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Melanoma: HELP
Articles by Victoria J. Mar
Based on 22 articles published since 2008
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Between 2008 and 2019, V. Mar wrote the following 22 articles about Melanoma.
 
+ Citations + Abstracts
1 Guideline Clinical practice guidelines for the diagnosis and management of melanoma: melanomas that lack classical clinical features. 2017

Mar, Victoria J / Chamberlain, Alex J / Kelly, John W / Murray, William K / Thompson, John F. ·Victorian Melanoma Service, Alfred Health, Melbourne, VIC victoria.mar@monash.edu. · Victorian Melanoma Service, Alfred Health, Melbourne, VIC. · Peter MacCallum Cancer Centre, Melbourne, VIC. ·Med J Aust · Pubmed #29020893.

ABSTRACT: INTRODUCTION: A Cancer Council Australia multidisciplinary working group is currently revising and updating the 2008 evidence-based clinical practice guidelines for the management of cutaneous melanoma. While there have been many recent improvements in treatment options for metastatic melanoma, early diagnosis remains critical to reducing mortality from the disease. Improved awareness of the atypical presentations of this common malignancy is required to achieve this. A chapter of the new guidelines was therefore developed to aid recognition of atypical melanomas. Main recommendations: Because thick, life-threatening melanomas may lack the more classical ABCD (asymmetry, border irregularity, colour variegation, diameter > 6 mm) features of melanoma, a thorough history of the lesion with regard to change in morphology and growth over time is essential. Any lesion that is changing in morphology or growing over a period of more than one month should be excised or referred for prompt expert opinion. Changes in management as a result of the guidelines: These guidelines provide greater emphasis on improved recognition of the atypical presentations of melanoma, in particular nodular, desmoplastic and acral lentiginous subtypes, with particular awareness of hypomelanotic and amelanotic lesions.

2 Review Clinicopathological characteristics and prognosis of patients with multiple primary melanomas. 2018

Adler, N R / Kelly, J W / Haydon, A / McLean, C A / Mar, V J. ·Victorian Melanoma Service, Alfred Hospital, Melbourne, Victoria, Australia. · School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. · Department of Medical Oncology, Alfred Hospital, Melbourne, Victoria, Australia. · Department of Anatomical Pathology, Alfred Hospital, Melbourne, Victoria, Australia. · Skin and Cancer Foundation, Carlton, Victoria, Australia. ·Br J Dermatol · Pubmed #28755438.

ABSTRACT: -- No abstract --

3 Review When is a sentinel node biopsy indicated for patients with primary melanoma? An update of the 'Australian guidelines for the management of cutaneous melanoma'. 2017

Gyorki, David E / Barbour, Andrew / Hanikeri, Mark / Mar, Victoria / Sandhu, Shahneen / Thompson, John F. ·Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. · Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia. · Upper Gastrointestinal and Soft Tissue Unit, Princess Alexandra Hospital, Brisbane, Queensland, Australia. · Surgical Oncology Laboratory, Discipline of Surgery, University of Queensland, Brisbane, Queensland, Australia. · Western Australia Melanoma Advisory Service, Perth, Western Australia, Australia. · Victorian Melanoma Service, Alfred Hospital, Melbourne, Victoria, Australia. · Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. · Skin and Cancer Foundation Inc., Melbourne, Victoria, Australia. · Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. · Melanoma Institute Australia, Poche Centre, Sydney, New South Wales, Australia. · Discipline of Surgery, University of Sydney, Sydney, New South Wales, Australia. · Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia. ·Australas J Dermatol · Pubmed #28718222.

ABSTRACT: A sentinel lymph node biopsy is a surgical staging procedure performed for patients with primary cutaneous melanoma who are clinically lymph-node negative to determine whether there is low volume nodal metastasis in the draining lymph node field. A systematic review was recently performed to update the Australian clinical practice guidelines for the diagnosis and management of melanoma, addressing the question, 'When is a sentinel lymph node biopsy indicated?' This article discusses the findings of the systematic review and the evidence base for the updated guidelines.

4 Review Metastatic pathways in patients with cutaneous melanoma. 2017

Adler, Nikki R / Haydon, Andrew / McLean, Catriona A / Kelly, John W / Mar, Victoria J. ·Victorian Melanoma Service, Alfred Hospital, Melbourne, Vic, Australia. · School of Public Health and Preventive Medicine, Monash University, Alfred Hospital, Melbourne, Vic, Australia. · Department of Medical Oncology, Alfred Hospital, Melbourne, Vic, Australia. · Department of Anatomical Pathology, Alfred Hospital, Melbourne, Vic, Australia. · Skin and Cancer Foundation, Carlton, Vic, Australia. ·Pigment Cell Melanoma Res · Pubmed #27900851.

