Expert Recommendations on Facilitating Personalized Approaches to Long-term Management of Actinic Keratosis: The Personalizing Actinic Keratosis Treatment (PAKT) Project.

Actinic keratoses are pre-malignant skin lesions that require personalized care, a lack of which may result in poor treatment adherence and suboptimal outcomes. Current guidance on personalizing care is limited, notably in terms of tailoring treatment to individual patient priorities and goals and supporting shared decision-making between healthcare professionals and patients. The aim of the Personalizing Actinic Keratosis Treatment panel, comprised of 12 dermatologists, was to identify current unmet needs in care and, using a modified Delphi approach, develop recommendations to support personalized, long-term management of actinic keratoses lesions. Panellists generated recommendations by voting on consensus statements. Voting was blinded and consensus was defined as ≥ 75% voting 'agree' or 'strongly agree'. Statements that reached consensus were used to develop a clinical tool, of which, the goal was to improve understanding of disease chronicity, and the need for long-term, repeated treatment cycles. The tool highlights key decision stages across the patient journey and captures the panellist's ratings of treatment options for attributes prioritized by patients. The expert recommendations and the clinical tool can be used to facilitate patient-centric management of actinic keratoses in daily practice, encompassing patient priorities and goals to set realistic treatment expectations and improve care outcomes.

Long-term efficacy and safety of 1% glycopyrronium bromide cream in patients with severe primary axillary hyperhidrosis: Results from a Phase 3b trial.

BACKGROUND: Primary axillary hyperhidrosis (PAHH) strongly affects the patient's quality of life. To date, topical treatment options are limited. One percent glycopyrronium bromide (GPB) showed promising efficacy and safety in a pivotal 4-week Phase 3a study. OBJECTIVES: To assess efficacy and safety of topical 1% GPB cream in patients with severe PAHH in a long-term study of 72 weeks versus baseline. METHODS: This was a long-term, open-label, Phase 3b trial for 72 weeks including 518 patients with severe PAHH. Patients were treated with 1% GPB cream once daily for 4 weeks, followed by a flexible dosing scheme (min. twice per week, max. once daily). Primary endpoint was the absolute change in sweat production from baseline to week 12. Further study endpoints included assessment of the severity of PAHH and the impact on quality of life. RESULTS: Total median sweat production decreased by 119.30 mg (-65.6%, both median) until week 12. Absolute change in sweat production from baseline to week 12 in logarithmic values was statistically significant (p < 0.0001). Patients' quality of life was improved at all study time points compared to baseline, as assessed by Hyperhidrosis Quality of Life Index and Dermatology Life Quality Index (p < 0.0001). Treatment was safe and locally well-tolerated with only few mild to moderate adverse drug reactions (ADRs). Dry mouth and application site erythema were the most common reported ADRs. CONCLUSIONS: Treatment with 1% GPB cream over 72 weeks significantly reduces sweat production and improves quality of life in patients with severe PAHH. One percent GPB cream is well-tolerated and provides an effective treatment option for long-term use in patients with severe PAHH.

S3 guideline "actinic keratosis and cutaneous squamous cell carcinoma" - update 2023, part 2: epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was updated and expanded by the topics cutaneous squamous cell carcinoma in situ (Bowen's disease) and actinic cheilitis. The guideline is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC. A separate guideline exists for patients and their relatives. In this part, we will address aspects relating to epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Red light photodynamic therapy with BF-200 ALA showed superior efficacy in the treatment of actinic keratosis on the extremities, trunk, and neck in a vehicle-controlled phase III study.

BACKGROUND: Actinic keratoses (AK) may occur in all sun-exposed skin areas. Those occurring outside the head area are generally more resistant to treatment than those on the face. OBJECTIVE: To determine efficacy and safety of BF-200 ALA versus vehicle in the treatment of mild-to-severe AK located on extremities, trunk, and neck with red light photodynamic therapy (PDT). METHODS: This phase III study had an intra-individual design with 50 patients in 6 centers in Germany. Each patient received a maximum of 2 field-directed PDTs. Clinical end points and 1-year follow-up results were recorded. RESULTS: BF-200 ALA was superior to the vehicle with respect to total lesion clearance rates (86.0% vs 32.9%; P < .0001) and patient complete clearance per patient's side (67.3% vs 12.2%, P < .0001). One-year overall lesion recurrence rate was 14.1% versus 27.4% (BF-200 ALA vs vehicle; P = .0068). Patients were more satisfied by the cosmetic outcome of BF-200 ALA/PDT than the vehicle/PDT. Adverse events were consistent with the known safety profile of BF-200 ALA/PDT. LIMITATIONS: Small number of severe lesions; limited sample size; unbalanced but representative distribution of AK. CONCLUSION: BF-200 ALA showed significantly higher AK clearance rates on extremities, trunk, and neck than the vehicle and was well tolerated.

