Publications by authors named "Anne E Cust"

125 Publications

Metastatic acral melanoma treatment outcomes: a systematic review and meta-analysis.

Melanoma Res 2021 10;31(5):482-486

Department of Surgery, The Whiteley-Martin Research Centre, Nepean Clinical School, University of Sydney, Penrith.

Acral melanomas are a unique subset of melanomas occurring on the palms, soles, and nails. There is poor prognosis with surgery alone and no specific guidelines for the treatment of metastatic acral melanoma. This meta-analysis explored the systemic therapy outcomes for metastatic acral melanoma. Medline, Pubmed, EMBASE, and the grey literature were searched from 2010 to August 2020 for studies specifying the treatment outcome of metastatic acral melanoma. Studies were assessed by two investigators. A random-effects meta-analysis was performed and pooled Kaplan-Meier curves for progression-free survival and overall survival were created. Critical appraisal was performed using the Newcastle-Ottawa Scale. Nineteen nonrandomized studies were included, comprising 646 patients with acral melanomas and 1609 patients with nonacral melanomas treated with systemic therapy including chemotherapy, KIT-targeted drugs, as well as anti-CTLA-4 and anti-PD-1 checkpoint inhibitor therapy. Thirteen studies included Kaplan-Meier curves for progression-free survival or overall survival and 11 studies reported treatment responses. Patients with acral melanomas had worse prognosis than nonacral cutaneous melanoma (acral overall survival: median 15 months, 95% CI, 13.7-16.3 months; nonacral cutaneous: median 24 months, 95% CI, 22.6-25.4 months, P < 0.001). Acral melanoma patients treated with anti-PD-1 monotherapy had higher overall survival at 12 months (53%) compared with anti-CTLA-4 monotherapy (34%; P < 0.001). This study provides estimates of treatment response for metastatic acral melanoma, demonstrating low activity across a breadth of approved drug therapies, including anti-PD-1, the most active therapy in melanoma to date. Further research into treatments for metastatic acral melanoma is needed.
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http://dx.doi.org/10.1097/CMR.0000000000000764DOI Listing
October 2021

Impact of personal genomic risk information on melanoma prevention behaviors and psychological outcomes: a randomized controlled trial.

Genet Med 2021 Aug 12. Epub 2021 Aug 12.

The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, NSW, Sydney, Australia.

Purpose: We evaluated the impact of personal melanoma genomic risk information on sun-related behaviors and psychological outcomes.

Methods: In this parallel group, open, randomized controlled trial, 1,025 Australians of European ancestry without melanoma and aged 18-69 years were recruited via the Medicare database (3% consent). Participants were randomized to the intervention (n = 513; saliva sample for genetic testing, personalized melanoma risk booklet based on a 40-variant polygenic risk score, telephone-based genetic counseling, educational booklet) or control (n = 512; educational booklet). Wrist-worn ultraviolet (UV) radiation dosimeters (10-day wear) and questionnaires were administered at baseline, 1 month postintervention, and 12 months postbaseline.

Results: At 12 months, 948 (92%) participants completed dosimetry and 973 (95%) the questionnaire. For the primary outcome, there was no effect of the genomic risk intervention on objectively measured UV exposure at 12 months, irrespective of traditional risk factors. For secondary outcomes at 12 months, the intervention reduced sunburns (risk ratio: 0.72, 95% confidence interval: 0.54-0.96), and increased skin examinations among women. Melanoma-related worry was reduced. There was no overall impact on general psychological distress.

Conclusion: Personalized genomic risk information did not influence sun exposure patterns but did improve some skin cancer prevention and early detection behaviors, suggesting it may be useful for precision prevention. There was no evidence of psychological harm.
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http://dx.doi.org/10.1038/s41436-021-01292-wDOI Listing
August 2021

Surveillance of patients with thin melanoma.

Australas J Dermatol 2021 Jul 22. Epub 2021 Jul 22.

Faculty of Medicine and Health and Melanoma Institute of Australia, The University of Sydney, Camperdown, New South Wales, Australia.

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http://dx.doi.org/10.1111/ajd.13670DOI Listing
July 2021

Knowledge, views and expectations for cancer polygenic risk testing in clinical practice: A cross-sectional survey of health professionals.

Clin Genet 2021 Oct 12;100(4):430-439. Epub 2021 Jul 12.

Dermatology Research Centre, The University of Queensland Diamantina Institute, University of Queensland, Brisbane, Australia.

Polygenic risk scores (PRS) are becoming increasingly available in clinical practice to evaluate cancer risk. However, little is known about health professionals' knowledge, attitudes, and expectations of PRS. An online questionnaire was distributed by relevant health professional organisations predominately in Australia, Canada and the US to evaluate health professionals' knowledge, views and expectations of PRS. Eligible participants were health professionals who provide cancer risk assessments. Results from the questionnaire were analysed descriptively and content analysis was undertaken of free-text responses. In total, 105 health professionals completed the questionnaire (genetic counsellors 84%; oncologists 6%; clinical geneticists 4%; other 7%). Although responses differed between countries, most participants (61%) had discussed PRS with patients, 20% had ordered a test and 14% had returned test results to a patient. Confidence and knowledge around interpreting PRS were low. Although 69% reported that polygenic testing will certainly or likely influence patient care in the future, most felt unprepared for this. If scaled up to the population, 49% expect that general practitioners would have a primary role in the provision of PRS, supported by genetic health professionals. These findings will inform the development of resources to support health professionals offering polygenic testing, currently and in the future.
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http://dx.doi.org/10.1111/cge.14025DOI Listing
October 2021

Identifying the 'Active Ingredients' of an Effective Psychological Intervention to Reduce Fear of Cancer Recurrence: A Process Evaluation.

Front Psychol 2021 7;12:661190. Epub 2021 Jun 7.

