Management and clinical practice of multiple face and scalp actinic keratosis in France.
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ABSTRACT:
SUBMITTER: Savary J
PROVIDER: S-EPMC6522955 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Actinic keratoses (AKs) are common skin lesions heralding an increased risk of developing squamous cell carcinoma (SCC) and other skin malignancies, arising principally due to excessive ultraviolet (UV) exposure. They are predominantly found in fair-skinned individuals, and increasingly, are a problem of the immunosuppressed. AKs may regress spontaneously, remain stable or transform to invasive SCC. The risk of SCC increases for those with more than 5 AKs, and the majority of SCCs arise from AKs. The main mechanisms of AK formation are inflammation, oxidative stress, immunosuppression, impaired apoptosis, mutagenesis, dysregulation of cell growth and proliferation, and tissue remodeling. Human papilloma virus has also been implicated in the formation of some AKs. Understanding these mechanisms guides the rationale behind the current available treatments for AKs. One of the main principles underpinning the management of AKs is that of field cancerization. Wide areas of skin are exposed to increasing amounts of UV light and other environmental insults as we age. This is especially true for the head, neck and forearms. These insults do not target only the skin where individual lesions develop, but also large areas where crops of AKs may appear. The skin between lesions is exposed to the same insults and is likely to contain as-yet undetectable preclinical lesions or areas of dysplastic cells. The whole affected area is known as the 'field'. Management is therefore divided into lesion-directed and field-directed therapies. Current therapies include lesion-directed cryotherapy and/or excision, and topical field-directed creams: 5-fluorouracil, imiquimod, diclofenac, photodynamic therapy and ingenol mebutate. Combining lesion- and field-directed therapies has yielded good results and several novel therapies are under investigation. Treatment is variable and tailored to the individual making a gold standard management algorithm difficult to design. This literature review article aims to describe the rationale behind the best available therapies for AKs in light of current understanding of pathophysiology and epidemiology. A PubMed and MEDLINE search of literature was performed between January 1, 2000 and September 18, 2013. Where appropriate, articles published prior to this have been referenced. This is not a systematic review or meta-analysis, but aims to highlight the most up to date understanding of AK disease and its management.
| S-EPMC4065271 | biostudies-literature
Project description:BackgroundSeveral treatments are available for actinic keratosis (AK) on the face and scalp. Most treatment modalities were compared to placebo and therefore little is known on their relative efficacy.ObjectivesTo compare the different treatments for mild to moderate AK on the face and scalp available in clinical practice in Europe.MethodsA network meta-analysis (NMA) was performed on the outcome "complete patient clearance". Ten treatment modalities were included: two 5-aminolaevulinic acid photodynamic therapies (ALA-PDT), applied as gel (BF-200 ALA) or patch; methyl-aminolevulinate photodynamic therapy (MAL-PDT); three modalities with imiquimod (IMI), applied as a 4-week or 16-week course with 5% imiquimod, or a 2-3 week course with 3.75% imiquimod; cryotherapy; diclofenac 3% in 2.5% hyaluronic acid; 0.5% 5-fluorouracil (5-FU); and ingenol mebutate (IMB). The only data available for 5% 5-FU was from one small study and was determined to be too limited to be reliably included in the analysis. For BF-200 ALA and MAL-PDT, data from illumination with narrow-band lights were selected as these are typically used in clinical practice. The NMA was performed with a random-effects Bayesian model.Results25 trials on 5,562 patients were included in the NMA. All active treatments were significantly better than placebo. BF-200 ALA showed the highest efficacy compared to placebo to achieve total patient clearance. BF-200 ALA had the highest probability to be the best treatment and the highest SUCRA score (64.8% and 92.1%), followed by IMI 5% 4 weeks (10.1% and 74.2%) and 5-FU 0.5% (7.2% and 66.8%).ConclusionsThis NMA showed that BF-200 ALA, using narrow-band lights, was the most efficacious treatment for mild to moderate AK on the face and scalp. This analysis is relevant for clinical decision making and health technology assessment, assisting the improved management of AK.
