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Background: Skin cancer is the most common cancer worldwide. Early diagnosis is crucial to improving patient survival and morbidity. Artificial intelligence (AI)-assisted smartphone applications (apps) for skin cancer potentially offer accessible, early risk assessment of suspicious skin lesions. However, the integration of novel technologies into dermatology pathways raises ethical concerns. Although ethical principles for AI governance are well known, how these principles should be applied to real-life AI apps readily available for public use is less well understood., Objectives: To conduct an ethical use-case analysis of commercially available skin cancer apps, to better understand the ethical issues arising from their development and use in a real-world context., Methods: Established methods for the ethical analysis of clinical AI applications were applied to two popular skin cancer apps in the UK: SkinVision and Scanoma. Systematic searches of published literature, regulatory documents and websites were conducted to review the evidence regarding app development, effectiveness and use. Screening for inclusion was undertaken by two researchers independently. Ethical concerns were identified with reference to previously described ethical concerns and principles for AI-assisted healthcare., Results: By conceptualizing ethical principles within the use-context of skin cancer apps, we identified specific ethical issues arising throughout the AI lifecycle of both apps. One company provided extensive detail regarding algorithm development and decision-making; this information was insufficiently reported for the other app. Other concerns identified were related to number, quality and consistency of studies assessing algorithm efficacy. Limited efforts to address potential skin tone biases and the exclusion of individuals with darker skin tones as target users by one app risks perpetuating existing inequalities. Inadequate regulatory oversight was identified., Conclusions: Findings from our ethical use-case analysis of two patient-facing AI-assisted skin cancer apps suggest inadequate incorporation of bioethical norms such as justice, responsibility and transparency into the development and deployment of both apps. Improved regulation should increase accountability. Ensuring ethics by design through integration between technology developers, dermatologists, ethicists and the public is urgently needed to prevent the potential benefits of AI-assisted skin cancer apps being overshadowed by potential ethical harms., Competing Interests: Conflicts of interest: R.N.M. is Chair of the AI Working Party Group at British Association of Dermatologists. H.D. is a member of the University of Warwick Research Governance and Ethics Committee, and has been appointed to the AI in research working group of that committee., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Skin cancers, including melanoma and keratinocyte cancers, are among the most common cancers worldwide, and their incidence is rising in most populations. Earlier detection of skin cancer leads to better outcomes for patients. Artificial intelligence (AI) technologies have been applied to skin cancer diagnosis, but many technologies lack clinical evidence and/or the appropriate regulatory approvals. There are few qualitative studies examining the views of relevant stakeholders or evidence about the implementation and positioning of AI technologies in the skin cancer diagnostic pathway., Objective: This study aimed to understand the views of several stakeholder groups on the use of AI technologies to facilitate the early diagnosis of skin cancer, including patients, members of the public, general practitioners, primary care nurse practitioners, dermatologists, and AI researchers., Methods: This was a qualitative, semistructured interview study with 29 stakeholders. Participants were purposively sampled based on age, sex, and geographical location. We conducted the interviews via Zoom between September 2022 and May 2023. Transcribed recordings were analyzed using thematic framework analysis. The framework for the Nonadoption, Abandonment, and Challenges to Scale-Up, Spread, and Sustainability was used to guide the analysis to help understand the complexity of implementing diagnostic technologies in clinical settings., Results: Major themes were "the position of AI in the skin cancer diagnostic pathway" and "the aim of the AI technology"; cross-cutting themes included trust, usability and acceptability, generalizability, evaluation and regulation, implementation, and long-term use. There was no clear consensus on where AI should be placed along the skin cancer diagnostic pathway, but most participants saw the technology in the hands of either patients or primary care practitioners. Participants were concerned about the quality of the data used to develop and test AI technologies and the impact this could have on their accuracy in clinical use with patients from a range of demographics and the risk of missing skin cancers. Ease of use and not increasing the workload of already strained health care services were important considerations for participants. Health care professionals and AI researchers reported a lack of established methods of evaluating and regulating AI technologies., Conclusions: This study is one of the first to examine the views of a wide range of stakeholders on the use of AI technologies to facilitate early diagnosis of skin cancer. The optimal approach and position in the diagnostic pathway for these technologies have not yet been determined. AI technologies need to be developed and implemented carefully and thoughtfully, with attention paid to the quality and representativeness of the data used for development, to achieve their potential., (©Owain Tudor Jones, Natalia Calanzani, Suzanne E Scott, Rubeta N Matin, Jon Emery, Fiona M Walter. Originally published in JMIR Cancer (https://cancer.jmir.org), 28.01.2025.)

