High variability in anatomic patterns of cutaneous photodamage: a population-based study.

BACKGROUND: Skin cancer is strongly associated with photodamaged skin, but body sites are often referred to as 'exposed' or 'unexposed' to sun without recognizing extent of site-specific variation. OBJECTIVES: To assess whole-body patterns of photodamage in an Australian population. METHODS: A random sample of adult residents of Queensland underwent imaging across 10 body sites. Photodamage was graded from images using an ordinal photonumeric scale. We used cluster analysis to identify whole-body photodamage patterns and prevalence proportion ratios (PPRs) to assess associated factors. RESULTS: Of 190 adults (median age 52; 58% males), 58% showed severe or moderate-to-severe photodamage on most body sites. A higher proportion of woman had severe photodamage on the arms (upper: P = 0.002, lower: P = 0.034). A higher proportion of men had moderate or severe photodamage on the lower back (P = 0.004). We identified four photodamage patterns: 'severe general' (n = 24, 13%), 'moderate-severe general' (n = 86, 45%), 'moderate-severe v-neck' (n = 40, 21%) and 'mild-moderate upper body' (n = 12, 6%). All participants with 'severe-general' photodamage were >50 years and more likely to have past skin cancer (PPR: 2.54, 95% CI: 1.44-4.49) than those with 'moderate-severe v-neck' photodamage. Those with 'moderate-severe general' photodamage showed similar associations and were more likely female (PPR: 1.33, 95% CI: 1.04-1.69). Past or current smoking was associated with having higher levels of photodamage, with no smokers in those with 'mild-moderate upper body' photodamage. CONCLUSIONS: Moderate-to-severe photodamage across much of the body is common in Queensland adults and associated with age, sex, past skin cancer and smoking. Assuming a universal pattern of site-specific sun exposure could lead to spurious correlations, while accurate and objective assessment of site-specific photodamage can add to understanding of the development of sun-associated skin cancers, in particular site-specific skin carcinogenesis. Additionally, degree of site-specific photodamage has the potential to assist skin cancer screening.

Risk factors for melanoma by anatomical site: an evaluation of aetiological heterogeneity.

BACKGROUND: Melanoma aetiology has been proposed to have two pathways, which are determined by naevi and type of sun exposure and related to the anatomical site where melanoma develops. OBJECTIVES: We examined associations with melanoma by anatomical site for a comprehensive set of risk factors including pigmentary and naevus phenotypes, ultraviolet radiation exposure and polygenic risk. METHODS: We analysed harmonized data from 2617 people with incident first invasive melanoma and 975 healthy controls recruited through two population-based case-control studies in Australia and the UK. Questionnaire data were collected by interview using a single protocol, and pathway-specific polygenic risk scores were derived from DNA samples. We estimated adjusted odds ratios using unconditional logistic regression that compared melanoma cases at each anatomical site with all controls. RESULTS: When cases were compared with control participants, there were stronger associations for many naevi vs. no naevi for melanomas on the trunk, and upper and lower limbs than on the head and neck (P-heterogeneity < 0·001). Very fair skin (vs. olive/brown skin) was more weakly related to melanoma on the trunk than to melanomas at other sites (P-heterogeneity = 0·04). There was no significant difference by anatomical site for polygenic risk. Increased weekday sun exposure was positively associated with melanoma on the head and neck but not on other sites. CONCLUSIONS: We found evidence of aetiological heterogeneity for melanoma, supporting the dual pathway hypothesis. These findings enhance understanding of risk factors for melanoma and can guide prevention and skin examination education and practices.

Development and external validation study of a melanoma risk prediction model incorporating clinically assessed naevi and solar lentigines.