Repetitive Daylight Photodynamic Therapy versus Cryosurgery for Prevention of Actinic Keratoses in Photodamaged Facial Skin: A Prospective, Randomized Controlled Multicentre Two-armed Study.

Actinic keratoses are a chronic condition in ultraviolet-damaged skin, with a risk of progressing to invasive skin cancer. The aim of this study was to investigate the preventive potential of field-directed repetitive daylight photodynamic therapy for actinic keratoses. A randomized trial was performed, including 58 patients with ≥5 actinic keratoses on photodamaged facial skin, who received either 5 full-face sessions of daylight photodynamic therapy within a period of 2 years or lesion-directed cryosurgery. Primary outcome was the mean cumulative number of new actinic keratoses developed between visits 2 and 6 (visit 6 being a follow-up). This outcome was lower after daylight photo-dynamic therapy (7.7) compared with cryosurgery (10.2), but the difference did not reach significance (-2.5, 95% confidence interval -6.2 to 1.2; p=0.18). Several signs of photoageing (fine lines, pigmentation, roughness, erythema, sebaceous gland hyperplasia) were significantly reduced after daylight photodynamic therapy, but not after cryosurgery. Significantly less pain and fewer side-effects were reported during daylight photodynamic therapy than during cryosurgery. This study found that repetitive daylight photodynamic therapy had photo-rejuvenating effects. However, the prevention of actinic keratoses by this therapy could not be proven in a statistically reliable manner.

S3 guideline for actinic keratosis and cutaneous squamous cell carcinoma - short version, part 1: diagnosis, interventions for actinic keratoses, care structures and quality-of-care indicators.

Actinic keratoses (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guideline is aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AK and cSCC. The guideline is also aimed at affected patients, their relatives, policy makers and insurance funds. In the first part, we will address aspects relating to diagnosis, interventions for AK, care structures and quality-of-care indicators.

S3 guideline for actinic keratosis and cutaneous squamous cell carcinoma (cSCC) - short version, part 2: epidemiology, surgical and systemic treatment of cSCC, follow-up, prevention and occupational disease.

Actinic keratoses (AKs) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guidelines for actinic keratosis and cutaneous squamous cell carcinoma were developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guidelines are aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AKs and cSCC. The guidelines are also aimed at affected patients, their relatives, policy makers and insurance funds. In the second part, we will address aspects relating to epidemiology, etiology, surgical and systemic treatment of cSCC, follow-up and disease prevention, and discuss AKs and cSCC in the context of occupational disease regulations.

Efficacy and safety of ingenol disoxate gel in field treatment of actinic keratosis on full face, scalp or large area (250 cm2) on the chest: results of four phase 3 randomized controlled trials.

INTRODUCTION: Actinic keratosis (AK) is a skin condition arising from chronic exposure to ultraviolet light and may lead to the development of malignancies. This trial aimed to evaluate efficacy and safety of ingenol disoxate gel (IngDsx, 0.018% for face/chest [FC]; 0.037% for scalp [S]), versus vehicle. METHODS: Four identical phase 3 trials in patients with AK on the full face/up to 250cm2 of chest or full balding scalp, with an initial 8-week period and 12-month follow-up, were conducted. FC and S trials were pooled for analysis. The primary endpoint was complete clearance at Week 8. RESULTS: Across trials, 616 patients were randomized to FC and 626 to S, with 410 and 420 assigned to receive IngDsx, respectively. In the FC and S trials, 25.9% and 24.5% of patients in the IngDsx group, respectively, achieved the primary endpoint. IngDsx was relatively well tolerated. During extended follow-up, there were more identified non-melanoma skin malignancies in the IngDsx group than vehicle group; HR: 2.38 (95% CI: 1.28, 4.41). CONCLUSION: Treatment with IngDsx was superior to vehicle on all clinical endpoints, patient-reported and cosmetic outcomes. During the 12-month follow-up, slightly increased skin malignancies in the treatment area were identified, potentially due to unintentional detection bias.