Cincinnati Children's Center for Heart Disease and Mental Health, Heart Institute and the Division of Behavioral Medicine & Clinical Psychology, Cincinnati Children's Hospital, Cincinnati, OH, United States.

Psychological interventions targeting fear of cancer recurrence (FCR) are effective in reducing fear and distress. Process evaluations are an important, yet scarce adjunct to published intervention trials, despite their utility in guiding the interpretation of study outcomes and optimizing intervention design for broader implementation. Accordingly, this paper reports the findings of a process evaluation conducted alongside a randomized controlled trial of a psychological intervention for melanoma patients. Men and women with a history of Stage 0-II melanoma at high-risk of developing new primary disease were recruited High Risk Melanoma Clinics across Sydney, Australia and randomly allocated to receive the psychological intervention ( = 80) or usual care ( = 84). Intervention participants received a tailored psycho-educational resource and three individual psychotherapeutic sessions delivered telehealth. Qualitative and quantitative data on intervention context, processes, and delivery (reach, dose, and fidelity), and mechanisms of impact (participant responses, moderators of outcome) were collected from a range of sources, including participant surveys, psychotherapeutic session audio-recordings, and clinical records. Almost all participants reported using the psycho-educational resource (97%), received all intended psychotherapy sessions (96%), and reported high satisfaction with both intervention components. Over 80% of participants would recommend the intervention to others, and a small proportion (4%) found discussion of melanoma-related experiences confronting. Perceived benefits included enhanced doctor-patient communication, talking more openly with family members about melanoma, and improved coping. Of potential moderators, only higher FCR severity at baseline (pre-intervention) was associated with greater reductions in FCR severity (primary outcome) at 6-month follow-up (primary endpoint). Findings support the acceptability and feasibility of a psychological intervention to reduce FCR amongst individuals at high risk of developing another melanoma. Implementation into routine melanoma care is an imperative next step, with FCR screening recommended to identify those most likely to derive the greatest psychological benefit.
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http://dx.doi.org/10.3389/fpsyg.2021.661190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215538PMC
June 2021

Changes in sun protection behaviours, sun exposure and shade availability among adults, children and adolescents in New South Wales, 2003-2016.

Aust N Z J Public Health 2021 May 24. Epub 2021 May 24.

Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW.

Objective: To inform skin cancer prevention policies and campaigns, we investigated changes over time in sun protection behaviours, sunburn, sun exposure and shade availability in public spaces among people living in New South Wales (NSW), Australia, between 2003 and 2016.

Methods: We analysed cross-sectional data from the NSW Population Health Survey collected in 2003, 2007, 2014 and 2016, which included approximately 15,000 respondents of all ages in each year. Logistic regression models were used to analyse overall changes over time and for different age, sex and sociodemographic groups.

Results: The use of sunscreen and protective clothing and the availability of shade increased between 2003 and 2016, but sunburn and sun exposure during peak times of ultraviolet radiation also increased. In subgroup analyses, there was no improvement in sun protection behaviours among adolescents and increases in sunburn and sun exposure were observed only among adults, particularly women and in areas with less social disadvantage.

Conclusions: Sun protection behaviours have improved over time among some population subgroups, but over-exposure to ultraviolet radiation remains prevalent. Implications for public health: Skin cancer prevention initiatives that specifically target adolescents and sun exposure during peak times are needed to help reduce population skin cancer risk.
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http://dx.doi.org/10.1111/1753-6405.13112DOI Listing
May 2021

Acceptability of risk-stratified population screening across cancer types: Qualitative interviews with the Australian public.

Health Expect 2021 Aug 11;24(4):1326-1336. Epub 2021 May 11.

Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, NSW, Australia.

Background: There is mounting evidence of the benefit of risk-stratified (risk-tailored) cancer population screening, when compared to standard approaches. However, shifting towards this approach involves changes to practice that may give rise to implementation challenges.

Objectives: To explore the public's potential acceptance of risk-stratified screening across different cancer types, including reducing screening frequency if at low risk and the use of personal risk information, to inform implementation strategies.

Method: Semi-structured interviews were conducted with 40 public participants; half had received personal genomic risk information and half had not. Participants were prompted to consider different cancers. Data were analysed thematically as one dataset.

Results: Themes included the following: (a) a sense of security; (b) tailored screening is common sense; (c) risk and the need to take action; (d) not every cancer is the same; and (e) trust and belief in health messages. Both groups expressed similar views. Participants were broadly supportive of risk-stratified screening across different cancer types, with strong support for increased screening frequency for high-risk groups. They were less supportive of reduced screening frequency or no screening for low-risk groups. Findings suggest the public will be amenable to reducing screening when the test is invasive and uncomfortable; be less opposed to forgo screening if offered the opportunity to screen at some stage; and view visible cancers such as melanoma differently.

Conclusions: Approaching distinct cancer types differently, tailoring messages for different audiences and understanding reasons for participating in screening may assist with designing future implementation strategies for risk-stratified cancer screening.
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http://dx.doi.org/10.1111/hex.13267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369084PMC
August 2021

Can patient-led surveillance detect subsequent new primary or recurrent melanomas and reduce the need for routinely scheduled follow-up? A protocol for the MEL-SELF randomised controlled trial.

Trials 2021 May 4;22(1):324. Epub 2021 May 4.

Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.

Background: Most subsequent new primary or recurrent melanomas might be self-detected if patients are trained to systematically self-examine their skin and have access to timely medical review (patient-led surveillance). Routinely scheduled clinic visits (clinician-led surveillance) is resource-intensive and has not been shown to improve health outcomes; fewer visits may be possible if patient-led surveillance is shown to be safe and effective. The MEL-SELF trial is a randomised controlled trial comparing patient-led surveillance with clinician-led surveillance in people who have been previously treated for localised melanoma.

