Treatment Of Actinic Keratosis Research Articles

Exploring Anti-Aging Effects of Topical Treatments for Actinic Keratosis

Background and Objectives: Actinic keratosis (AK) is a precancerous cutaneous lesion driven by chronic ultraviolet (UV) exposure, often coexisting with features of photoaging, such as wrinkles and pigmentary irregularities. Recent evidence suggests that treatments for AK may also counteract photoaging through shared molecular pathways, including oxidative stress and inflammation. This narrative review explores the dual benefits of AK therapies, highlighting their potential anti-aging and skin-lightening effects, and implications for improving skin appearance alongside lesion clearance. Materials and Methods: The literature was analyzed to assess the efficacy, mechanisms, and cosmetic outcomes of commonly used AK treatments, including topical agents (5-fluorouracil (5-FU), imiquimod, diclofenac, and tirbanibulin), and photodynamic therapy (PDT). Studies highlighting their effects on photoaged skin, collagen remodeling, pigmentation, and patient satisfaction were reviewed. Results: PDT emerged as the most validated treatment, demonstrating improved collagen synthesis, skin texture, and pigmentation. 5-FU showed remodeling of the dermal matrix and increased procollagen levels, but local skin reactions represent a major limitation. Imiquimod enhanced dermal fibroplasia and reduced solar elastosis, while diclofenac provided mild photodamage improvements with minimal adverse effects. Tirbanibulin showed promising aesthetic outcomes, including skin lightening and a reduction in mottled pigmentation, with favorable tolerability. Conclusions: AK therapies offer a dual-purpose strategy, addressing both precancerous lesions and cosmetic concerns associated with photoaging. While PDT remains the gold standard, emerging agents like tirbanibulin ointment exhibit substantial potential. Future research should focus on optimizing treatment protocols and evaluating long-term cosmetic outcomes to enhance patient satisfaction and compliance.

Linear porokeratosis and the rationale of combining calcipotriol with 5-fluorouracil

Linear porokeratosis is one of the rare forms of porokeratosis and is also pre-malignant in nature. The term porokeratosis is a misnomer, as it is not a disorder of the sweat gland ducts, but rather a disorder of keratinization. There is no standard of therapy for porokeratosis and many topical therapies exist such as topical retinoids; keratolytics such as salicylic acid and urea; topical vitamin D3 analogs such as calcipotriol and calcipotriene, along with the newer 2% lovastatin creams with or without 2% cholesterol cream. We report this case of linear porokeratosis since we have combined 5% 5-fluorouracil cream and 0.005% calcipotriol ointment for both clinical cure and cancer immunotherapy. Although it is a common combination used in the treatment of actinic keratosis, another premalignant dermatosis, it has been uncommonly used in porokeratosis of Mibelli and never reported to be used in linear porokeratosis.

Association Between Local Skin Reactions and Efficacy with 5-Fluorouracil 4% Cream in Actinic Keratosis: A Post-Hoc Analysis of Two Randomised Clinical Trials.

Topical 5-fluorouracil (5-FU), 5% or 4% cream, is recommended among first-line treatments for actinic keratosis (AK). Local skin reactions (LSRs) are an expected and transient response to treatment with 5-FU but can lead to treatment discontinuation when severe. This analysis aimed to investigate whether the severity of LSRs during the treatment was associated with lesion clearance assessed 4 weeks after completing treatment. This post hoc analysis pooled data from two randomised clinical trials (HD-FUP3B-048 and HD-FUP3B-049). Only patients treated with once-daily 5-FU 4% for 4 weeks were considered. Analyses included LSR severity at week 2 and 4 and clearance 4 weeks after completing treatment (week 8). Analysed LSRs were erythema, scaling, oedema, crusting, erosions, stinging and pruritus, which were each categorised as mild, moderate, severe or none. Response was categorised as complete clearance (CC; clearance of all lesions), partial clearance (PC; ≥ 75% clearance) or no clearance (NC; < 75% or for subgroup analyses NC < 100%). Data from 397 patients were included. The median number of AK was 11 (lower quartile Q1 = 7 and upper quartile Q3 = 18) and grades were mild to moderate (86.4% of patients) and severe. At week 8, 321 patients (80.9%) had CC/PC and 76 (19.1%) had NC. Patients who achieved CC/PC had, at baseline, more lesions, a more severe disease and lesions preferentially on the ears/face than patients with NC. In adjusted logistic regression analyses and across all LSR grades, CC/PC at week 8 was associated with occurrence of erythema, oedema, crusting and stinging at week 2 and all LSRs at week 4. Severe erythema observed at week 2 was significantly associated with lesion clearance compared with mild erythema. At week 4, both severe and moderate erythema, moderate scaling and moderate pruritus were significantly associated with lesion clearance at week 8 compared with mild LSRs. Results according to the LSR severity for patients who had 100% clearance are quite similar. Our analysis showed that the severity of LSRs during 5-FU 4% treatment for AK was associated with a higher clearance rate. It appears that severe LSRs did not compromise treatment efficacy. Because LSRs can still be unpleasant, strategies must be developed to relieve patients to allow continued 5-FU 4% application.