Background: Usability is an important method for evaluating mobile health apps from a user perspective. Yet many publicly available apps lack adequate attention to their design, development and evaluation., Objectives: To assess usability evaluation and reporting for mobile health apps targeting patients with skin diseases., Methods: The protocol was registered with PROSPERO (CRD42022347184). A search strategy combined terms for usability evaluation, user experience, skin disease and mobile health apps (search date 2012-2023). Six databases (Embase, MEDLINE, CINAHL, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, Scopus) were searched, identifying 18 052 results. Nine studies (comprising nine apps) were included in the final analysis., Results: Skin conditions and issues targeted included skin cancer (n = 3); sun protection (n = 3); chronic pruritus (n = 2); cutaneous leishmaniasis (n = 1); spina bifida (n = 1); and a study of acne, psoriasis, rosacea, laser treatments, actinic damage, monitoring benign moles, alopecia and inflammatory rash. All studies assessed app usability and feasibility, with the majority concluding that the apps were deemed useful and easy to use. Qualitative methods, such as usability questionnaires and semistructured interviews, were predominantly employed. Common emerging themes included ease of use and navigation, comprehensibility, security and privacy concerns, data sharing issues, customizability, costs, and the ability to track progress or self-monitor., Conclusions: While smartphone apps for skin disorders show promising usability across diverse diseases, the limited literature compared with the rapid development of apps highlights the need for meticulous user-centred design and rigorous evaluation. The study emphasizes the importance of evaluating and reporting usability findings to optimize the long-term adoption of mobile health apps, particularly those targeting skin diseases., Competing Interests: Conflicts of interest: GK is an Associate Editor for Clinical and Experimental Dermatology., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Without careful dissection of the ways in which biases can be encoded into artificial intelligence (AI) health technologies, there is a risk of perpetuating existing health inequalities at scale. One major source of bias is the data that underpins such technologies. The STANDING Together recommendations aim to encourage transparency regarding limitations of health datasets and proactive evaluation of their effect across population groups. Draft recommendation items were informed by a systematic review and stakeholder survey. The recommendations were developed using a Delphi approach, supplemented by a public consultation and international interview study. Overall, more than 350 representatives from 58 countries provided input into this initiative. 194 Delphi participants from 25 countries voted and provided comments on 32 candidate items across three electronic survey rounds and one in-person consensus meeting. The 29 STANDING Together consensus recommendations are presented here in two parts. Recommendations for Documentation of Health Datasets provide guidance for dataset curators to enable transparency around data composition and limitations. Recommendations for Use of Health Datasets aim to enable identification and mitigation of algorithmic biases that might exacerbate health inequalities. These recommendations are intended to prompt proactive inquiry rather than acting as a checklist. We hope to raise awareness that no dataset is free of limitations, so transparent communication of data limitations should be perceived as valuable, and absence of this information as a limitation. We hope that adoption of the STANDING Together recommendations by stakeholders across the AI health technology lifecycle will enable everyone in society to benefit from technologies which are safe and effective., Competing Interests: Declaration of interests JEA is a named researcher on grants funded by the Engineering and Physical Sciences Research Council (EPSRC), the National Institute for Health and Care Research (NIHR), and the Medical Research Council (MRC); is co-organiser of the Alan Turing Institute Clinical AI Interest Group; and was an NIHR Academic Clinical Fellow from 2017 to 2020. EL is employed as a research fellow at University Hospitals Birmingham NHS Foundation Trust and received support to attend the Symposium for Artificial Intelligence Learning Health Systems conference (May, 2023). JO is an employee of Roche Diagnostics but contributed while an employee of the UK MHRA; declares support from the AIRIS 2024 committee; and has shares in Roche Group. MG is a Canadian Institute for Advanced Research (CIFAR) AI Chair, CIFAR Azrieli Global Scholar, Herman L F von Helmholtz Career Development Professor, and Jameel Clinic Affiliate, and acknowledges support from these programmes. SRP is an employee of Google Research and has stock in Google. JS is an employee of Harrison.ai. NR is an employee of Google Research. HC-L is an employee of Google and has stock or stock options in Google. DS is Acting Deputy Editor of The Lancet Digital Health, Elsevier. BG was scientific advisor for Kheiron Medical Technologies (January, 2018, to September, 2021) and has had part-time employment with stock options as part of the standard compensation package (since October, 2021); has part-time employment at HeartFlow with stock options as part of the standard compensation package (since September, 2018); and is the Royal Academy of Engineering Research Chair in Safe Deployment of Medical Imaging AI. MCa is Director of the Birmingham Health Partners Centre for Regulatory Science and Innovation, Director of the Centre for Patient Reported Outcomes Research, and an NIHR Senior Investigator. MCa, NIHR Birmingham Biomedical Research Centre, Applied Research Collaboration West Midlands, UK SPINE, Research England, the European Regional Development Fund DEMAND Hub at the University of Birmingham, the University Hospitals Birmingham NHS Foundation Trust, and the NIHR Blood and Transplant Research Unit in Precision Transplant and Cellular Therapeutics; funding from Health Data Research UK, Innovate UK (part of UKRI), Macmillan Cancer Support, UCB Pharma, GSK, Anthony Nolan, Gilead Sciences, European Commission, European Federation of Pharmaceutical Industries and Associations, Janssen, Merck, and The Brain Tumor Charity; and personal fees from Aparito, ICON, CIS Oncology, Takeda Pharmaceuticals, Merck, Daiichi Sankyo, Glaukos, GSK, Halfloop, the Patient-Centered Outcomes Research Institute (PCORI), Pfizer, Genentech, and Vertex Pharmaceuticals, outside of the submitted work. MCa also declares royalties via revenue share from the commercial licence of Symptom Burden Questionnaire-Long COVID; payment or honoraria from the University of Maastricht, South-Eastern Norway Regional Health Authority, Cochrane Portugal, Singapore National Medical Research Council; and stock in GSK held by a family member. MCa has a leadership or fiduciary role in PROTEUS consortium (paid via a consultancy fee from Genetech and PCORI). TJP declares NIH awards (OT2OD032701 and R01EB030362), and grants or contracts from Google Cloud and Amazon Web Services. SK was an employee of Hardian Health. L-AF received consulting fees from Therapeutic Goods Administration, Australia, and WHO, and is a member of the AI in Healthcare Committee for Standards Australia and Director of Tethyan Consulting. CS received research funding from UKRI, NIHR, and the Wellcome Trust to support their research programme. BAM reports grants or contracts from MRC, the British Heart Foundation, the United States Agency for International Development, and HDRUK; consulting fees and support for attending meetings from the Bill & Melinda Gates Foundation; and was an employee of the Wellcome Trust at the time of the Delphi study. KH is an employee of Google Research. AK is an employee of Google and receives Google stock reimbursement. MM was an employee of Genomics England, Founder and Director of One HealthTech and Data Science for Health Equity (within One HealthTech), and received support from Nature Journals and Conde Nast. RP is an employee of MHRA. AKM is Deputy Editor of NEJM AI, NEJM Group. PM has a data custodian role as Director of the Clinical Practice Research Datalink and is an employee of MHRA. ZK was employed by Health Research Authority at the time of the consensus process. AAk received grants from the Economic and Social Care Research Council (ADR Wales ES/W012227/1) and HDRUK (HDR-9006). LB received support from the US National Institutes of Health (NIH) All of Us Research Programme to attend STANDING Together meetings. JWG is on the 2022 Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Programme; declares support from the Radiological Society of North America Health Disparities grant (EIHD2204), Lacuna Fund (67), Gordon and Betty Moore Foundation, and NIH (NIBIB) Medical Imaging and Data Resource Center grant under contracts 75N92020C00008 and 75N92020C00021; has received honoraria from the National Bureau of Economic Research for authorship in their 2022 conference collection; has participated on the American Heart Association Deracing Algorithms advisory board; and is a board member of Hl7 and SIIM. LR is Senior Editor of the journal Nature Medicine, Nature Research, Springer Nature. MCh is an NIHR Academic Clinical Fellow. AAr is a panel member for various NIH Research committees, has received honoraria from HDRUK for attending panel meetings, and has an honorary affiliation with Moorfield's Eye Hospital. SP is employed by WHO. ES has had research funded by UK Research and Innovation (UKRI), NIHR, Wellcome Trust, Health Data Research UK (HDRUK), MRC, EPSRC, and Innovate UK, and declares support from the European Respiratory Society, British Thoracic Society, and Gilead. VT is Head of UK Approved Body as at the British Standards Institution. AD reports institutional research grants awarded by the NIHR, MRC, and EPSRC, and is an NIHR Senior Investigator, Director of the UK's incubator for Regulatory Science in AI and Digital Healthcare, deputy director of the Centre for Regulatory Science and Innovation, Birmingham Health Partners, system lead for AI diagnostics to NHS England, and a member of the UK Government's Regulatory Horizons Council. XL reports funding from the NIHR, the UK National Health Service AI Lab, The Health Foundation, Research England, the MHRA, the National Institute for Health and Care Excellence, and Hardian Health, and was previously a Health Studies Scientist at Apple; reports grants from the Medical Research Council, Wellcome Trust, NIHR, and Moorfields Eye Hospital Charity; received payment or honoraria for talks and book chapter reviews from the University of Turku and Elsevier; and received support from Harvard Medical School, SingHealth, and The Ada Lovelace Institute. All other authors declare no competing interests., (© 2024 World Health Organization. Published by Elsevier Ltd. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Competing Interests: RNM is a Specialist Steering committee member (unpaid) on NICE EVA AI for technologies assessing skin lesions (https://www.nice.org.uk/guidance/indevelopment/gid-dg10086) and chairs the British Association of Dermatologists AI working party group. All other authors declare no competing interests. OTJ is in receipt of funding from CRUK through a CRUK Cambridge Centre Clinical Research Fellowship, this fellowship includes funding for travel to attend meetings. The funder had no role in the writing of the manuscript or the decision to submit it for publication.