Methods: Stage 0/I/II melanoma patients (n = 600) from dermatology, surgical, or general practice clinics in NSW Australia, will be randomised (1:1) to the intervention (patient-led surveillance, n = 300) or control (usual care, n = 300). Patients in the intervention will undergo a second randomisation 1:1 to polarised (n = 150) or non-polarised (n = 150) dermatoscope. Patient-led surveillance comprises an educational booklet, skin self-examination (SSE) instructional videos; 3-monthly email/SMS reminders to perform SSE; patient-performed dermoscopy with teledermatologist feedback; clinical review of positive teledermoscopy through fast-tracked unscheduled clinic visits; and routinely scheduled clinic visits following each clinician's usual practice. Clinician-led surveillance comprises an educational booklet and routinely scheduled clinic visits following each clinician's usual practice. The primary outcome, measured at 12 months, is the proportion of participants diagnosed with a subsequent new primary or recurrent melanoma at an unscheduled clinic visit. Secondary outcomes include time from randomisation to diagnosis (of a subsequent new primary or recurrent melanoma and of a new keratinocyte cancer), clinicopathological characteristics of subsequent new primary or recurrent melanomas (including AJCC stage), psychological outcomes, and healthcare use. A nested qualitative study will include interviews with patients and clinicians, and a costing study we will compare costs from a societal perspective. We will compare the technical performance of two different models of dermatoscope (polarised vs non-polarised).

Discussion: The findings from this study may inform guidance on evidence-based follow-up care, that maximises early detection of subsequent new primary or recurrent melanoma and patient wellbeing, while minimising costs to patients, health systems, and society.

Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000176864 . Registered on 18 February 2021.
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http://dx.doi.org/10.1186/s13063-021-05231-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096155PMC
May 2021

Birth cohort-specific trends of sun-related behaviors among individuals from an international consortium of melanoma-prone families.

BMC Public Health 2021 04 23;21(1):692. Epub 2021 Apr 23.

Department of Dermatology, Leiden University Medical Centre, Leiden, The Netherlands.

Background: Individuals from melanoma-prone families have similar or reduced sun-protective behaviors compared to the general population. Studies on trends in sun-related behaviors have been temporally and geographically limited.

Methods: Individuals from an international consortium of melanoma-prone families (GenoMEL) were retrospectively asked about sunscreen use, sun exposure (time spent outside), sunburns, and sunbed use at several timepoints over their lifetime. Generalized linear mixed models were used to examine the association between these outcomes and birth cohort defined by decade spans, after adjusting for covariates.

Results: A total of 2407 participants from 547 families across 17 centers were analyzed. Sunscreen use increased across subsequent birth cohorts, and although the likelihood of sunburns increased until the 1950s birth cohort, it decreased thereafter. Average sun exposure did not change across the birth cohorts, and the likelihood of sunbed use increased in more recent birth cohorts. We generally did not find any differences in sun-related behavior when comparing melanoma cases to non-cases. Melanoma cases had increased sunscreen use, decreased sun exposure, and decreased odds of sunburn and sunbed use after melanoma diagnosis compared to before diagnosis.

Conclusions: Although sunscreen use has increased and the likelihood of sunburns has decreased in more recent birth cohorts, individuals in melanoma-prone families have not reduced their overall sun exposure and had an increased likelihood of sunbed use in more recent birth cohorts. These observations demonstrate partial improvements in melanoma prevention and suggest that additional intervention strategies may be needed to achieve optimal sun-protective behavior in melanoma-prone families.
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http://dx.doi.org/10.1186/s12889-021-10424-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063451PMC
April 2021

Diagnostic tools used for melanoma: A survey of Australian general practitioners and dermatologists.

Australas J Dermatol 2021 Aug 16;62(3):300-309. Epub 2021 Apr 16.

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

Background/objective: Diagnostic tools such as dermoscopy, sequential digital dermoscopy imaging (SDDI), total body photography (TBP) and automated diagnostic tools are available to assist in early melanoma diagnosis. The use, accessibility and barriers of dermoscopy have been well studied; however, there are few similar studies regarding SDDI, TBP and automated diagnostic tools. We aim to understand the use of these diagnostic aids amongst Australian general practitioners (GPs) and dermatologists.

Methods: Between June 2019 and January 2020, GPs and dermatologists across Australia were invited to participate in an online survey. Surveys were distributed through GP and dermatology organisations.

Results: A total of 227 survey responses were received, 175 from GPs and 52 from dermatologists. Amongst GPs, 44.6% worked in a skin cancer clinic. Dermoscopy was used at least occasionally by 98.9% of all GPs. SDDI was used by 93.6% of skin cancer GPs, 80.8% of dermatologists and 45.3% of generalist GPs. TBP was used or recommended by 77.1% of generalist GPs, 82.3% of skin cancer GPs and 86.5% of dermatologists. The most common barriers to the use of TBP were cost, limited accessibility, poor patient compliance, and time required for both patients and doctors. Very few clinicians reported using automated diagnostic tools. There was an interest in future diagnostic aids for melanoma in 88% of GPs and dermatologists.

Conclusion: Dermoscopy, SDDI and TBP were commonly used by responding Australian skin cancer GPs and dermatologists in this survey. Automated diagnostic tools were not reported to be used routinely. Several barriers were identified for use of TBP.
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http://dx.doi.org/10.1111/ajd.13595DOI Listing
August 2021

Genomic Risk Score for Melanoma in a Prospective Study of Older Individuals.

J Natl Cancer Inst 2021 Apr 10. Epub 2021 Apr 10.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.

Background: Recent genome-wide association meta-analysis for melanoma doubled the number of previously identified variants. We assessed the performance of an updated polygenic risk score (PRS) in a population of older individuals, where melanoma incidence and cumulative ultraviolet radiation exposure is greatest.