From basic to clinical and therapeutic insights: news on actinic keratosis and skin squamous cell carcinoma.

Squamous cell carcinoma (SCC) is the second most common skin cancer, with an increasing incidence. This review highlights this past year's advances regarding the understanding of its pathogenesis, newly introduced diagnostic methods and updates in prevention and treatment. While the pathogenesis of SCC progression remains unclear, new sequencing techniques are helping to better characterize these tumours at the molecular level. Recently introduced noninvasive imaging techniques are rapidly transforming SCC diagnosis and follow-up. Although nicotinamide has not demonstrated significant benefit in reducing SCC incidence among transplant recipients, larger studies are needed to achieve statistical power. Tirbanibulin, a new field treatment for actinic keratosis is now available and well tolerated for use in areas up to 100 cm2. Surgery remains the cornerstone of SCC treatment and can now be complemented with cemiplimab, when advanced. Recent years have seen a diagnostic revolution in dermatology, driven by noninvasive imaging and artificial intelligence; however, the physiopathogenesis of SCC progression remains poorly understood. In treatment, immune checkpoint inhibitors have shown good survival outcomes for advanced SCC. Research continues in the neoadjuvant setting and among transplanted patients, with encouraging preliminary results.

Clinical and Dermoscopic Comparison of the Efficacy and Safety of 5% Fluorouracil Topical Cream and 1% Niacinamide Topical Gel in the Treatment of Actinic Keratosis: A Randomized Controlled Trial.

Actinic keratosis (AK) is a common skin condition treated by dermatologists; however, the effectiveness, superiority, and potential side effects of current treatment protocols are still debated. This study aimed to compare the effectiveness and safety of 5% fluorouracil topical cream and 1% niacinamide topical gel in patients with AK. In a randomized clinical trial, 26 patients with 95 AK lesions were assigned to receive either 5% fluorouracil topical cream twice daily for 4 weeks or 1% niacinamide topical gel twice daily for 3 months. Photography and dermoscopy before and after treatment were used to evaluate the outcomes. The study included 26 patients who underwent randomization and treatment. Analysis of the improvement response after treatment through photography and dermoscopy scores, as well as patients' perspectives, showed that the fluorouracil group had significantly better outcomes than the niacinamide group. However, treatment complications including burning, itching, and erythema were significantly more frequent in the fluorouracil group than in the niacinamide group. Although 5% fluorouracil cream is more effective than 1% niacinamide gel in treating AK lesions, it is also associated with more frequent side effects.