Competing Interests: Conflicts of interest R.N.M. is chair of the AI Working Party Group at the British Association of Dermatologists and an Associate Editor of the BJD; N.R. is chair of the British Society of Investigative Dermatology. The other authors declare no conflicts of ­interest.

During the COVID-19 pandemic, artificial intelligence (AI) models were created to address health-care resource constraints. Previous research shows that health-care datasets often have limitations, leading to biased AI technologies. This systematic review assessed datasets used for AI development during the pandemic, identifying several deficiencies. Datasets were identified by screening articles from MEDLINE and using Google Dataset Search. 192 datasets were analysed for metadata completeness, composition, data accessibility, and ethical considerations. Findings revealed substantial gaps: only 48% of datasets documented individuals' country of origin, 43% reported age, and under 25% included sex, gender, race, or ethnicity. Information on data labelling, ethical review, or consent was frequently missing. Many datasets reused data with inadequate traceability. Notably, historical paediatric chest x-rays appeared in some datasets without acknowledgment. These deficiencies highlight the need for better data quality and transparent documentation to lessen the risk that biased AI models are developed in future health emergencies., Competing Interests: Declaration of interests JEA is a named researcher on grants from the Medical Research Council (MRC) and the Engineering & Physical Sciences Research Council with payments made to his institution for the delivery of other research projects; and is the co-organiser of Alan Turing Institute Clinical AI interest group (unpaid). ELe has received grants from the NHS AI Lab. MCa has received grants from the National Institute for Health and Care Research (NIHR), Health Data Research UK (HDR-UK), Innovate UK, Macmillan Cancer Support, GlaxoSmithKline, UCB Pharma, Research England as part of United Kingdom Research and Innovation (UKRI), European Commission, European Federation of Pharmaceutical Industries and Associations, Brain Tumour Charity, Gilead, Janssen, UKRI, and Merck for the delivery of other research projects; has received payment for delivering lectures from the University of Maastricht; has received a speaker fee from Cochrane Portugal; payments for reviewing from the South-Eastern Norway Regional Health Authority and Singapore National Medical Research Council; consulting fees from Aparito, CIS Oncology, Takeda, Merck, Daiichi Sankyo, Glaukos, GlaxoSmithKline, Patient-Centered Outcomes Research Institute, Genentech, Vertex, ICON, Halfloop, and Pfizer; and is associated with Proteus Consortium. MG has received grants from the Canadian Institute for Advanced Research, Helmsley Trust, Wellcome Trust, Moore Foundation, Volkswagen Foundation, I-Clinic, IBM-AI, Janssen research and development, Takeda, Quanta Computing, and Microsoft Research; and has acted as an advisor for the Symposium on Artificial Intelligence for Learning Health Systems and Conference on Health, Inference, and Learning. MDM has received grants from the Canadian Institutes of Health Research, AMS Healthcare, and the SickKids Foundation. JO works or has previously worked with AdvaMed AI Framework Group member (unpaid), AdvaMed Software Working Group member (unpaid), MedTech Europe AI Working Group member (unpaid), and MedTech Europe Digital Health Committee member (unpaid). CS has received grants from NIHR, UKRI, MRC, and NIHR Cambridge Biomedical Research Centre. RNM has received grants from MRC, British Heart Foundation, United States Agency for International Development, and HDR-UK. AKD has received grants from MRC and NIHR. XL has received grants from NIHR, Wellcome Trust, Research England, Moorfields Eye Hospital Charity; has received consulting fees from Hardian Health; has received payment or honoraria from the University of Turku; and is employed by Apple as a health scientist. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

