[Tirbanibulin in large field of cancerization: new approach for sequential treatment of contiguous areas.] / Tirbanibulina nel grande campo di cancerizzazione: nuovo approccio per il trattamento sequenziale di aree contigue.

Actinic keratosis (AK) is a common cutaneous keratinocyte dysplasia characterized by the abnormal proliferation of atypical epidermal keratinocytes; an area that presents photoinduced subclinical changes, similar to those found in AKs, on the periphery of clinically visible AKs is defined as a field of cancerization. Its treatment, rather than a treatment aimed at the single lesion, is more recommended as it manages the subclinical damage and prevents the onset of a possible squamous cell carcinoma. Among the field therapies, tirbanibulin has recently been introduced with an innovative mechanism of action that determines cellular apoptosis and consequently a poor local inflammatory reaction. We present the case of an 82-year-old patient, known for previous removals of squamous cell carcinomas at the vertex and currently suffering from a large field of cancerization in the nose and scalp, to whom we proposed a sequential treatment with three cycles of tirbanibulin in contiguous areas. The treatment was well tolerated and allowed complete clearance to be obtained on the nose and > 95% on the scalp, with a reduction of the Actinic Keratosis Area and Severity Index (AKASI) from 9.4 to 1.4.

[Tirbanibulin in the treatment of actinic keratoses: description of a case with instrumental evaluation and long-term follow-up.] / La tirbanibulina nel trattamento delle cheratosi attiniche: descrizione di un caso con valutazione strumentale e follow-up a lungo termine.

A 72-year-old man presented with actinic keratosis (AK) of the scalp confirmed by line-field confocal optical coherence tomography (LC-OCT) a novel non-invasive skin imaging technique. Patient was treated with Tirbanibulin 1% ointment once a day for 5 consecutive days and, after 8 days from baseline, mild erythema and desquamation was observed on the treated area, associated with mild pruritus. At the same time-point, L'LC-OCT revealed the presence of intraepidermal "targeted-like" cells, corresponding to apoptotic keratinocytes. After 2 months, clinical and instrumental examination showed the almost total disappearance of the AK. At the same time-point, a strong improvement of photoaging was noted at the level of the treated area. At 1-year follow-up, no relapse and/or new AK were observed. In conclusion, the reported case is emblematic of the short and long-term efficacy and safety of tirbanibulin in the treatment of AK, as already reported in the literature, as well as of the usefulness of non-invasive imaging technique such as LC-OCT in the therapeutic monitoring.

[Efficacy of topical tirbanibulin in treating grade 2 actinic keratosis.] / Efficacia della tirbanibulina topica nel trattamento della cheratosi attinica di grado 2.

Actinic keratoses (AK) are common precancerous lesions usually arising on chronic sun-exposed areas. Field of cancerization (FC) is a chronically UV-exposed area in which subclinical multifocal AKs are found. Therapeutic choice is mainly made according to the Olsen grade of AKs. We report the case of a 76-year-old man with numerous AKs of the face and scalp. The patient had undergone numerous topical physical and medical therapies with poor results. On the left cheek, grade I and grade II AKs were found in a large FC, so he was prescribed topical therapy with tirbanibulin 1% ointment. After 10 days erythema and crusts were objectified and a burning sensation was reported on the area of application and on surrounding areas. At 8 weeks follow-up, the patient had total resolution of disease and no residual local side effects. Although tirbanibulin 1% ointment has indication for type I AKs of face and scalp, this case reported its efficacy and benefit also on type II AKs, demonstrating safety and a minimal and manageable degree of discomfort caused to the patient. Therefore, it fits fully among the treatments of grade I AKs but numerous still may be its indications as demonstrated in our case, where efficacy, safety and compliance were combined.

Calcipotriol and 5-Fluorouracil Combination Therapy for the Treatment of Actinic Keratosis in the Clinic: A Review Article.