Safety and Efficacy of Photodynamic Therapy with ALA 10% Topical Gel Activated by Red Light versus ALA 20% Topical Solution Activated by Blue Light for the Treatment of Actinic Keratosis on the Upper Extremities: A Blinded Randomized Study

Background: Actinic keratosis (AKs) is a pre-cancerous skin neoplasm that can appear as erythematous to pink scaly plaques at sites of ultraviolet light damage. Photodynamic therapy (PDT) using aminolaevulinic acid (ALA) 10% gel activated by red light is approved by the FDA for the treatment of AKs on the face and scalp, and ALA 20% solution activated by blue light is approved for PDT treatment of AKs on the face, scalp, and upper extremities. While both options have been proven to an effective treatment on the upper extremity, there has been no direct side-by-side comparison. This study aimed to compare the safety and efficacy of both PDT on the upper extremities. Design: This was a prospective, single-center, split-arm randomized clinical trial with 20 adult subjects presenting with 4-17 clinically confirmed mild-moderate AKs (Olsen grading) on each distal upper extremity. Subjects were treated with ALA 10% gel/red light and ALA 20% solution/blue light PDT on respective randomly selected upper extremities. Lesion complete clearance rate (LCCR) served as the primary endpoint. Secondary endpoints included complete clearance per patient side (PatCR), LCCR of moderate lesions, LCCR 12 weeks after PDT-1, PatCR 12 weeks after PDT-1, overall cosmetic outcome assessed by the investigator, and patient satisfaction. Results: The LCCR was significantly greater for ALA10% vs. ALA20% at Day 120; no significant differences were observed at the other observed time points. 30 patients were enrolled in the study and received their first treatment (PDT1). LCCRs after PDT1 were 65.4% and 58.4% for ALA10% and ALA 20%, respectively. 25 patients received a second treatment (PDT2), resulting in LCCRs of 88.2% and 72.1% respectively. 22 patients returned for follow-up 6 months after their last PDT treatment (PDT1 or PDT2), with LCCR of 83.7% (ALA10%) and 79.3% (ALA20%). 17 patients returned for follow-up 12 months after the last PDT treatment, with LCCRs of 81.5% (ALA10%) and 87.6% (ALA20%). There were no statistical differences between ALA10% and ALA20% for subject-reported pain or satisfaction ratings. ALA10% was rated as significantly easier to apply compared to ALA20% by the investigator. Conclusion: Both ALA10% and ALA20% appear to be safe and effective for PDT treatment of AKs on the upper extremities. There is a trend for increased efficacy with ALA10%, and it may be easier to apply. Additional data is in the process of being collected as the study continues.

Evaluating the safety and efficacy of aminolevulinic acid 20% topical solution activated by blue light in the treatment of facial cutaneous squamous cell carcinoma in situ

Background: Cutaneous squamous cell carcinoma in situ (isSCC) is a common skin cancer occurring from sun exposure and often appears on the face. Treatment is primarily surgical but less invasive treatments are desirable. Currently, aminolevulinic acid for photodynamic therapy (ALA-PDT) is approved in the US and Canada for the treatment of single and multiple non-hyperkeratotic actinic keratoses of the face and scalp. This study evaluated the safety, tolerability, and efficacy of ALA-PDT for treatment of facial isSCC.Methods: Thirty-two patients with biopsy-confirmed isSCC on the face were recruited. Lesions 0.4–1.3 cm in diameter were included. Per the actinic keratosis treatment protocol, the lesion was debrided with a 4 x 4 gauze and ALA 20% topical solution was applied to the lesion and adjacent skin and incubated for 18–24 hours, followed by blue light therapy 16 minutes 40 seconds at 10 J/cm2. Patients underwent two treatments with ALA-PDT spaced 28 +/- 3 days apart. The area of the original lesion was excised eight weeks following the second treatment for histopathological assessment. The primary efficacy endpoint was the complete absence histologically of the isSCC at end of treatment. The secondary efficacy endpoint was the achievement of clinical clearance of the skin lesion. Safety assessment was done through adverse events and local skin reactions (LSRs; erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) and site pain within 15 minutes of each treatment session.Results: Of the 32 patients enrolled, two did not complete the study. No residual SCCis was detected in 30/30 (100%) patients. Clinical clearance was achieved in 30/30 (100%) of the patients by the end of treatment. None of the patients experienced related adverse events and only 2/30 (5%) experienced an AE of hypertension and was considered to be unrelated. The most common LSRs were erythema and scaling and were primarily mild, seen to occur immediately after both treatments and diminished over time. The average median ± SD immediate post-treatment pain score was 2.56 ± 2.15 on the VAS scale.Conclusion: The ALA-PDT protocol outlined in this study appears to be a very effective, safe and well-tolerated treatment option for isSCC on the face.