We report the cases of 10 patients with oral squamous cell carcinoma (SCC) post-haematopoietic stem cell transplant (HSCT). Median latency from HSCT to oral SCC diagnosis was 10 years (range: 4-17 years), with 90% (9/10) reporting a history of chronic graft-versus-host disease (cGVHD) and 40% (4/10) exhibiting active severe manifestations of oral GvHD. Clinical findings at diagnosis included induration, ulceration, tenderness, bleeding, hyperkeratosis, speckling and lymphadenopathy. The tongue and buccal mucosa were the most common sites affected. The disease stage at presentation ranged from T1N0M0 to T4N2M0. Management included surgical resection in 90% (9/10) of patients with or without chemotherapy and/or radiotherapy. The median follow-up for the cohort was 1 year, with a 50% (5/10) mortality rate. SCC-specific mortality was 30% (3/10). Our data highlight the importance of regular, active oral and cutaneous surveillance of patients post-HSCT in specialized dermatology clinics, irrespective of GvHD severity and length of iatrogenic immunosuppression., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Online symptom checkers are increasingly popular health technologies that enable patients to input their symptoms to produce diagnoses and triage advice. However, there is concern regarding the performance and safety of symptom checkers in diagnosing and triaging patients with life-threatening conditions. This retrospective cross-sectional study aimed to evaluate and compare commercially available symptom checkers for performance in diagnosing and triaging myocardial infarctions (MI). Symptoms and biodata of MI patients were inputted into 8 symptom checkers identified through a systematic search. Anonymised clinical data of 100 consecutive MI patients were collected from a tertiary coronary intervention centre between 1st January 2020 to 31st December 2020. Outcomes included (1) diagnostic sensitivity as defined by symptom checkers outputting MI as the primary diagnosis (D1), or one of the top three (D3), or top five diagnoses (D5); and (2) triage sensitivity as defined by symptom checkers outputting urgent treatment recommendations. Overall D1 sensitivity was 48±31% and varied between symptom checkers (range: 6-85%). Overall D3 and D5 sensitivity were 73±20% (34-92%) and 79±14% (63-94%), respectively. Overall triage sensitivity was 83±13% (55-91%). 24±16% of atypical cases had a correct D1 though for female atypical cases D1 sensitivity was only 10%. Atypical MI D3 and D5 sensitivity were 44±21% and 48±24% respectively and were significantly lower than typical MI cases (p<0.01). Atypical MI triage sensitivity was significantly lower than typical cases (53±20% versus 84±15%, p<0.01). Female atypical cases had significantly lower diagnostic and triage sensitivity than typical female MI cases (p<0.01).Given the severity of the pathology, the diagnostic performance of symptom checkers for correctly diagnosing an MI is concerningly low. Moreover, there is considerable inter-symptom checker performance variation. Patients presenting with atypical symptoms were under-diagnosed and under-triaged, especially if female. This study highlights the need for improved clinical performance, equity and transparency associated with these technologies., Competing Interests: VS joined Google Health UK as an employee only after this work was completed. All other authors declare no financial or non-financial competing interests., (Copyright: © 2024 Wallace et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Artificial intelligence (AI) solutions for skin cancer diagnosis continue to gain momentum, edging closer towards broad clinical use. These AI models, particularly deep-learning architectures, require large digital image datasets for development. This review provides an overview of the datasets used to develop AI algorithms and highlights the importance of dataset transparency for the evaluation of algorithm generalizability across varying populations and settings. Current challenges for curation of clinically valuable datasets are detailed, which include dataset shifts arising from demographic variations and differences in data collection methodologies, along with inconsistencies in labelling. These shifts can lead to differential algorithm performance, compromise of clinical utility, and the propagation of discriminatory biases when developed algorithms are implemented in mismatched populations. Limited representation of rare skin cancers and minoritized groups in existing datasets are highlighted, which can further skew algorithm performance. Strategies to address these challenges are presented, which include improving transparency, representation and interoperability. Federated learning and generative methods, which may improve dataset size and diversity without compromising privacy, are also examined. Lastly, we discuss model-level techniques that may address biases entrained through the use of datasets derived from routine clinical care. As the role of AI in skin cancer diagnosis becomes more prominent, ensuring the robustness of underlying datasets is increasingly important., Competing Interests: Conflicts of interest R.N.M. is the Chair of AI Working Party Group at the British Association of Dermatologists. D.W., A.S. and E.T. have no conflicts of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: BRAF+MEK inhibitors extend life expectancy of patients with BRAF V600 mutant advanced melanoma. Acquired resistance limits duration of benefit, but preclinical and case studies suggest intermittent dosing could overcome this limitation. INTERIM was a phase 2 trial evaluating an intermittent dosing regimen., Methods: Patients with BRAF V600 mutant advanced melanoma due to start dabrafenib+trametinib were randomised to receive either continuous (CONT), or intermittent (INT; dabrafenib d1-21, trametinib d1-14 every 28 days) dosing. A composite primary endpoint included progression-free survival (PFS) and quality of life (QoL). Secondary endpoints included response rate (ORR), overall survival (OS) and adverse events (AEs). Mutant BRAF V600E ctDNA was measured by droplet digital PCR (ddPCR), using mutant allele frequency of > 1 % as the detection threshold., Results: 79 patients (39 INT, 40 CONT) were recruited; median age 67 years, 65 % AJCC (7th ed) stage IV M1c, 29 % had brain metastases. With 19 months median follow-up, INT was inferior in all efficacy measures: median PFS 8.5 vs 10.7mo (HR 1.39, 95 %CI 0.79-2.45, p = 0.255); median OS 18.1mo vs not reached (HR 1.69, 95 %CI 0.87-3.28, p = 0.121), ORR 57 % vs 77 %. INT patients experienced fewer treatment-related AEs (76 % vs 88 %), but more grade > 3 AEs (53 % vs 42 %). QoL favoured CONT. Detection of BRAF V600E ctDNA prior to treatment correlated with worse OS (HR 2.55, 95 %CI 1.25-5.21, p = 0.01) in both arms. A change to undetected during treatment did not significantly predict better OS., Conclusion: INTERIM findings are consistent with other recent clinical trials reporting that intermittent dosing does not improve efficacy of BRAF+MEK inhibitors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Primary cutaneous leiomyosarcoma (LMS) is a rare soft tissue tumour type with two subtypes, dermal and subcutaneous. As deeper tumours confer a worse prognosis, they require a more aggressive approach. Conversely, a more conservative surgical approach for dermal LMS has been suggested. Few studies have comprehensively reported both clinical surgical and histological excision margins. Therefore, we sought to provide margin recommendations based on our experience and review of the existing literature. We undertook a retrospective case-note review (1998-2019) of cutaneous LMS management to establish histological/surgical margins using pathology/electronic patient records. The diagnosis was made and classified by an experienced dermatopathologist according to the World Health Organization classification. In the dermal LMS cohort (n = 35), mean peripheral and deep histological margins were 5.4 mm (range 0.5-20) and 5.6 mm (range 0.1-14.5), respectively. The incomplete excision rate was 31% (11 of 35). There were no recurrences. In the subcutaneous LMS cohort (n = 10), mean peripheral and deep histological margins were 5.7 mm (range 0.2-14) and 1.1 mm (range 0.2-1.7), respectively. The incomplete excision rate was 40% (4 of 10). The recurrence rate was 20% (2 of 10) despite achieving histological clearance after 1 year. One lung metastasis occurred 1 year following an adequately excised primary scalp LMS. Thus, for dermal LMS we propose a clinical margin of 5-10 mm (depending on lesion size) at the initial excision or at scar re-excision following involved/close histological peripheral and/or deep margins (i.e. < 1 mm). For subcutaneous LMS, we suggest a clinical margin of 15-20 mm (depending on lesion size) to achieve a peripheral histological clearance of 10 mm and negative deep margin (i.e. > 1 mm), down to the periosteum/fascia/muscle according to anatomical site. If this is not achieved, a re-excision would be recommended. However, prospective studies are needed for optimal guidance., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Abstract: Immunodeficiency-associated lymphoproliferative disorders (IA-LPDs) constitute a diverse range of conditions including posttransplant lymphoproliferative disorders, other iatrogenic IA-LPDs, and lymphoproliferative disorders associated with an underlying primary immune disorder or HIV infection. IA-LPDs are clinically and pathologically heterogeneous, and there is a lack of standardization of diagnostic terminology. They can represent a potential serious diagnostic pitfall because the histological features of clinically indolent proliferations may mimic those of high-grade lymphoma. However, correct identification of these entities is essential given that complete remission may occur upon reversal of the underlying cause of immunosuppression without the need for systemic therapy. IA-LPDs presenting in the skin are rare but well documented. One form of iatrogenic IA-LPD, methotrexate-associated lymphoproliferative disorder (MTX-LPD), can present with cutaneous nodules, plaques, or ulcers. Predominantly, MTX-LPD develops in the context of long-term treatment of autoimmune conditions, such as rheumatoid arthritis, dermatomyositis, and Sjögren syndrome, and may be associated with underlying Epstein-Barr virus (EBV) infection. We present 4 cases of cutaneous EBV-positive B-cell MTX-LPD and describe their clinical and morphological findings. Comparison of our histological findings to the diagnostic criteria for EBV-positive mucocutaneous ulcer (EBVMCU) revealed significant overlap, highlighting the intersection between MTX-LPD and EBVMCU. Withdrawal of methotrexate resulted in healing of all lesions at a mean time of 2 months. In summary, close clinicopathological correlation is vital to identify MTX-LPD presenting as cutaneous EBVMCU given that the initial treatment strategy is that of withdrawal of methotrexate without the need for immediate systemic therapy., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Conflicts of interest R.N.M. is Chair of the British Association of Dermatologists Artificial Intelligence Working Party Group.