ABSTRACT: Metastasis represents the end product of an elaborate biological process, which is determined by a complex interplay between metastatic tumour cells, host factors and homoeostatic mechanisms. Cutaneous melanoma can metastasize haematogenously or lymphogenously. The three predominant models that endeavour to explain the patterns of melanoma progression are the stepwise spread model, the simultaneous spread model and the model of differential spread. The time course to the development of metastases differs between the different metastatic routes. There are several clinical and histopathological risk factors for the different metastatic pathways. In particular, patient sex and the anatomical location of the primary tumour influence patterns of disease progression. There is limited existing evidence regarding the relationship between tumour mutation status, other diagnostic and prognostic biomarkers and the metastatic pathways of primary cutaneous melanoma. This knowledge gap needs to be addressed to better identify patients at high risk of disease recurrence and personalize surveillance strategies.

5 Article Concordance of somatic mutational profile in multiple primary melanomas. 2018

Adler, Nikki R / McLean, Catriona A / Wolfe, Rory / Kelly, John W / McArthur, Grant A / Haydon, Andrew / Tra, Thien / Cummings, Nicholas / Mar, Victoria J. ·Victorian Melanoma Service, Alfred Hospital, Melbourne, Vic., Australia. · School of Public Health and Preventive Medicine, Monash University, Melbourne, Vic., Australia. · Department of Anatomical Pathology, Alfred Hospital, Melbourne, Vic., Australia. · Divisions of Research and Cancer Medicine, Peter MacCallum Cancer Centre, East Melbourne, Vic., Australia. · Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Vic., Australia. · Department of Medical Oncology, Alfred Hospital, Melbourne, Vic., Australia. · Skin and Cancer Foundation Inc., Carlton, Vic., Australia. ·Pigment Cell Melanoma Res · Pubmed #29603877.

ABSTRACT: This study aimed to determine the frequency and concordance of BRAF and NRAS mutation in tumours arising in patients with multiple primary melanoma (MPM). Patients with MPM managed at one of three tertiary referral centres in Melbourne, Australia, from 2010 to 2015 were included. Incident and subsequent melanomas underwent mutation testing. Cohen's kappa (κ) coefficient assessed agreement between incident and subsequent primary melanomas for both BRAF and NRAS mutation status (mutant versus wild-type). Mutation testing of at least two primary tumours from 64 patients was conducted. There was poor agreement for both BRAF and NRAS mutation status between incident and subsequent melanomas (κ = 0.10, 95% CI -0.10 to 0.42; κ = 0.06, 95% CI -0.10 to 0.57, respectively). In view of the low concordance in BRAF mutation status between incident and subsequent melanomas, mutational analysis of metastatic tissue, rather than of a primary melanoma, in patients with MPM should be used to guide targeted therapy.

6 Article Primary Tumor Thickness is a Prognostic Factor in Stage IV Melanoma: A Retrospective Study of Primary Tumor Characteristics. 2018

Luen, Stephen / Wong, Siew Wei / Mar, Victoria / Kelly, John W / McLean, Catriona / McArthur, Grant A / Haydon, Andrew. ·Departments of Medical Oncology. · Victorian Melanoma Service, The Alfred Hospital. · Anatomical Pathology. · Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Vic., Australia. ·Am J Clin Oncol · Pubmed #26325493.

ABSTRACT: INTRODUCTION: Stage IV melanoma exhibits a diverse range of tumor biology from indolent to aggressive disease. Many important prognostic factors have already been identified. Despite this, the behavior of metastatic melanoma remains difficult to predict. We sought to determine if any primary tumor characteristics affect survival following the diagnosis of stage IV melanoma. METHODS: All patients diagnosed with stage IV melanoma between January 2003 and December 2012 were identified from the Victorian Melanoma Service database. Retrospective chart review was performed to collect data on primary tumor characteristics (thickness, ulceration, mitotic rate, melanoma subtype, or occult primary). Known and suspected prognostic factors were additionally collected (time to diagnosis of stage IV disease, age, sex, stage, receipt of chemotherapy, and era of recurrence). The effect of primary tumor characteristics on overall survival from the date of diagnosis of stage IV disease was assessed. RESULTS: A total of 227 patients with a median follow-up of 5 years from diagnosis of stage IV disease were identified. Median overall survival of the cohort was 250 days.Of the primary tumor characteristics assessed, only tumor thickness affected survival from diagnosis of stage IV disease, hazard ratio=1.09 (1.02 to 1.16), P=0.008. This remained significant in multivariate analysis, P=0.007. Other primary tumor characteristics did not significantly influence survival. CONCLUSIONS: Primary tumor thickness is a significant prognostic factor in stage IV melanoma. Our data suggest that the biology of the primary melanoma may persist to influence the behavior of metastatic disease.

7 Article Tumour mutation status and sites of metastasis in patients with cutaneous melanoma. 2017

Adler, Nikki R / Wolfe, Rory / Kelly, John W / Haydon, Andrew / McArthur, Grant A / McLean, Catriona A / Mar, Victoria J. ·Victorian Melanoma Service, Alfred Hospital, Melbourne, Victoria 3004, Australia. · School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria 3004, Australia. · Department of Medical Oncology, Alfred Hospital, Melbourne, Victoria 3004, Australia. · Divisions of Research and Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia. · Sir Peter MacCallum Department of Oncology, University of Melbourne, Victoria 3000, Australia. · Department of Anatomical Pathology, Alfred Hospital, Melbourne, Victoria 3004, Australia. · Skin and Cancer Foundation, Carlton, Victoria 3053, Australia. ·Br J Cancer · Pubmed #28787433.

