Publications by authors named "John W Kelly"

70 Publications

Australian general practitioners' attitudes and knowledge of sentinel lymph node biopsy in melanoma management.

Aust J Gen Pract 2020 06;49(6):355-362

MPH (Hons), PhD, Head of Cancer Epidemiology and Prevention Research Group, Sydney School of Public Health and Melanoma Institute Australia, University of Sydney, NSW; Professor of Cancer Epidemiology, Sydney Medical School, University of Sydney, NSW.

Background And Objectives: In Australia, the uptake of the sentinel lymph node biopsy (SLNB) appears low despite clinical practice guideline recommendations. The aim of this study was to describe the knowledge and attitudes of general practitioners (GPs) to SLNB.

Method: GPs were recruited at an annual conference and a skin cancer skills workshop, and using GP professional communications. A mixed methods approach comprised a cross-sectional questionnaire and, for a subset of participants, semi-structured interviews.

Results: Overall, 231 GPs completed the questionnaire, of whom 23 were interviewed. One-third (32%) described themselves as quite or very familiar with the guidelines, and two-thirds (68%) thought that SLNB had an important role in the management of patients with melanoma. Of GPs who would discuss SLNB with eligible patients, <40% correctly identified that SLNB is recommended for patients with an invasive melanoma >1 mm thick.

Discussion: GPs were generally supportive of SLNB. Familiarity with the guidelines was low, particularly regarding which patients should be considered for SLNB.
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http://dx.doi.org/10.31128/AJGP-10-19-5138DOI Listing
June 2020

Acral lentiginous melanoma: Clinicopathologic and survival differences according to tumour location.

Australas J Dermatol 2020 Nov 3;61(4):312-317. Epub 2020 May 3.

Victorian Melanoma Service, Alfred Hospital, Melbourne, Victoria, Australia.

Background/objectives: Acral lentiginous melanoma (ALM) is a melanoma subtype associated with atypical locations on the hands and feet and advanced disease at diagnosis. There is a limited understanding of whether the survival is similar for nail, non-nail, lower limb and upper limb ALM patients. We therefore explored clinicopathologic characteristics and melanoma-specific survival of ALM patients according to tumour location.

Methods: A prospectively collected cohort study was performed of all primary invasive cutaneous acral lentiginous melanomas with known thickness and tumour location reviewed at a tertiary referral centre over 21 years.

Results: A total of 101 ALM patients were reviewed from 1994 until 2016. The majority of cases (82/101) occurred on the feet. Hand ALMs were thicker and more likely to be ulcerated than feet ALMs (P = 0.05 and 0.02, respectively); however, survival was not statistically different between these two groups (univariate HR 0.48 P = 0.11, 95% CI, 0.20-1.17; multivariate HR 0.67 P = 0.40, 95% CI, 0.27-1.69, respectively). Non-nail ALM patients had longer survival when compared to nail ALM on univariate analysis (HR 0.40, 95% CI, 0.17 to 0.90) which was accounted for by Breslow thickness and ulceration (multivariate HR 0.56, 95% CI, 0.24 to 1.34).

Conclusions: The reduced melanoma-specific survival in nail ALM patients was likely due to their greater thickness and ulceration. Although hand ALMs are thicker and more frequently ulcerated, this is likely due to the higher proportion of nail ALMs present in this location.
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http://dx.doi.org/10.1111/ajd.13310DOI Listing
November 2020

Identifying challenges to implementation of clinical practice guidelines for sentinel lymph node biopsy in patients with melanoma in Australia: protocol paper for a mixed methods study.

BMJ Open 2020 02 27;10(2):e032636. Epub 2020 Feb 27.

Australian Institute of Health Innovation, Macquarie University, Sydney, New South Wales, Australia.

Introduction: Sentinel lymph node biopsy (SLNB) is a diagnostic procedure developed in the 1990s. It is currently used to stage patients with primary cutaneous melanoma, provide prognostic information and guide management. The Australian Clinical Practice Guidelines state that SLNB should be considered for patients with cutaneous melanoma >1 mm in thickness (or >0.8 mm with high-risk pathology features). Until recently, sentinel lymph node (SLN) status was used to identify patients who might benefit from a completion lymph node dissection, a procedure that is no longer routinely recommended. SLN status is now also being used to identify patients who might benefit from systemic adjuvant therapies such as anti-programmed cell death 1 (PD1) checkpoint inhibitor immunotherapy or BRAF-directed molecular targeted therapy, treatments that have significantly improved relapse-free survival for patients with resected stage III melanoma and improved overall survival of patients with unresectable stage III and stage IV melanoma. Australian and international data indicate that approximately half of eligible patients receive an SLNB.