Background: Providing detailed skin cancer statistics, including incidence and survival, by tumour type and patient characteristics is important for up-to-date epidemiological information., Objectives: To create a new clinically relevant consensus-based classification for registered skin tumours using tumour type and patient characteristics and to describe its application to all registered tumours in England between 2013 and 2019., Methods: Tumours with skin topographical codes (ICD-10) and morphology and behaviour (ICD-O3) were grouped together in an iterative process creating a hierarchical tree structure. The primary-level grouping partitioned skin tumours into skin cancer, melanoma in situ, extramammary Paget disease (EMPD) and tumours of uncertain malignant potential. Second-level groups split skin cancer into keratinocyte cancer (KC), melanoma and rare cancers. The third-level group split KC into basal cell carcinoma (BCC) and squamous cell carcinoma (cSCC). Further groups were split into genital or non-genital, first or subsequent tumour, age, gender, stage, or National Health Service (NHS) region. Incidence counts, Kaplan-Meier and net survival estimates and referral routes [two-week wait (TWW), general practitioner (GP), outpatient] categorisations were calculated for each grouping across all years., Results: A total of 1 445 377 skin cancers and 49 123 precancerous lesions and undefined entities were registered in England between 2013 and 2019. Skin tumours and skin cancer incidence rates are increasing for most tumour types. The most common type of skin cancer was BCC with an incidence rate of 282.36 per 100 000 person-years (PYs) [n = 158 934, 95% confidence interval (CI) 280.98-283.76] in 2019, followed by cSCC with an incidence rate of 85.24 per 100 000 PYs (n = 47 977, 95% CI 84.48-86.00) and melanoma with 27.24 (n = 15 332, 95% CI 26.81-27.67) per 100 000 PYs. Each year approximately 1800 rare skin cancers, 1500 genital cSCCs and 100 cases of EMPD are registered. Of 15 000 melanoma cases, 120 cases of melanoma occur in individuals aged < 25 years annually. One-year and five-year overall net survival varies by tumour type. cSCC 5-year net survival (89.8%, 95% CI 88.8-90.9) was comparable to the net survival of all melanomas (89.6%, 95% CI 88.7-90.6). BCC had excellent survival (overall net survival > 100%). Patients with late-stage melanoma, Merkel cell carcinoma and genital cSCC have a 5-year net survival < 60%. Older patients received fewer TWW referrals than their younger counterparts with the same tumour type at the same location. Patients with acral lentiginous melanoma had fewer TWW referrals and more standard GP referrals than patients with common melanomas., Conclusions: 'Get Data Out' Skin provides detailed and up-to-date statistics on all registrable skin tumours in England, including for the first time precancerous lesions and rare subtypes of common cancers. These data can be used by clinicians, researchers and commissioners to better understand skin cancer and improve resource allocation., Competing Interests: Conflicts of interest B.v.B. is an employee of the British Association of Dermatologists. N.J.L. is a trustee of the British Association of Dermatologists. N.R. is a Deputy Editor at the BJD., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Keratinocyte cancers (KCs) are the most common type of cancer in the White population worldwide, with associated high healthcare costs. Understanding the epidemiological trends for KCs, namely basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (SCCs), is required to assess burden of disease, project future trends and identify strategies for addressing this pressing global health issue., Objectives: To report trends in BCC and SCC incidence, and SCC mortality and disability-adjusted life-years (DALYs)., Methods: An observational study of the Global Burden of Disease (GBD) database between 1990 and 2017 was performed. European Union countries and other selected high-income countries, including the UK and the USA, classified as having high-quality mortality data, were included. Annual age-standardized incidence rates (ASIRs), age-standardized death rates (ASDRs) and DALYs for each country were obtained from the GBD database. Trends were described using joinpoint regression analysis., Results: Overall, 33 countries were included. For both BCC and SCC in 2015-2017, the highest ASIRs were observed in the USA and Australia. Males had higher ASIRs than females at the end of the observation period in all countries for SCC, and in all countries but two for BCC. In contrast, the highest ASDRs for SCC were observed in Australia and Latvia for males, and in Romania and Croatia for females. The highest DALYs for SCC for both sexes were seen in Australia and Romania. Over the observation period, there were more countries demonstrating decreasing trends in mortality than in incidence, and disparities were observed between which countries had comparatively high mortality rates and which had high incidence rates. Overall reductions in SCC DALYs were observed in 24 of 33 countries for males, and 25 countries for females., Conclusions: Over the past 27 years, although trends in SCC incidence have risen in most countries, there is evidence that mortality rates have been decreasing. Burden of disease as assessed using DALYs has decreased in the majority of countries. Future work will explore potential explanatory factors for the observed disparity in trends in SCC incidence and mortality., Competing Interests: Conflicts of interest: The authors declare they have no conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Checkpoint inhibitor (CPI) therapy has significantly improved overall survival in several cancers including metastatic melanoma (MM) and in the adjuvant setting. Cutaneous immune-related adverse events (irAEs) secondary to CPIs are commonly observed; however, autoimmune blistering disorders such as bullous pemphigoid (BP) are rare., Objectives: To review the prevalence, incidence risk, clinicopathological features and management of toxicity in bullous cutaneous irAEs associated with CPI therapy., Methods: A multicentre, retrospective, observational study of CPI-associated bullous irAEs in adults with all cancers across four UK specialist centres between 2006 and 2019., Results: In total, 7391 patients were identified. CPI-associated bullous irAEs including BP (n = 16) occurred in 0·3% (n = 22). The median age of onset was 76 years, and there was a male predominance. Most patients had cutaneous melanoma (73%, n = 16), of which 81% (13 of 16) were BRAF wildtype. Grade 1, 2, 3 and 4 skin toxicity occurred in 9%, 45%, 41% and 5%, respectively. The mucosae were involved in 27%, and 25% of confirmed cases of BP did not present with bullae. The median time to onset of bullous irAEs was 12 months, with a median total symptom duration of 6 months. Single PD-1/PD-L1 agents had a longer time to onset of symptoms than combination therapy (median 12 vs. 7 months, respectively). Overall, 91%, 64% and 9% of patients required one, two or three lines of treatment, respectively. Two cases occurred after completion of CPIs (1 and 3 months). Of the 20 cases that presented while on CPIs this was permanently discontinued in 55% (11 of 20) and temporarily held in 20% (four of 20). In the four held cases of CPI, bullous eruption reflared in 50%., Conclusions: CPI-associated bullous skin toxicity is a rare cutaneous irAE occurring in approximately 0·3% of cases over 13 years of treated patients in this series. Not all cases are diagnostic of BP, but management remains the same. There is a prolonged latency of onset compared with other cutaneous irAEs, with a median time of 12 months, and they can occur after cessation of therapy. Discontinuation of CPIs may be required. Recognizing bullous irAEs promptly and referral to dermatology are essential to optimize management and improve patient outcomes and tumour responses. What is already known about this topic? Checkpoint inhibitor (CPI)-associated bullous pemphigoid is a rare dermatological immune-related adverse event (irAE) that has been reported in small case series and reports. What does this study add? This is the largest multicentre, observational study conducted in the UK over the longest period of 13 years, which demonstrates an overall incidence of bullous cutaneous irAEs secondary to CPIs of 0·3%. Clinical presentation is variable, with one-quarter of patients with bullous pemphigoid presenting without bullae, and mucosal involvement was noted in 27%. Prolonged pruritus is frequently a prodromal symptom. The median time to diagnosis is 12 months and irAEs rarely present after cessation of treatment. Time to onset of symptoms is longer with a single CPI, but with a shorter duration of symptoms compared with combination CPI therapy. Most patients had cutaneous melanoma, of which 81% were BRAF wildtype., (© 2022 British Association of Dermatologists.)