ABSTRACT: BACKGROUND: Cutaneous melanoma can metastasise haematogenously and/or lymphogenously to form satellite/in-transit, lymph node or distant metastasis. This study aimed to determine if BRAF and NRAS mutant and wild-type tumours differ in their site of first tumour metastasis and anatomical metastatic pathway. METHODS: Prospective cohort of patients with a histologically confirmed primary cutaneous melanoma at three tertiary referral centres in Melbourne, Australia from 2010 to 2015. Multinomial regression determined clinical, histological and mutational factors associated with the site of first metastasis and metastatic pathway. RESULTS: Of 1048 patients, 306 (29%) developed metastasis over a median 4.7 year follow-up period. 73 (24%), 192 (63%) and 41 (13%) developed distant, regional lymph node and satellite/in-transit metastasis as the first site of metastasis, respectively. BRAF mutation was associated with lymph node metastasis (adjusted RRR 2.46 95% CI 1.07-5.69, P=0.04) and sentinel lymph node positivity (adjusted odds ratio [aOR] OR 1.55, 95% CI 1.14-2.10, P=0.005). BRAF mutation and NRAS mutation were associated with increased odds of developing liver metastasis (aOR 3.09, 95% CI 1.49-6.42, P=0.003; aOR 3.17, 95% CI 1.32-7.58, P=0.01) and central nervous system (CNS) metastasis (aOR 4.65, 95% CI 2.23-9.69, P<0.001; aOR 4.03, 95% CI 1.72-9.44, P=0.001). NRAS mutation was associated with lung metastasis (aOR 2.44, 95% CI 1.21-4.93, P=0.01). CONCLUSIONS: BRAF mutation was found to be associated with lymph node metastasis as first metastasis and sentinel lymph node positivity. BRAF and NRAS mutations were associated with CNS and liver metastasis and NRAS mutation with lung metastasis. If these findings are validated in additional prospective studies, a role for heightened visceral organ surveillance may be warranted in patients with tumours harbouring these somatic mutations.

8 Article Computer-assisted diagnosis for skin cancer: have we been outsmarted? 2017

Mar, Victoria J / Scolyer, Richard A / Long, Georgina V. ·Victorian Melanoma Service, Alfred Hospital, Melbourne, VIC, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia; Skin and Cancer Foundation Inc, Melbourne, VIC, Australia. · Melanoma Institute Australia, The University of Sydney and Royal Prince Alfred Hospital, Sydney, NSW 2060, Australia. · Melanoma Institute Australia, The University of Sydney and Royal North Shore Hospital, Sydney, NSW, Australia. Electronic address: georgina.long@sydney.edu.au. ·Lancet · Pubmed #28534744.

ABSTRACT: -- No abstract --

9 Article Impact of scalp location on survival in head and neck melanoma: A retrospective cohort study. 2017

Xie, Charles / Pan, Yan / McLean, Catriona / Mar, Victoria / Wolfe, Rory / Kelly, John. ·Victorian Melanoma Service, Alfred Hospital, Melbourne, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. Electronic address: chen.xie@monash.edu. · Victorian Melanoma Service, Alfred Hospital, Melbourne, Australia. · Victorian Melanoma Service, Alfred Hospital, Melbourne, Australia; Skin and Cancer Foundation, Carlton, Australia. · School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. ·J Am Acad Dermatol · Pubmed #28413056.

ABSTRACT: BACKGROUND: Scalp melanomas have more aggressive clinicopathological features than other melanomas and mortality rates more than twice that of melanoma located elsewhere. OBJECTIVE: We sought to describe the survival of patients with scalp melanoma versus other cutaneous head and neck melanoma (CHNM), and explore a possible independent negative impact of scalp location on CHNM survival. METHODS: A retrospective cohort study was performed of all invasive primary CHNM cases seen at a tertiary referral center over a 20-year period. Melanoma-specific survival (MSS) was compared between scalp melanoma and other invasive CHNM. Multivariable Cox proportional hazards regression was performed to determine associations with survival. RESULTS: On univariate analysis, patients with scalp melanoma had worse MSS than other CHNM (hazard ratio 2.22, 95% confidence interval 1.59-3.11). Scalp location was not associated with MSS in CHNM on multivariable analysis (hazard ratio 1.11, 95% confidence interval 0.77-1.61) for all tumors together, but remained independently associated with MSS for the 0.76- to 1.50-mm thickness stratum (hazard ratio 5.51, 95% confidence interval 1.55-19.59). LIMITATIONS: Disease recurrence was not assessed because of unavailable data. CONCLUSION: The poorer survival of scalp melanoma is largely explained by greater Breslow thickness and a higher proportion of male patients.