Methods And Analysis: This mixed-methods study seeks to understand the structural, contextual and cultural factors affecting implementation of the SLNB guidelines. Data collection will include: (1) cross-sectional questionnaires and semistructured interviews with general practitioners and dermatologists; (2) semistructured interviews with other healthcare professionals involved in the diagnosis and early definitive care of melanoma patients and key stakeholders including researchers, representatives of professional colleges, training organisations and consumer melanoma groups; and (3) documentary analysis of documents from government, health services and non-government organisations. Descriptive analyses and multivariable regression models will be used to examine factors related to SLNB practices and attitudes. Qualitative data will be analysed using thematic analysis.

Ethics And Dissemination: Ethics approval has been granted by the University of Sydney. Results will be disseminated through publications and presentations to clinicians, patients, policymakers and researchers and will inform the development of strategies for implementing SLNB guidelines in Australia.
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http://dx.doi.org/10.1136/bmjopen-2019-032636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050375PMC
February 2020

The increasing use of shave biopsy for diagnosing invasive melanoma in Australia.

Med J Aust 2020 03 12;212(5):238-238.e1. Epub 2020 Feb 12.

Victorian Melanoma Service, Alfred Health, Melbourne, VIC.

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http://dx.doi.org/10.5694/mja2.50502DOI Listing
March 2020

The anatomic distribution of cutaneous melanoma: A detailed study of 5141 lesions.

Australas J Dermatol 2020 May 27;61(2):125-133. Epub 2019 Dec 27.

Victorian Melanoma Service, Alfred Health, Melbourne, Victoria, Australia.

Background/objectives: There is evidence that cutaneous melanomas at different anatomic sites present with distinctive clinicopathologic features. We examined the anatomic distribution of cutaneous melanoma and its variation by patient characteristics, subtype and Breslow thickness, using high-resolution anatomic site data.

Methods: A cross-sectional study was performed of all primary cutaneous melanoma cases managed at a tertiary referral centre, analysing prospectively collected clinical data across 50 anatomic subsites.

Results: The study included 5141 in situ or invasive melanomas; most were invasive (76.2%), and the median Breslow thickness of invasive lesions was 1.0 mm. Superficial spreading (57.2%), lentigo maligna (20.8%) and nodular (12.2%) were the most common histopathological subtypes. Sun-exposed sites such as the female nose and cheek, the male ear, as well as the upper back in both sexes had the highest incidence of melanoma per unit area. When compared to the posterior forearm, the scalp, ear, preauricular, perioral, subungual and plantar sites had thicker invasive melanomas (each P < 0.05). The peri-auricular, ear and cheek had the highest incidence of nodular melanoma per unit area. There were subtype-, age- and sex-specific differences in melanoma anatomic distribution.

Conclusion: Melanoma most commonly arises in sun-exposed facial areas, as well as the upper back. Increased thickness is found for melanoma in acral and many head and neck sites. Nodular melanoma is more likely to occur in head and neck sites including the peri-auricular area, ear and cheek. Clinicians should carefully assess these sites during skin examinations.
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http://dx.doi.org/10.1111/ajd.13223DOI Listing
May 2020

The increasing use of shave biopsy for diagnosing invasive melanoma in Australia.

Med J Aust 2019 09 22;211(5):213-218. Epub 2019 Jul 22.

Victorian Melanoma Service, Alfred Hospital, Melbourne, VIC.

Objective: To assess changes in the choice of skin biopsy technique for assessing invasive melanoma in Victoria, and to examine the impact of partial biopsy technique on the accuracy of tumour microstaging.

Design: Retrospective cross-sectional review of Victorian Cancer Registry data on invasive melanoma histologically diagnosed in Victoria during 2005, 2010, and 2015.

Setting, Participants: 400 patients randomly selected from each of the three years, stratified by final tumour thickness: 200 patients with thin melanoma (< 1.0 mm), 100 each with intermediate (1.0-4.0 mm) and thick melanoma (> 4.0 mm).

Main Outcome Measures: Partial and excisional biopsies, as proportions of all skin biopsies; rates of tumour base transection and T-upstaging, and mean tumour thickness underestimation following partial biopsy.

Results: 833 excisional and 337 partial diagnostic biopsies were undertaken. The proportion of partial biopsies increased from 20% of patients in 2005 to 36% in 2015 (P < 0.001); the proportion of shave biopsies increased from 9% in 2005 to 20% in 2015 (P < 0.001), with increasing rates among dermatologists and general practitioners. Ninety-four of 175 shave biopsies (54%) transected the tumour base; wide local excision subsequently identified residual melanoma in 65 of these cases (69%). Twenty-one tumours diagnosed by shave biopsy (12%) were T-upstaged. With base-transected shave biopsies, tumour thickness was underestimated by a mean 2.36 mm for thick, 0.48 mm for intermediate, and 0.07 mm for thin melanomas.

