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Spitzoid morphology in familial melanoma has been associated with germline variants in POT1, a telomere maintenance gene (TMG), suggesting a link between telomere biology and spitzoid differentiation.

IMPORTANCE: Despite many cases being preventable, cutaneous melanoma remains the most serious skin cancer worldwide. Understanding the scale and profile of the disease is vital to concentrate and reinforce global prevention efforts. OBJECTIVE: To examine global patterns of cutaneous melanoma in 2020 and to provide projected estimates of cases and deaths by 2040. DESIGN, SETTING, AND PARTICIPANTS: This population-based study used the GLOBOCAN 2020 database for global epidemiological assessment of new cases and deaths due to invasive melanoma. MAIN OUTCOMES AND MEASURES: Age-standardized incidence and mortality rates were calculated per 100 000 person-years by country, world region, and 4-tier level of human development. Estimated numbers of cases and deaths were calculated for the year 2040. RESULTS: A worldwide total of 325 000 new melanoma cases (174 000 males, 151 000 females) and 57 000 deaths (32 000 males, 25 000 females) was estimated for 2020. Large geographic variations existed across countries and world regions, with the highest incidence rates among males (42 per 100 000 person-years) and females (31 per 100 000 person-years) observed in Australia/New Zealand, followed by Western Europe (19 per 100 000 person-years for males and females), North America (18 per 100 000 person-years for males, 14 per 100 000 person-years for females), and Northern Europe (17 per 100 000 person-years for males, 18 per 100 000 person-years for females). Melanoma continued to be rare in most African and Asian countries, with incidence rates commonly less than 1 per 100 000 person-years. Mortality rates peaked at 5 per 100 000 person-years in New Zealand, and geographic variations were less pronounced than for incidence. Melanoma was more frequent among males than females in most world regions. If 2020 rates continue, the burden from melanoma is estimated to increase to 510 000 new cases (a roughly 50% increase) and to 96 000 deaths (a 68% increase) by 2040. CONCLUSIONS AND RELEVANCE: This epidemiological assessment suggests that melanoma remains an important challenge to cancer control and public health globally, especially in fair-skinned populations of European descent.

IMPORTANCE: Patient-led surveillance is a promising new model of follow-up care following excision of localized melanoma. OBJECTIVE: To determine whether patient-led surveillance in patients with prior localized primary cutaneous melanoma is as safe, feasible, and acceptable as clinician-led surveillance. DESIGN, SETTING, AND PARTICIPANTS: This was a pilot for a randomized clinical trial at 2 specialist-led clinics in metropolitan Sydney, Australia, and a primary care skin cancer clinic managed by general practitioners in metropolitan Newcastle, Australia. The participants were 100 patients who had been treated for localized melanoma, owned a smartphone, had a partner to assist with skin self-examination (SSE), and had been routinely attending scheduled follow-up visits. The study was conducted from November 1, 2018, to January 17, 2020, with analysis performed from September 1, 2020, to November 15, 2020. INTERVENTION: Participants were randomized (1:1) to 6 months of patient-led surveillance (the intervention comprised usual care plus reminders to perform SSE, patient-performed dermoscopy, teledermatologist assessment, and fast-tracked unscheduled clinic visits) or clinician-led surveillance (the control was usual care). MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of eligible and contacted patients who were randomized. Secondary outcomes included patient-reported outcomes (eg, SSE knowledge, attitudes, and practices, psychological outcomes, other health care use) and clinical outcomes (eg, clinic visits, skin surgeries, subsequent new primary or recurrent melanoma). RESULTS: Of 326 patients who were eligible and contacted, 100 (31%) patients (mean [SD] age, 58.7 [12.0] years; 53 [53%] men) were randomized to patient-led (n = 49) or clinician-led (n = 51) surveillance. Data were available on patient-reported outcomes for 66 participants and on clinical outcomes for 100 participants. Compared with clinician-led surveillance, patient-led surveillance was associated with increased SSE frequency (odds ratio [OR], 3.5; 95% CI, 0.9 to 14.0) and thoroughness (OR, 2.2; 95% CI, 0.8 to 5.7), had no detectable adverse effect on psychological outcomes (fear of cancer recurrence subscale score; mean difference, −1.3; 95% CI, −3.1 to 0.5), and increased clinic visits (risk ratio [RR], 1.5; 95% CI, 1.1 to 2.1), skin lesion excisions (RR, 1.1; 95% CI, 0.6 to 2.0), and subsequent melanoma diagnoses and subsequent melanoma diagnoses (risk difference, 10%; 95% CI, −2% to 23%). New primary melanomas and 1 local recurrence were diagnosed in 8 (16%) of the participants in the intervention group, including 5 (10%) ahead of routinely scheduled visits; and in 3 (6%) of the participants in the control group, with none (0%) ahead of routinely scheduled visits (risk difference, 10%; 95% CI, 2% to 19%). CONCLUSIONS AND RELEVANCE: This pilot of a randomized clinical trial found that patient-led surveillance after treatment of localized melanoma appears to be safe, feasible, and acceptable. Experiences from this pilot study have prompted improvements to the trial processes for the larger trial of the same intervention. TRIAL REGISTRATION: http://anzctr.org.au Identifier: ACTRN12616001716459