Methods: We assessed a PRS for cutaneous melanoma comprising 55 variants in a prospective study of 12,712 individuals in the ASPirin in Reducing Events in the Elderly trial. We evaluated incident melanomas diagnosed during the trial and prevalent melanomas diagnosed pre-enrolment (self-reported). Multivariable models examined associations between PRS as a continuous variable (per standard deviation [SD]), and categorical (low-risk [0-20%], medium-risk [21-80%], high-risk [81-100%] groups) with incident melanoma. Logistic regression examined the association between PRS and prevalent melanoma.

Results: At baseline, mean participant age was 75 years; 55.0% were female, and 528 (4.2%) had prevalent melanomas. During follow-up (median = 4.7 years), 120 (1.0%) incident cutaneous melanomas occurred, 98 of which were in participants with no history. PRS was associated with incident melanoma (hazard ratio = 1.46 per SD, 95% confidence interval [CI] = 1.20-1.77) and prevalent melanoma (odds ratio [OR]=1.55 per SD, 95% CI = 1.42-1.69). Participants in the highest-risk PRS group had increased risk compared to the low-risk group for incident (OR = 2.51, 95% CI = 1.28-4.92) and prevalent (OR = 3.66, 95% CI = 2.69-5.05). When stratifying by sex, only males had an association between the PRS and incident melanoma, whereas both sexes had an association between the PRS and prevalent melanoma.

Conclusion: A genomic risk score is associated with melanoma risk in older individuals, and may contribute to targeted surveillance.
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http://dx.doi.org/10.1093/jnci/djab076DOI Listing
April 2021

Efficiency of Detecting New Primary Melanoma Among Individuals Treated in a High-risk Clinic for Skin Surveillance.

JAMA Dermatol 2021 05;157(5):521-530

Melanoma Institute Australia, The University of Sydney, Sydney, Australia.

Importance: A previous single-center study observed fewer excisions, lower health care costs, thinner melanomas, and better quality of life when surveillance of high-risk patients was conducted in a melanoma dermatology clinic with a structured surveillance protocol involving full-body examinations every 6 months aided by total-body photography (TBP) and sequential digital dermoscopy imaging (SDDI).

Objective: To examine longer-term sustainability and expansion of the surveillance program to numerous practices, including a primary care skin cancer clinic setting.

Design, Setting, And Participants: This prospective cohort study recruited 593 participants assessed from 2012 to 2018 as having very high risk of melanoma, with a median of 2.9 years of follow-up (interquartile range, 1.9-3.3 years), from 4 melanoma high-risk clinics (3 dermatology clinics and 1 primary care skin cancer clinic) in New South Wales, Australia. Data analyses were conducted from February to September 2020.

Exposures: Six-month full-body examination with the aid of TBP and SDDI. For equivocal lesions, the clinician performed SDDI at 3 or 6 months.

Main Outcomes And Measures: All suspect monitored or excised lesions were recorded, and pathology reports obtained. Outcomes included the incidence and characteristics of new lesions and the association of diagnostic aids with rates of new melanoma detection.

Results: Among 593 participants, 340 (57.3%) were men, and the median age at baseline was 58 years (interquartile range, 47-66 years). There were 1513 lesions excised during follow-up, including 171 primary melanomas. The overall benign to malignant excision ratio, including keratinocyte carcinomas, was 0.8:1.0; the benign melanocytic to melanoma excision ratio was 2.4:1.0; and the melanoma in situ to invasive melanoma ratio was 2.2:1.0. The excision ratios were similar across the 4 centers. The risk of developing a new melanoma was 9.0% annually in the first 2 years and increased with time, particularly for those with multiple primary melanomas. The thicker melanomas (>1-mm Breslow thickness; 7 of 171 melanomas [4.1%]) were mostly desmoplastic or nodular (4 of 7), self-detected (2 of 7), or clinician detected without the aid of TBP (3 of 7). Overall, new melanomas were most likely to be detected by a clinician with the aid of TBP (54 of 171 [31.6%]) followed by digital dermoscopy monitoring (50 of 171 [29.2%]).

Conclusions And Relevance: The structured surveillance program for high-risk patients may be implemented at a larger scale given the present cohort study findings suggesting the sustainability and replication of results in numerous settings, including a primary care skin cancer clinic.
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http://dx.doi.org/10.1001/jamadermatol.2020.5651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970391PMC
May 2021

School-based interventions to improve sun-safe knowledge, attitudes and behaviors in childhood and adolescence: A systematic review.

Prev Med 2021 05 17;146:106459. Epub 2021 Feb 17.

Cancer Epidemiology and Prevention Research Group, University of Sydney, Sydney, New South Wales, Australia; Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia. Electronic address:

Ultraviolet radiation exposure is the leading cause of skin cancer, and childhood and adolescence is a particularly susceptible life period for exposure. This systematic review assessed whether interventions in elementary and secondary school settings reduced sun exposure, sunburns, and development of melanocytic nevi, and improved sun-safe knowledge, attitudes and sun protection behaviors in childhood and adolescence. A systematic search up to June 2020 of MEDLINE, Embase, CINAHL, Cochrane and ProQuest databases was undertaken, for studies conducted among students in an elementary or secondary school setting that compared an intervention group with a pre-intervention or separate control group. Data were summarized using qualitative synthesis. Pooled effects from meta-analysis with random effects were also reported where appropriate. Sixty-five studies were included (22 randomized, 43 non-randomized). Most studies assessed measures of sun-safe behaviors, knowledge and attitudes (57, 48 and 33 studies, respectively), and observed improved sun protection behaviors and sun-safe knowledge, whereas few studies reduced time in the sun. About half improved participants' attitudes towards tanning desirability. Sunburns and nevus counts were less frequently assessed, but about half of these studies observed a reduction. There was substantial heterogeneity for outcomes except attitudes towards the desirability of tanning (pooled odds ratio from 6 studies: 0.81, 95% confidence interval 0.70-0.94). Key positive intervention features included: elementary school settings, interactive features or multiple components, and incorporating social norm influences. Most studies were classified at high risk of bias. In conclusion, school-based sun-related interventions had positive impacts on behaviors and attitudes among elementary and secondary school children.
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http://dx.doi.org/10.1016/j.ypmed.2021.106459DOI Listing
May 2021

Germline variants are associated with increased primary melanoma tumor thickness at diagnosis.