Conclusion: Partial biopsy, particularly shave biopsy, was increasingly used for diagnosing invasive melanoma between 2005 and 2015. Shave biopsy has a high rate of base transection, reducing the accuracy of tumour staging, which is crucial for planning appropriate therapy, including definitive surgery and adjuvant therapy.
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http://dx.doi.org/10.5694/mja2.50289DOI Listing
September 2019

Improving diagnostic accuracy for suspicious melanocytic skin lesions: New Australian melanoma clinical practice guidelines stress the importance of clinician/pathologist communication.

Aust J Gen Pract 2019 06;48(6):357-362

MD, Chairman, Australian Melanoma Clinical Practice Guidelines Working Party; Professor of Melanoma and Surgical Oncology, University of Sydney, Sydney, NSW; Surgeon, Royal Prince Alfred Hospital and Melanoma Institute Australia, Sydney, NSW.

Background: Incorrect or delayed diagnosis of melanoma may lead to inappropriate treatment, poor clinical outcomes, increased cost and medicolegal consequences. The provision of pertinent clinical information is essential for accurate pathological diagnosis of cutaneous melanocytic tumours. Failure to provide this information may contribute to poor outcomes.

Objective: The aim of this article is to highlight important clinical information that clinicians can provide to pathologists to facilitate accurate diagnosis of melanocytic tumours.

Discussion: Pertinent clinical information includes patient age, sex, tumour site, specimen orientation (if appropriate), history of the lesion, presence of any clinically or dermoscopically suspicious areas within the lesion (including apparent regression), access to any relevant clinical and/or dermoscopic photographs and prior pathology reports, melanoma history and risk factors, and history of concurrent or recent pregnancy. If the clinical features are not concordant with the pathology findings, the clinician and pathologist should discuss the case to identify the reason for incongruence.
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http://dx.doi.org/10.31128/AJGP-11-18-4759DOI Listing
June 2019

Anatomic location of primary melanoma: Survival differences and sun exposure.

J Am Acad Dermatol 2019 Aug 19;81(2):500-509. Epub 2019 Apr 19.

Victorian Melanoma Service, Alfred Hospital, Melbourne, Victoria, Australia.

Background: Anatomic location of melanoma has been shown to independently influence melanoma-specific survival (MSS).

Objective: We aimed to compare the MSS of specific anatomic subsites and between chronically, intermittently, and rarely sun-exposed sites.

Methods: A prospective cohort study was performed of primary invasive cutaneous melanomas with known thickness and location reviewed at a tertiary referral center over 21 years.

Results: Overall, 3570 primary cutaneous invasive melanoma cases were included. After adjustment for clinicopathologic variables (including thickness, ulceration, mitotic rate, sex, age, and subtype), posterior scalp melanoma was associated with worse MSS (hazard ratio [HR], 2.46; 95% confidence interval [CI], 1.38-4.40) compared with the upper back, whereas melanoma on the thighs, forearms/hands, and anterior upper arms had better MSS. Intermittent (HR, 0.56; 95% CI, 0.41-0.76) and chronically sun-exposed sites (HR, 0.70; 95% CI, 0.51-0.96) had improved survival compared with rarely exposed sites on multivariate analysis.

Limitations: Potential selection bias of a tertiary referral center selecting for advanced cases.

Conclusion: Altered MSS in the posterior scalp, thighs, forearms, hands, and anterior upper arms appears to be independent of clinicopathologic factors. Results were similar for both sexes and age groups. The posterior scalp should be considered a poor prognosis site.
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http://dx.doi.org/10.1016/j.jaad.2019.04.034DOI Listing
August 2019

Accuracy of partial biopsies in the management of cutaneous melanoma.

Australas J Dermatol 2019 Aug 17;60(3):209-213. Epub 2019 Feb 17.

Melanoma and Skin Service and Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Background: The recommended method for histopathological diagnosis of cutaneous melanoma is excisional biopsy, although partial biopsies (shave and punch) are often used. Following a partial biopsy, treatment guidelines recommend a narrow excisional biopsy to plan definitive management. There is limited evidence on the benefits of direct wide local excision (WLE) following diagnostic partial biopsies.

Methods: Retrospective cohort study of cutaneous melanoma cases, from two tertiary referral centres from January 2013 to December 2015. Demographic and histopathological data, including tumour thickness (T-stage) from initial biopsy and subsequent excisions, were collected. Logistic regression was used to examine histopathological T-staging between biopsy and subsequent excisions (upstaging).