IMPORTANCE: Early melanoma diagnosis is associated with better health outcomes, but there is insufficient evidence that screening, such as having routine skin checks, reduces mortality. OBJECTIVE: To assess melanoma-specific and all-cause mortality associated with melanomas detected through routine skin checks, incidentally or patient detected. A secondary aim was to examine patient, sociodemographic, and clinicopathologic factors associated with different modes of melanoma detection. DESIGN, SETTING, AND PARTICIPANTS: This prospective, population-based, cohort study included patients in New South Wales, Australia, who were diagnosed with melanoma over 1 year from October 23, 2006, to October 22, 2007, in the Melanoma Patterns of Care Study and followed up until 2018 (mean [SD] length of follow-up, 11.9 [0.3] years) by using linked mortality and cancer registry data. All patients who had invasive melanomas recorded at the cancer registry were eligible for the study, but the number of in situ melanomas was capped. The treating doctors recorded details of melanoma detection and patient and clinical characteristics in a baseline questionnaire. Histopathologic variables were obtained from pathology reports. Of 3932 recorded melanomas, data were available and analyzed for 2452 (62%; 1 per patient) with primary in situ (n = 291) or invasive (n = 2161) cutaneous melanoma. Data were analyzed from March 2020 to January 2021. MAIN OUTCOMES AND MEASURES: Melanoma-specific mortality and all-cause mortality. RESULTS: A total of 2452 patients were included in the analyses. The median age at diagnosis was 65 years (range, 16-98 years), and 1502 patients (61%) were men. A total of 858 patients (35%) had their melanoma detected during a routine skin check, 1148 (47%) self-detected their melanoma, 293 (12%) had their melanoma discovered incidentally when checking another skin lesion, and 153 (6%) reported “other” presentation. Routine skin-check detection of invasive melanomas was associated with 59% lower melanoma-specific mortality (subhazard ratio, 0.41; 95% CI, 0.28-0.60; P < .001) and 36% lower all-cause mortality (hazard ratio, 0.64; 95% CI, 0.54-0.76; P < .001), adjusted for age and sex, compared with patient-detected melanomas. After adjusting for prognostic factors including ulceration and mitotic rate, the associations were 0.68 (95% CI, 0.44-1.03; P = .13), and 0.75 (95% CI, 0.63-0.90; P = .006), respectively. Factors associated with higher odds of routine skin-check melanoma detection included being male (female vs male, odds ratio [OR], 0.73; 95% CI, 0.60-0.89; P = .003), having previous melanoma (vs none, OR, 2.36; 95% CI, 1.77-3.15; P < .001), having many moles (vs not, OR, 1.39; 95% CI, 1.10-1.77; P = .02), being 50 years or older (eg, 50-59 years vs <40 years, OR, 2.89; 95% CI, 1.92-4.34; P < .001), and living in nonremote areas (eg, remote or very remote vs major cities, OR, 0.23; 95% CI, 0.05-1.04; P = .003). CONCLUSIONS AND RELEVANCE: In this cohort study, melanomas diagnosed through routine skin checks were associated with significantly lower all-cause mortality, but not melanoma-specific mortality, after adjustment for patient, sociodemographic, and clinicopathologic factors.

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

Evidence indicates that a melanoma prevention program using personalized genomic risk provision and genetic counseling can affect prevention behaviors, including reducing sunburns in adults with no melanoma history. This analysis evaluated its longer-term cost-effectiveness from an Australian health system perspective.

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.

Supplemental Digital Content is available in the text.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.

It is unclear to what degree genomic and traditional (phenotypic and environmental) risk factors overlap in their prediction of melanoma risk. We evaluated the incremental contribution of common genomic variants (in pigmentation, nevus, and other pathways) and their overlap with traditional risk factors, using data from two population-based case-control studies from Australia (n = 1,035) and the United Kingdom (n = 1,460) that used the same questionnaires. Polygenic risk scores were derived from 21 gene regions associated with melanoma and odds ratios from published meta-analyses. Logistic regression models were adjusted for age, sex, center, and ancestry. Adding the polygenic risk score to a model with traditional risk factors increased the area under the receiver operating characteristic curve (AUC) by 2.3% (P = 0.003) for Australia and by 2.8% (P = 0.002) for Leeds. Gene variants in the pigmentation pathway, particularly MC1R, were responsible for most of the incremental improvement. In a cross-tabulation of polygenic by traditional tertile risk scores, 59% (Australia) and 49% (Leeds) of participants were categorized in the same (concordant) tertile. Of participants with low traditional risk, 9% (Australia) and 21% (Leeds) had high polygenic risk. Testing of genomic variants can identify people who are susceptible to melanoma despite not having a traditional phenotypic risk profile.

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.

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 × 10−8) 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.

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.