Hum Mol Genet 2021 01;29(21):3578-3587

Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, 4006, Australia.

Germline genetic variants have been identified, which predispose individuals and families to develop melanoma. Tumor thickness is the strongest predictor of outcome for clinically localized primary melanoma patients. We sought to determine whether there is a heritable genetic contribution to variation in tumor thickness. If confirmed, this will justify the search for specific genetic variants influencing tumor thickness. To address this, we estimated the proportion of variation in tumor thickness attributable to genome-wide genetic variation (variant-based heritability) using unrelated patients with measured primary cutaneous melanoma thickness. As a secondary analysis, we conducted a genome-wide association study (GWAS) of tumor thickness. The analyses utilized 10 604 individuals with primary cutaneous melanoma drawn from nine GWAS datasets from eight cohorts recruited from the general population, primary care and melanoma treatment centers. Following quality control and filtering to unrelated individuals with study phenotypes, 8125 patients were used in the primary analysis to test whether tumor thickness is heritable. An expanded set of 8505 individuals (47.6% female) were analyzed for the secondary GWAS meta-analysis. Analyses were adjusted for participant age, sex, cohort and ancestry. We found that 26.6% (SE 11.9%, P = 0.0128) of variation in tumor thickness is attributable to genome-wide genetic variation. While requiring replication, a chromosome 11 locus was associated (P < 5 × 10-8) with tumor thickness. Our work indicates that sufficiently large datasets will enable the discovery of genetic variants associated with greater tumor thickness, and this will lead to the identification of host biological processes influencing melanoma growth and invasion.
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http://dx.doi.org/10.1093/hmg/ddaa222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788289PMC
January 2021

Mendelian Randomization in Cardiovascular Research: Establishing Causality When There Are Unmeasured Confounders.

Circ Cardiovasc Qual Outcomes 2021 01 5;14(1):e005623. Epub 2021 Jan 5.

School of Public Health, Faculty of Medicine and Health, The University of Sydney, Australia. Westmead Millennium Institute for Medical Research (A.T-P.).

Mendelian randomization is an epidemiological approach to making causal inferences using observational data. It makes use of the natural randomization that occurs in the generation of an individual's genetic makeup in a way that is analogous to the study design of a randomized controlled trial and uses instrumental variable analysis where the genetic variant(s) are the instrument (analogous to random allocation to treatment group in an randomized controlled trial). As with any instrumental variable, there are 3 assumptions that must be made about the genetic instrument: (1) it is associated (not necessarily causally) with the exposure (relevance condition); (2) it is associated with the outcome only through the exposure (exclusion restriction condition); and (3) it does not share a common cause with the outcome (ie, no confounders of the genetic instrument and outcome, independence condition). Using the example of type II diabetes and coronary artery disease, we demonstrate how the method may be used to investigate causality and discuss potential benefits and pitfalls. We conclude that although Mendelian randomization studies can usually not establish causality on their own, they may usefully contribute to the evidence base and increase our certainty about the effectiveness (or otherwise) of interventions to reduce cardiovascular disease.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.119.005623DOI Listing
January 2021

Prevalence of skin examination behaviours among Australians over time.

Cancer Epidemiol 2021 02 17;70:101874. Epub 2020 Dec 17.

Sydney School of Public Health, Building A27, The University of Sydney, NSW 2006, Australia; Melanoma Institute Australia, The University of Sydney, 40 Rocklands Rd, Wollstonecraft, NSW 2065, Australia. Electronic address:

Background: We aimed to examine the prevalence and correlates of opportunistic skin check behaviours among Australians and whether changes over time might explain increasing underlying rates of melanoma in situ.

Methods: The National Sun Protection Survey involved periodic telephone-based cross-sectional surveys during summer since 2003. Skin checks by a doctor in the past 12 months was asked in four summers over 2006-2017, and responses from 23,374 Australians aged 12-69 years were analysed. Prevalence estimates were weighted to be representative of the Australian population. Chi-square tests compared the prevalence over time and by characteristics.

Results: The overall proportion reporting whole-body skin checks in the past 12 months was 20 % in 2006-07 and 2010-11, 21 % in 2013-14, and 22 % in 2016-17; but increased from 29 % in 2006-07 to 37 % in 2016-17 for those aged 45-69 years (p < 0.0001). In 2016-17, 5% reported a skin check of part-body and 9% for a specific mole or spot. The proportion reporting no skin checks increased from 61 % to 64 % over time (p < 0.0001). Whole-body skin checks were more common among older respondents, females, and also varied by residence location, skin sensitivity, skin colour, risk perception, and socio-economic index (all p < 0.001).

Conclusion: Approximately one third of Australians had their skin checked by a doctor within a 12-month period, but this varied across population sub-groups. Skin check behaviours were relatively stable over time, with modest increases in the prevalence of skin checks for those aged 45-69 years. These findings do not explain underlying large increases in rates of melanoma in situ.
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http://dx.doi.org/10.1016/j.canep.2020.101874DOI Listing
February 2021

Knowledge and attitudes of Australian dermatologists towards sentinel lymph node biopsy for melanoma: a mixed methods study.

Australas J Dermatol 2021 May 5;62(2):168-176. Epub 2020 Dec 5.