This review examines the pharmacology, efficacy and safety, dosage and administration, and place in therapy of the combination of 5-fluorouracil (5-FU) and calcipotriol for the treatment of actinic keratosis. Currently, 5% 5-FU topical cream is approved for actinic keratosis treatment, while calcipotriol is indicated for plaque psoriasis in adults. The typical administration of 5-FU involves topical application twice daily for up to 4 weeks, whereas calcipotriol is applied in a thin layer once or twice daily as directed by a physician. Adverse effects of 5-FU are primarily localized, including skin irritation, ulceration, pruritus, erythema, crusting, and eczematous reactions due to minimal systemic absorption. Calcipotriol may cause burning, itching, and skin irritation. This review details clinical trials that investigate the innovative approach of combining topical 5-FU with calcipotriol for actinic keratosis treatment, highlighting the significant outcomes. Notably, the clinical trials indicate that all participants experienced either a reduction in lesion size or complete lesion clearance, with minimal adverse effects impacting treatment success. The combination of 5-FU and calcipotriol effectively treats actinic keratosis by enhancing the immune response and targeting cell overgrowth, while reducing local site reactions and the lengthy treatment time often associated with existing therapies.

If patients had a choice - Treatment satisfaction and patients' preference in therapy of actinic keratoses.

BACKGROUND: Actinic keratoses (AK) are increasing in incidence and represent the most common (pre-)cancerous lesion in the fair-skinned population, with a high unmet medical need. In order to increase treatment adherence, it is very important to assess patients' therapy-related evaluations of different treatment options. PATIENTS AND METHODS: 100 patients with AK who were treated with at least two different treatment options were included. They rated their therapies using the Treatment Satisfaction Questionnaire for Medication (TSQM, maximum 100 points per category) and a Likert scale (LS, 1  =  very satisfied; 6  =  not satisfied). Patients were also asked about their needs in terms of treatment goal, cost, type, duration, and location of treatment. RESULTS: 81% of the study participants were male and on average 74 years old. 95% had field cancerization. Eight frequently used therapy procedures were evaluated by the patients (surgery, cryotherapy, various topical agents, photodynamic therapy). The TSQM satisfaction scores ranged from 78.47 ± 16.07 (surgical procedures) to 53.03 ± 22.13 (diclofenac-HA). Statistically significant differences between the procedures were only found in the area of efficacy. Side effects were classified as low. Low recurrence rate and safe removal were the most important treatment goals (LS: 1.18 ± 0.44 and 1.27 ± 0.53, respectively). CONCLUSIONS: Understanding patient preferences is essential for adherence and is therefore of great importance for the success of AK therapy. Personalized approaches should be considered in the choice of therapy.

Effective treatment of actinic keratosis on the hands with red light photodynamic therapy using BF-200 ALA.

BACKGROUND: Acral actinic keratosis (AK) lesions are considered difficult to treat, and published data for photodynamic therapy (PDT) on these lesions is limited. Thus, we evaluated sustained efficacy, safety, and satisfaction after PDT for AK on the hands. METHODS: We analysed subgroup data for treatment on the hands from a randomised, double-blind, intra-individual phase III study. All participants previously underwent up to two field-directed red light PDTs with 10 % 5-aminolevulinic acid nanoemulsion gel (BF-200 ALA). Assessments included pain during PDT, clearance and recurrence rates, and satisfaction. RESULTS: 24 participants treated on the hands were included; 21 participants were analysed. Complete clearance rates with BF-200 ALA were 90.9 % (lesion-based) and 76.2 % (per participant's side), both markedly higher than with vehicle. The lesion recurrence rate with BF-200 ALA was 29.0 %. Adverse events reflected the mode of action. Mean pain intensities were 4.8 ± 3.8 (BF-200 ALA) and 0.8 ± 2.1 (vehicle) on an 11-point numeric rating scale. Most participants (81.0 %) rated their satisfaction with BF-200 ALA as very good or good. CONCLUSION: This subgroup analysis indicates that PDT with BF-200 ALA provides a suitable treatment for AK lesions on the hands.