BRAFand NRASmutations arise early in melanoma development, but their associations with low-penetrance melanoma susceptibility loci remain unknown. In the Genes, Environment and Melanoma Study, 1,223 European-origin participants had their incident invasive primary melanomas screened for BRAF/NRASmutations and germline DNA genotyped for 47 single-nucleotide polymorphisms identified as low-penetrant melanoma-risk variants. We used multinomial logistic regression to simultaneously examine each single-nucleotide polymorphism’s relationship to BRAFV600E, BRAFV600K, BRAFother, and NRAS+ relative to BRAF–/NRAS–melanoma adjusted for study features. IRF4rs12203592*T was associated with BRAFV600E (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.43–0.79) and V600K (OR = 0.65, 95% CI = 0.41–1.03), but not BRAFother or NRAS+melanoma. A global test of etiologic heterogeneity (Pglobal = 0.001) passed false discovery (Pglobal = 0.0026). PLA2G6rs132985*T was associated with BRAFV600E (OR = 1.32, 95% CI = 1.05–1.67) and BRAFother (OR = 1.82, 95% CI = 1.11–2.98), but not BRAFV600K or NRAS+melanoma. The test for etiologic heterogeneity (Pglobal) was 0.005. The IRF4rs12203592 associations were slightly attenuated after adjustment for melanoma-risk phenotypes. The PLA2G6rs132985 associations were independent of phenotypes. IRF4and PLA2G6inherited genotypes may influence melanoma BRAF/NRASsubtype development.

Associations of MC1Rwith BRAFmutations in melanoma have been inconsistent between studies. We sought to determine for 1,227 participants in the international population-based Genes, Environment, and Melanoma (GEM) study whether MC1Rand phenotypes were associated with melanoma BRAF/NRASsubtypes. We used logistic regression adjusted by age, sex, and study design features and examined effect modifications. BRAF+were associated with younger age, blond/light brown hair, increased nevi, and less freckling, and NRAS+with older age relative to the wild type (BRAF–/NRAS–) melanomas (all P< 0.05). Comparing specific BRAFsubtypes to the wild type, BRAFV600E was associated with younger age, blond/light brown hair, and increased nevi and V600K with increased nevi and less freckling (all P< 0.05). MC1Rwas positively associated with BRAFV600E cases but only among individuals with darker phototypes or darker hair (Pinteraction< 0.05) but inversely associated with BRAFV600K (Ptrend = 0.006) with no significant effect modification by phenotypes. These results support distinct etiologies for BRAFV600E, BRAFV600K, NRAS+, and wild-type melanomas. MC1R’s associations with BRAFV600E cases limited to individuals with darker phenotypes indicate that MC1Rgenotypes specifically provide information about BRAFV600E melanoma risk in those not considered high risk based on phenotype. Our results also suggest that melanin pathways deserve further study in BRAFV600E melanomagenesis.

Recent reports have revealed that solariums, or sunbeds, which are largely banned in Australia due to the increased risk of skin cancer, are being rebranded as "collarium" sunbeds. These collarium sunbeds emit both UV radiation and a mix of visible wavelength colors to produce a pink or red light. Despite claims by manufacturers and operators that collarium sunbeds provide a longer-lasting tan and stimulate collagen production, experts argue that these claims are not supported by evidence. The use of sunbeds, including collarium sunbeds, has been linked to an increased risk of melanoma and other types of skin cancer. Queensland Health is currently investigating whether salons marketing collarium sunbeds are breaching radiation safety laws. Experts recommend avoiding sunbeds and instead opting for safer alternatives such as spray tans. [Extracted from the article]

Factors associated with non-adherence to guideline-recommended complete excision of suspicious cutaneous lesions are unclear.

IMPORTANCE: Skin self-examination (SSE) is a key factor in the early detection of melanoma, and many new and recurrent melanomas are first detected by patients themselves or their family members. OBJECTIVE: To explore the views of patients with melanoma regarding SSE in general, as well as their attitudes toward using novel digital technologies to support their own SSE. DESIGN, SETTING, AND PARTICIPANTS: Qualitative study with semistructured interviews that were conducted from June 20 to December 12, 2016, with 37 individuals in Sydney, Australia, who were previously treated for a first primary localized melanoma during 2014 and had not had a recurrence or new primary melanoma in the time since treatment. MAIN OUTCOMES AND MEASURES: Patients’ views and experiences, analyzed thematically. RESULTS: A total of 37 patients (11 women and 26 men; median age, 67 years [interquartile range, 59.5-72 years]) were interviewed. Participants perceived SSE as important for the early identification of local recurrence or new primary melanomas. Despite this belief, participants did not report undertaking full-body SSE on a regular basis. Factors that influenced their low engagement in thorough SSE included lack of self-efficacy, reliance on clinician consultations as the primary means of melanoma detection, and fear of cancer recurrence. Regarding the use of digital technology to assist with SSE, the key motivating factors in favor of such tools were the ability to track changes in lesions over time and the use of automated reminders to undertake SSE. Deterrents included a lack of confidence in undertaking SSE and in using new technology. CONCLUSIONS AND RELEVANCE: Patients with melanoma are aware of the importance of thorough skin examinations. However, a lack of confidence in their ability to undertake SSE and reliance on clinicians as the primary means of melanoma detection may inhibit patients from undertaking regular and thorough SSE. Patients may benefit from new digital technologies that assist them in undertaking SSE, provided they have appropriate education and technical support.