Results: 2304 melanomas (2157 patients) were identified; 455 shave, 308 punch, 14 incisional and 1527 excisional biopsies. Out of 1527, 5 (<1%) excisional biopsies were upstaged from original biopsy T-stage to final WLE; compared to 28/455 (6%) for shave, 45/308 (15%) for punch and 2/14 (14%) for incisional biopsies. Histopathology upstaging were increased with punch (OR, 52.1; 95% CI, 20.5-132.4. P < 0.001) and shave biopsy (OR, 20.0; 95% CI, 7.7-52.0. P < 0.001) compared to excisional biopsy. Upstaging rates of 9.4% for desmoplastic (OR, 6.9; 95% CI, 2.4-19.7. P < 0.001) and 21.9% for acral lentiginous (OR, 18.4; 95% CI, 6.9-49.2. P < 0.001) melanomas were elevated compared to 1.4% for superficial spreading melanoma.

Conclusions: In most cases, partial biopsy (particularly shave biopsy) can provide sufficient information to plan for definitive surgical melanoma management. Punch and incisional biopsies have elevated upstaging rates, a consideration in planning therapy. Partial biopsies of desmoplastic or acral lentiginous melanomas have high rates of upstaging and should have a complete excision prior to definitive treatment.
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http://dx.doi.org/10.1111/ajd.13004DOI Listing
August 2019

Methods of melanoma detection and of skin monitoring for individuals at high risk of melanoma: new Australian clinical practice.

Med J Aust 2019 01 2;210(1):41-47. Epub 2018 Dec 2.

Melanoma Institute Australia, Sydney, NSW.

Introduction: The evidence-based national clinical practice guidelines for the management of cutaneous melanoma published in 2008 are currently being updated. This article summarises the findings from multiple chapters of the guidelines on different methods of melanoma detection and of monitoring the skin for patients at high risk of melanoma. Early detection of melanoma is critical, as thinner tumours are associated with enhanced survival; therefore, strategies to improve early detection are important to reduce melanoma-related mortality.

Main Recommendations: Clinicians who perform skin examinations for the purpose of detecting skin cancer should be trained in and use dermoscopy. The use of short term sequential digital dermoscopy imaging to detect melanomas that lack dermoscopic features of melanoma is recommended to assess individual melanocytic lesions of concern. The use of long term sequential digital dermoscopy imaging to detect melanomas that lack dermoscopic features of melanoma is recommended to assess individual or multiple melanocytic lesions for routine surveillance of high risk patients. The use of total body photography should be considered in managing patients at increased risk for melanoma, particularly those with high naevus counts and dysplastic naevi. There is insufficient evidence to recommend the routine use of automated instruments for the clinical diagnosis of primary melanoma.

Management Overview: Determining the relative indications for each diagnostic method and how each method should be introduced into the surveillance of a patient requires careful consideration and an individualised approach.
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http://dx.doi.org/10.5694/mja2.12033DOI Listing
January 2019

Clinically amelanotic or hypomelanotic melanoma: Anatomic distribution, risk factors, and survival.

J Am Acad Dermatol 2018 Oct;79(4):645-651.e4

Victorian Melanoma Service, Alfred Health, Melbourne, Australia.

Background: The recognition and diagnosis of clinically amelanotic or hypomelanotic melanoma is a challenge.

Objective: This study aimed to examine the anatomic distribution and risk factors associated with clinically amelanotic or hypomelanotic melanoma and compare the survival of patients with clinically amelanotic or hypomelanotic melanoma with that of patients with pigmented melanoma.

Methods: A prospective cohort study of all cases of primary invasive melanoma managed at a tertiary referral center was performed.

Results: There were a total of 3913 invasive melanomas, and 384 (9.8%) were clinically amelanotic or hypomelanotic. Skin phototype I; red as well as blonde hair color; actinic keratoses; nodular, desmoplastic, and lentigo maligna subtype; increased Breslow thickness; and mitoses were independently associated with amelanotic or hypomelanotic melanoma (P < .05). After adjustment for subtype and thickness, the face, ears, lateral aspect of the neck, upper portion of the arm, posterior aspect of the forearm, dorsal aspect of the hand, and anterior aspect of the lower portion of the leg were associated with increased odds of amelanotic or hypomelanotic melanoma when compared with the upper portion of the back (P < .05). Mortality risk from melanoma appeared greater for amelanotic or hypomelanotic melanoma than for pigmented melanoma (hazard ratio, 1.5; 95% confidence interval, 1.1-2.1) but was similar once Breslow thickness was taken into account.

Limitations: Single tertiary referral center.