BACKGROUND: Melanoma risk prediction models could be useful for matching preventive interventions to patients' risk. OBJECTIVES: To develop and validate a model for incident first-primary cutaneous melanoma using clinically assessed risk factors. METHODS: We used unconditional logistic regression with backward selection from the Australian Melanoma Family Study (461 cases and 329 controls) in which age, sex and city of recruitment were kept in each step, and we externally validated it using the Leeds Melanoma Case-Control Study (960 cases and 513 controls). Candidate predictors included clinically assessed whole-body naevi and solar lentigines, and self-assessed pigmentation phenotype, sun exposure, family history and history of keratinocyte cancer. We evaluated the predictive strength and discrimination of the model risk factors using odds per age- and sex-adjusted SD (OPERA) and the area under curve (AUC), and calibration using the Hosmer-Lemeshow test. RESULTS: The final model included the number of naevi ≥ 2 mm in diameter on the whole body, solar lentigines on the upper back (a six-level scale), hair colour at age 18 years and personal history of keratinocyte cancer. Naevi was the strongest risk factor; the OPERA was 3·51 [95% confidence interval (CI) 2·71-4·54] in the Australian study and 2·56 (95% CI 2·23-2·95) in the Leeds study. The AUC was 0·79 (95% CI 0·76-0·83) in the Australian study and 0·73 (95% CI 0·70-0·75) in the Leeds study. The Hosmer-Lemeshow test P-value was 0·30 in the Australian study and < 0·001 in the Leeds study. CONCLUSIONS: This model had good discrimination and could be used by clinicians to stratify patients by melanoma risk for the targeting of preventive interventions. What's already known about this topic? Melanoma risk prediction models may be useful in prevention by tailoring interventions to personalized risk levels. For reasons of feasibility, time and cost many melanoma prediction models use self-assessed risk factors. However, individuals tend to underestimate their naevus numbers. What does this study add? We present a melanoma risk prediction model, which includes clinically-assessed whole-body naevi and solar lentigines, and self-assessed risk factors including pigmentation phenotype and history of keratinocyte cancer. This model performs well on discrimination, the model's ability to distinguish between individuals with and without melanoma, and may assist clinicians to stratify patients by melanoma risk for targeted preventive interventions.

Associations of pigmentary and naevus phenotype with melanoma risk in two populations with comparable ancestry but contrasting levels of ambient sun exposure.

BACKGROUND: People at high risk of developing melanoma are usually identified by pigmentary and naevus phenotypes. OBJECTIVE: We examined whether associations of these phenotypes with melanoma risk differed by ambient sun exposure or participant characteristics in two population-based, case-control studies with comparable ancestry but different ambient sun exposure. METHODS: Data were analysed from 616 cases and 496 controls from the Australian Melanoma Family Study and 2012 cases and 504 controls from the Leeds (UK) case-control study. Questionnaire, interview and dermatological skin examination data were collected using the same measurement protocols. Relative risks were estimated as odds ratios using unconditional logistic regression, adjusted for potential confounders. RESULTS: Hair and skin colour were the strongest pigmentary phenotype risk factors. All associations of pigmentary phenotype with melanoma risk were similar across countries. The median number of clinically assessed naevi was approximately three times higher in Australia than Leeds, but the relative risks for melanoma associated with each additional common or dysplastic naevus were higher for Leeds than Australia, especially for naevi on the upper and lower limbs. Higher naevus counts on the head and neck were associated with a stronger relative risk for melanoma for women than men. The two countries had similar relative risks for melanoma based on self-reported naevus density categories, but personal perceptions of naevus number differed by country. There was no consistent evidence of interactions between phenotypes on risk. CONCLUSIONS: Classifying people at high risk of melanoma based on their number of naevi should ideally take into account their country of residence, type of counts (clinical or self-reported), body site on which the naevus counts are measured and sex. The presence of naevi may be a stronger indicator of a genetic predisposition in the UK than in Australia based on less opportunity for sun exposure to influence naevus development.

Effects and moderators of psychosocial interventions on quality of life, and emotional and social function in patients with cancer: An individual patient data meta-analysis of 22 RCTs.

OBJECTIVE: This individual patient data (IPD) meta-analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention-related characteristics. METHODS: Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed-effect model analyses were used to study intervention effects on the post-intervention values of QoL, EF, and SF (z-scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention-related characteristics, and conducted subsequent stratified analyses for significant moderator variables. RESULTS: PSI significantly improved QoL (ß = 0.14,95%CI = 0.06;0.21), EF (ß = 0.13,95%CI = 0.05;0.20), and SF (ß = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types. CONCLUSIONS: PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention-related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients.

Variations in outcomes for Indigenous women with breast cancer in Australia: A systematic review.