10 Article Scalp melanoma: Distinctive high risk clinical and histological features. 2017

Xie, Charles / Pan, Yan / McLean, Catriona / Mar, Victoria / Wolfe, Rory / Kelly, John W. ·Victorian Melanoma Service, The Alfred Hospital, Melbourne, Victoria, Australia. · School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. ·Australas J Dermatol · Pubmed #26768190.

ABSTRACT: BACKGROUND/OBJECTIVES: Scalp melanoma has a worse prognosis than melanoma elsewhere, though the reasons for this are poorly understood. Current literature describing the clinicopathological associations of scalp melanoma is sparse. This study aims to compare clinical and histological features of scalp melanoma with other cutaneous head and neck melanomas (CHNM). METHODS: A cross-sectional study was performed of all primary CHNM cases seen by the Victorian Melanoma Service between 1994 and 2014, using prospectively recorded clinical data. Invasive and in situ melanomas were compared separately. RESULTS: Invasive scalp melanoma was associated with male sex (OR, 2.7; 95% CI, 1.9-3.9), increasing age (OR, 1.02 per year increase in age; 95% CI, 1.01-1.03), being first noticed by a person other than self, spouse/relative or doctor (OR, 2.9; 95% CI, 1.5-5.7), amelanosis (OR, 1.6; 95% CI, 1.1-2.3), and increased growth rate (OR, 1.14 per 1 mm/month growth rate increase; 95% CI, 1.04-1.26). Compared with other CHNM, scalp melanoma had greater median Breslow thickness (2.8  vs 1.2 mm) and was independently associated with satellite metastases (OR, 4.7; 95% CI, 1.9-11.5) and nodular subtype (OR, 1.8; 95% CI, 1.1-3.1). In situ scalp melanoma was associated with male sex, increasing age and solar keratoses. CONCLUSION: Scalp melanoma tends to occur in older men, is often rapidly growing and amelanotic, and is associated with high risk histological features. As it is likely to be overlooked, increased recognition of the atypical presentations of scalp melanoma is required.

11 Article Clinicopathological characteristics associated with BRAF(K601E) and BRAF(L597) mutations in melanoma. 2016

Voskoboynik, Mark / Mar, Victoria / Mailer, Sonia / Colebatch, Andrew / Fennessy, Anne / Logan, Aleksandra / Hewitt, Chelsee / Cebon, Jonathon / Kelly, John / McArthur, Grant. ·Peter MacCallum Cancer Centre, East Melbourne, Vic., Australia. · Victorian Melanoma Service, Alfred Hospital, Prahran, Melbourne, Vic., Australia. · Skin and Cancer Foundation, Melbourne, Vic., Australia. · Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia. · School of Cancer Medicine, La Trobe University, Olivia Newton-John Cancer Research Institute, Heidelberg, Vic., Australia. · Melbourne University, Parkville, Vic., Australia. ·Pigment Cell Melanoma Res · Pubmed #26643848.

ABSTRACT: BRAF mutations at codons L597 and K601 occur uncommonly in melanoma. Clinical and pathological associations of these mutations were investigated in a cohort of 1119 patients with known BRAF mutation status. A BRAF mutation was identified in 435 patients; Mutations at L597 and the K601E mutation were seen in 3.4 and 3.2% of these, respectively. K601E melanomas tended to occur in male patients, a median age of 58 yr, were generally found on the trunk (64%) and uncommonly associated with chronically sun-damaged (CSD) skin. BRAF L597 melanomas occurred in older patients (median 66 yr), but were associated with CSD skin (extremities or head and neck location - 73.3%, P = 0.001). Twenty-three percent of patients with V600E- and 43% of patients with K601E-mutant melanomas presented with nodal disease at diagnosis compared to just 14% of patients with BRAF wild-type tumors (P = 0.001 and 0.006, respectively). Overall, these mutations represent a significant minority of BRAF mutations, but have distinct clinicopathological phenotypes and clinical behaviors.

12 Article The role of BRAF mutations in primary melanoma growth rate and survival. 2015

Mar, V J / Liu, W / Devitt, B / Wong, S Q / Dobrovic, A / McArthur, G A / Wolfe, R / Kelly, J W. ·Victorian Melanoma Service, Alfred Hospital, Melbourne, Vic., 3181, Australia. · Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., 3181, Australia. · Division of Cancer Research, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Vic., 3002, Australia. · Department of Oncology, St Vincent's Hospital, Fitzroy, Vic., 3065, Australia. · Translational Genomics and Epigenomics Laboratory, Ludwig Institute for Cancer Research, Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Vic., 3084, Australia. ·Br J Dermatol · Pubmed #25752325.