Conclusion: Although clinically amelanotic or hypomelanotic melanoma can occur on all body sites, it is more common on chronically sun-exposed areas. Clinicians should have an increased index of suspicion in patients with a sun-sensitive skin phenotype, red hair, and associated actinic keratoses.
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http://dx.doi.org/10.1016/j.jaad.2018.04.045DOI Listing
October 2018

Dermoscopy improves diagnostic accuracy for clinically amelanotic nodules.

Australas J Dermatol 2019 Feb 19;60(1):45-49. Epub 2018 Aug 19.

Victorian Melanoma Service, Alfred Hospital, Melbourne, Victoria, Australia.

Background/objectives: Amelanotic nodular melanomas are notoriously difficult to diagnose and are responsible for a disproportionate burden of melanoma mortality. It is important to distinguish them from other amelanotic nodules. This study aimed to describe the dermoscopic features of a series of nodular melanomas and other amelanotic nodules and to determine whether dermoscopy improves diagnostic accuracy.

Method: Retrospective analysis of 150 clinically amelanotic nodules with macroscopic and dermoscopic images.

Results: In terms of classifying the nodules as malignant, dermoscopy was superior to unaided eye (specificity 89%; 95% CI 71-98% vs 67%; 95% CI 46-83%, P = 0.03). Dermoscopy enhanced sensitivity for the diagnosis of both amelanotic melanoma and SCC. In 19% of cases, using dermoscopy, the most likely diagnosis was changed from incorrect to correct. This included 26% of amelanotic melanomas which had a macroscopic misdiagnosis overturned to the correct diagnosis. Polymorphous vascular structures were more common in malignant nodules. 76% of amelanotic melanomas/Merkel cell carcinomas had polymorphous vessels compared with 38% of SCCs/KAs/BCCs and 22% of benign nodules (P < 0.001).

Conclusion: Dermoscopy improves diagnostic accuracy for amelanotic melanomas and other amelanotic nodules. Although dermoscopy improves diagnostic accuracy for amelanotic melanomas, these aggressive melanomas remain diagnostically difficult.
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http://dx.doi.org/10.1111/ajd.12902DOI Listing
February 2019

Tumour mutation status and melanoma recurrence following a negative sentinel lymph node biopsy.

Br J Cancer 2018 05 14;118(10):1289-1295. Epub 2018 May 14.

Victorian Melanoma Service, Alfred Hospital, Melbourne, VIC, 3004, Australia.

Background: A proportion of patients develop recurrence following a tumour-negative sentinel lymph node biopsy (SLNB). This study aimed to explore whether melanoma patients with BRAF or NRAS mutant tumours have an increased risk of developing disease recurrence following a negative SLNB compared to patients with wild-type tumours.

Methods: Prospective cohort study of melanoma patients at three tertiary referral centres in Melbourne, who underwent SLNB. Clinical, pathological and molecular characteristics and recurrence data were prospectively recorded. Multivariate Cox proportional hazards regression models estimated the adjusted hazard ratio (aHR) and corresponding 95% confidence interval (CI) for the association between mutation status and development of recurrence following a negative-SLNB.

Results: Overall, 344/477 (72.1%) patients had a negative SLNB. Of these, 54 (15.7%) developed subsequent recurrence. The risk of disease recurrence following a negative SLNB was increased for patients with either a BRAF or NRAS mutant tumour compared to wild-type tumours (aHR 1.92, 95% CI: 1.02-3.60, p = 0.04).

Conclusion: Melanoma patients with BRAF or NRAS mutant tumours had an increased risk compared to patients with BRAF/NRAS wild-type tumours of developing disease recurrence following a tumour-negative SLNB. The findings also confirm the importance of continued surveillance to monitor for disease recurrence among SLNB-negative patients.
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http://dx.doi.org/10.1038/s41416-018-0088-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959932PMC
May 2018

Concordance of somatic mutational profile in multiple primary melanomas.

Pigment Cell Melanoma Res 2018 09 15;31(5):592-603. Epub 2018 Apr 15.

Victorian Melanoma Service, Alfred Hospital, Melbourne, Vic., Australia.

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.
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http://dx.doi.org/10.1111/pcmr.12702DOI Listing
September 2018

You should get that mole checked out: Ethical and legal considerations of the unsolicited clinical opinion.

Aust Fam Physician 2017 Dec;46(12):949-951

Background: Legal and ethical obligations do not always align when doctors become aware of a clinical situation involving a person with whom they have no pre existing therapeutic relationship. Noting a potentially malignant skin lesion, such as a melanoma on a person outside the clinical setting, provides a pertinent example.