Germline variants in the melanocortin 1 receptor gene (MC1R)might increase the risk of childhood and adolescent melanoma, but a clear conclusion is challenging because of the low number of studies and cases. We assessed the association of MC1Rvariants with childhood and adolescent melanoma in a large study comparing the prevalence of MC1Rvariants in child or adolescent patients with melanoma to that in adult patients with melanoma and in healthy adult controls.

IMPORTANCE: There are limited data among young adults on sunscreen use during childhood and adulthood and on the association of sunscreen use with melanoma risk. OBJECTIVE: To assess correlates of early-life sunscreen use and the association between sunscreen use and risk of cutaneous melanoma before age 40 years. DESIGN, SETTING, AND PARTICIPANTS: This population-based, case-control family study analyzed Australian Melanoma Family Study data for persons with questionnaire data on sunscreen use collected by interview from 2001 to 2005 across 3 states in Australia, representing two-thirds of the country’s population. Case participants (aged 18-39 years) had confirmed first primary melanoma. Siblings of case participants were included, and case participants without a sibling control were excluded. Unrelated controls (aged 18-44 years) were recruited from the electoral roll or were a spouse, partner, or friend nominated by case participants. Data analyses were conducted from October 2017 to February 2018. EXPOSURES: Self- and parent-reported sunscreen use, sun exposure, and other candidate risk factors during childhood and adulthood. MAIN OUTCOMES AND MEASURES: Logistic regression analyses adjusted for potential confounders were used to estimate odds ratios (ORs) for melanoma and for correlates of sunscreen use. RESULTS: Participation was 629 of 830 contactable cases (76%) (629 of 1197 overall [53%]), 240 of 570 contactable controls (42%) from the electoral roll (240 of 1068 overall [23%]), and 295 of 371 nominated spouse or friend controls (80%); analysis incuded 603 cases and 1088 controls. The median (interquartile range) age was 32 (28-36) years for 603 cases, 35 (30-38) years for 478 unrelated controls, and 34 (29-38) years for 610 sibling controls. There were more women than men (range, 57%-62%) in all groups, approximately 40% (range, 39%-43%) of participants had a university education, and most participants (range, 58%-73%) had British/northern European ethnicity. Risk of melanoma was less with higher use of sunscreen in childhood (OR for highest vs lowest tertiles, 0.60; 95% CI, 0.42-0.87; P = .02 for trend) and across the lifetime (OR, 0.65; 95% CI, 0.45-0.93; P = .07 for trend). Subgroup analyses suggested that the protective association of sunscreen with melanoma was stronger for people reporting blistering sunburn, receiving a diagnosis of melanoma at a younger age, or having some or many nevi. Total lifetime sun exposure was unrelated to melanoma risk (OR for highest vs lowest tertile, 0.97; 95% CI, 0.66-1.43; P = .94 for trend). By contrast, total sun exposure inversely weighted by sunscreen use (as a measure of sun exposure unprotected by sunscreen) was significantly associated with melanoma risk (OR, 1.80; 95% CI, 1.22-2.65; P = .007 for trend) and appeared stronger for people having lighter pigmentation or some or many nevi or using sunscreen to stay longer in the sun. Regular users of sunscreen were more likely to be female, younger, and of British or northern European ancestry and to have higher educational levels, lighter skin pigmentation, and a stronger history of blistering sunburn. CONCLUSIONS AND RELEVANCE: Our findings provided evidence that regular sunscreen use is significantly associated with reduced risk of cutaneous melanoma among young adults and identified several characteristics associated with less sunscreen use.

The aim of this research was to understand how genomics-based personal melanoma risk information impacts psychological and emotional health outcomes in the general population. In a pilot randomized controlled trial, participants (n= 103) completed the Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire, 3 months after receiving personal melanoma genomic risk information. Mean scores for MICRA items and subscales were stratified by genomic risk group (low, average, high), gender, education, age, and family history of melanoma. Pvalues were obtained from t-tests and analysis of variance tests. We found that overall, participants (mean age: 53 years, range: 21–69; 52% female) had a total MICRA mean score of 18.6 (standard deviation: 11.1, range: 1–70; possible range: 0–105). The high genomic risk group had higher mean scores for the total (24.2, F2,100= 6.7, P= 0.0019), distress (3.3, F2,100= 9.4, P= 0.0002) and uncertainty (8.5, F2,100= 6.5, P= 0.0021) subscales compared with average (17.6, 1.1, and 4.5, respectively) and low-risk groups (14.1, 0.5, and 2.5, respectively). Positive experiences scores were consistent across risk groups. In conclusion, MICRA scores for the total, distress and uncertainty subscales in our study were relatively low overall, but people who receive a high genomic risk result may benefit from increased support following testing.