Background: Individuals with a prior diagnosis of chronic lymphocytic leukaemia (CLL) have a higher risk of developing melanoma and exhibit poorer outcomes than patients without CLL. However, there are limited data reporting the clinicopathological features of melanoma diagnosed in patients with CLL., Aims: To review clinicopathological characteristics of patients with coexisting diagnoses of melanoma and CLL., Methods: A retrospective review was undertaken for patients with coexisting diagnoses of melanoma and CLL between 2005 and 2015 in 11 centres in the UK and Ireland., Results: Overall, 46 cutaneous melanomas identified in 45 patients were included. In 28 (62.2%) patients, melanoma was diagnosed after an existing diagnosis of CLL. In this group, mean Breslow thickness was 2.7 mm (range 0.2-25 mm). Ten patients (35.7%) developed locoregional recurrence and 8 (28.6%) developed distant metastases. Melanoma-specific mortality was 5 of 28 (17.9%) and all-cause mortality was 13 of 28 (46.4%). In 17 patients, melanoma was diagnosed before CLL. In this group, mean BT was 2.9 mm (range 0.4-14 mm); five patients (29.4%) developed locoregional recurrence and three (17.6%) developed distant metastases. Melanoma-specific mortality was 1 of 17 (5.8%) and all-cause mortality was 5 of 17 (29.4%) in this group., Conclusions: To our knowledge, this is the first and largest cohort study to report clinicopathological data of coexisting melanoma and CLL in the UK and Ireland. Although the thickness of primary melanoma was not different before or after a CLL diagnosis, melanoma recurrence and melanoma-specific mortality appear to be more common in patients with a prior diagnosis of CLL., (© 2022 British Association of Dermatologists.)

Background: There is variation in the outcomes reported in clinical studies of basal cell carcinoma. This can prevent effective meta-analyses from answering important clinical questions., Objective: To identify a recommended minimum set of core outcomes for basal cell carcinoma clinical trials., Methods: Patient and professional Delphi process to cull a long list, culminating in a consensus meeting. To be provisionally accepted, outcomes needed to be deemed important (score, 7-9, with 9 being the maximum) by 70% of each stakeholder group., Results: Two hundred thirty-five candidate outcomes identified via a systematic literature review and survey of key stakeholders were reduced to 74 that were rated by 100 health care professionals and patients in 2 Delphi rounds. Twenty-seven outcomes were provisionally accepted. The final core set of 5 agreed-upon outcomes after the consensus meeting included complete response; persistent or serious adverse events; recurrence-free survival; quality of life; and patient satisfaction, including cosmetic outcome., Limitations: English-speaking patients and professionals rated outcomes extracted from English language studies., Conclusion: A core outcome set for basal cell carcinoma has been developed. The use of relevant measures may improve the utility of clinical research and the quality of therapeutic guidance available to clinicians., Competing Interests: Conflicts of interest Dr Kirkham is involved with the COMET and CS-COUSIN Methods groups. Drs Schmitt and Alam are involved with the CS-COUSIN Methods group. Dr Armstrong has served as a research investigator and/or scientific advisor to AbbVie, Almirall, Arcutis, ASLAN, Beiersdorf, BI, BMS, EPI, Incyte, Leo, UCB, Janssen, Lilly, Nimbus, Novartis, Ortho Dermatologics, Sun, Dermavant, Dermira, Sanofi, Regeneron, Pfizer, and Modmed. The remaining authors have no relevant conflicts to disclose., (Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The risk of cutaneous squamous cell carcinoma (cSCC) is significantly increased in organ transplant recipients (OTRs). Clearance of actinic keratoses (AKs) is generally regarded as a surrogate biomarker for cSCC prevention. OTR-cSCC chemoprevention with topical AK treatments has not been investigated in randomized controlled trials (RCTs), although there is evidence that 5% 5-fluorouracil (5-FU) may be chemoprotective in immunocompetent patients., Objectives: To assess the feasibility, activity and evaluation outcomes relevant to the design of a future phase III RCT of topical cSCC chemoprevention in OTRs., Methods: OTRs with 10 or more AKs in predefined areas were randomized 1 : 1 : 1 to topical 5-FU, 5% imiquimod (IMIQ) or sunscreen (sun-protective factor 30+) in a phase II, open-label RCT over 15 months. Feasibility outcomes included proportions of eligible OTRs randomized, completing treatment and willing to be re-treated. AK activity [AK clearance, new AK development, patient-centred outcomes (toxicity, health-related quality of life, HRQoL)] and evaluation methodology (clinical vs. photographic) were assessed., Results: Forty OTRs with 903 AKs were randomized. All feasibility outcomes were met (56% of eligible OTRs were randomized; 89% completed treatment; 81% were willing to be re-treated). AK activity analyses found 5-FU and IMIQ were superior to sunscreen for AK clearance and prevention of new AKs. 5-FU was more effective than IMIQ in AK clearance and prevention in exploratory analyses. Although toxicity was greater with 5-FU, HRQoL outcomes were similar., Conclusions: Trials of topical AK treatments in OTRs for cSCC chemoprevention are feasible and AK activity results support further investigation of 5-FU-based treatments in future phase III trials. What is already known about this topic? Cutaneous squamous cell carcinoma (cSCC) is significantly more common in immunocompromised individuals including organ transplant recipients (OTRs) compared with immunocompetent populations. cSCC chemoprevention activity of sunscreen and 5-fluorouracil-based (5-FU) actinic keratosis (AK) treatments has been demonstrated in randomized controlled trials (RCTs) in immunocompetent populations but not in OTRs. AKs are cSCC precursors and their clearance and prevention are generally regarded as surrogate endpoint biomarkers for potential cSCC chemoprevention activity. What does this study add? SPOT (SCC Prevention in OTRs using Topical treatments) has confirmed that RCTs of OTR-cSCC chemoprevention with topical AK treatments are feasible. It also suggests that topical 5-FU may be superior to 5% imiquimod and sunscreen in AK clearance and prevention. Together with recent evidence from several RCTs in the general population, these data provide a compelling rationale for further studies of intervention with 5-FU-based topical chemoprevention approaches in OTR-cSCC prevention., (© 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

A woman who had undergone haematopoietic stem cell transplantation presented with cutaneous features suggestive of graft-versus-host disease. Histopathological examination revealed a diffuse dermal infiltration of atypical monomorphic cells with a high proliferative index. Immunohistochemistry revealed positivity for monocytic markers, but negativity for T-cell markers., (© 2022 British Association of Dermatologists.)

Objectives: The FACE-Q Skin Cancer module is a patient-reported outcome measure (PROM) for facial skin cancer. It has been anglicised for the UK population and undergone psychometric testing using classical test theory. In this study, further evaluation of construct validity using Rasch measurement theory and hypothesis testing was performed., Methods: Patients were prospectively recruited to the Patient-Reported Outcome Measures In Skin Cancer Reconstruction (PROMISCR) study and asked to complete the anglicised FACE-Q Skin Cancer module. The scalability and unidimensionality of the data were assessed with a Mokken analysis prior to Rasch analysis. Response thresholds, targeting, fit statistics, local dependency, and internal consistency were examined for all items and subscales. Four a priori hypotheses were tested to evaluate the convergent and divergent validity. We additionally hypothesised that the median 'cancer worry' score would be lower in post-operative than pre-operative patients., Results: 239 patients self-completed the questionnaire between August 2017 and May 2019. Of the ten subscales assessed, five showed relative fit to the Rasch model. Unidimensionality was present for all five subscales, with most demonstrating ordered item thresholds and appropriate fit statistics. Two items in the 'cancer worry' subscale had either disordered or very close response thresholds. Subscales of the FACE-Q Skin Cancer module demonstrated convergent and divergent validity with relevant Skin Cancer Index comparators (p < 0.001). Median 'cancer worry' was lower in post-operative patients (44 vs 39, p < 0.001)., Conclusion: The anglicised FACE-Q Skin Cancer module shows psychometric validity through hypothesis testing, and both classical and modern test theory., (Copyright © 2021 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Skin cancer is the most common malignancy in the UK, and up to a third of lesions are ulcerated at the time of excision. Ulceration has been shown to increase the risk of developing surgical site infection following excision, with some studies finding infection rates of 33%. However, no specific guidelines for the use of antibiotic prophylaxis in such cases exist. We surveyed 129 clinicians (covering Dermatology, Plastic Surgery, Ear, Nose and Throat Surgery, and Oral and Maxillofacial Surgery) who all excise skin lesions on a regular basis. There was significant variability in their practice with regard to antibiotic prophylaxis, with 9% always prescribing them and 19% never prescribing them. Variation exists both among and between specialities. This variation increases the risk of antimicrobial resistance and shows a paucity of good clinical evidence, indicating that a well-designed clinical trial is needed to guide future practice., (© 2021 British Association of Dermatologists.)