The Application of High-Frequency Ultrasonography in Post-Therapeutic Assessment of Actinic Keratosis After Photodynamic Therapy.

Actinic keratoses (AKs) are one of the most common reasons for consultation in the elderly population. This study aimed to assess the efficacy of 5-ALA PDT in AK treatment using high-frequency ultrasonography (HFUS) to evaluate skin layer changes during therapy. In our study, we included 44 AK patients aged 53 to 89 years. All patients had lesions clinically evaluated with the Olsen and AKASI scale. HFUS imaging was performed on seemingly healthy skin and lesions before and at 4, 8, and 12 weeks of therapy. Ultrasound markers such as skin thickness, echogenicity, and pixel intensity were measured. 5-ALA was applied under occlusion for 3 h. After removing the occlusive dressing, 5-ALA was removed with a saline solution and a directed therapy with a BF-200 lamp. Full follow-ups of 56 markers of suitable quality were selected. The thickness of SLEB significantly decreased in the following weeks compared to the pre-therapy results, reaching its lowest values after 12 weeks. The average pixel intensity significantly increased in each skin layer after therapy (p < 0.01). For SLEB, there were statistically significant differences in LEP, MEP and contrast. The AKASI score before and after treatment was determined for the 39 patients who underwent follow-up at week 12. The median AKASI score was 3.2 (1.2-8.6) before treatment and 0.6 (0-2.8) after. According to the literature data, this is the first study describing the ALA-PDT treatment efficacy in different AK severities evaluated in HFUS. HFUS provides a valuable non-invasive tool for monitoring the efficacy of PDT in AK treatment, showing significant improvements in skin texture and structure.

Prebiotic and panthenol-containing dermocosmetic improves tolerance from artificial daylight photodynamic therapy: A randomized controlled trial in patients with actinic keratosis

Introduction & ObjectivesTreatment with daylight photodynamic therapy (dPDT) of actinic keratosis (AK) is associated with local skin reactions (LSR), which may affect patients’ quality of life and treatment acceptability. This study explores the potential of a prebiotic and panthenol-containing Dermocosmetic Cream (DC) to enhance tolerance and mitigate post-dPDT induced LSR in the treatment of AKs. Materials & MethodsThis randomized controlled, intra-individual trial included 20 patients with ≥10 AKs in two symmetrical areas on their face or décolleté, treated with a single session of artificial dPDT. After treatment, the two areas were randomized to DC twice daily for 14 days or No-DC. Primary outcomes included clinical signs of LSR graded from 0=none to 3=severe, calculated as a composite score, and assessed on Days 2, 7, 14, and 30 post-treatment, along with AK clearance rate. Secondary outcomes encompassed objectively measured erythema, and clinical and objective skin photoaging assessment. ResultsTopical application of DC following dPDT significantly improved post-treatment tolerance up to two weeks. By Day 2, DC-treated skin had milder LSR (median 3.0, IQR 2.0-4.8) compared to No-DC skin (median 4.0, IQR 3.0-5.0; p=0.011). This improvement continued on Day 7 (DC median 3.0, IQR 2.0-3.8 vs. No-DC median 4.5, IQR 3.0-5.8; p<0.001) and Day 14 (DC median 1.0, IQR 0.0-1.0 vs. No-DC median 1.0, IQR 1.0-2.0; p=0.004). Objective measurements showed milder erythema in DC-treated areas on Day 2 (p=0.045) and Day 7 (p=0.005). Crusting resolved more effectively in DC-treated areas by Day 7 (40% vs. 20%; p=0.039). No significant difference in complete lesion response rate was observed between DC and No-DC skin (p=0.850). By Day 30, clinical photoaging assessment demonstrated significant improvement in dyspigmentation (p=0.004) and skin texture (p<0.001) in both locations. Moreover, objective measurements revealed reduced dyspigmentation in both DC and No-DC treated skin (p≤0.001). ConclusionApplication of a prebiotic and panthenol-containing multipurpose DC significantly enhanced tolerance from artificial dPDT and accelerated healing time up to 14 days after treatment. The use of DC cream did not affect the overall treatment efficacy of dPDT, indicating its potential to enhance patient comfort following dPDT.