Cancer Epidemiology and Prevention Research, Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia.

Background/objectives: In melanoma management, sentinel lymph node biopsy (SLNB) is used to stage patients and to indicate prognosis. More recently, it has been used to select patients for adjuvant therapy. This study aimed to report knowledge of and attitudes towards SLNB for patients with melanoma among Australian dermatologists.

Methods: Mixed methods study using cross-sectional questionnaires (n = 88) and semi-structured interviews (n = 13), May-September 2019.

Results: Of the dermatologists surveyed, 56% thought SLNB had an important role in melanoma management, 26% were unsure and 18% thought SLNB unimportant. Of the 92% who would discuss SLNB with their patients, the main stated value of SLNB was for assessing eligibility for adjuvant therapies (79%); only 60% indicated SLNB was of value for providing prognostic information, and just over half (53%) thought it could improve staging. Interview data indicated that attitudes towards SLNB are shifting among dermatologists, driven by data from landmark clinical trials and the influence of professional networks. Accordingly, interviewees adopted one of three positions in relation to SLNB: (a) believed in utility of SLNB and adhered to the guidelines; (b) were unconvinced about utility of SLNB but adhered to the guidelines; and (c) were unconvinced about utility of SLNB and did not adhere to the guidelines.

Conclusion: Although most of the dermatologists surveyed were familiar with and follow the SLNB recommendations, some disagreement with and distrust of the recommendations was evident. Greater acceptance of the SLNB recommendations appeared to be driven by the improved outcomes demonstrated in stage III patients receiving adjuvant systemic therapy.
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http://dx.doi.org/10.1111/ajd.13518DOI Listing
May 2021

FRAMe: Familial Risk Assessment of Melanoma-a risk prediction tool to guide CDKN2A germline mutation testing in Australian familial melanoma.

Fam Cancer 2021 07 29;20(3):231-239. Epub 2020 Sep 29.

Centre for Cancer Research, Westmead Institute for Medical Research, University of Sydney, Westmead, NSW, 2145, Australia.

Germline mutations in CDKN2A greatly increase risk of developing cutaneous melanoma. We have constructed a risk prediction model, Familial Risk Assessment of Melanoma (FRAMe), for estimating the likelihood of carrying a heritable CDKN2A mutation among Australian families, where the prevalence of these mutations is low. Using logistic regression, we analysed characteristics of 299 Australian families recruited through the Sydney site of GenoMEL (international melanoma genetics consortium) with at least three cases of cutaneous melanoma (in situ and invasive) among first-degree blood relatives, for predictors of the presence of a pathogenic CDKN2A mutation. The final multivariable prediction model was externally validated in an independent cohort of 61 melanoma kindreds recruited through GenoMEL Queensland. Family variables independently associated with the presence of a CDKN2A mutation in a multivariable model were number of individuals diagnosed with melanoma under 40 years of age, number of individuals diagnosed with more than one primary melanoma, and number of individuals blood related to a melanoma case in the first degree diagnosed with any cancer excluding melanoma and non-melanoma skin cancer. The number of individuals diagnosed with pancreatic cancer was not independently associated with mutation status. The risk prediction model had an area under the receiver operating characteristic curve (AUC) of 0.851 (95% CI 0.793, 0.909) in the training dataset, and 0.745 (95%CI 0.612, 0.877) in the validation dataset. This model is the first to be developed and validated using only Australian data, which is important given the higher rate of melanoma in the population. This model will help to effectively identify families suitable for genetic counselling and testing in areas of high ambient ultraviolet radiation. A user-friendly electronic nomogram is available at www.melanomarisk.org.au .
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http://dx.doi.org/10.1007/s10689-020-00209-xDOI Listing
July 2021

Association of Known Melanoma Risk Factors with Primary Melanoma of the Scalp and Neck.

Cancer Epidemiol Biomarkers Prev 2020 11 20;29(11):2203-2210. Epub 2020 Aug 20.

School of Population and Global Health, The University of Western Australia, Perth, Western Australia, Australia.

Background: Scalp and neck (SN) melanoma confers a worse prognosis than melanoma of other sites but little is known about its determinants. We aimed to identify associations between SN melanoma and known risk genes, phenotypic traits, and sun exposure patterns.

Methods: Participants were cases from the Western Australian Melanoma Health Study ( = 1,200) and the Genes, Environment, and Melanoma Study ( = 3,280). Associations between risk factors and SN melanoma, compared with truncal and arm/leg melanoma, were investigated using binomial logistic regression. Facial melanoma was also compared with the trunk and extremities, to evaluate whether associations were subregion specific, or reflective of the whole head/neck region.

Results: Compared with other sites, increased odds of SN and facial melanoma were observed in older individuals [SN: OR = 1.28, 95% confidence interval (CI) = 0.92-1.80, = 0.016; Face: OR = 4.57, 95% CI = 3.34-6.35, < 0.001] and those carrying -rs12203592*T (SN: OR = 1.35, 95% CI = 1.12-1.63, = 0.002; Face: OR = 1.29, 95% CI = 1.10-1.50, = 0.001). Decreased odds were observed for females (SN: OR = 0.49, 95% CI = 0.37-0.64, < 0.001; Face: OR = 0.66, 95% CI = 0.53-0.82, < 0.001) and the presence of nevi (SN: OR = 0.66, 95% CI = 0.49-0.89, = 0.006; Face: OR = 0.65, 95% CI = 0.52-0.83, < 0.001).

Conclusions: Differences observed between SN melanoma and other sites were also observed for facial melanoma. Factors previously associated with the broader head and neck region, notably older age, may be driven by the facial subregion. A novel finding was the association of -rs12203592 with both SN and facial melanoma.

