Challenges in assessing the sunscreen-melanoma association.
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ABSTRACT:
SUBMITTER: Rueegg CS
PROVIDER: S-EPMC6451658 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceThere are limited data among young adults on sunscreen use during childhood and adulthood and on the association of sunscreen use with melanoma risk.ObjectiveTo 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 participantsThis 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.ExposuresSelf- and parent-reported sunscreen use, sun exposure, and other candidate risk factors during childhood and adulthood.Main outcomes and measuresLogistic regression analyses adjusted for potential confounders were used to estimate odds ratios (ORs) for melanoma and for correlates of sunscreen use.ResultsParticipation 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 relevanceOur 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.
| S-EPMC6143037 | biostudies-literature
Project description:The past few years have witnessed major advances in the understanding of the molecular landscape of uveal melanoma (UM). The discovery of a mutational background that is completely different from the one of skin melanoma has granted to UM a stand-alone status. The absence of effective therapy for metastatic disease offers now a chessboard for targeted therapy but at the same time urges preclinical science to develop accordingly, to guide the use of economical resources to the best profit of patients. This review describes the current knowledge on the biology of this disease and discusses the challenges that must be undertaken to translate this knowledge into real benefit for patients.
| S-EPMC4815787 | biostudies-literature
Project description:We conducted the Reproducibility Project: Cancer Biology to investigate the replicability of preclinical research in cancer biology. The initial aim of the project was to repeat 193 experiments from 53 high-impact papers, using an approach in which the experimental protocols and plans for data analysis had to be peer reviewed and accepted for publication before experimental work could begin. However, the various barriers and challenges we encountered while designing and conducting the experiments meant that we were only able to repeat 50 experiments from 23 papers. Here we report these barriers and challenges. First, many original papers failed to report key descriptive and inferential statistics: the data needed to compute effect sizes and conduct power analyses was publicly accessible for just 4 of 193 experiments. Moreover, despite contacting the authors of the original papers, we were unable to obtain these data for 68% of the experiments. Second, none of the 193 experiments were described in sufficient detail in the original paper to enable us to design protocols to repeat the experiments, so we had to seek clarifications from the original authors. While authors were extremely or very helpful for 41% of experiments, they were minimally helpful for 9% of experiments, and not at all helpful (or did not respond to us) for 32% of experiments. Third, once experimental work started, 67% of the peer-reviewed protocols required modifications to complete the research and just 41% of those modifications could be implemented. Cumulatively, these three factors limited the number of experiments that could be repeated. This experience draws attention to a basic and fundamental concern about replication - it is hard to assess whether reported findings are credible.
| S-EPMC8651289 | biostudies-literature
Project description:The field of genomic biomarkers in melanoma has evolved dramatically in the past few decades. Whereas much of the prior focus was on molecular assessment of tumor tissue, circulating tumor cells (CTCs), and cell-free circulating tumor DNA (ctDNA) as sources of a "liquid biopsy" in cancer patients provide promising potential as a method to assess tumor progression, identify targets for therapy, and evaluate clinical response to treatment. Blood biomarker assays have the advantage of being noninvasive, allow for dynamic evaluation of disease over a serial time frame, and help to address the issue of tissue sampling bias and tumor heterogeneity. However, there remains an assortment of technologies and techniques to isolate and detect CTCs and ctDNA and a standardized method has yet to be established. Despite these challenges, multiple studies have already demonstrated the clinical prognostic utility of blood-based genomic biomarker assays. With the advent of next-generation sequencing and genome-wide ctDNA analysis, this will undoubtedly lead to an improved understanding of tumor progression, help to identify new targets for treatment, and improve monitoring of treatment response and development of resistance.