Cost-Effectiveness Analysis of Topical Treatments for Actinic Keratosis in Italian National Health System.

Introduction: Actinic keratosis (AK) is a widespread pre-cancerous skin condition that may evolve to squamous cell carcinoma, a non-melanoma skin cancer, which is able to become locally invasive and metastatic. Thus, it is important to treat AK. Methods: We conducted a cost-effectiveness analysis for the field-directed therapeutic approaches: local application of drugs containing 5-fluorouracil, both alone at a 4% concentration and associated to 10% salicylic acid at a 0.5% concentration (0.5% 5-FU + 10% SA cut. sol.); diclofenac-hyaluronic acid gel; imiquimod, both at 3.75% and 5% (5% IMQ cream) concentrations; and tirbanibulin ointment. The effectiveness data were abstracted from the literature. The cost-effectiveness analysis was performed by considering the prices reported by Agenzia Italiana del Farmaco (AIFA) for each medicine. Results: We obtained the total cost for each treatment by computing the cost of a single treatment for its duration. Application of 0.5% 5-FU + 10% SA cut. sol. appeared as the most convenient approach, as it was more effective and less expensive than all treatments except for 5% IMQ cream. For this last option, the incremental cost/effectiveness ratio analysis showed that a modest gain in effectiveness has a cost of EUR 7.94, therefore making it less cost effective.

High efficacy of red light photodynamic therapy with 10 % aminolevulinic acid gel irrespective of the extent of keratinocyte atypia in actinic keratosis – exploratory post-hoc analysis of three pivotal phase III trials

BackgroundPrimary endpoints of clinical studies investigating treatments for actinic keratosis (AK) are mainly based on clinical evaluation, but a recent study showed that in AK, clinical classification according to Olsen and the extent of keratinocyte atypia do not necessarily correlate. The influence of the epidermal extent of atypia on treatment efficacy is usually not investigated and therefore remains largely unknown. ObjectiveTo evaluate whether the extent of keratinocyte atypia influences efficacy of photodynamic therapy (PDT) when treating AK. MethodsWe performed a post-hoc analysis of histological (keratinocyte intraepithelial neoplasia (KIN)), and clinical (Olsen) data of biopsied lesions of three pivotal studies evaluating PDT using 10 % aminolevulinic acid (ALA) gel or vehicle and narrow- or broad-spectrum red light lamps. ResultsOverall, 514 biopsied lesions were considered. Clearance rates after red light PDT with 10 % ALA gel were comparable for KIN I-III (88.2 %, 92.0 % and 87.9 %) and Olsen I-II lesions for any given lamp type. Generally, clearance rates were higher using narrow- compared to broad-spectrum lamps. For both lamp types, the variation in clearance rates from KIN I-III was low. Clearance was lower with vehicle. LimitationsVarying lesion numbers in the subgroups and a remaining risk of bias due to the biopsies are potential limitations. ConclusionOur results suggest that red light PDT with 10 % ALA gel is an effective treatment option for AK regardless of the extent of keratinocyte atypia.

Update in the diagnosis and treatment of actinic keratosis

Actinic keratosis (AK) is among the most common conditions in dermatology in an increasingly aging population. However, the presence of severe field cancerization with large treatment fields showing multiple lesions with distinct features often poses atherapeutic challenge. The most accurate possible characterization of the treatment field, risk assessment concerning the occurrence of cutaneous squamous cell carcinoma, and knowledge of the efficacy and local side effects of the available interventions are of paramount importance for effective management and preventive efforts. This article summarizes current developments in the diagnosis and treatment of AK and discusses their application in everyday clinical practice. In particular, the focus is on the increasing value of non-invasive diagnostic techniques like "line-field" confocal optical coherence tomography, and the recently approved topical agents tirbanibulin 1% ointment and 5‑fluorouracil 4% cream, as well as current developments of photodynamic therapy and prevention.