This systematic review examines variations in outcomes along the breast cancer continuum for Australian women by Indigenous status. Multiple databases were systematically searched for peer-reviewed articles published from 1 January 1990 to 1 March 2015 focussing on adult female breast cancer patients in Australia and assessing survival, patient and tumour characteristics, diagnosis and treatment by Indigenous status. Sixteen quantitative studies were included with 12 rated high, 3 moderate and 1 as low quality. No eligible studies on referral, treatment choices, completion or follow-up were retrieved. Indigenous women had poorer survival most likely reflecting geographical isolation, advanced disease, patterns of care, comorbidities and disadvantage. They were also more likely to be diagnosed when younger, have advanced disease or comorbidities, reside in disadvantaged or remote areas, and less likely to undergo mammographic screening or surgery. Despite wide heterogeneity across studies, an overall pattern of poorer survival for Indigenous women and variations along the breast cancer continuum of care was evident. The predominance of state-specific studies and small numbers of included Indigenous women made forming a national perspective difficult. The review highlighted the need to improve Indigenous identification in cancer registries and administrative databases and identified key gaps notably the lack of qualitative studies in current literature.

A systematic review of inequalities in psychosocial outcomes for women with breast cancer according to residential location and Indigenous status in Australia.

BACKGROUND: The aim of this systematic review was to examine variations in psychosocial outcomes by residential location and Indigenous status in women diagnosed with breast cancer (BC) in Australia. METHODS: Systematic searches were undertaken using multiple databases covering articles between 1 January 1990 and 1 March 2015 focusing on adult women with BC in an Australian setting and measuring quality of life (QOL), psychological distress or psychosocial support. RESULTS: Thirteen quantitative and three qualitative articles were included. Two quantitative and one qualitative article were rated high quality, seven moderate and the remaining were low quality. No studies examining inequalities by Indigenous status were identified. Non-metropolitan women were more likely to record lower QOL relating to breast cancer-specific concerns and reported a lack of information and resources specific to their needs. Continuity of support, ongoing care and access to specialist and allied health professionals were major concerns for non-metropolitan women. Non-metropolitan women identified unmet needs in relation to travel, fear of cancer recurrence and lack of psychosocial support. CONCLUSIONS: Overall, there was a lack of evidence relating to variations in psychosocial outcomes for women with BC according to residential status or Indigenous status. While the review identified some specific concerns for non-metropolitan women with BC, it was limited by the lack of good quality studies using standardised measures. Copyright © 2016 John Wiley & Sons, Ltd.

A multidisciplinary team approach minimises prophylactic mastectomy rates.

BACKGROUND: Prophylactic mastectomy (PM) has become increasingly common but is not without complications especially if accompanied by reconstructive surgery. In patients with sporadic unilateral breast cancer, contralateral PM offers no survival advantage. Multidisciplinary team (MDT) communication and interaction may facilitate shared decision-making and curtail PM rates. The aim of this study was investigate the effect of a regional MDT meeting on PM decision-making. METHODS: We conducted an observational study involving retrospective review of prospectively recorded MDT meeting records for a 151 patient requests for PM from 2011 to 2014. Final MDT decisions were recorded as PM 'accepted', 'declined' or 'pending'. For MDT sanctioned requests, the factors justifying PM were recorded. Where PM was declined, justification for MDT refusal was sought and recorded. RESULTS: Approximately half of all requests for PM have been upheld (53.0%) and 1/3 of requests have been declined (32.5%). Of those declined, low risk of contralateral breast cancer versus relatively high risk of systemic relapse were commonly cited as justification for PM refusal (45.7%). A proportion of patients who initiated PM discussion subsequently changed their minds (19.6%), or failed to attend clinic appointments (6.5%). Some patients were deemed medically unfit for complex reconstructive surgery (13%), or were declined on the basis of an apparent cosmetic drive for surgery (6.5%), concerns regarding depression or anxiety (2.2%) and/or if family history could not be substantiated (6.5%). DISCUSSION: MDT meetings facilitate cross-specialty interrogation of requests for PM, minimise unnecessary surgery and restrict PM to those likely to derive maximum benefit.

Geographic remoteness and risk of advanced colorectal cancer at diagnosis in Queensland: a multilevel study.

BACKGROUND: We examine the relationships between geographic remoteness, area disadvantage and risk of advanced colorectal cancer. METHODS: Multilevel models were used to assess the area- and individual-level contributions to the risk of advanced disease among people aged 20-79 years diagnosed with colorectal cancer in Queensland, Australia between 1997 and 2007 (n=18,561). RESULTS: Multilevel analysis showed that colorectal cancer patients living in inner regional (OR=1.09, 1.01-1.19) and outer regional (OR=1.11, 1.01-1.22) areas were significantly more likely to be diagnosed with advanced cancer than those in major cities (P=0.045) after adjusting for individual-level variables. The best-fitting final model did not include area disadvantage. Stratified analysis suggested this remoteness effect was limited to people diagnosed with colon cancer (P=0.048) and not significant for rectal cancer patients (P=0.873). CONCLUSION: Given the relationship between stage and survival outcomes, it is imperative that the reasons for these rurality inequities in advanced disease be identified and addressed.