| S-EPMC5326707 | biostudies-literature
Project description:ImportanceA prior pilot study demonstrated the systemic absorption of 4 sunscreen active ingredients; additional studies are needed to determine the systemic absorption of additional active ingredients and how quickly systemic exposure exceeds 0.5 ng/mL as recommended by the US Food and Drug Administration (FDA).ObjectiveTo assess the systemic absorption and pharmacokinetics of the 6 active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate) in 4 sunscreen products under single- and maximal-use conditions.Design, setting, and participantsRandomized clinical trial at a clinical pharmacology unit (West Bend, Wisconsin) was conducted in 48 healthy participants. The study was conducted between January and February 2019.InterventionsParticipants were randomized to 1 of 4 sunscreen products, formulated as lotion (n = 12), aerosol spray (n = 12), nonaerosol spray (n = 12), and pump spray (n = 12). Sunscreen product was applied at 2 mg/cm2 to 75% of body surface area at 0 hours on day 1 and 4 times on day 2 through day 4 at 2-hour intervals, and 34 blood samples were collected over 21 days from each participant.Main outcomes and measuresThe primary outcome was the maximum plasma concentration of avobenzone over days 1 through 21. Secondary outcomes were the maximum plasma concentrations of oxybenzone, octocrylene, homosalate, octisalate, and octinoxate over days 1 through 21.ResultsAmong 48 randomized participants (mean [SD] age, 38.7 [13.2] years; 24 women [50%]; 23 white [48%], 23 African American [48%], 1 Asian [2%], and 1 of unknown race/ethnicity [2%]), 44 (92%) completed the trial. Geometric mean maximum plasma concentrations of all 6 active ingredients were greater than 0.5 ng/mL, and this threshold was surpassed on day 1 after a single application for all active ingredients. For avobenzone, the overall maximum plasma concentrations were 7.1 ng/mL (coefficient of variation [CV], 73.9%) for lotion, 3.5 ng/mL (CV, 70.9%) for aerosol spray, 3.5 ng/mL (CV, 73.0%) for nonaerosol spray, and 3.3 ng/mL (CV, 47.8%) for pump spray. For oxybenzone, the concentrations were 258.1 ng/mL (CV, 53.0%) for lotion and 180.1 ng/mL (CV, 57.3%) for aerosol spray. For octocrylene, the concentrations were 7.8 ng/mL (CV, 87.1%) for lotion, 6.6 ng/mL (CV, 78.1%) for aerosol spray, and 6.6 ng/mL (CV, 103.9%) for nonaerosol spray. For homosalate, concentrations were 23.1 ng/mL (CV, 68.0%) for aerosol spray, 17.9 ng/mL (CV, 61.7%) for nonaerosol spray, and 13.9 ng/mL (CV, 70.2%) for pump spray. For octisalate, concentrations were 5.1 ng/mL (CV, 81.6%) for aerosol spray, 5.8 ng/mL (CV, 77.4%) for nonaerosol spray, and 4.6 ng/mL (CV, 97.6%) for pump spray. For octinoxate, concentrations were 7.9 ng/mL (CV, 86.5%) for nonaerosol spray and 5.2 ng/mL (CV, 68.2%) for pump spray. The most common adverse event was rash, which developed in 14 participants.Conclusions and relevanceIn this study conducted in a clinical pharmacology unit and examining sunscreen application among healthy participants, all 6 of the tested active ingredients administered in 4 different sunscreen formulations were systemically absorbed and had plasma concentrations that surpassed the FDA threshold for potentially waiving some of the additional safety studies for sunscreens. These findings do not indicate that individuals should refrain from the use of sunscreen.Trial registrationClinicalTrials.gov Identifier: NCT03582215.
| S-EPMC6990686 | biostudies-literature
Project description:Five years ago, the Melanoma Research Foundation (MRF) conducted an assessment of the challenges and opportunities facing the melanoma research community and patients with melanoma. Since then, remarkable progress has been made on both the basic and clinical research fronts. However, the incidence, recurrence, and death rates for melanoma remain unacceptably high and significant challenges remain. Hence, the MRF Scientific Advisory Council and Breakthrough Consortium, a group that includes clinicians and scientists, reconvened to facilitate intensive discussions on thematic areas essential to melanoma researchers and patients alike, prevention, detection, diagnosis, metastatic dormancy and progression, response and resistance to targeted and immune-based therapy, and the clinical consequences of COVID-19 for patients with melanoma and providers. These extensive discussions helped to crystalize our understanding of the challenges and opportunities facing the broader melanoma community today. In this report, we discuss the progress made since the last MRF assessment, comment on what remains to be overcome, and offer recommendations for the best path forward.
| S-EPMC8127340 | biostudies-literature
Project description:The expanded use of clinical process-of-care measures to assess the quality of health care in the context of public reporting and pay-for-performance applications has led to a desire to demonstrate the value of such efforts in terms of improved patient outcomes. The inability to observe associations between improved delivery of clinical processes and improved clinical outcomes in practice has raised concerns about the value of holding providers accountable for delivery of clinical processes of care. Analyses that attempt to investigate this relationship are fraught with many challenges, including selection of an appropriate outcome, the proximity of the outcome to the receipt of the clinical process, limited power to detect an effect, small expected effect sizes in practice, potential bias due to unmeasured confounding factors, and difficulties due to changes in measure specification over time. To avoid potentially misleading conclusions about an observed or lack of observed association between a clinical process of care and an outcome in the context of observational studies, individuals conducting and interpreting such studies should carefully consider, evaluate, and acknowledge these types of challenges.