Impact: Understanding the epidemiology of site-specific melanoma will enable tailored strategies for risk factor reduction and site-specific screening campaigns.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641988PMC
November 2020

Melanomas and stress patterns on the foot: A systematic review and meta-analysis.

J Am Acad Dermatol 2021 Jul 22;85(1):256-258. Epub 2020 Aug 22.

The Whiteley-Martin Research Centre, Department of Surgery, Nepean Clinical School, The University of Sydney, Penrith, New South Wales, Australia.

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http://dx.doi.org/10.1016/j.jaad.2020.08.078DOI Listing
July 2021

Multiplex melanoma families are enriched for polygenic risk.

Hum Mol Genet 2020 10;29(17):2976-2985

Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.

Cancers, including cutaneous melanoma, can cluster in families. In addition to environmental etiological factors such as ultraviolet radiation, cutaneous melanoma has a strong genetic component. Genetic risks for cutaneous melanoma range from rare, high-penetrance mutations to common, low-penetrance variants. Known high-penetrance mutations account for only about half of all densely affected cutaneous melanoma families, and the causes of familial clustering in the remainder are unknown. We hypothesize that some clustering is due to the cumulative effect of a large number of variants of individually small effect. Common, low-penetrance genetic risk variants can be combined into polygenic risk scores. We used a polygenic risk score for cutaneous melanoma to compare families without known high-penetrance mutations with unrelated melanoma cases and melanoma-free controls. Family members had significantly higher mean polygenic load for cutaneous melanoma than unrelated cases or melanoma-free healthy controls (Bonferroni-corrected t-test P = 1.5 × 10-5 and 6.3 × 10-45, respectively). Whole genome sequencing of germline DNA from 51 members of 21 families with low polygenic risk for melanoma identified a CDKN2A p.G101W mutation in a single family but no other candidate high-penetrance melanoma susceptibility genes. This work provides further evidence that melanoma, like many other common complex disorders, can arise from the joint action of multiple predisposing factors, including rare high-penetrance mutations, as well as via a combination of large numbers of alleles of small effect.
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http://dx.doi.org/10.1093/hmg/ddaa156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566496PMC
October 2020

The Melanoma Genomics Managing Your Risk Study randomised controlled trial: statistical analysis plan.

Trials 2020 Jun 30;21(1):594. Epub 2020 Jun 30.

The University of Sydney, Melanoma Institute Australia, Sydney, NSW, Australia.

Background: The Melanoma Genomics Managing Your Risk Study is a randomised controlled trial that aims to evaluate the efficacy of providing information on personal genomic risk of melanoma in reducing ultraviolet radiation (UV) exposure, stratified by traditional risk group (low or high phenotypic risk) in the general population. The primary outcome is objectively measured total daily Standard Erythemal Doses at 12 months. Secondary outcomes include UV exposure at specific time periods, self-reported sun protection and skin-examination behaviours, psychosocial outcomes, and ethical considerations surrounding offering genomic testing at a population level. A within-trial and modelled economic evaluation will be undertaken from an Australian health system perspective to assess the cost-effectiveness of the intervention.

Objective: To publish the pre-determined statistical analysis plan (SAP) before database lock and the start of analysis.

Methods: This SAP describes the data synthesis, analysis principles and statistical procedures for analysing the outcomes from this trial. The SAP was approved after closure of recruitment and before completion of patient follow-up. It outlines the planned primary analyses and a range of subgroup and sensitivity analyses. Health economic outcomes are not included in this plan but will be analysed separately. The SAP will be adhered to for the final data analysis of this trial to avoid potential analysis bias that may arise from knowledge of the outcome data.

Results: This SAP is consistent with best practice and should enable transparent reporting.

Conclusion: This SAP has been developed for the Melanoma Genomics Managing Your Risk Study and will be followed to ensure high-quality standards of internal validity and to minimise analysis bias.

Trial Registration: Prospectively registered with the Australian New Zealand Clinical Trials Registry, ID: ACTR N12617000691347 . Registered on 15 May 2017.
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http://dx.doi.org/10.1186/s13063-020-04351-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329549PMC
June 2020

Implementation considerations for offering personal genomic risk information to the public: a qualitative study.

BMC Public Health 2020 Jun 29;20(1):1028. Epub 2020 Jun 29.

Faculty of Medicine and Health, Sydney School of Public Health, Cancer Epidemiology and Prevention Research, The University of Sydney, Sydney, Australia.

Background: Genomic risk information, based on common genomic susceptibility variants associated with risk of complex diseases such as cancer, may be incorporated into personalised prevention and screening strategies. We aimed to engage with members of the public, who are important stakeholders in this process, to further inform program development and other implementation outcomes such as acceptability and appropriateness.

Methods: Semi-structured interviews were undertaken with 30 participants (aged 24-69 years, 50% female) recruited from a pilot trial in which they received personalised genomic risk information for melanoma. We explored participants' views and attitudes towards offering general personal genomic risk information to the broader population. The data were analysed thematically.

Results: Two overarching themes relevant to implementation considerations were identified. Firstly, participants' preferences for accepting an offer of genomic risk information were based on family history, disease incidence and the possibility of prevention. Secondly, participants felt that the processes for offering risk information should be based on individual preferences, triaged according to risk and be supported by a health professional trained in genomics.

Conclusions: Participants felt that offering personal genomic risk information to the general population to inform prevention and early detection recommendations is acceptable, particularly for common, complex conditions such as cancer. Understanding participants' preferences for receiving genomic risk information will assist with communication strategies and health workforce planning. We anticipate that these findings will contribute to the development of implementation strategies for incorporating genomic risk information into routine clinical practice.
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http://dx.doi.org/10.1186/s12889-020-09143-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325160PMC
June 2020

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

'There is a lot of good in knowing, but there is also a lot of downs': public views on ethical considerations in population genomic screening.

J Med Ethics 2020 May 20. Epub 2020 May 20.