Body-site distribution of skin cancer, pre-malignant and common benign pigmented lesions excised in general practice.

BACKGROUND: Concern about skin cancer is a common reason for people from predominantly fair-skinned populations to present to primary care doctors. OBJECTIVES: To examine the frequency and body-site distribution of malignant, pre-malignant and benign pigmented skin lesions excised in primary care. METHODS: This prospective study conducted in Queensland, Australia, included 154 primary care doctors. For all excised or biopsied lesions, doctors recorded the patient's age and sex, body site, level of patient pressure to excise, and the clinical diagnosis. Histological confirmation was obtained through pathology laboratories. RESULTS: Of 9650 skin lesions, 57·7% were excised in males and 75·0% excised in patients ≥ 50 years. The most common diagnoses were basal cell carcinoma (BCC) (35·1%) and squamous cell carcinoma (SCC) (19·7%). Compared with the whole body, the highest densities for SCC, BCC and actinic keratoses were observed on chronically sun-exposed areas of the body including the face in males and females, the scalp and ears in males, and the hands in females. The density of BCC was also high on intermittently or rarely exposed body sites. Females, younger patients and patients with melanocytic naevi were significantly more likely to exert moderate/high levels of pressure on the doctor to excise. CONCLUSIONS: More than half the excised lesions were skin cancer, which mostly occurred on the more chronically sun-exposed areas of the body. Information on the type and body-site distribution of skin lesions can aid in the diagnosis and planned management of skin cancer and other skin lesions commonly presented in primary care.

TLR5 activation induces secretory interleukin-1 receptor antagonist (sIL-1Ra) and reduces inflammasome-associated tissue damage.

Toll-like receptor-5 (TLR5)-mediated detection of flagellin induces nuclear factor (NF)-κB-mediated transcription of host defense gene expression, whereas recognition of intracellular flagellin by interleukin (IL)-1-converting enzyme protease-activation factor (IPAF) results in maturation/secretion of the inflammasome cytokine IL-1ß. The potent effects of IL-1ß are counter-regulated by secretory IL-1 receptor antagonist (sIL-1Ra). We studied the roles of flagellin receptors in regulating the expression of IL-1ß and sIL-1Ra and their subsequent roles in inflammation. Flagellin induced sIL-1Ra in intestinal epithelia and macrophages in a dose- and time-dependent manner, whereas IL-1ß was only induced in macrophages. In vivo, flagellin-induced sIL-1Ra, but not IL-1ß, was absolutely dependent upon TLR5 expressed on non-hemopioetic cells. Thus, loss of TLR5 increased the IL-1ß/sIL-1Ra ratio on flagellin treatment, which correlated with increased inflammatory pathology in response to this product. Furthermore, the flagellin/TLR5 interaction was important for the induction of sIL-1Ra and limiting inflammatory pathology on Salmonella infection. Finally, reduced sIL-1Ra levels in TLR5KO mice correlated with spontaneous colitis. Taken together, we demonstrate that intestinal epithelia, despite not expressing IL-1ß, secrete sIL-1Ra in a TLR5-dependent manner suggesting that loss of TLR5 may promote inflammation by increasing IL-1ß activity. Thus, optimizing the balance between inflammasome cytokines and their endogenous inhibitors might prove a useful strategy to treat inflammatory disorders.

Population-based survival estimates for childhood cancer in Australia during the period 1997-2006.

BACKGROUND: This study provides the latest available relative survival data for Australian childhood cancer patients. METHODS: Data from the population-based Australian Paediatric Cancer Registry were used to describe relative survival outcomes using the period method for 11,903 children diagnosed with cancer between 1983 and 2006 and prevalent at any time between 1997 and 2006. RESULTS: The overall relative survival was 90.4% after 1 year, 79.5% after 5 years and 74.7% after 20 years. Where information onstage at diagnosis was available (lymphomas, neuroblastoma, renal tumours and rhabdomyosarcomas), survival was significantly poorer for more-advanced stage. Survival was lower among infants compared with other children for those diagnosed with leukaemia, tumours of the central nervous system and renal tumours but higher for neuroblastoma. Recent improvements in overall childhood cancer survival over time are mainly because of improvements among leukaemia patients. CONCLUSION: The high and improving survival prognosis for children diagnosed with cancer in Australia is consistent with various international estimates. However, a 5-year survival estimate of 79% still means that many children who are diagnosed with cancer will die within 5 years, whereas others have long-term health morbidities and complications associated with their treatments. It is hoped that continued developments in treatment protocols will result in further improvements in survival.