ABSTRACT: BACKGROUND: The clinical behaviour and prognosis of primary melanomas harbouring BRAF mutations is not fully understood. OBJECTIVES: To investigate the effect of mutation status on primary melanoma growth rate and melanoma-specific survival (MSS). METHODS: A prospective cohort of 196 patients with stage I-III primary cutaneous melanoma were followed for a median of 92 months, pre-dating the institution of BRAF inhibitor therapy. Clinicopathological variables were correlated with mutation status and hazard ratios (HRs) estimated for MSS. RESULTS: Of 196 tumours, 77 (39.2%) were BRAF V600E, 10 (5.1%) BRAF V600K and 33 (16.8%) were NRAS mutant. BRAF V600E mutant melanomas were associated with favourable clinical characteristics and tended to be slower growing compared with BRAF V600K, NRAS mutant or BRAF/NRAS wild-type tumours (0.12 mm per month, 0.61 mm per month, 0.36 mm per month and 0.23 mm per month, respectively; P = 0.05). There were 39 melanoma deaths, and BRAF mutant melanomas were associated with poorer MSS in stage I-III disease [HR 2.60, 95% confidence interval (CI) 1.20-5.63; P = 0.02] and stage I-II disease (HR 3.39, 95% CI 1.12-10.22; P = 0.03) after adjusting for other prognostic variables. Considered separately, BRAF V600E mutant melanomas were strongly associated with MSS independently of thickness and nodal status (HR 3.89, 95% CI 1.67-9.09; P < 0.01) but BRAF V600K mutant tumours were not (HR 1.19, 95% CI 0.36-3.92; P = 0.77). CONCLUSIONS: The presence of a BRAF mutation does not necessarily 'drive' more rapid tumour growth but is associated with poorer MSS in patients with early-stage disease.

13 Article Whole exome sequencing identifies a recurrent RQCD1 P131L mutation in cutaneous melanoma. 2015

Wong, Stephen Q / Behren, Andreas / Mar, Victoria J / Woods, Katherine / Li, Jason / Martin, Claire / Sheppard, Karen E / Wolfe, Rory / Kelly, John / Cebon, Jonathan / Dobrovic, Alexander / McArthur, Grant A. ·Division of Cancer Research, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. · Ludwig Institute for Cancer Research, Olivia Newton-John Cancer and Wellness Centre Heidelberg, Victoria, Australia. · School of Cancer Medicine, La Trobe University, Bundoora, Victoria, Australia. · Victorian Melanoma Service, Alfred Hospital, Prahran, Victoria, Australia. · Department of Epidemiology and Preventive Medicine, Monash University, Clayton, Victoria, Australia. · Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria, Australia. · Department of Pathology, University of Melbourne, Parkville, Victoria, Australia. · Division of Cancer Research, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.Department of Pathology, University of Melbourne, Parkville, Victoria, Australia. ·Oncotarget · Pubmed #25544760.

ABSTRACT: Melanoma is often caused by mutations due to exposure to ultraviolet radiation. This study reports a recurrent somatic C > T change causing a P131L mutation in the RQCD1 (Required for Cell Differentiation1 Homolog) gene identified through whole exome sequencing of 20 metastatic melanomas. Screening in 715 additional primary melanomas revealed a prevalence of ~4%. This represents the first reported recurrent mutation in a member of the CCR4-NOT complex in cancer. Compared to tumors without the mutation, the P131L mutant positive tumors were associated with increased thickness (p = 0.02), head and neck (p = 0.009) and upper limb (p = 0.03) location, lentigo maligna melanoma subtype (p = 0.02) and BRAF V600K (p = 0.04) but not V600E or NRAS codon 61 mutations. There was no association with nodal disease (p = 0.3). Mutually exclusive mutations of other members of the CCR4-NOT complex were found in ~20% of the TCGA melanoma dataset suggesting the complex may play an important role in melanoma biology. Mutant RQCD1 was predicted to bind strongly to HLA-A0201 and HLA-Cw3 MHC1 complexes. From thirteen patients with mutant RQCD1, an anti-tumor CD8⁺ T cell response was observed from a single patient's peripheral blood mononuclear cell population stimulated with mutated peptide compared to wildtype indicating a neoantigen may be formed.

14 Article Clinical and pathological associations of the activating RAC1 P29S mutation in primary cutaneous melanoma. 2014

Mar, Victoria J / Wong, Stephen Q / Logan, Aleksandra / Nguyen, Trung / Cebon, Jonathan / Kelly, John W / Wolfe, Rory / Dobrovic, Alexander / McLean, Catriona / McArthur, Grant A. ·Victorian Melanoma Service, Alfred Hospital, Melbourne, Vic., Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Vic., Australia. ·Pigment Cell Melanoma Res · Pubmed #25043693.

ABSTRACT: Activating mutations in the GTPase RAC1 are a recurrent event in cutaneous melanoma. We investigated the clinical and pathological associations of RAC1(P29S) in a cohort of 814 primary cutaneous melanomas with known BRAF and NRAS mutation status. The RAC1(P29S) mutation had a prevalence of 3.3% and was associated with increased thickness (OR=1.6 P = 0.001), increased mitotic rate (OR=1.3 P = 0.03), ulceration (OR=2.4 P = 0.04), nodular subtype (OR=3.4 P = 0.004), and nodal disease at diagnosis (OR=3.3 P = 0.006). BRAF mutant tumors were also associated with nodal metastases (OR=1.9 P = 0.004), despite being thinner at diagnosis than BRAF WT (median 1.2 mm versus 1.6 mm, P < 0.001). Immunohistochemical analysis of 51 melanomas revealed that 47% were immunoreactive for RAC1. Melanomas were more likely to show RAC1 immunoreactivity if they were BRAF mutant (OR=5.2 P = 0.01). RAC1 may therefore be important in regulating the early migration of BRAF mutant tumors. RAC1 mutations are infrequent in primary melanomas but may accelerate disease progression.