| S-EPMC4043670 | biostudies-literature
Project description:Actinic keratosis (AK) is a chronic skin condition that may progress to cutaneous squamous cell carcinoma. We conducted a systematic review of efficacy and safety for key treatments for AK of the face and scalp, including the novel 5-day tirbanibulin 1% ointment. MEDLINE, PubMed, Embase, Cochrane Library, clinical trial registries and regulatory body websites were searched. The review included 46 studies, of which 35 studies included interventions commonly used in Europe and were sufficiently homogenous to inform a Bayesian network meta-analysis of complete clearance against topical placebo or vehicle. The network meta-analysis revealed the following odds ratios and 95% credible intervals: cryosurgery 13.4 (6.2-30.3); diclofenac 3% 2.9 (1.9-4.3); fluorouracil 0.5% + salicylic acid 7.6 (4.6-13.5); fluorouracil 4% 30.3 (9.1-144.7); fluorouracil 5% 35.0 (10.2-164.4); imiquimod 3.75% 8.5 (3.5-22.4); imiquimod 5% 17.9 (9.1-36.6); ingenol mebutate 0.015% 12.5 (8.1-19.9); photodynamic therapy with aminolevulinic acid 24.1 (10.9-52.8); photodynamic therapy with methyl aminolevulinate 11.7 (6.0-21.9); tirbanibulin 1% 11.1 (6.2-20.9). Four sensitivity analyses, from studies assessing efficacy after one treatment cycle only, for ≤25 cm2 treatment area, after 8 weeks post-treatment, and with single placebo/vehicle node confirmed the findings from the base case. Safety outcomes were assessed qualitatively. These results suggest that tirbanibulin 1% offers a novel treatment for AK, with a single short treatment period, favourable safety profile and efficacy, in line with existing topical treatments available in Europe.
| S-EPMC8952421 | biostudies-literature
Project description:BackgroundActinic keratoses (AKs) are common premalignant skin lesions triggered by excessive ultraviolet exposure. The majority of AKs regress or persist, but some progress to squamous cell carcinomas. Biomarkers associated with their persistence, progression and regression have not been characterized.ObjectivesWe performed skin biopsies in patients with extensive actinic damage to identify biomarkers that correlate with clinical progression and regression of AKs.MethodsThis was an observational study of a cohort of patients with extensive actinic damage. AKs were mapped on a clear plastic template in 26 patients at months 3, 6, 9 and 11. Biopsies were taken from randomly selected, predetermined AKs and were evaluated for p53, E-cadherin, Snail, Slug and Twist. The study is registered at Clinicaltrials.gov: NCT00027976.Resultsp53 exhibited greater expression in clinically apparent AKs (histological score 2·89 ± 1·45) than in regressed AKs (0·75 ± 0·96); P < 0·01. There was also significantly less membrane E-cadherin, the lack of which is a marker of epithelial-mesenchymal transition, in clinically apparent AKs (1·89 ± 1·81) than in sun-exposed skin (3·07 ± 1·75); P < 0·005. The E-cadherin transcription repressors Snail, Slug and Twist were increased in AKs compared with sun-exposed skin. A limitation of the study is that measurement of histological biomarkers was not a primary end point. In addition, patients were allowed to apply sunscreens.ConclusionsAt the molecular level, loss of E-cadherin and an increase in p53 are linked to the dynamic interplay between the persistence, progression and regression of AKs. What's already known about this topic? Actinic keratoses (AKs) are common dysplastic epidermal lesions that result from chronic and excessive ultraviolet exposure. Biomarkers associated with progression and regression of AK have not been characterized. What does this study add? Decreased E-cadherin and increased p53, Snail, Slug and Twist (E-cadherin transcription factors) were associated with progression from AK to nonmelanoma skin cancer. What is the translational message? Strategies targeting these molecules may be effective in reversing rising skin cancer rates. E-cadherin, p53, Snail, Slug and Twist are potential biomarkers that may be used to assess the efficacy of existing chemopreventive agents.
| S-EPMC7309433 | biostudies-literature
Project description:Actinic keratoses (AKs) are lesions of epidermal keratinocyte dysplasia and are precursors for invasive cutaneous squamous cell carcinoma (cSCC). Identifying the specific genomic alterations driving the progression from normal skin to skin with AK to skin with invasive cSCC is challenging because of the massive UVR-induced mutational burden characteristic at all stages of this progression. In this study, we report the largest AK whole-exome sequencing study to date and perform a mutational signature and candidate driver gene analysis on these lesions. We demonstrate in 37 AKs from both immunosuppressed and immunocompetent patients that there are significant similarities between AKs and cSCC in terms of mutational burden, copy number alterations, mutational signatures, and patterns of driver gene mutations. We identify 44 significantly mutated AK driver genes and confirm that these genes are similarly altered in cSCC. We identify azathioprine mutational signature in all AKs from patients exposed to the drug, providing further evidence for its role in keratinocyte carcinogenesis. cSCCs differ from AKs in having higher levels of intrasample heterogeneity. Alterations in signaling pathways also differ, with immune-related signaling and TGFβ signaling significantly more mutated in cSCC. Integrating our findings with independent gene expression datasets confirms that dysregulated TGFβ signaling may represent an important event in AK‒cSCC progression.
