraz.at. · Department of Clinical Cancer Research, Oslo University Hospital, Oslo, Norway. Electronic address: marnya@ous-hf.no. · Unit of Investigational Cancer Drugs, Instituto Oncologico Fundación Arturo López Pérez, Santiago, Chile. Electronic address: oncodemia@yahoo.com. · Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: tarhiniaa@upmc.edu. · Division of Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands. Electronic address: c.blank@nki.nl. · Department of Dermatology, Medical University of Vienna, Vienna, Austria. Electronic address: christoph.hoeller@meduniwien.ac.at. · Division of Oncology, Rambam Health Care Campus, Haifa, Israel. Electronic address: g_barsela@rambam.health.gov.il. · Wellington Blood and Cancer Centre, Wellington Hospital, Wellington, New Zealand. Electronic address: Catherine.Barrow@ccdhb.org.nz. · Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium. Electronic address: pascalwolter@hotmail.com. · Department of BARDS, Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: honghongz@gmail.com. · Companion Diagnostics, Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: kenneth.emancipator@merck.com. · LDS - Medical Communications, Merck & Co., Inc., North Wales, PA, USA. Electronic address: erin_jensen2@merck.com. · Department of Clinical Oncology, Merck & Co., Inc., North Wales, PA, USA. Electronic address: scot_ebbinghaus@merck.com. · Department of Clinical Oncology, Merck & Co., Inc., North Wales, PA, USA. Electronic address: nageatte.ibrahim@merck.com. · University of California, San Francisco, San Francisco, CA, USA. Electronic address: adaud@medicine.ucsf.edu. ·Eur J Cancer · Pubmed #30096704.

ABSTRACT: BACKGROUND: Predictive biomarkers of patients likely to benefit from anti-programmed death 1 inhibitor therapy have clinical relevance. We examined whether line of therapy or tumour programmed death ligand 1 (PD-L1) expression affects the efficacy and safety of pembrolizumab, compared with ipilimumab, in advanced melanoma. METHODS: Of 834 patients enrolled in the randomised, open-label phase III KEYNOTE-006 study, 833 were included in this analysis. Patients were randomly assigned 1:1:1 to receive pembrolizumab 10 mg/kg every 2 or 3 weeks (for 24 months) or ipilimumab 3 mg/kg every 3 weeks (for four doses) until disease progression/intolerable toxicity. This analysis evaluated progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). Data cut-off: 03 November 2016. RESULTS: Of the patients, 60.3% were male, 65.9% were treatment naive and 80.6% had PD-L1-positive tumours (median follow-up was 33.9 months). Twenty-four-month survival rates were higher with pembrolizumab than with ipilimumab in treatment-naive (PFS 31.0% versus 14.6%; OS 58.0% versus 44.7%) and previously treated patients (PFS 25.7% versus 11.3%; OS 49.2% versus 37.9%). Twenty-four-month survival rates were higher with pembrolizumab than with ipilimumab in patients with PD-L1-positive tumours (PFS 33.2% versus 13.1%; OS 58.4% versus 45.0%) and similar in PD-L1-negative tumours (PFS 14.9% versus NR [no data at 24 months for a PFS estimate]; OS 43.6% versus 31.8%). Safety of pembrolizumab by subgroup was consistent with previous reports. CONCLUSIONS: Findings support pembrolizumab monotherapy as standard of care in patients with advanced melanoma, regardless of first- or second-line therapy or PD-L1 status. CLINICALTRIALS. GOV IDENTIFIER: NCT01866319.

25 Clinical Trial Survival and prognostic factors for patients with melanoma brain metastases in the era of modern systemic therapy. 2018

Tio, Martin / Wang, Xuan / Carlino, Matteo S / Shivalingam, Brindha / Fogarty, Gerald B / Guminski, Alexander D / Lo, Serigne / Hong, Angela M / Menzies, Alexander M / Long, Georgina V. ·Department of Medical Oncology, Royal North Shore Hospital, St Leonards, NSW, Australia. · Peking University Cancer Hospital and Institute, Beijing, China. · Melanoma Institute Australia, North Sydney, NSW, Australia. · Crown Princess Mary Cancer Centre Westmead, Sydney, NSW, Australia. · Sydney Medical School, The University of Sydney, Camperdown, NSW, Australia. · Royal Prince Alfred Hospital, Camperdown, NSW, Australia. · Mater Hospital, North Sydney, NSW, Australia. · Genesis Cancer Care, Mater Radiation Oncology, North Sydney, NSW, Australia. ·Pigment Cell Melanoma Res · Pubmed #29277979.

ABSTRACT: Historically, the prognosis of patients with melanoma brain metastases is poor, with median overall survival (OS) of 4-6 months. Little is known of OS in the era of modern systemic therapies and local therapy with stereotactic radiosurgery (SRS) or surgery. Patients diagnosed with melanoma brain metastases at Melanoma Institute Australia from January 2011 to December 2014 were included. OS and prognostic factors were analysed using Cox regression and Kaplan-Meier survival analyses.355 patients were included. The median OS was 7.1 months (95% confidence interval [CI] 6.0-8.1). Median OS differed by treatment modality: systemic therapy and SRS and/or surgery 14.9 months (95% CI 10.7-19.0), SRS and/or surgery with or without whole brain radiotherapy (WBRT) 6.4 months (95% CI 5.4-7.5), systemic therapy 5.4 months (95% CI 3.1-7.7), systemic therapy and WBRT 5.2 months (95% CI 4.1-6.4), WBRT 4.4 months (95% CI 2.4-6.3), and best supportive care 1.8 months (95% CI 1.2-2.3). OS for patients with melanoma brain metastases appears improved in the modern era, particularly for patients who are candidates for systemic therapy with SRS and/or surgery.

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