Trends in incidence of childhood cancer in Australia, 1983-2006.

BACKGROUND: There are few population-based childhood cancer registries in the world containing stage and treatment data. METHODS: Data from the population-based Australian Paediatric Cancer Registry were used to calculate incidence rates during the most recent 10-year period (1997-2006) and trends in incidence between 1983 and 2006 for the 12 major diagnostic groups of the International Classification of Childhood Cancer. RESULTS: In the period 1997-2006, there were 6184 childhood cancer (at 0-14 years) cases in Australia (157 cases per million children). The commonest cancers were leukaemia (34%), that of the central nervous system (23%) and lymphomas (10%), with incidence the highest at 0-4 years (223 cases per million). Trend analyses showed that incidence among boys for all cancers combined increased by 1.6% per year from 1983 to 1994 but have remained stable since. Incidence rates for girls consistently increased by 0.9% per year. Since 1983, there have been significant increases among boys and girls for leukaemia, and hepatic and germ-cell tumours, whereas for boys, incidence of neuroblastomas and malignant epithelial tumours has recently decreased. For all cancers and for both sexes combined, there was a consistent increase (+0.7% per year, 1983-2006) at age 0-4 years, a slight non-significant increase at 5-9 years, and at 10-14 years, an initial increase (2.7% per year, 1983-1996) followed by a slight non-significant decrease. CONCLUSION: Although there is some evidence of a recent plateau in cancer incidence rates in Australia for boys and older children, interpretation is difficult without a better understanding of what underlies the changes reported.

The skin awareness study: promoting thorough skin self-examination for skin cancer among men 50 years or older.

BACKGROUND: Incidence and mortality from skin cancers including melanoma are highest among men 50 years or older. Thorough skin self-examination may be beneficial to improve skin cancer outcomes. OBJECTIVES: To develop and conduct a randomized-controlled trial of a video-based intervention to improve skin self-examination behavior among men 50 years or older. METHODS: Pilot work ascertained appropriate targeting of the 12-minute intervention video towards men 50 years or older. Overall, 968 men were recruited and 929 completed baseline telephone assessment. Baseline analysis assessed randomization balance and demographic, skin cancer risk and attitudinal factors associated with conducting a whole-body skin self-examination or receiving a whole-body clinical skin examination by a doctor during the past 12 months. RESULTS: Randomization resulted in well-balanced intervention and control groups. Overall 13% of men reported conducting a thorough skin self-examination using a mirror or the help of another person to check difficult to see areas, while 39% reported having received a whole-body skin examination by a doctor within the past 12 months. Confidence in finding time for and receiving advice or instructions by a doctor to perform a skin self-examination were among the factors associated with thorough skin self-examination at baseline. CONCLUSIONS: Men 50 years or older can successfully be recruited to a video-based intervention trial with the aim to reduce their burden through skin cancer. Randomization by computer generated randomization list resulted in good balance between control and intervention group and baseline analysis determined factors associated with skin cancer early detection behavior.

Evaluating bone health in women with oestrogen receptor positive breast cancer (ERBC) starting aromatase inhibitors.

AIMS: There is an increase in fractures in women with oestrogen receptor positive breast cancer (ERBC) particularly those taking aromatase inhibitors (AIs). How to identify women at osteoporosis risk, assess bone health and who to treat, are questions not adequately answered by previous studies. METHODS: We present an audit of osteoporosis risk factors, bone mineral density (BMD) measurement and other data relevant to bone health (falls and laboratory tests) in 85 women with ERBC starting AIs. RESULTS: Only 9/85 (11%) women overall and only 2/13 with previous peripheral fragility fractures had osteoporosis. Of note, secondary hyperparathyroidism was present in 40% of women <60 years; 67% of women 60-69 years and 75% of women >70 years. CONCLUSIONS: Reliance on BMD alone to guide decisions for osteoporosis prevention treatment in those taking AIs would lead to few women being treated. Osteoporosis risk in women taking AIs is likely influenced by factors other than those encompassed by BMD alone.