Publicly available skin image datasets are increasingly used to develop machine learning algorithms for skin cancer diagnosis. However, the total number of datasets and their respective content is currently unclear. This systematic review aimed to identify and evaluate all publicly available skin image datasets used for skin cancer diagnosis by exploring their characteristics, data access requirements, and associated image metadata. A combined MEDLINE, Google, and Google Dataset search identified 21 open access datasets containing 106 950 skin lesion images, 17 open access atlases, eight regulated access datasets, and three regulated access atlases. Images and accompanying data from open access datasets were evaluated by two independent reviewers. Among the 14 datasets that reported country of origin, most (11 [79%]) originated from Europe, North America, and Oceania exclusively. Most datasets (19 [91%]) contained dermoscopic images or macroscopic photographs only. Clinical information was available regarding age for 81 662 images (76·4%), sex for 82 848 (77·5%), and body site for 79 561 (74·4%). Subject ethnicity data were available for 1415 images (1·3%), and Fitzpatrick skin type data for 2236 (2·1%). There was limited and variable reporting of characteristics and metadata among datasets, with substantial under-representation of darker skin types. This is the first systematic review to characterise publicly available skin image datasets, highlighting limited applicability to real-life clinical settings and restricted population representation, precluding generalisability. Quality standards for characteristics and metadata reporting for skin image datasets are needed., Competing Interests: Declaration of interests LS, JC, LZ, and CdBP were employed by Databiology (Oxford, UK) when this work was completed. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Early detection of melanoma is essential to reduce mortality. Total body photography (TBP) can facilitate the detection of melanoma in high-risk individuals. However, the accuracy of TBP in diagnosing melanoma remains unclear., Objectives: To determine the diagnostic accuracy of TBP for the detection of melanoma in adults., Methods: MEDLINE, Embase, Cochrane and Centre for Reviews databases were searched from inception to 26 May 2020. Studies that included TBP for diagnosing melanoma with at least one follow-up appointment were eligible for inclusion in the systematic review if they provided data to calculate at least one diagnostic accuracy measure. Two authors independently screened articles, extracted data and assessed quality. Disagreements were resolved by a third reviewer., Results: In total, 10 studies were included, comprising 41 703 patients who underwent TBP and 6203 biopsies. Melanoma in situ (MIS) was diagnosed in 315 (5·1%) lesions and invasive melanoma was diagnosed in 187 (3·0%) lesions biopsied. Summary estimates for TBP in diagnosing melanoma were calculated as follows: mean percentage of biopsies positive for MIS or melanoma was 15% [95% confidence interval (CI) 10-21], number needed to biopsy (NNB) was 8·6 (range 2·3-19·6), naevus : melanoma ratio was 7·6 (range 1·3-18·6), and MIS : melanoma ratio was 1·7 (1·0-3·5). Regression analysis showed a negative correlation between NNB and MIS : melanoma ratio., Conclusions: Available data regarding the diagnostic accuracy of TBP are heterogeneous, owing to variability in the risk profile of cohorts and TBP protocols. Best current estimates suggest that TBP for diagnosing melanoma has an acceptable NNB in high-risk patients. However, prospective diagnostic test accuracy studies are needed to gauge the diagnostic accuracy of TBP., (© 2020 British Association of Dermatologists.)

Background: The lack of uniformity in the outcomes reported in clinical studies of the treatment of cutaneous squamous cell carcinoma (cSCC) complicates efforts to compare treatment effectiveness across trials., Objectives: To develop a core outcome set (COS), a minimum set of agreed-upon outcomes to be measured in all clinical trials of a given disease or outcome, for the treatment of cSCC., Methods: One hundred and nine outcomes were identified via a systematic literature review and interviews with 28 stakeholders. After consolidation of this long list, 55 candidate outcomes were rated by 19 physician and 10 patient stakeholders, in two rounds of Delphi exercises. Outcomes scored 'critically important' (score of 7, 8 or 9) by ≥ 70% of patients and ≥ 70% of physicians were provisionally included. At the consensus meeting, after discussion and voting of 44 international experts and patients, the provisional list was reduced to a final core set, for which consensus was achieved among all meeting participants., Results: A core set of seven outcomes was finalized at the consensus meeting: (i) serious or persistent adverse events, (ii) patient-reported quality of life, (iii) complete response, (iv) partial response, (v) recurrence-free survival, (vi) progression-free survival and (vii) disease-specific survival., Conclusions: In order to increase the comparability of results across trials and to reduce selective reporting bias, cSCC researchers should consider reporting these core outcomes. Further work needs to be performed to identify the measures that should be reported for each of these outcomes., (© 2020 British Association of Dermatologists.)

Smartphone applications ("apps") with artificial intelligence (AI) algorithms are increasingly used in healthcare. Widespread adoption of these apps must be supported by a robust evidence-base and app manufacturers' claims appropriately regulated. Current CE marking assessment processes inadequately protect the public against the risks created by using smartphone diagnostic apps.

Background: Immune checkpoint blockers (ICBs) activate CD8 + T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear., Methods: Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab-sICB) or combination (nivolumab and ipilimumab-cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8 + T cells was sequenced and differential gene expression according to irAE development assessed., Results: 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9-33.4) versus not-reached (P = 2.8 × 10 -6 ). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8 + T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment., Conclusions: Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.

Background: Dermatofibrosarcoma protuberans (DFSP) is a rare skin cancer. Standard treatment in the UK is either wide local excision (WLE) or Mohs micrographic surgery (MMS). It is unclear which approach has the lower recurrence rate., Objectives: We undertook a retrospective comparative review of surgical management of DFSP in the UK National Health Service in order to define (i) current surgical practice for primary and recurrent DFSP, (ii) local recurrence rates for primary DFSP and (iii) survival outcomes for DFSP., Methods: A retrospective clinical case-note review of patients with histologically confirmed DFSP (January 2004 to December 2013) who have undergone surgical treatment., Results: The surgical management of 483 primary and 64 recurrent DFSP in 11 plastic surgery and 15 dermatology departments was analysed. Almost 75% of primary DFSP (n = 362) were treated with WLE and 20% (n = 97) with MMS. For recurrent DFSP, 69% (n = 44) and 23% (n = 15) of patients underwent WLE and MMS, respectively. Recurrent primary DFSP occurred in six patients after WLE and none after MMS. The median follow-up time was 25·5 months (interquartile range 6·8-45·1) for new and 19·8 (IQR 4·5-44·5) for recurrent DFSP [Correction added on 1 Feb 2021, after first online publication: 4.8 years (interquartile range 3.5-5.8) was incorrect], with eight reported deaths during the follow-up analysis period (one confirmed to be DFSP related)., Conclusions: WLE was the most common surgical modality used to treat DFSP across the UK. The local recurrence rate was very low, occurring only after WLE. Although a prospective randomized controlled trial may provide more definitive outcomes, in the absence of a clearly superior surgical modality, treatment decisions should be based on patient preference, clinical expertise and cost., (© 2020 British Association of Dermatologists.)