Tirbanibulin as a Novel Treatment in Actinic Keratosis: A Literature Review

Introduction and purpose: Actinic keratosis (AK) is a common dermatological condition that primarily affects fair-skinned individuals due to cumulative ultraviolet light exposure, potentially leading to squamous cell carcinoma (SCC). AK therapy is divided into two main branches: lesion-directed therapy (cryotherapy, lasers, and surgical methods) and field cancerization-directed therapy (photodynamic therapy and topical agents). Unfortunately, the occurrence of local skin reactions (LSRs) and the therapy duration counted in weeks disrupt patient compliance. This study aims to review the clinical trials concerning the efficacy, safety, and adverse effects of tirbanibulin, a novel promising treatment for AK, which led to its approval and therapeutic development. Materials and methods: Literature available in PubMed and GoogleScholar databases were reviewed using the following keywords: actinic keratosis; actinic keratosis treatment; tirbanibulin. Results: Tirbanibulin's mechanism involves inducing apoptosis by inhibiting microtubule polymerization, which distinguishes it from other treatments that often cause significant inflammation. Clinical trials demonstrate its high efficacy in clearing AK lesions with a favorable safety profile, leading to regulatory approval. The ease of use and short therapy duration (5 days) ensure patient compliance and satisfaction with the treatment. Conclusion: Further longitudinal studies are necessary to confirm the long-term benefits and positioning of tirbanibulin in AK therapy. Raising public awareness about AK and the importance of early treatment with effective options like tirbanibulin is crucial for improving public health outcomes.

Chloro-aluminum phthalocyanine encapsulation into liquid crystalline nanodispersions enhance skin penetration and phototoxicity in skin cancer cells

Non-melanoma skin cancer is one of the most common tumors in the world. Photodynamic therapy (PDT) is currently a non-invasive therapeutic option for the treatment of skin cancer and actinic keratosis. Chloro-aluminum phthalocyanine (AlClPc) is a second-generation photosensitizer that has been studied for application in PDT. However, it has the disadvantage of self-aggregating in a biological environment, which impairs its therapeutic action, making it a candidate for nanocarrier delivery. Among the nanocarriers, liquid crystalline nanodispersions (LCN) are biocompatible and present unique organizational characteristics that make them suitable for skin delivery of drugs. Herein, a new LCN based on oleic acid (OA), Phosal 75SA® containing or not D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) was developed and characterized aiming its application for skin cancer. The selected LCN with AlClPc showed nanometric size (152.3 ± 1.93 nm), adequate PDI (0.231 ± 0.009) and encapsulation efficiency (70.26 ± 3.87 %) and stability for 30 days. Also, LCN were characterized by polarized light microscopy and small angle X-ray diffraction (SAXS) resulting in hexagonal liquid crystalline nanodispersions. In the in vitro skin penetration test, LCN-AlClPc showed better penetration into the deeper skin layers than the control. LCN-AlClPc showed greater phototoxicity in the A431 tumor cell line than the control in the same cell line and also greater phototoxicity in A431 when compared to L929 fibroblast cells. Thus, LCN developed could improve the phototoxicity and skin penetration in vitro and are potential drug delivery systems for the treatment of non-melanoma skin cancer.

A Randomized Comparative study of efficacy and safety between %20 and %30 Hydrogen peroxide in the Treatment of Actinic keratosis