15 Article An objective measure of growth rate using partial biopsy specimens of melanomas that were initially misdiagnosed. 2014

Lin, Matthew J / Mar, Victoria / McLean, Catriona / Kelly, John W. ·Victorian Melanoma Service, Alfred Hospital, Melbourne, Australia. Electronic address: drmatthewlin@gmail.com. · Victorian Melanoma Service, Alfred Hospital, Melbourne, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. · Victorian Melanoma Service, Alfred Hospital, Melbourne, Australia; Department of Anatomical Pathology, Alfred Hospital, Melbourne, Australia. · Victorian Melanoma Service, Alfred Hospital, Melbourne, Australia. ·J Am Acad Dermatol · Pubmed #24976443.

ABSTRACT: BACKGROUND: To calculate melanoma rate of growth (ROG), previous studies have relied on subjective patient recall to estimate time delay to diagnosis. OBJECTIVE: To objectively calculate ROG by measuring the rate of increase in melanoma thickness between 2 sequential biopsy specimens over time. METHODS: This was a retrospective review of 51 melanomas in which pathologic misdiagnosis of a partial biopsy specimen caused a delay before referral and excisional biopsy between January 1998 and January 2013. ROG was calculated as rate of increase in tumor thickness between biopsy specimens. RESULTS: The median delay between the 2 biopsy specimens was 27 months (range, 3-89 months). Biopsy specimens of melanomas that were obtained initially in their in situ phase were thinner at excision compared to those that were first obtained as invasive tumors (median, 0.7 vs. 3.2 mm; P<.01) and had a lower ROG (median, 0.04 vs. 0.11 mm/month; P=.05). Faster growth was associated with increased tumor thickness, higher mitotic rate, symptoms, elevation, and amelanosis. LIMITATIONS: Partial biopsy specimens may not be representative of deepest tumor thickness. CONCLUSION: We have demonstrated an objective measure of melanoma growth rate using sequential biopsy specimens. The correlation between faster growth and aggressive tumor features supports what others have found and validates the historical measure of growth rate as a reliable clinical marker.

16 Article Bioinformatics pipelines for targeted resequencing and whole-exome sequencing of human and mouse genomes: a virtual appliance approach for instant deployment. 2014

Li, Jason / Doyle, Maria A / Saeed, Isaam / Wong, Stephen Q / Mar, Victoria / Goode, David L / Caramia, Franco / Doig, Ken / Ryland, Georgina L / Thompson, Ella R / Hunter, Sally M / Halgamuge, Saman K / Ellul, Jason / Dobrovic, Alexander / Campbell, Ian G / Papenfuss, Anthony T / McArthur, Grant A / Tothill, Richard W. ·Bioinformatics, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia; Department of Mechanical Engineering, The University of Melbourne, Parkville, VIC, Australia. · Bioinformatics, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia. · Department of Mechanical Engineering, The University of Melbourne, Parkville, VIC, Australia; YourGene Biosciences Australia, Southbank, VIC, Australia. · Molecular Pathology Research and Development Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia. · Victorian Melanoma Service, Alfred Hospital, Prahran, VIC, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Clayton, VIC, Australia; Molecular Oncology Laboratory, Oncogenic Signaling and Growth Control Program, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia. · Sarcoma Genetics and Genomics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia; Bioinformatics and Cancer Genomics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia. · Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia. · Department of Mechanical Engineering, The University of Melbourne, Parkville, VIC, Australia. · Molecular Pathology Research and Development Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia; Translational Genomics & Epigenomics Laboratory, Ludwig Institute for Cancer Research, Heidelberg, VIC, Australia. · Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia. · Bioinformatics division, The Walter and Eliza Hall Institute for Medical Research, Parkville, VIC, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia; Bioinformatics and Cancer Genomics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia. · Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia; Molecular Oncology Laboratory, Oncogenic Signaling and Growth Control Program, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia; Translational Research Laboratory, Cancer Therapeutics Program, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia; Department of Medicine, St. Vincent's Hospital, Fitzroy, VIC, Australia; Department of Pathology, University of Melbourne, Parkville, VIC, Australia. · Translational Research Laboratory, Cancer Therapeutics Program, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia; Department of Pathology, University of Melbourne, Parkville, VIC, Australia. ·PLoS One · Pubmed #24752294.