Objective: The aim of this article is to describe the legal, ethical and professional considerations surrounding proffering a dermatological opinion in the case of suspected melanoma outside the clinical setting.

Discussion: The application of professional and ethical standards may require the doctor to act in some way to alert the person of their findings in a context whereby there is no defined positive duty to do so in Australian law. The degree to which the doctor is ethically obligated to provide an unsolicited dermatological opinion is affected by numerous and, oftentimes, competing factors.
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December 2017

A novel clinical sign to aid in the diagnosis of superficial basal cell carcinoma.

J Am Acad Dermatol 2017 Dec;77(6):e155-e156

Victorian Melanoma Service, Alfred Hospital, Melbourne, Australia.

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http://dx.doi.org/10.1016/j.jaad.2017.05.054DOI Listing
December 2017

Nodular melanoma is less likely than superficial spreading melanoma to be histologically associated with a naevus.

Med J Aust 2017 Oct;207(8):333-338

Victorian Melanoma Service, Alfred Hospital, Melbourne, VIC.

Objectives: To determine the frequency of naevus-associated melanoma among superficial spreading and nodular subtypes; and to investigate associations between naevus-associated melanoma and other clinico-pathological characteristics.

Design, Setting And Participants: Cross-sectional study of all patients with nodular and superficial spreading melanomas diagnosed between 1994 and 2015 at the Victorian Melanoma Service, Melbourne.

Methods And Main Outcome Measures: Clinical and pathological characteristics of naevus-associated and de novo melanomas were assessed in univariable and multivariable logistic regression analyses.

Results: Of 3678 primary melanomas, 1360 (37.0%) were histologically associated with a naevus and 2318 (63.0%) were de novo melanomas; 71 of 621 nodular (11.4%) and 1289 of 3057 superficial spreading melanomas (42.2%) were histologically associated with a naevus. In multivariable analyses, the odds of being associated with a naevus were higher for melanomas located on the trunk (v head and neck: adjusted odds ratio [OR], 2.27; 95% CI, 1.73-2.96; P < 0.001), while the odds were lower for thicker tumours (adjusted OR, 0.75 per millimetre increase in Breslow thickness; 95% CI, 0.69-0.81; P < 0.001), amelanotic/hypomelanotic melanomas (adjusted OR, 0.68; 95% CI, 0.48-0.97; P = 0.035), and older age (patients 70 years or older v patients under 30 at diagnosis: adjusted OR, 0.28; 95% CI, 0.20-0.40; P < 0.001). After adjusting for confounders, the odds of an associated naevus was three times as high for superficial spreading melanomas as for nodular melanomas (adjusted OR, 3.05; 95% CI, 2.24-4.17; P < 0.001).

Conclusion: Melanomas are most likely to arise in the absence of a pre-existing naevus, particularly nodular melanomas. Public health campaigns should therefore emphasise the detection of suspicious de novo lesions, as well as of changing lesions.
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http://dx.doi.org/10.5694/mja17.00232DOI Listing
October 2017

Clinical practice guidelines for the diagnosis and management of melanoma: melanomas that lack classical clinical features.

Med J Aust 2017 Oct;207(8):348-350

Peter MacCallum Cancer Centre, Melbourne, VIC.

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.
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http://dx.doi.org/10.5694/mja17.00123DOI Listing
October 2017

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

Br J Cancer 2017 Sep 8;117(7):1026-1035. Epub 2017 Aug 8.

Victorian Melanoma Service, Alfred Hospital, Melbourne, Victoria 3004, Australia.

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.
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http://dx.doi.org/10.1038/bjc.2017.254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625668PMC
September 2017

Metastatic pathways in patients with cutaneous melanoma.

Pigment Cell Melanoma Res 2017 01 30;30(1):13-27. Epub 2016 Nov 30.

Victorian Melanoma Service, Alfred Hospital, Melbourne, Vic, Australia.

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.
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http://dx.doi.org/10.1111/pcmr.12544DOI Listing
January 2017

Single institution experience of paediatric melanoma in Victoria, Australia.

Australas J Dermatol 2017 May 28;58(2):117-121. Epub 2016 Jan 28.

Victorian Melanoma Service, The Alfred Hospital, Melbourne, Victoria, Australia.

Background/objectives: Paediatric melanoma is an uncommon presentation of melanoma that accounts for 3% of all paediatric cancers. The objective was to describe a series of paediatric melanoma cases presenting to a state-wide tertiary referral service over the past 19 years.

Methods: A search of the Victorian Melanoma Service database was performed to identify all patients under the age of 20 years diagnosed with melanoma from 1994 to 2013. Histological, demographic and phenotypical information for each patient was collected. Patients were matched against the Victorian Death Registry to identify those who had died. Fisher's exact test was used to examine associations. Melanoma-specific survival was estimated using the Kaplan-Meier method.