Faculty of Medicine and Health, Sydney School of Public Health, Sydney Health Ethics, The University of Sydney, Sydney, New South Wales, Australia

Publics are key stakeholders in population genomic screening and their perspectives on ethical considerations are relevant to programme design and policy making. Using semi-structured interviews, we explored social views and attitudes towards possible future provision of personalised genomic risk information to populations to inform prevention and/or early detection of relevant conditions. Participants were members of the public (n=30) who had received information on their personal genomic risk of melanoma as part of a research project. The focus of the analysis presented here is participants' views regarding ethical considerations relevant to population genomic screening more generally. Data were analysed thematically and four key themes related to ethical considerations were identified: (i) personal responsibility for health: 'forewarned is forearmed'; (ii) perceptions of, and responses to, genetic fatalism; (iii) implications for parenting and reproduction; (iv) divided views on choosing to receive genomic risk information. Ethical considerations underlying these themes include the valorisation of information and choice, paternalism, non-directiveness and increasing responsibilisation of individuals in health and healthcare. These findings arguably indicate a thin public conceptualisation of population genomic testing, which draws heavily on how these themes tend to be described in existing social discourses. Findings suggest that further public engagement is required to increase complexity of debate, to consider (for example) the appropriate place of individual and social interests in population genomic testing. Further discernment of relevant ethical approaches, drawing on ethical frameworks from both public health and clinical settings, will also assist in determining the appropriate implementation of population genomic screening for complex conditions.
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http://dx.doi.org/10.1136/medethics-2019-105934DOI Listing
May 2020

Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility.

Nat Genet 2020 05 27;52(5):494-504. Epub 2020 Apr 27.

Department of Dermatology, Instituto Valenciano de Oncología, Valencia, Spain.

Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 × 10) loci with 68 independent single nucleotide polymorphisms. Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation. Combining this meta-analysis with GWAS of nevus count and hair color, and transcriptome association approaches, uncovered 31 potential secondary loci for a total of 85 cutaneous melanoma susceptibility loci. These findings provide insights into cutaneous melanoma genetic architecture, reinforcing the importance of nevogenesis, pigmentation and telomere maintenance, together with identifying potential new pathways for cutaneous melanoma pathogenesis.
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http://dx.doi.org/10.1038/s41588-020-0611-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255059PMC
May 2020

GPs' involvement in diagnosing, treating, and referring patients with suspected or confirmed primary cutaneous melanoma: a qualitative study.

BJGP Open 2020 23;4(2). Epub 2020 Jun 23.

Professor of Cancer Epidemiology, Cancer Epidemiology and Prevention Research, Sydney School of Public Health, The University of Sydney, Sydney, Australia.

Background: In Australia, melanoma is managed in primary and secondary care settings. An individual concerned about a suspicious lesion typically presents first to their GP.

Aim: To identify factors influencing GPs' decisions to diagnose, treat, or refer patients with suspected melanoma.

Design & Setting: Semi-structured interviews were undertaken with 23 GPs working in general practice or skin cancer clinics in Australia.

Method: The semi-structured interviews were audio-recorded, de-identified, and professionally transcribed. Thematic analysis was used to analyse the data.

Results: Considerable variation existed in GPs' self-reported confidence and involvement in melanoma management. Multiple factors were identified as influencing GPs' decisions to diagnose, treat, or refer patients with suspected or confirmed melanoma. Health system level factors included the overlapping roles of GPs and specialists, and access to and/or availability of specialists. Practice level factors included opportunities for formal and informal training, and having a GP with a special interest in skin cancer within their practice. GP and patient level factors included the GP's clinical interests, the clinical features (for example, site and size) and histopathology of the suspected melanoma, eligibility for possible sentinel lymph node biopsy, and patient preferences. For some GPs, concerns over misdiagnosis and the option of referring patients at any stage in the melanoma management continuum appeared to affect their interest and confidence in melanoma management.

Conclusion: GP involvement in melanoma patient care can extend well beyond cancer screening, prevention and supportive care roles to include provision of definitive melanoma patient management. GPs with an interest in being involved in melanoma management should be encouraged and supported to develop the skills needed to manage these patients, and to refer when appropriate.
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http://dx.doi.org/10.3399/bjgpopen20X101028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330208PMC
June 2020

Early detection of melanoma: a consensus report from the Australian Skin and Skin Cancer Research Centre Melanoma Screening Summit.

Aust N Z J Public Health 2020 Apr 19;44(2):111-115. Epub 2020 Mar 19.

QIMR Berghofer Medical Research Institute, Queensland.

Introduction: A Melanoma Screening Summit was held in Brisbane, Australia, to review evidence regarding current approaches for early detection of melanomas and explore new opportunities.

Results: Formal population-based melanoma screening is not carried out in Australia, but there is evidence of considerable opportunistic screening as well as early detection. Biopsy rates are rising and most melanomas are now diagnosed when in situ. Based on evidence review and expert opinion, the Summit attendees concluded that there is currently insufficient information in terms of comparative benefits, harms and costs to support change from opportunistic to systematic screening. Assessment of gains in precision and cost-effectiveness of integrating total body imaging, artificial intelligence algorithms and genetic risk information is required, as well as better understanding of clinical and molecular features of thin fatal melanomas.

Conclusions: Research is needed to understand how to further optimise early detection of melanoma in Australia. Integrating risk-based population stratification and more precise diagnostic tests is likely to improve the balance of benefits and harms of opportunistic screening, pending assessment of cost-effectiveness. Implications for public health: The Summit Group identified that the personal and financial costs to the community of detecting and treating melanoma are rising, and this may be mitigated by developing and implementing a more systematic process for diagnosing melanoma.
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http://dx.doi.org/10.1111/1753-6405.12972DOI Listing
April 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
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