Introduction:Clinical research has established exercise as a safe and effective intervention to counteract the adverse physical and psychological effects of cancer and its treatment. This article summarises the position of the Clinical Oncology Society of Australia (COSA) on the role of exercise in cancer care, taking into account the strengths and limitations of the evidence base. It provides guidance for all health professionals involved in the care of people with cancer about integrating exercise into routine cancer care. Main recommendations:COSA calls for: exercise to be embedded as part of standard practice in cancer care and to be viewed as an adjunct therapy that helps counteract the adverse effects of cancer and its treatment;all members of the multidisciplinary cancer team to promote physical activity and recommend that people with cancer adhere to exercise guidelines; andbest practice cancer care to include referral to an accredited exercise physiologist or physiotherapist with experience in cancer care. Changes in management as a result of the guideline:COSA encourages all health professionals involved in the care of people with cancer to: discuss the role of exercise in cancer recovery;recommend their patients adhere to exercise guidelines (avoid inactivity and progress towards at least 150 minutes of moderate intensity aerobic exercise and two to three moderate intensity resistance exercise sessions each week); andrefer their patients to a health professional who specialises in the prescription and delivery of exercise (ie, accredited exercise physiologist or physiotherapist with experience in cancer care).

IMPORTANCE: The diagnosis of a life-threatening disease like melanoma can affect all aspects of a person’s life, including health-related quality of life (HRQOL) and psychological aspects of melanoma such as fear of cancer recurrence (FCR). Economic evaluations of psychological interventions require preference-based (utility) instruments that are sensitive to changes in well-being and HRQOL; however, very few studies have evaluated the sensitivity of these instruments when used for people with melanoma. OBJECTIVE: To compare utility scores from the multiple-attribute instrument Assessment of Quality of Life—8-Dimension Scale (AQoL-8D) with the mapped utility scores of the Functional Assessment of Cancer Therapy–Melanoma (FACT-M) and to investigate the sensitivity of both instruments in identifying the influence of FCR on HRQOL. DESIGN, SETTING, AND PARTICIPANTS: This assessment of data from a randomized clinical trial of a psychoeducational intervention to reduce FCR, conducted at 3 high-risk melanoma clinics in Australia, evaluated 164 patients with early-stage melanoma and a high risk of developing a second primary melanoma. MAIN OUTCOMES AND MEASURES: The FACT-M and AQoL-8D were used to assess HRQOL and FCR among the study participants. Concurrent validity was assessed by comparing the total and subdomain scores of the 2 instruments, and the strength of associations was assessed using Pearson correlation coefficient. Convergent validity was assessed by comparing participants’ HRQOL, demographic, and clinical characteristics using the χ2 test and F statistic. Both the FACT-M and AQoL-8D utilities were regressed on FCR Inventory (FCRI) severity scores to estimate the effect of elevated FCR on HRQOL. RESULTS: A total of 164 participants completed the baseline questionnaires, but only 163 met all inclusion criteria and underwent the full analysis: 72 were women; 91 were men; and mean (SD) age was 58.2 (12.1) years. Both the AQoL-8D and FACT-M instruments showed good concurrent validity and could differentiate between relevant subgroups including level of FCRI severity. The AQoL-8D and FACT-M utilities were strongly correlated (r2 = 0.57). Respondents had a mean (SD) AQoL-8D utility of 0.77 (0.2), and a mean (SD) FACT-M utility score of 0.76 (0.07). High levels of FCRI severity were associated with a decrease in utility of 0.12 (95% CI, −0.19 to −0.05) as measured by AQoL-8D, and a decrease of 0.03 (95% CI, −0.05 to −0.01) as measured by the FACT-M. CONCLUSIONS AND RELEVANCE: For economic evaluations of psychological interventions in melanoma, the AQoL-8D and FACT-M are valid measures of utility; however, the AQoL-8D demonstrates greater sensitivity to FCRI severity. Our results suggest a significant association between FCR and HRQOL.

Germline mutations in CDKN2Aare frequently identified among melanoma kindreds and are associated with increased atypical nevus counts. However, a clear relationship between pathogenic CDKN2Amutation carriage and other nevus phenotypes including counts of common acquired nevi has not yet been established. Using data from GenoMEL, we investigated the relationships between CDKN2Amutation carriage and 2-mm, 5-mm, and atypical nevus counts among blood-related members of melanoma families. Compared with individuals without a pathogenic mutation, those who carried one had an overall higher prevalence of atypical (odds ratio = 1.64; 95% confidence interval = 1.18–2.28) nevi but not 2-mm nevi (odds ratio = 1.06; 95% confidence interval = 0.92–1.21) or 5-mm nevi (odds ratio = 1.26; 95% confidence interval = 0.94–1.70). Stratification by case status showed more pronounced positive associations among non-case family members, who were nearly three times (odds ratio = 2.91; 95% confidence interval = 1.75–4.82) as likely to exhibit nevus counts at or above the median in all three nevus categories simultaneously when harboring a pathogenic mutation (vs. not harboring one). Our results support the hypothesis that unidentified nevogenic genes are co-inherited with CDKN2Aand may influence carcinogenesis.