ABSTRACT: Targeted resequencing by massively parallel sequencing has become an effective and affordable way to survey small to large portions of the genome for genetic variation. Despite the rapid development in open source software for analysis of such data, the practical implementation of these tools through construction of sequencing analysis pipelines still remains a challenging and laborious activity, and a major hurdle for many small research and clinical laboratories. We developed TREVA (Targeted REsequencing Virtual Appliance), making pre-built pipelines immediately available as a virtual appliance. Based on virtual machine technologies, TREVA is a solution for rapid and efficient deployment of complex bioinformatics pipelines to laboratories of all sizes, enabling reproducible results. The analyses that are supported in TREVA include: somatic and germline single-nucleotide and insertion/deletion variant calling, copy number analysis, and cohort-based analyses such as pathway and significantly mutated genes analyses. TREVA is flexible and easy to use, and can be customised by Linux-based extensions if required. TREVA can also be deployed on the cloud (cloud computing), enabling instant access without investment overheads for additional hardware. TREVA is available at http://bioinformatics.petermac.org/treva/.

17 Article Diagnostic accuracy of malignant melanoma according to subtype. 2014

Lin, Matthew J / Mar, Victoria / McLean, Catriona / Wolfe, Rory / Kelly, John W. ·Victorian Melanoma Service, The Alfred, Melbourne, Victoria, Australia. ·Australas J Dermatol · Pubmed #24283461.

ABSTRACT: BACKGROUND/OBJECTIVE: Although there has been improvement in clinical diagnosis of pigmented superficial spreading melanomas (SSM), less common melanoma subtypes have different clinical features and may be more difficult to diagnose. The objective was to assess diagnostic accuracy for different melanoma subtypes. METHODS: A retrospective review was made of a random selection of SSM, nodular melanomas (NM), desmoplastic melanomas (DM) and acral lentiginous melanomas (ALM) biopsied between February 2001 and May 2012 and referred to the Victorian Melanoma Service. Clinical differential diagnoses listed on pre-operative biopsy pathology request forms were recorded. Sensitivity for the diagnosis of melanoma was used as a marker of diagnostic accuracy. RESULTS: In total 111 SSM, 121 NM, 43 DM and 30 ALM were biopsied by 222 clinicians. Whereas diagnostic sensitivity for SSM and ALM were similar (77%, 95% CI 69-85% and 73%, 95% CI 58-89%, respectively) diagnostic sensitivity was lower for NM (41%, 95% CI 33-50%) and DM (21%, 95% CI 9-33%). Both NM and DM were diagnosed at greater tumour thickness (median 3.0 mm and 4.0 mm) than SSM and ALM (both median 1.0 mm). Amelanosis was associated with lower diagnostic sensitivity for SSM (0 vs 82%, P < 0.01), NM (19 vs 51%, P < 0.01) andDM (10 vs 32%, P = 0.07). Dermatologists were more accurate than non-dermatologists for NM (diagnostic sensitivity 57 vs 32%, P < 0.01) and ALM (diagnostic sensitivity 94 vs 43%, P = 0.02). CONCLUSIONS: Misdiagnosis of melanoma varies according to subtype and is particularly problematic for NM, DM and hypopigmented melanomas. Greater awareness of the different criteria required to diagnose these melanomas is needed.

18 Article BRAF/NRAS wild-type melanomas have a high mutation load correlating with histologic and molecular signatures of UV damage. 2013

Mar, Victoria J / Wong, Stephen Q / Li, Jason / Scolyer, Richard A / McLean, Catriona / Papenfuss, Anthony T / Tothill, Richard W / Kakavand, Hojabr / Mann, Graham J / Thompson, John F / Behren, Andreas / Cebon, Jonathan S / Wolfe, Rory / Kelly, John W / Dobrovic, Alexander / McArthur, Grant A. ·Molecular Oncology Laboratory, Oncogenic Signaling and Growth Control Program, Peter MacCallum Cancer Centre, East Melbourne, Australia. ·Clin Cancer Res · Pubmed #23833303.

ABSTRACT: PURPOSE: The mutation load in melanoma is generally high compared with other tumor types due to extensive UV damage. Translation of exome sequencing data into clinically relevant information is therefore challenging. This study sought to characterize mutations identified in primary cutaneous melanomas and correlate these with clinicopathologic features. EXPERIMENTAL DESIGN: DNA was extracted from 34 fresh-frozen primary cutaneous melanomas and matched peripheral blood. Tumor histopathology was reviewed by two dermatopathologists. Exome sequencing was conducted and mutation rates were correlated with age, sex, tumor site, and histopathologic variables. Differences in mutations between categories of solar elastosis, pigmentation, and BRAF/NRAS mutational status were investigated. RESULTS: The average mutation rate was 12 per megabase, similar to published results in metastases. The average mutation rate in severely sun damaged (SSD) skin was 21 per Mb compared with 3.8 per Mb in non-SSD skin (P=0.001). BRAF/NRAS wild-type (WT) tumors had a higher average mutation rate compared with BRAF/NRAS-mutant tumors (27 vs. 5.6 mutations per Mb; P=0.0001). Tandem CC>TT/GG>AA mutations comprised 70% of all dinucleotide substitutions and were more common in tumors arising in SSD skin (P=0.0008) and in BRAF/NRAS WT tumors (P=0.0007). Targetable and potentially targetable mutations in WT tumors, including NF1, KIT, and NOTCH1, were spread over various signaling pathways. CONCLUSION: Melanomas arising in SSD skin have higher mutation loads and contain a spectrum of molecular subtypes compared with BRAF- and NRAS-mutant tumors indicating multigene screening approaches and combination therapies may be required for management of these patients.