Results: A total of 65 paediatric melanoma patients were included for analysis, in whom 72.3% of melanomas were diagnosed when they were 16-19 years of age with a mean age at diagnosis of 16 years. The mean Breslow thickness was 1.4 mm. It was greatest (3.4 mm) in the youngest age group (< 12 years of age). Ten patients developed nodal metastatic disease, eight of which progressed to visceral metastatic disease. The 5-year melanoma-specific survival rate was 96.8%.

Conclusion: This is the first descriptive epidemiological study of paediatric melanoma in Victoria. Further large, population-based, multi-institutional studies of paediatric melanoma are warranted to provide a clearer understanding of this group of melanoma patients.
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http://dx.doi.org/10.1111/ajd.12436DOI Listing
May 2017

Scalp melanoma: Distinctive high risk clinical and histological features.

Australas J Dermatol 2017 Aug 14;58(3):181-188. Epub 2016 Jan 14.

Victorian Melanoma Service, The Alfred Hospital, Melbourne, Victoria, Australia.

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.
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http://dx.doi.org/10.1111/ajd.12437DOI Listing
August 2017

Frequency of residual melanoma in wide local excision (WLE) specimens after complete excisional biopsy.

J Am Acad Dermatol 2016 Jan 23;74(1):102-7. Epub 2015 Oct 23.

Victorian Melanoma Service, Alfred Hospital, Melbourne, Victoria, Australia.

Objective: We sought to better understand the role of wide local excision (WLE) in the treatment of cutaneous melanoma by analyzing residual or locally metastatic disease in WLE specimens of melanomas initially diagnosed with a complete excisional biopsy.

Methods: This was a retrospective review of 807 consecutive WLEs of melanomas diagnosed after complete excisional biopsy. All specimens were reviewed by a single dermatopathologist. Risk of residual or locally metastatic disease was analyzed using univariate and multivariate logistic regression models.

Results: In the 807 WLE specimens, further melanoma was found in 34 cases (4.2%; 95% confidence interval [CI] 2.9-5.8). Residual primary melanoma was found in 33 of these. On univariate analysis, features associated with residual or locally metastatic disease were histologic subtype (odds ratio 3.0; 95% CI 1.3-7.1, P = .01) and tumor location (odds ratio 7.3; 95% CI 2.0-26.6, P < .01). On multivariate analysis, lentigo maligna was independently associated with melanoma remaining in WLE specimens (odds ratio 2.7; 95% CI 1.0-7.3, P = .04).

Conclusion: Residual melanoma in WLE specimens after histologically assessed complete excisional biopsy is not uncommon. Patients with lentigo maligna subtype melanomas are most at risk. Our findings indicate that the procedure of WLE is most important therapeutically for its role in controlling the primary tumor, rather than in preventing local metastatic recurrence.
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http://dx.doi.org/10.1016/j.jaad.2015.08.065DOI Listing
January 2016

An assessment of clinical pathways and missed opportunities for the diagnosis of nodular melanoma versus superficial spreading melanoma.

Australas J Dermatol 2016 May 12;57(2):97-101. Epub 2015 Nov 12.

Victorian Melanoma Service, Alfred Hospital, Melbourne, Victoria, Australia.

Background: Missed opportunities in the diagnosis of nodular melanoma (NM) carry high prognostic penalties due to the rapid rate of NM growth. To date, an assessment of the pathways to diagnosis of NM versus superficial spreading melanoma (SSM) specifically comparing numbers of opportunities missed to undertake biopsy has not been performed.

Methods: A retrospective questionnaire of 120 patients (60 NM patients, age and sex matched to 60 SSM patients) from the Victorian Melanoma Service (VMS) database was undertaken to assess pathways to diagnosis. The numbers of opportunities missed to undertake a biopsy and doctor behaviour at such encounters were recorded. Diagnostic delay (overall, patient's and doctor's delay) in terms of time was assessed.

Results: Significant differences in opportunities missed to make a diagnosis of NM compared to SSM were found. In all, 43% of NM were biopsied at a first encounter compared to 70% of SSM. All SSM were diagnosed within three reviews. Overall, 33% of NM required at least three and up six reviews until biopsy. Patients with NM were more likely than those with SSM to be reassured that their lesions were benign. No significant differences in terms of time delay to diagnosis between NM and SSM were found.