IMPORTANCE: We previously reported that survival is poorer from histopathologically amelanotic than pigmented melanoma because of more advanced stage at diagnosis. Identifying patients at risk of amelanotic melanoma might enable earlier diagnosis and improved survival; however, the phenotypic characteristics and underlying genetics associated with amelanotic melanoma are unknown. OBJECTIVE: To determine whether phenotypic characteristics, carriage of MC1R variants, and history of amelanotic melanoma are associated with histopathologically amelanotic melanoma. DESIGN, SETTING, AND PARTICIPANTS: The Genes, Environment, and Melanoma (GEM) study is an international cohort study that enrolled patients with incident primary cutaneous melanomas from population-based and hospital-based cancer registries (1998 to 2003). The GEM participants included here were 2387 patients with data for phenotypes, MC1R genotype, and primary melanomas scored for histopathologic pigmentation. Of these 2387 patients with incident melanomas scored for pigmentation, 527 had prior primary melanomas also scored for pigmentation. MAIN OUTCOMES AND MEASURES: Associations of phenotypic characteristics (freckles, nevi, phenotypic index) and MC1R status with incident amelanotic melanomas were evaluated using logistic regression models adjusted for age, sex, study center, and primary status (single or multiple primary melanoma); odds ratios (ORs) and 95% CIs are reported. Association of histopathologic pigmentation between incident and prior melanomas was analyzed using an exact logistic regression model. RESULTS: This study included 2387 patients (1065 women, 1322 men; mean [SD] age at diagnosis, 58.3 [16.1] years) and 2917 primary melanomas. In a multivariable model including phenotypic characteristics, absence of back nevi, presence of many freckles, and a sun-sensitive phenotypic index were independently associated with amelanotic melanoma. Carriage of MC1R variants was associated with amelanotic melanoma but lost statistical significance in a model with phenotype. Further, patients with incident primary amelanotic melanomas were more likely to have had a prior primary amelanotic melanoma (OR, 4.62; 95% CI, 1.25-14.13) than those with incident primary pigmented melanomas. CONCLUSIONS AND RELEVANCE: Absence of back nevi, presence of many freckles, a sun-sensitive phenotypic index, and prior amelanotic melanoma increase odds for development of amelanotic melanoma. An increased index of suspicion for melanoma in presenting nonpigmented lesions and more careful examination for signs of amelanotic melanoma during periodic skin examination in patients at increased odds of amelanotic melanoma might lead to earlier diagnosis and improved survival.

Shared decision making (SDM) is now firmly established within national clinical standards for accrediting hospitals, day procedure services, public dental services and medical education in Australia, with plans to align general practice, aged care and disability service. Implementation of these standards and training of health professionals is a key challenge for the Australian health sector at this time. Consumer involvement in health research, policy and clinical service governance has also increased, with a major focus on encouraging patients to ask questions during their clinical care. Tools to support shared decision making are increasingly used but there is a need for more systemic approaches to their development, cultural adaptation and implementation. Sustainable solutions to ensure tools are kept up-to-date with the best available evidence will be important for the future.

IMPORTANCE: The identification of a subgroup at higher risk of melanoma may assist in early diagnosis. OBJECTIVE: To characterize melanoma patients and the clinical features associated with their melanomas according to patient risk factors: many nevi, history of previous melanoma, and family history of melanoma, to assist with improving the identification and treatment of a higher-risk subgroup. DESIGN, SETTING, AND PARTICIPANTS: The Melanoma Patterns of Care study was a population-based observational study of physicians’ reported treatment of 2727 patients diagnosed with an in situ or invasive primary melanoma over a 12-month period from October 2006 to 2007 conducted in New South Wales. Our analysis of these data took place from 2015 to 2016. MAIN OUTCOMES AND MEASURES: Age at diagnosis and body site of melanoma. RESULTS: Of the 2727 patients with melanoma included, 1052 (39%) were defined as higher risk owing to a family history of melanoma, multiple primary melanomas, or many nevi. Compared with patients with melanoma who were at lower risk (ie, without any of these risk factors), the higher-risk group had a younger mean age at diagnosis (62 vs 65 years, P &lt; .001), but this differed by risk factor (56 years for patients with a family history, 59 years for those with many nevi, and 69 years for those with a previous melanoma). These age differences were consistent across all body sites. Among higher-risk patients, those with many nevi were more likely to have melanoma on the trunk (41% vs 29%, P &lt; .001), those with a family history of melanoma were more likely to have melanomas on the limbs (57% vs 42%, P &lt; .001), and those with a personal history were more likely to have melanoma on the head and neck (21% vs 15%, P = .003). CONCLUSIONS AND RELEVANCE: These findings suggest that a person’s risk factor status could be used to tailor surveillance programs and education about skin self-examination.