Clinical trial of two-step photodynamic therapy for reduced pain in the treatment of precancerous squamous lesions (Actinic keratoses).

BACKGROUND: Pain associated with aminolevulinic acid photodynamic therapy (ALA-PDT) for the treatment of facial dermatoses results in low patient compliance. Two-step photodynamic therapy (two-step PDT) may improve comfort by optimizing light amplitude and exposure time. OBJECTIVE: To investigate the efficacy of two-step PDT in reducing the pain generated during the treatment of facial skin disorders. METHODS: Twenty-six patients with AK were randomly divided into two groups; the experimental group was treated with two-step photodynamic therapy and the control group was treated with conventional photodynamic therapy. The pain intensity of the patients at different times was assessed using the pain numerical rating scale (NRS). RESULTS: A total of 26 patients completed three ALA-PDT treatments, 13 and 13 patients in each group, respectively. The mean NRS scores of patients in the experimental group (3.28±1.41, 3.33±1.43, 3.42±1.78) were lower than those of the control group (5.00±1.94, 5.09±1.86, 4.86±1.64) on each occasion. The incidence of certain adverse reactions was lower in the experimental group than in the control group. There was no difference between the two groups in terms of clinical outcome, recurrence rate and patient satisfaction. CONCLUSION: Two-step photodynamic therapy can reduce pain and the incidence of some adverse reactions, but does not affect clinical efficacy, recurrence rate and patient satisfaction.

Anti-tumor effects of tirbanibulin in squamous cell carcinoma cells are mediated via disruption of tubulin-polymerization.

Topical tirbanibulin is a highly effective and well tolerated novel treatment option for actinic keratoses (AKs). This study aimed to characterize the mode of action of tirbanibulin in keratinocytes (NHEK) and cutaneous squamous cell carcinoma (cSCC) cell lines (A431, SCC-12) in vitro. Tirbanibulin significantly reduced proliferation in a dose-dependent manner in all investigated cell lines, inhibited migration, and induced G2/M-cell cycle arrest only in the cSCC cell lines analyzed, and induced apoptosis solely in A431, which showed the highest sensitivity to tirbanibulin. In general, we detected low basal expression of phosphorylated SRC in all cell lines analyzed, therefore, interference with SRC signaling does not appear to be the driving force regarding the observed effects of tirbanibulin. The most prominent tirbanibulin-mediated effect was on ß-tubulin-polymerization, which was especially impaired in A431. Additionally, tirbanibulin induced an increase of the proinflammatory cytokines IL-1α, bFGF and VEGF in A431. In conclusion, tirbanibulin mediated anti-tumor effects predominantly in A431, while healthy keratinocytes and more dedifferentiated SCC-12 were less influenced. These effects of tirbanibulin are most likely mediated via dysregulation of ß-tubulin-polymerization and may be supported by proinflammatory aspects.

Reflectance confocal microscopy as noninvasive tool for monitoring tirbanibulin efficacy in actinic keratosis.

Actinic keratosis (AK) is a common precancerous condition found on sun-damaged skin. Tirbanibulin 1 % ointment has been approved for the topical treatment of non-hyperkeratotic facial and scalp Olsen grade I AKs over a contiguous area of 25 cm2 with a daily application for 5 consecutive days. Our aim was to investigate the use of in vivo RCM in the assessment of the response of AKs treated with tirbanibulin, as it has never been described in the published Literature. A total of 10 AKs in 10 consecutive outpatients were enrolled in the present study in May 2023. The follow-up visit was scheduled after 30 days from last application of tirbanibulin ointment. At follow-up visit, a complete response was described by clinical, dermoscopic and in vivo RCM examination in 10 out of 10 lesions, with a recovery of stratum corneum, decrease in atypical honeycomb pattern and changes in dermal collagen. All patients were followed up for at least 8 months and further recurrences were not registered. Based on our experience, we confirm the efficacy and safety of tirbanibulin in treating AKs and the usefulness of RCM in vivo examination for the therapeutic monitoring of such lesions, even in a very early stage.