A 36-year-old renal transplant recipient presented 15 months post-transplantation with a cutaneous spindle cell neoplasm with features of smooth muscle differentiation treated with local excision. 1.4 years later, a magnetic resonance imaging liver scan with gadolinium demonstrated multiple bilobar enhancing hepatic lesions, in keeping with metastases. A core biopsy revealed morphological appearances similar to the previous cutaneous spindle cell neoplasm. Epstein-Barr virus early RNA (EBER) in situ hybridization demonstrated strong diffuse staining of both cutaneous and liver tumor cells for EBER indicative of Epstein-Barr virus (EBV) infection. This is a rare presentation of multifocal EBV-associated smooth muscle tumors first presenting in the skin in an adult renal transplant recipient, which, despite being multifocal and involving the liver, may confer a better prognosis than predicted., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Graft-versus-host disease (GVHD) is a significant cause of morbidity and mortality following allogeneic stem cell transplantation. These patients face unique challenges due to the complexity of GVHD which can affect multiple organ systems, and the toxicity of treatments. Despite the known impact on quality of life (QOL), qualitative data within the bone marrow transplantation (BMT) literature is rare, and there has been no qualitative work exploring patient experience of specialist healthcare provision for GVHD in the United Kingdom., Methods: We conducted a primary explorative qualitative study of the experience of QOL issues and multidisciplinary care in patients with chronic GVHD following allogeneic stem cell transplantation. Eight patients were identified using convenience sampling from specialist BMT outpatient clinics. Following consent, patients were interviewed individually via telephone. Transcripts of interviews were analyzed using an inductive thematic approach., Results: Mean participant age was 61-years-old (range 45-68), with a mean time post-transplant of 3 years at time of interview (range 3 months-15 years). Five key QOL themes were identified: (1) 'Restricted as to what I can do'; (2) Troubling symptoms-'you can sort of get GVHD anywhere'; (3) Confusion/uncertainty over GVHD symptoms-'Is this the GVHD?'; (4) Unpredictable course and uncertainty about the future; and (5) Adapting to the sick role. In addition, four themes related to experience of service provision were identified: (1) personal care and close relationship with BMT nurses; (2) efficiency versus long waits-'On the case straight away'; (3) information provision-'went into it with a bit of a rosy view'; and (4) the role of support groups., Conclusions: These qualitative data reflect the heterogeneity of experiences of the GVHD patient population, reflecting the need for a flexible and nuanced approach to patient care with emphasis on comprehensive information provision. We have identified the key role that BMT specialist nurses within the multidisciplinary team play in supporting patients. We advocate future research should focus on ways to meet the complex needs of this patient group and ensure that the personal care and close relationships are not lost in service redesigns embracing remote consultations.

Importance: The incidence of skin cancer is increasing and evaluation of the utility of total body skin examination (TBSE) in detecting incidental skin cancers is warranted., Objectives: To evaluate the proportion and rate of incidental skin cancer detection in urgent skin cancer clinics and investigate the rate of incidental skin cancer detection in 2 groups based on the degree of clinical suspicion of the index lesion for malignancy., Design, Setting, and Participants: A multicenter retrospective cohort study with a case note review of consecutive secondary care consultations was conducted using data from 2 urgent suspected skin cancer screening clinics in UK National Health Service trusts. The study was performed from January 1, 2015, to March 31, 2016, and data analysis was performed from October 14, 2018, to February 1, 2019. Patients included those presenting with a skin lesion suspicious of malignancy who were referred to the urgent suspected skin cancer clinic (N = 5944) over 15 months. Patients who accepted and received a TBSE were subsequently included in the analysis., Main Outcomes and Measures: The proportion and rate of incidental skin cancer detection through TBSE and whether a clinically suspicious (malignant) index lesion was associated with a higher chance of having a malignant incidental lesion., Results: Of the 5944 patients referred to the clinic, 4726 individuals (79.5%) were evaluated. In the cohort included in the analyses, the median age was 57 years (interquartile range, 39-73 years); 2567 patients (54.3%) were women. A total of 1117 skin cancers were identified; of these, 242 lesions (21.7%) were detected incidentally through TBSE, including 197 of 570 (34.6%) basal cell carcinomas, 16 of 250 (6.4%) squamous cell carcinomas, and 25 of 215 (11.6%) melanomas. The detection rate of incidental malignant lesions was 5.1 lesions per 100 patients examined (5.1%; 95% CI, 4.5%-5.8%). There was a higher detection rate of histologically confirmed incidental malignant lesions in individuals with clinically suspicious index lesions requiring biopsy (10.9%; 95% CI, 9.5%-12.5%) compared with those presenting with clinically benign index lesions (2.0%; 95% CI, 1.6%-2.5%) (P < .001)., Conclusions and Relevance: The findings of this study support the use of TBSE for urgent skin cancer referrals, highlighting the potential harms of solitary lesion assessment in a subgroup. Individuals presenting with a clinically suspicious index lesion requiring biopsy are most likely to benefit from TBSE and should be counseled regarding the benefit.

Targeting the MAPK pathway by combined inhibition of BRAF and MEK has increased overall survival in advanced BRAF-mutant melanoma in both therapeutic and adjuvant clinical settings. However, a significant proportion of tumors develop acquired resistance, leading to treatment failure. We have previously shown p63 to be an important inhibitor of p53-induced apoptosis in melanoma following genotoxic drug exposure. Here, we investigated the role of p63 in acquired resistance to MAPK inhibition and show that p63 isoforms are upregulated in melanoma cell lines chronically exposed to BRAF and MEK inhibition, with consequent increased resistance to apoptosis. This p63 upregulation was the result of its reduced degradation by the E3 ubiquitin ligase FBXW7. FBXW7 was itself regulated by MDM2, and in therapy-resistant melanoma cell lines, nuclear accumulation of MDM2 caused downregulation of FBXW7 and consequent upregulation of p63. Consistent with this, both FBXW7-inactivating mutations and MDM2 upregulation were found in melanoma clinical samples. Treatment of MAPK inhibitor-resistant melanoma cells with MDM2 inhibitor Nutlin-3A restored FBXW7 expression and p63 degradation in a dose-dependent manner and sensitized these cells to apoptosis. Collectively, these data provide a compelling rationale for future investigation of Nutlin-3A as an approach to abrogate acquired resistance of melanoma to MAPK inhibitor targeted therapy. SIGNIFICANCE: Upregulation of p63, an unreported mechanism of MAPK inhibitor resistance in melanoma, can be abrogated by treatment with the MDM2 inhibitor Nutlin-3A, which may serve as a strategy to overcome resistance., (©2020 American Association for Cancer Research.)