IMPORTANCE: Identifying individuals at high risk of melanoma can optimize primary and secondary prevention strategies. OBJECTIVE: To develop and externally validate a risk prediction model for incident first-primary cutaneous melanoma using self-assessed risk factors. DESIGN, SETTING, AND PARTICIPANTS: We used unconditional logistic regression to develop a multivariable risk prediction model. Relative risk estimates from the model were combined with Australian melanoma incidence and competing mortality rates to obtain absolute risk estimates. A risk prediction model was developed using the Australian Melanoma Family Study (629 cases and 535 controls) and externally validated using 4 independent population-based studies: the Western Australia Melanoma Study (511 case-control pairs), Leeds Melanoma Case-Control Study (960 cases and 513 controls), Epigene-QSkin Study (44 544, of which 766 with melanoma), and Swedish Women’s Lifestyle and Health Cohort Study (49 259 women, of which 273 had melanoma). MAIN OUTCOMES AND MEASURES: We validated model performance internally and externally by assessing discrimination using the area under the receiver operating curve (AUC). Additionally, using the Swedish Women’s Lifestyle and Health Cohort Study, we assessed model calibration and clinical usefulness. RESULTS: The risk prediction model included hair color, nevus density, first-degree family history of melanoma, previous nonmelanoma skin cancer, and lifetime sunbed use. On internal validation, the AUC was 0.70 (95% CI, 0.67-0.73). On external validation, the AUC was 0.66 (95% CI, 0.63-0.69) in the Western Australia Melanoma Study, 0.67 (95% CI, 0.65-0.70) in the Leeds Melanoma Case-Control Study, 0.64 (95% CI, 0.62-0.66) in the Epigene-QSkin Study, and 0.63 (95% CI, 0.60-0.67) in the Swedish Women’s Lifestyle and Health Cohort Study. Model calibration showed close agreement between predicted and observed numbers of incident melanomas across all deciles of predicted risk. In the external validation setting, there was higher net benefit when using the risk prediction model to classify individuals as high risk compared with classifying all individuals as high risk. CONCLUSIONS AND RELEVANCE: The melanoma risk prediction model performs well and may be useful in prevention interventions reliant on a risk assessment using self-assessed risk factors.

IMPORTANCE: NRAS and BRAF mutations in melanoma inform current treatment paradigms, but their role in survival from primary melanoma has not been established. Identification of patients at high risk of melanoma-related death based on their primary melanoma characteristics before evidence of recurrence could inform recommendations for patient follow-up and eligibility for adjuvant trials. OBJECTIVE: To determine tumor characteristics and survival from primary melanoma by somatic NRAS and BRAF status. DESIGN, SETTING, AND PARTICIPANTS: A population-based study with a median follow-up of 7.6 years (through 2007), including 912 patients from the United States and Australia in the Genes, Environment, and Melanoma (GEM) Study, with first primary cutaneous melanoma diagnosed in the year 2000 and analyzed for NRAS and BRAF mutations. MAIN OUTCOMES AND MEASURES: Tumor characteristics and melanoma-specific survival of primary melanoma by NRAS and BRAF mutational status. RESULTS: The melanomas were 13% NRAS+, 30% BRAF+, and 57% with neither NRAS nor BRAF mutation (wildtype [WT]). In a multivariable model including clinicopathologic characteristics, relative to WT melanoma (with results reported as odds ratios [95% CIs]), NRAS+ melanoma was associated with presence of mitoses (1.8 [1.0-3.3]), lower tumor-infiltrating lymphocyte (TIL) grade (nonbrisk, 0.5 [0.3-0.8]; and brisk, 0.3 [0.5-0.7] [vs absent TILs]), and anatomic site other than scalp/neck (0.1 [0.01-0.6] for scalp/neck vs trunk/pelvis), and BRAF+ melanoma was associated with younger age (ages 50-69 years, 0.7 [0.5-1.0]; and ages >70 years, 0.5 [0.3-0.8] [vs &lt;50 years]), superficial spreading subtype (nodular, 0.5 [0.2-1.0]; lentigo maligna, 0.4 [0.2-0.7]; and unclassified/other, 0.2 [0.1-0.5] [vs superficial spreading]), and presence of mitoses (1.7 [1.1-2.6]) (P &lt; .05 for all). There was no significant difference in melanoma-specific survival (reported as hazard ratios [95% CIs]) for melanoma harboring mutations in NRAS (1.7 [0.8-3.4]) or BRAF (1.5 [0.8-2.9]) compared with WT melanoma, as adjusted for age, sex, site, American Joint Committee on Cancer (AJCC) tumor stage, TIL grade, and study center. However, melanoma-specific survival was significantly poorer for higher-risk (T2b or higher stage) tumors with NRAS (2.9 [1.1-7.7]) or BRAF (3.1 [1.2-8.5]) mutations (P = .04) but not for lower-risk (T2a or lower) tumors with NRAS (0.9 [0.3-3.0]) or BRAF (0.6 [0.2-1.7]) (P = .65), as adjusted for age, sex, site, AJCC tumor stage, TIL grade, and study center. CONCLUSIONS AND RELEVANCE: Lower TIL grade for NRAS+ melanoma suggests it has a more immunosuppressed microenvironment, which may affect its response to immunotherapies. The approximate 3-fold increased risk of death for higher-risk tumors harboring NRAS or BRAF mutations after adjusting for other prognostic factors compared with WT melanomas indicates that the prognostic implication of these mutations deserves further investigation, particularly in higher–AJCC stage primary melanomas.