Background and objectives: Actinic keratosis is a premalignant skin lesion that presents clinically as a sand-like macule or papule on an erythematous base with a superficial scale due to atypical proliferation of keratinocytes and may progress to squamous cell carcinoma. The aim of this study was to compare the efficacy of hydrogen peroxide in treatment of actinic keratosis between two different concentrations (%20 and %30). Methods: This is a randomized open label therapeutic trial of twenty patients with actinic keratosis has been enrolled, it was conducted from April 2022 to August 2022 at Sulaimaniah dermatology teaching center. Patients were divided to two treatment groups. Hydrogen peroxide %20 applied to the actinic lesions of group A, while group B applied 30% Hydrogen peroxide to the lesions. The solution was applied to the lesions in a circular motion for 20 seconds, for four rounds per session Patients were seen after a first session in two weeks. Maximum four sessions spaced out by 15 days are given until clearance. Result: we conducted a randomized open label therapeutic trial. It was conducted from April 2022 to August 2022 at Sulaimaniah dermatology teaching center. Regarding response in Group A out of twenty actinic lesions, marked and moderate improvement was recorded in %40, %30 of the lesions respectively while the remaining lesions %30 of them showed slight improvement and no clinically clearance has been recorded. In comparsison, Group B out of twenty lesions %60 of them clinically cleared and slight improvement was recorded only in %20 of lesions. There were statistically significant differences between (20% &amp; 30% Hydrogen peroxide ) in response (p-value=0.000). Regarding side effects; majority of patients (85%) in both groups had recorded burning sensation, irritation and transient erythema, while no scarring, pigmentation, atrophy has been recorded. There were no statically significant differences between two groups. Conclusion: Hydrogen peroxide can be used as safe, alternative method to other modalities in treatment of actinic keratosis lesions, results would be better if higher concentration %30 used

52758 Patient and clinician-reported outcomes with tirbanibulin 1% treatment for actinic keratosis in routine clinical practice across the U.S. according to treated area location (PROAK study)

52758 Patient and clinician-reported outcomes with tirbanibulin 1% treatment for actinic keratosis in routine clinical practice across the U.S. according to treated area location (PROAK study)

Photodynamic therapy reduces the burden of small ultraviolet-induced epidermal clones in human and mouse skin.

Actinic keratoses (AKs) and keratinocyte carcinomas (KCs) arise from prolonged UV exposure, with precursor UV-induced clonal mutations (CMs) appearing in sun-damaged skin. Photodynamic therapy (PDT) is a common field treatment for AKs and early KCs, but its impact on subclinical CMs is unknown. This study examines CMs using targeted ultra-deep sequencing on epidermal samples. By comparing skin before and after PDT in five patients and a mouse model of chronic UV carcinogenesis, a significant reduction in low-frequency mutations post-treatment was revealed. These findings highlight PDT’s potential in modifying subclinical damage and propose low-variant allele frequency CMs as biomarkers for field treatment efficacy.

Epidemiology and Risk Factors of Actinic Keratosis. What is New for The Management for Sun-Damaged Skin.

Actinic keratosis (AK) is considered a chronic skin disease mostly caused by long-term exposure to UV radiation and other risk factors such as immunosuppression, leading to an individual susceptibility for skin cancer manifestation. The treatment of AK is laborious and costly, and the incidence of skin cancer is forecasted to double until the year 2030 in an aging society.Risk factors in AK for malignant transformation in cutaneous squamous cell carcinoma (cSCC) are not fully understood, but studies suggest that histological features, such as atypia in the basal epidermal third and basal proliferation (PRO score) in AK play a pivotal role for development of malignancy. As the clinical appearance of AK does not correlate with the risk for malignancy, guidelines suggest treating every single AK lesion upon diagnosis. Skin imaging techniques, such as line-field confocal optical coherence tomography (LC-OCT) can help to provide an individual holistic follow-up for AK lesions by non-invasive visualization of atypia and basal proliferation. A follow-up for patients with AK may be critical for treatment success in terms of strengthening therapy adherence. When AK presents therapy refractory, cSCC manifests in nearly 30% of the cases after several years. Patients with AK suffering from field cancerization and immunosuppression are susceptible for a severe course of disease including metastasis and high mortality rates. Those vulnerable subgroups benefit from close skin cancer screening, early adequate treatment and chemoprevention, such as niacinamide or acitretin. Skin cancer prevention is substantial. Primary prevention should include chemical and physical UV-light protection and avoidance of indoor tanning. Secondary prevention is essential in high-risk populations, such as fair skin type elderly men and STORs. Tertiary prevention should comprise adequate treatment strategies to prevent therapy resistance, reoccurrence and cSCC, especially when field cancerization and immunosuppression are present.