| S-EPMC4351283 | biostudies-literature
Project description:Clinical research infrastructure is one of the unsung heroes of the scientific response to the current COVID-19 pandemic. The extensive, long-term funding into research support structures, skilled people, and technology allowed the United Kingdom research response to move off the starting blocks at pace by utilizing pre-existing platforms. The increasing focus from funders on evaluating the outcomes and impact of research infrastructure investment requires both a reframing and progression of the current models in order to address the contribution of the underlying support infrastructure. The majority of current evaluation/outcome models focus on a "pipeline" approach using a methodology which follows the traditional research funding route with the addition of quantitative metrics. These models fail to embrace the complexity caused by the interplay of previous investment, the coalescing of project outputs from different funders, the underlying infrastructure investment, and the parallel development across different parts of the system. Research infrastructure is the underpinning foundation of a project-driven research system and requires long-term, sustained funding and capital investment to maintain scientific and technological expertise. Therefore, the short-term focus on quantitative metrics that are easy to collect and interpret and that can be assessed in a roughly 5-year funding cycle needs to be addressed. The significant level of investment in research infrastructure necessitates investment to develop bespoke methodologies that develop fit-for-purpose, longer-term/continual approach(es) to evaluation. Real-world research should reflect real-world evaluation and allow for the accrual of a narrative of value indicators that build a picture of the contribution of infrastructure to research outcomes. The linear approach is not fit for purpose, the research endeavour is a complex, twisted road, and the evaluation approach needs to embrace this complexity through the development of realist approaches and the rapidly evolving data ecosystem. This paper sets out methodological challenges and considers the need to develop bespoke methodological approaches to allow a richer assessment of impact, contribution, attribution, and evaluation of research infrastructure. This paper is the beginning of a conversation that invites the community to "take up the mantle" and tackle the complexity of real-world research translation and evaluation.
| S-EPMC8371591 | biostudies-literature
Project description:Strategies and Opportunities to STOP Colon Cancer in Priority Populations (STOP CRC) was a pragmatic cluster-randomized trial conducted at federally qualified health centers and designed to "Reach" as many unscreened patients as possible by directly mailing them fecal screening tests. STOP CRC used an electronic health record registry to identify individuals' needing CRC screening and mail interventions to them. The registry was updated daily removing individuals completing CRC screening or those who no longer were clinic patients. Reach, a component RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance), is defined as the absolute number, percent, and representativeness of individuals "willing to participate in" or "exposed to" an initiative. We describe the complexities of measuring Reach in a pragmatic trial. Overall 21,134 patients were on the registry list for at least one day, with 18,226 remaining after removing patients completing screening before any mailings. Observed Reached (the percent of individuals exposed to the intervention) using each denominator was 30.7% and 35.6% respectively. Reach improved only modestly after accounting for factors that made it impossible for clinics to send mailings. Few differences were observed in demographic and health care utilization factors among individuals Reached versus not Reached, suggesting that health center Implementation was more influential than patients' willingness or ability to participate. A pragmatic definition of Reach that accounted for dynamic changes the absolute number eligible and the proportion exposed was more useful than traditional definitions of Reach. Actual Reach was dependent on Implementation and not patient level characteristics. Clinical Trials Registration Number: ClincalTrials.gov (NCT01742065).
| S-EPMC6558213 | biostudies-literature
Project description:There will be an estimated 76,100 new cases of melanoma diagnosed in 2015 and 9710 deaths. Patients with stage I/II disease have excellent outcomes, and the treatment landscape for patients with metastatic disease has been transformed by the approval of several immune checkpoint inhibitors and molecular targeted therapies. Patients with stage III disease, however, continue to have very limited options, as the only agent shown to improve survival in the adjuvant setting is high-dose IFN-?. Neoadjuvant trials of chemotherapy and chemobiotherapy have not been successful, and while neoadjuvant ipilimumab and high-dose interferon have shown promise in small trials, neither agent has been approved. Current trials are testing immune therapy and targeted therapy combinations in the neoadjuvant setting.
| S-EPMC6094612 | biostudies-literature