IMPORTANCE: Regular surveillance of individuals at high risk for cutaneous melanoma improves early detection and reduces unnecessary excisions; however, a cost analysis of this specialized service has not been undertaken. OBJECTIVE: To determine the mean cost per patient of surveillance in a high-risk clinic from the health service and societal perspectives. DESIGN, SETTING, AND PARTICIPANTS: We used a bottom-up microcosting method to measure resource use in a consecutive sample of 102 patients treated in a high-risk hospital-based clinic in Australia during a 12-month period. EXPOSURE: Surveillance and treatment of melanoma. MAIN OUTCOMES AND MEASURES: All surveillance and treatment procedures were identified through direct observation, review of medical records, and interviews with staff and were valued using scheduled fees from the Australian government. Societal costs included transportation and loss of productivity. RESULTS: The mean number of clinic visits per year was 2.7 (95% CI, 2.5-2.8) for surveillance and 3.8 (95% CI, 3.4-4.1) for patients requiring surgical excisions. The mean annual cost per patient to the health system was A $882 (95% CI, A $783-$982) (US $599 [95% CI, US $532-$665]); the cost discounted across 20 years was A $11 546 (95% CI, A $10 263-$12 829) (US $7839 [95% CI, US $6969-$8710]). The mean annual societal cost per patient (excluding health system costs) was A $972 (95% CI, A $899-$1045) (US $660 [95% CI, US $611-$710]); the cost discounted across 20 years was A $12 721 (95% CI, A $12 554-$14 463) (US $8637 [95% CI, US $8523-$9820]). Diagnosis of melanoma or nonmelanoma skin cancer and frequent excisions for benign lesions in a relatively small number of patients was responsible for positively skewed health system costs. CONCLUSIONS AND RELEVANCE: Microcosting techniques provide an accurate cost estimate for the provision of a specialized service. The high societal cost reflects the time that patients are willing to invest to attend the high-risk clinic. This alternative model of care for a high-risk population has relevance for decision making about health policy.

IMPORTANCE Currently, there is no comprehensive assessment of melanoma risk prediction models. OBJECTIVE To systematically review published studies reporting multivariable risk prediction models for incident primary cutaneous melanoma for adults. EVIDENCE REVIEW EMBASE, MEDLINE, PREMEDLINE, and Cochrane databases were searched to April 30, 2013. Eligible studies were hand searched and citation tracked. Two independent reviewers extracted information. FINDINGS Nineteen studies reporting 28 melanoma prediction models were included. The number of predictors in the final models ranged from 2 to 13; the most common were nevi, skin type, freckle density, age, hair color, and sunburn history. There was limited reporting and substantial variation among the studies in model development and performance. Discrimination (the ability of the model to differentiate between patients with and without melanoma) was reported in 9 studies and ranged from fair to very good (area under the receiver operating characteristic curve, 0.62-0.86). Few studies assessed internal or external validity of the models or their use in clinical and public health practice. Of the published melanoma risk prediction models, the risk prediction tool developed by Fears and colleagues, which was designed for the US population, appears to be the most clinically useful and may also assist in identifying high-risk groups for melanoma prevention strategies. CONCLUSIONS AND RELEVANCE Few melanoma risk prediction models have been comprehensively developed and assessed. More external validation and prospective evaluation will help translate melanoma risk prediction models into useful tools for clinical and public health practice.

The article focuses on the potential of incorporating genomics into public health strategies. It discusses how genomic risk awareness could help in improving population health through prevention and early detection of diseases and its impact on behaviour change. According to the article, this is a novel approach to encouraging risk-reducing behaviours, more comprehensive studies are required to make more informed decisions.

Self-reported confidence ratings have been used in other research disciplines as a tool to assess data quality, and may be useful in epidemiologic studies.

In an effort to understand the difference between melanomas diagnosed in Australia (New South Wales) and Canada, where the incidence in New South Wales is almost three times greater than in Canada, and mortality is twice as high although survival is slightly more favorable, we had one pathologist review 1,271 melanomas from British Columbia and Ontario, Canada, to compare these to melanomas in New South Wales, Australia. We hypothesized that histopathologic characteristics might provide insight into divergent pathways to melanoma development. We found a number of differences in risk factors and tumor characteristics between the two geographic areas. There were higher mole counts and darker phenotypes in the Canadian patients, while the Australian patients had greater solar elastosis, more lentigo maligna melanomas, and more tumor infiltrating lymphocytes. We hypothesize that the differences observed may illustrate different etiologies – the cumulative exposure pathway among Australian patients and the nevus pathway among Canadian patients. This is one of the largest studies investigating the divergent pathway hypothesis and is particularly robust due to the evaluation of all lesions by one dermatopathologist.

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.