Conclusions: NM contributes disproportionately to melanoma mortality in Australia. Addressing earlier diagnosis of NM with renewed focus may make the biggest impact on the overall mortality of melanoma. The message that a period of observation is not appropriate for patients re-presenting with lesions of concern must be more effectively communicated.
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http://dx.doi.org/10.1111/ajd.12416DOI Listing
May 2016

The Victorian Melanoma Service: A 20-year review of an Australian multidisciplinary cancer service.

Australas J Dermatol 2016 Aug 12;57(3):235-7. Epub 2015 Nov 12.

Victorian Melanoma Service, Alfred Hospital, Victoria, Australia.

Australia has the highest incidence and mortality rates for melanoma in the world. The Victorian Melanoma Service began operation in 1994 as one of the first multidisciplinary melanoma clinics in Victoria. We conducted a review of the Victorian Melanoma Service database of 6721 patients and present the trends observed in a statewide referral centre in Australia. Our results highlight the importance of multidisciplinary care of melanoma patients and emphasise the significance of histological reviews and dermatological skin assessments for the detection of synchronous melanoma.
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http://dx.doi.org/10.1111/ajd.12413DOI Listing
August 2016

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

Am J Clin Oncol 2018 Jan;41(1):90-94

Departments of Medical Oncology.

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.
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http://dx.doi.org/10.1097/COC.0000000000000226DOI Listing
January 2018

Letter to the editor.

Australas J Dermatol 2015 Feb;56(1):66

Victorian Melanoma Service, Alfred Hospital, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/ajd.12234DOI Listing
February 2015

Prognosis associated with cutaneous melanoma metastases.

Australas J Dermatol 2015 Feb;56(1):25-8

Victorian Melanoma Service, The Alfred, Melbourne, Victoria, Australia.

Background/objective: Information on the prognosis for patients with regional cutaneous melanoma metastases has been sparse and difficult to establish. In 2009 the American Joint Committee on Cancer (AJCC) melanoma staging has for the first time provided survival rates for patients who manifest intralymphatic metastases. We sought to validate the new staging system in this contemporary, prospectively collected cohort of patients following the development of cutaneous metastases as the first evidence of metastatic disease and explored the factors that influenced their prognosis.

Methods: The Victorian Melanoma Service database was searched to identify all patients with cutaneous melanoma metastases. Patients who were found to have lymph node or visceral metastases at the time they were diagnosed with cutaneous metastatic disease were excluded. Survival curves were generated and univariate and multivariate assessments of prognostic factors associated with survival were performed.

Results: In total, 72 patients presented with cutaneous metastases as the first evidence of metastatic disease. The median melanoma-specific survival of patients with only regional cutaneous metastases (n = 56) was 5.07 years and their 5-year survival rate was 52%. Distant cutaneous metastases and thickness of the primary melanoma were found to be significant negative predictors of survival.

Conclusion: We were able to validate the new AJCC melanoma staging system survival for patients with cutaneous metastatic disease. Patients presenting with regional cutaneous metastases have a much better prognosis than those with distant cutaneous metastases.
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http://dx.doi.org/10.1111/ajd.12293DOI Listing
February 2015

Dermoscopic features of clear cell acanthoma: five new cases and a review of existing published cases.

Australas J Dermatol 2015 Aug 13;56(3):206-11. Epub 2014 Dec 13.

Victorian Melanoma Service, Alfred Hospital, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/ajd.12206DOI Listing
August 2015

An Adaptive Filter for the Removal of Drifting Sinusoidal Noise Without a Reference.

IEEE J Biomed Health Inform 2016 Jan 2;20(1):213-21. Epub 2014 Dec 2.

This paper presents a method for filtering sinusoidal noise with a variable bandwidth filter that is capable of tracking a sinusoid's drifting frequency. The method, which is based on the adaptive noise canceling (ANC) technique, will be referred to here as the adaptive sinusoid canceler (ASC). The ASC eliminates sinusoidal contamination by tracking its frequency and achieving a narrower bandwidth than typical notch filters. The detected frequency is used to digitally generate an internal reference instead of relying on an external one as ANC filters typically do. The filter's bandwidth adjusts to achieve faster and more accurate convergence. In this paper, the focus of the discussion and the data is physiological signals, specifically electrocorticographic (ECoG) neural data contaminated with power line noise, but the presented technique could be applicable to other recordings as well. On simulated data, the ASC was able to reliably track the noise's frequency, properly adjust its bandwidth, and outperform comparative methods including standard notch filters and an adaptive line enhancer. These results were reinforced by visual results obtained from real ECoG data. The ASC showed that it could be an effective method for increasing signal to noise ratio in the presence of drifting sinusoidal noise, which is of significant interest for biomedical applications.
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http://dx.doi.org/10.1109/JBHI.2014.2375318DOI Listing
January 2016