19 Article Nodular melanoma: a distinct clinical entity and the largest contributor to melanoma deaths in Victoria, Australia. 2013

Mar, Victoria / Roberts, Hugh / Wolfe, Rory / English, Dallas R / Kelly, John W. ·Victorian Melanoma Service, Alfred Hospital, Melbourne, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia; Peter MacCallum Cancer Center, Melbourne, Australia. Electronic address: torimar@ymail.com. · Victorian Melanoma Service, Alfred Hospital, Melbourne, Australia. · Victorian Melanoma Service, Alfred Hospital, Melbourne, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. · Cancer Council Victoria, Melbourne, Australia; Melbourne School of Population Health, University of Melbourne, Melbourne, Australia. ·J Am Acad Dermatol · Pubmed #23182058.

ABSTRACT: BACKGROUND: There is a growing body of evidence that nodular melanoma (NM), because of its association with increased growth rate and thickness at diagnosis, accounts for a substantial proportion of melanoma deaths. OBJECTIVE: We sought to assess the contribution of NM to melanoma deaths in comparison with other tumor subtypes. METHODS: Four cohorts were established comprising 5775 cases of invasive primary cutaneous melanoma reported to the Victorian Cancer Registry during 1989, 1994, 1999, and 2004. Original pathology reports were reviewed. Age-standardized melanoma incidence rates were compared from 1989 to 2004 with annual percentage change using Poisson regression. RESULTS: The incidence of thick tumors (>4 mm) increased by 3.8% (95% confidence interval 1.4 to 6.2) and 2.5% (95% confidence interval -0.5 to 5.5) per year for male and female patients, respectively. The median thickness of NM at diagnosis was 2.6 mm compared with 0.6 mm for superficial spreading melanoma. A third of patients who died from melanoma during the follow-up period had thick tumors (>4 mm), most of which were nodular subtype (61%). NM accounted for 14% of invasive melanomas, but was responsible for 43% of melanoma deaths in a total of 57,461 person-years of follow-up. By comparison, superficial spreading melanoma contributed 56% of invasive melanoma but only 30% of deaths. LIMITATIONS: Pathology review was limited to reports only. Mortality information relied mostly on death certificate information. CONCLUSION: The incidence of thick melanomas continues to increase. Nodular melanoma is clinically distinct and the predominant contributor to melanoma-related deaths, representing a public health challenge in reducing skin cancer mortality.

20 Article Predicting melanoma risk for the Australian population. 2011

Mar, Victoria / Wolfe, Rory / Kelly, John W. ·Victorian Melanoma Service, The Alfred Hospital, Melbourne, Victoria, Australia. torimar@ymail.com ·Australas J Dermatol · Pubmed #21605094.

ABSTRACT: BACKGROUND: As melanoma incidence in Australia continues to rise, targeting high-risk individuals for early detection is of paramount importance. OBJECTIVES: We aimed to design a population-specific risk assessment tool to improve on the use of intuition alone for assignment of surveillance strategies for high-risk individuals and help communicate risk more accurately and effectively to patients. METHODS: Methods used in the development of breast cancer risk models were adopted. Data from a large meta-analysis was used to determine risk estimates. Attributable risk was calculated for each risk factor using data from the Victorian Melanoma Service. Local prevalence data from state cancer registries was incorporated to estimate 5-year risk of melanoma. RESULTS: Independent risk factors identified were common naevi, atypical naevi, hair colour, freckles, family history of melanoma and personal history of non-melanoma skin cancer. Personal history of melanoma was the strongest risk factor for developing another (relative risk 7.28, 7.24). Absolute risk for individuals varies greatly with age, risk factor profiles and proximity to the equator. CONCLUSION: We have developed a melanoma risk assessment tool based on the best available information (http://www.victorianmelanomaservice.org/calculator). The tool is easily modified as new information becomes available.

21 Minor Differing trends in thickness and survival between nodular and non-nodular primary cutaneous melanoma in Victoria, Australia. 2015

Smithson, Sarah L / Pan, Yan / Mar, Victoria. ·Victorian Melanoma Service, Melbourne, VIC, Australia. ·Med J Aust · Pubmed #26126561.

ABSTRACT: -- No abstract --

22 Minor Letter to the editor. 2015

Lin, Matthew J / Mar, Victoria / McLean, Catriona / Wolfe, Rory / Kelly, John W. ·Victorian Melanoma Service, Alfred Hospital, Melbourne, Victoria, Australia. ·Australas J Dermatol · Pubmed #25688701.

ABSTRACT: -- No abstract --