Interest in Skin Cancer in Urban Populations: A Retrospective Analysis of Google Search Terms in Nine Large German Cities.

Skin cancer is a major public health issue, which could be reduced through prevention programmes. How-ever, prevention utilization is not very prevalent. It is therefore important to understand individuals' interest in skin cancer. Google AdWords Keyword Planner was used to identify the search volume of terms relating to skin cancer in 9 German cities between July 2014 and June 2018. From a total of 1,203 identified keywords, 1,047 search terms were related to skin cancer, which had a search volume of 3,460,980 queries for the study period. Most terms referred to "identifying skin cancer". For melanoma, the number of Google searches per 100,000 inhabitants correlated with the cancer registry data for melanoma incidence rates (men: r = 0.810, women: r = 0.569). Assessment of this data for the different cities further enabled identification of regional variations, which could help to identify areas with a high need for targeted prevention campaigns.

Phototherapy-induced elevation of serum level of melanoma inhibitory activity.

BACKGROUND: Phototherapy is a frequently used treatment modality for a variety of dermatologic diseases. UV radiation has different effects on the skin, for example increased production and release of cytokines and other proteins, and is involved in the initiation and progression of skin cancer. Objective of this clinical trial was to investigate potential systemic effects of UV phototherapy on cytokine profiles in blood. METHODS: In a prospective, mono-centric, one-armed study, the serum levels of the melanoma tumour marker "melanoma inhibitory activity" (MIA), Il-1α, Il-4, Il-6, Il-10, TNF-α and IFN-γ of 115 patients with different skin diseases were compared before and 24-48 hours as well as 2-4 weeks after the first phototherapy with PUVA (psoralen and ultraviolet A), UVA or UVB, or both. Data were analysed using linear mixed models. RESULTS: Estimated marginal means of MIA levels were 6.05 ng/mL (95%-CI: 5.37-6.72, range: 2.83-14.49) before the first treatment, which had significantly increased to 6.79 ng/mL 2-4 weeks after the first phototherapy (CI 95%: 6.12-7.47, range: 3.09-15.45; P = 0.0042). MIA levels 2-4 weeks after the first phototherapy were significantly higher than 24-48 hours after the first phototherapy (P = 0.0083). 2-4 weeks after the first treatment, TNF-α levels had decreased significantly (P = 0.033) more in patients with psoriasis who had responded well to phototherapy than in patients unresponsive to treatment. Serum levels of the other cytokines had not changed significantly. CONCLUSIONS: Short-term phototherapy significantly increased the serum levels of the melanoma tumour marker MIA. The potential clinical relevance of these findings (ie an increased risk of melanoma) is unclear and should be further investigated.

Commentary on the "Evidence- and Consensus-Based (S3) Guidelines for the Treatment of Actinic Keratosis" Published by the International League of Dermatological Societies in Cooperation with the European Dermatology Forum.

In 2015, the International League of Dermatological Societies and the European Dermatology Forum published a guideline for the treatment of actinic keratosis, which is classified as an evidence- and consensus-based S3 guideline. From the point of view of the GD Task Force "Licht.Hautkrebs.Prävention," an interdisciplinary expert panel of the Society for Dermopharmacy for the prevention and treatment of skin cancer, this guideline reveals strengths and weaknesses but, in summary, does not meet the claim for an evidence- and consensus-based S3 guideline.

Structured Expert Consensus on Actinic Keratosis: Treatment Algorithm Focusing on Daylight PDT.

BACKGROUND: A practical and up-to-date consensus among experts is paramount to further improve patient care in actinic keratosis (AK). OBJECTIVES: To develop a structured consensus statement on the diagnosis, classification, and practical management of AK based on up-to-date information. METHODS: A systematic review of AK clinical guidelines was conducted. This informed the preparation of a 3-round Delphi procedure followed by a consensus meeting, which combined the opinions of 16 clinical experts from 13 countries, to construct a structured consensus statement and a treatment algorithm positioning daylight photodynamic therapy (dl-PDT) among other AK treatment options. RESULTS: The systematic review found deficiencies in current guidelines with respect to new AK treatments such as ingenol mebutate and dl-PDT. The Delphi panel established consensus statements across definition, diagnosis, classification, and management of AK. While the diagnosis of AK essentially rests on the nature of lesions, treatment decisions are based on several clinical and nonclinical patient factors and diverse environmental attributes. Participants agreed on ranked treatment preferences for the management of AK and on classifying AK in 3 clinical situations: isolated AK lesions requiring lesion-directed treatment, multiple lesions within a small field, and multiple lesions within a large field, both requiring specific treatment approaches. Different AK treatment options were discussed for each clinical situation. CONCLUSIONS: The results provide practical recommendations for the treatment of AK, which are readily transferable to clinical practice, and incorporate the physician's clinical judgement. The structured consensus statement positioned dl-PDT as a valuable option for patients with multiple AKs in small or large fields.