| S-EPMC8221374 | biostudies-literature
Project description:BackgroundBecause of the increasing incidence of actinic keratosis (AK), optimal use of limited healthcare resources is essential. Although most patients can be managed in primary care, dermatology referrals are common. More profound knowledge of general practitioners' (GPs) considerations might assist in enhancing AK care.MethodsThe aim of the current study was to gain insight into AK management in primary care by exploring the needs and challenges among GPs in the Netherlands. A qualitative study was conducted based on semi-structured in-depth interviews with 15 conveniently sampled Dutch GPs, focusing on the needs and challenges in AK management. A literature-informed, predefined topic list guided the interviews, which were recorded, transcribed ad verbatim, and thematically analysed using the Framework Method.ResultsAll GPs reported AK to be a clinical diagnosis and most GPs indicated that most AK patients could be managed in primary care. Cryotherapy was preferred and experience with 5-FU therapy was limited. Most GPs applied cryotherapy without discussing other treatment options with patients. Reasons for dermatology referrals included an incomplete treatment response, extensive lesions, difficult-to-treat areas, and serious doubts about the diagnosis. GPs reported a need for more education, especially on 5-FU therapy. Their main challenges were dealing with diagnostic uncertainty, treating extensive lesions, managing treatment-related skin reactions, and reconciling patient misconceptions.ConclusionsThis study shows various AK management approaches among Dutch GPs with suboptimal guideline compliance due to diverse underlying barriers. It suggests that more education might contribute to a more standardised and uniform AK management and supports further transition of AK care from hospital to primary care.
| S-EPMC10693056 | biostudies-literature
Project description:ImportanceActinic keratosis (AK), a skin growth induced by ultraviolet light exposure, requires chronic management because a small proportion can progress into squamous cell skin cancer. Spending for AK management was more than $1 billion in 2004. Investigating geographic variation in AK spending presents an opportunity to decrease waste or recoup excess spending.ObjectiveTo evaluate geographic variation in health care cost for management of AKs and the association with patient-related and health-related factors.Design, setting, and participantsThis retrospective cohort study was performed using data from the MarketScan medical claims database of 488 324 continuously enrolled members with 2 or more claims for AK. Data from January 1, 2008, to December 31, 2012, was used.Main outcomes and measuresAnnual costs of care were calculated for outpatient visits, AK destruction, and medications for AKs, and the total of these components. Costs were adjusted for inflation to 2014 US dollars. To display cost variation, we calculated the ratio of mean cost in the highest quintile (Q5) relative to the mean in the lowest quintile (Q1), or the Q5:Q1 ratio; Q5:Q1 ratios were adjusted based on age, sex, history of nonmelanoma skin cancer, US geographic region, and population density (metropolitan statistical area).ResultsOverall, data from 488 324 continuously enrolled members (mean [SD] age, 53.1 [7.5] years; 243 662 women) with 2 or more claims for AK were included. Overall, patients had 1 085 985 claims related to AK, and dermatologists accounted for 71.0% of claims. The 2-year total cost was $111.5 million, with $52.4 million in 2011 and $59.1 million in 2012. The unadjusted Q5:Q1 ratios for total annual cost per patient ranged from 9.49 to 15.10. Adjusted ratios ranged from 1.72 to 1.80.Conclusions and relevanceThere is variation in AK management cost within and between regions. This is not fully explained by differences in patient characteristics such as age, sex, or comorbidities. The annual cost for 10 common conditions from Medicare had lower Q5:Q1 ratios that ranged from 1.33 (joint degeneration of back/neck) to 1.69 (chronic sinusitis) when compared with 1.72 to 1.80 for AKs. This suggests an opportunity to investigate and improve the value of health care delivery in the management of AKs.