Efficacy of Photodynamic Therapy in the Treatment of Actinic Keratosis: A Network Meta-Analysis.

Photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AK) and uses different light sources as well as photosensitizers. In addition, PDT is often combined with other physical therapies or drugs. This study was aimed to compare the efficacy of different PDTs against AK lesions based on Complete Response (CR) by conducting a network meta-analysis (NMA). Randomized controlled trials (RCTs) using PDT for AK were screened and a Bayesian model was developed to perform an NMA of CR at 3 months after the first treatment. Twenty-six trials involving 2285 patients and 14 treatments were included. The treatments were broadly divided into mono-PDT and combination therapy. The photodynamic monotherapies included methyl 5-aminolevulinic acid (MAL)-daylight (DL)-PDT, MAL-light-emitting diode (LED)-PDT, 5-aminolevulinic acid (ALA)-LED-PDT, etc. Combination therapies included ablative fractional laser (AFL)-assisted MAL-LED-PDT, calcipotriol (CAL)-assisted MAL-LED-PDT, and 5-fluorouracil (5-Fu)-assisted MAL-DL-PDT. The results of the NMA showed that there is a high probability that AFL-MAL-LED-PDT is the most effective treatment option, followed by CAL-MAL-LED-PDT and ALA-LED-PDT. The subgroup analysis showed that MAL-based PDT had better efficacy when using LED versus other light sources, while LED-based PDT was likely to have better efficacy when using ALA versus other photosensitizers. The results of this NMA suggest that AFL-MAL-LED-PDT may be the superior choice for achieving complete clearance of AK lesions. PDT using LED as the light source and ALA as the photosensitizer may be more effective for the treatment of AK. However, more RCTs are needed to verify the results of this analysis.

Development and evaluation of imiquimod-loaded nanoemulsion-based gel for the treatment of skin cancer

BackgroundThe human skin, as the body’s largest organ, is particularly sensitive to many chemical mutagens and carcinogens encountered in daily life. Skin cancer has become a notable global health concern, partly due to increased exposure to environmental pollutants and UV rays. Various treatments are available to treat skin cancer. Imiquimod is approved for the treatment of actinic keratosis and basal cell carcinoma. The present investigation aimed to develop nanoemulsion-based gel with imiquimod (2.5% w/w) and carbopol ultrez 10 NF using a modified method to enhance the solubility, permeation, and therapeutic effectiveness of imiquimod to treat skin cancer. Combinations of rose oil and oleic acid, with Tween 20/Propylene glycol as Smix, were used in the formulation. The formulation underwent evaluation for parameters such as % drug content, in vitro drug diffusion studies, viscosity, skin irritation, in vitro cytotoxicity assay (MTT assay) and the DMBA/ croton oil skin cancer in vivo model.ResultsThe formulation showed a minimum globule size of 118 nm, a zeta potential– 56.26 mV, a PDI of 0.378 and a drug content of 99.77%. In vitro drug release exhibited 45.00% of imiquimod release within 8 h, while approximately 34.32% release was found from the commercial cream. The imiquimod-loaded nanoemulsion-based gel showed significant cytotoxicity (p < 0.001) against the A431 cell line compared to Imiquad cream. The IC50 value of the imiquimod-loaded nanoemulsion-based gel was noted to be 10.76 ± 2.54 µg/mL. In vivo results showed a significant reduction in tumor incidence (16.66%), tumor volume (140.26 ± 3.48 mm3), tumor burden (5.50 mm3) and tumor mass (0.66 ± 0.05 g) compared with the DMBA/croton oil carcinogen treatment control group. Histopathological finding showed the absence of keratinized pearls, epidermal hyperplasia, and acanthosis in the formulation treated group.ConclusionThe results revealed that the nanoemulsion-based gel, with half the IMQ concentration of the commercial cream and incorporating Carbopol Ultrez 10NF, is a promising method for treating skin carcinogenesis. It potentially reduces dose-dependent side effects and demonstrating enhanced efficacy.Graphical abstract