Quality of life assessment in patients with nonmelanoma skin cancer - psychometric validation of the EORTC QLQ-C30 questionnaire.

BACKGROUND: Nonmelanoma skin cancer (NMSC) is a chronic and sometimes difficult-to-treat condition affecting the quality of life (QL). The present study was conducted to investigate whether the European Organization for Research and Treatment of Cancer (EORTC) core QL Questionnaire - Cancer (QLQ-C30) is a suitable tool for the assessment of QL in patients with NMSC. PATIENTS AND METHODS: In order to define the psychometric properties of the questionnaire, the QLQ-C30 and the Dermatology Life Quality Index (DLQI) were handed out to 172 patients of the Department of Dermatology at the University Hospital Regensburg, Germany. RESULTS: Internal consistencies of all multi-item scales (except one) were acceptable, with Cronbach's alpha ranging from 0.71 to 0.93. The hypothesized scale structure was supported by item/scale and interscale correlations within the QLQ-C30. Related scales of the QLQ-C30 and the DLQI correlated significantly, thus establishing construct validity. At the same time, the proportion of substantial correlations (6 % ≥ 0.40) indicated that the two questionnaires assessed distinct components of QL. The QLQ-C30 significantly differentiated between clinically distinct patient groups, indicating that severe clinical conditions were associated with greater impairment in physical, role, and cognitive functioning (p ≤ 0.030). CONCLUSIONS: These results confirm the QLQ-C30 to be a suitable tool for the assessment of QL in patients with NMSC.

Efficacy of low-dose 5-fluorouracil/salicylic acid in actinic keratoses in relation to treatment duration.

BACKGROUND: In Germany, the number of actinic keratoses (AKs) diagnosed and dermatologically treated has steadily risen in recent years. As AKs represent an early form of squamous cell carcinoma, prompt initiation of treatment is pivotal. The objective of this non-interventional study (NIS) was to determine the efficacy of a low-dose (0.5 %) fluorouracil/10 % salicylic acid (low-dose 5-FU/SA) solution in the treatment of AKs (clinical grade I and II according to Olsen) in relation to treatment duration. PATIENTS AND METHODS: This NIS followed 1,051 AK patients from 212 centers who were treated with low-dose 5-FU/SA. Data were collected at the start of treatment, at an optional follow-up appointment during the treatment period, at the end of treatment, and during the final assessment. RESULTS: During the observation period, there was a decrease in the mean number of lesions by approximately 70 % and in mean size by approximately 80 %. Roughly one-half of the patients were treated for less than six weeks. In the final global assessment, efficacy was rated as very good or good in approximately 89 % of patients; tolerability as very good or good in 87 %. CONCLUSIONS: Under routine clinical conditions, treatment with low-dose 5-FU/SA effectively reduced AK lesions even during short treatment periods, while exhibiting good tolerability. These findings are in keeping with results obtained from a clinical phase III trial.

Daylight PDT with MAL - current data and practical recommendations of an expert panel.

Photodynamic Therapy (PDT) is one of the standard treatment modalities for actinic keratoses (AKs). Daylight PDT (DL-PDT) with MAL cream is a rather recent development, which, instead of an artificial light source, uses daylight for the activation of the photosensitizer. The present review summarizes available data based on a selective literature search, highlights practical aspects, and reflects the authors' expert knowledge in using DL-PDT. With respect to efficacy, study data shows that DL-PDT is noninferior to conventional PDT (cPDT). However, given that DL-PDT is markedly less painful, it is significantly better tolerated than cPDT. In Europe, DL-PDT can be performed from March to October, on sunny as well as on cloudy days. UV protection of untreated areas of the body should be observed. Outside temperature should not fall below 10°C. On hot days, patients should be advised to stay in the shade if necessary. Representing a useful addition to current therapeutic options, DL-PDT with MAL cream is, among others, suitable for patients with field cancerization and/or those who have experienced severe pain associated with cPDT.