| S-EPMC5470414 | biostudies-literature
Project description:BackgroundActinic keratoses (AK) are pre-malignant cutaneous lesions caused by prolonged exposure to ultraviolet radiation. As AKs lesions are generally accepted to be the initial lesions in a disease continuum that progresses to squamous cell carcinoma (SCC), AK lesions have to be treated. They are also the second most common reason for visits to the dermatologist. Several treatments are available but their efficacy still needs to be improved. The UV-B-induced KA lesion mouse model is used in preclinical studies to assess the efficacy of novel molecules, even though it is often more representative of advanced AK or SCC.ObjectivesHere we report on a translational study, comparing the various stages of AK development in humans and in the UV-B irradiated mouse model, as well as the optimization of photograph acquisition of AK lesions on mouse skin.MethodsHuman and mouse skin lesions were analysed by histology and immunohistochemistry. Mouse lesions were also assessed using a digital dermatoscope.ResultsAn histological and phenotypic analysis, including p53, Ki67 and CD3 expression detection, performed on human and mouse AK lesions, shows that overall AK modelling in mice is relevant in the clinical situation. Some differences are observed, such as disorganization of keratinocytes of the basal layer and a number of atypical nuclei which are more numerous in human AK, whereas much more pronounced acanthosis is observed in skin lesion in mice. Thanks to this translational study, we are able to select appropriate experimental conditions for establishing either early or advanced stage AK or an SCC model. Furthermore, we optimized photograph acquisition of AK lesions on mouse skin by using a digital dermatoscope which is also used in clinics and allows reproducible photograph acquisition for further reliable assessment of mouse lesions. Use of this camera is illustrated through a pharmacological study assessing the activity of CARAC®.ConclusionThese data demonstrate that this mouse model of UV-B-induced skin lesions is predictive for the identification of novel therapeutic treatments for both early and advanced stages of the disease.
| S-EPMC5491107 | biostudies-literature
Project description:BackgroundPatient recruitment is a major cause of delays in randomized controlled trials (RCT). Online recruitment is evolving into an alternative to conventional in-clinic recruitment for RCT. The objective of this study was to test the effectiveness of online patient recruitment for an RCT on actinic keratosis (AK).MethodsIn this proof-of-concept study, adults with AK were recruited for a Phase I/IIa RCT (NCT05164393) via social media using targeted advertising Interested users were directed to a landing page to learn about the study, respond to questionnaires, and upload self-obtained smartphone pictures of potential AK. Facebook Analytics was used to track the number of advertisement views, individual users exposed to the advertisement, and advertisement clicks. Following eligibility-review by remote dermatologists, candidates were contacted for an in-clinic visit. A review of pertinent RCTs on AK (2012-2022) was conducted to compare recruitment metrics.ResultsThe online campaign served 886,670 views, reached 309,000 users, and generated 27,814 clicks. A total of 556 users underwent eligibility review, leading to 140 pre-evaluated potential study subjects. The RCT's enrollment target of 60 patients (68.8 ± 7.1 years, 43.3 % female) was reached in 53 days after screening 90 participants in-clinic, corresponding to a screen failure rate of 33.3 %. The total cost of this online recruitment campaign was 14,285 USD i.e. 238 USD per randomized patient. Compared to the existing literature (44 RCTs), our online approach resulted in 9 times more time-efficient recruitment per site.ConclusionUsing targeted advertisements, 60 patients with AK were recruited for a single-center Phase I/IIa RCT in 53 days. Social media appears to be an efficient platform for online recruitment of patients with low-grade AK for RCT.
| S-EPMC10792556 | biostudies-literature
Project description:Non-melanoma skin cancer is the most common skin cancer with an incidence that varies widely worldwide. Among them, actinic keratosis (AK), considered by some authors as in situ squamous cell carcinoma (SCC), are the most common and reflect an abnormal multistep skin cell development due to the chronic ultraviolet (UV) light exposure. No ideal treatment exists, but the potential risk of their development in a more invasive form requires prompt treatment. As patients usually present with multiple AK on fields of actinic damage, there is a need for effective, safe, simple and short treatments which allow the treatment of large areas. To achieve this, daylight photodynamic therapy (DL-PDT) is an innovative treatment for multiple mild actinic keratosis, well tolerated by patients. Patients allocated to the PDT unit, affected by multiple mild-moderate and severe actinic keratosis on sun-exposed areas treated with DL-PDT, were clinically evaluated at baseline and every three months with an Antera 3D, Miravex(©) camera. Clinical and 3D images were performed at each clinical check almost every three months. In this retrospective study, 331 patients (56.7% male, 43.3% female) were treated with DL-PDT. We observed a full clearance in more than two-thirds of patients with one or two treatments. Different responses depend on the number of lesions and on their severity; for patients with 1-3 lesions and with grade I or II AK, a full clearance was reached in 85% of cases with a maximum of two treatments. DL-PDT in general improved skin tone and erased sun damage. Evaluating each Antera 3D images, hemoglobin concentration and pigmentation, a skin color and tone improvement in 310 patients was observed. DL-PDT appears as a promising, effective, simple, tolerable and practical treatment for actinic damage associated with AK, and even treatment of large areas can be with little or no pain. The 3D imaging allowed for quantifying in real time the aesthetic benefits of DL-PDT's increasing compliance.
| S-EPMC4964483 | biostudies-literature