Patient- and Clinician-Reported Outcomes for Tirbanibulin in Actinic Keratosis in Clinical Practice Across the United States (PROAK).

BACKGROUND: The Patient-Reported Outcomes in Actinic Keratosis (PROAK) study evaluated patient- and clinician-reported outcomes (PRO; ClinRO) during 24 weeks of follow-up among adult patients with actinic keratosis (AK) on the face or scalp who were administered tirbanibulin 1% ointment in real-world community practices in the United States.  Methods: Quality of life (QoL) was assessed by Skindex-16 at week (W) 8. Additionally, effectiveness (Investigator Global Assessment [IGA]), PRO and ClinRO (Treatment Satisfaction Questionnaire for Medication and Expert Panel Questionnaire), safety, and tolerability were assessed at W8 and W24. RESULTS: The safety population included 300 patients; the full analysis set included 290 patients (278 patients at W24). At W8, a statistically significant difference (P<0.03) was observed for Skindex-16 domains in all assessed subgroups. Clinicians and patients reported high global satisfaction (mean [SD] scores of 74.9 [23.9] and 72.0 [24.6], respectively) at W24. Overall skin appearance improved from baseline to W24 (83.6% clinicians; 78.5% patients). IGA success (IGA score of 0-1) was achieved by 71.9% of patients at W24 with a similar % at W8 (73.8%) suggesting a stable effectiveness over time. About 5% of patients reported at least one adverse event, 4% reported at least one serious adverse event and no patients reported serious adverse drug reactions. At W8, the most frequently reported local skin reactions were mild/moderate erythema (47.6%) and flaking/scaling (49.6%). CONCLUSIONS: Treatment with tirbanibulin demonstrated effectiveness in the management of AK lesions and a favorable safety and tolerability profile. Furthermore, QoL was improved as early as W8, and both patients and clinicians reported high levels of treatment satisfaction, independently of patients' characteristics. J Drugs Dermatol. 2024;23(5):338-346. doi:10.36849/JDD.8264.

Topical Calcipotriol Plus 5-Fluorouracil in the Treatment of Actinic Keratosis, Bowen's Disease, and Squamous Cell Carcinoma: A Systematic Review.

BACKGROUND/OBJECTIVES: Actinic keratoses (AK) are premalignant skin lesions caused by chronic sun exposure, topically managed by 5-fluorouracil (5-FU), diclofenac 3% gel, and imiquimod. Despite their effectiveness, long treatment duration and severe adverse local skin reactions have limited patient concordance. Calcipotriol has recently been used as a combination agent for existing topical AK treatments. A systematic review was performed to determine the clinical efficacy of 5-FU and calcipotriol for the treatment of AK, Bowen's disease, and squamous cell carcinoma (SCC). METHODS: A systematic literature search was conducted on Medline, Embase, and Cochrane Library. Among the 84 records screened, 12 were retrieved for full-text review and 8 were included in the final analysis. RESULTS: Among the 8 studies, there were 214 control patients and 288 patients who received the intervention. The combination 5% 5-FU with calcipotriol resulted in a significant reduction in the number of AKs on the face, scalp, right upper extremity, and left upper extremity for all sites at 8 weeks (P < .0001). No significant difference in SCC incidence was observed at 1 or 2 years, but there was a significant reduction observed at 3 years for SCC on face and scalp. No study assessed the combination for Bowen's disease. CONCLUSIONS: Combination 5% 5-FU with calcipotriol is an effective treatment for Aks; however, future trials may consider longer treatment and follow-up periods for the treatment and prevention of AK, SCC in situ, and SCC.

Mobile health technologies in an interventional hybrid study on actinic keratosis: Results from an early phase randomized controlled trial investigating the safety and efficacy of a cytosolic phospholipase A2 inhibitor gel in photodamaged skin.

Hybrid trials are a new trend in dermatological research that leverage mobile health technologies to decentralize a subset of clinical trial elements and thereby reduce the number of in-clinic visits. In a Phase I/IIa randomized controlled hybrid trial, the safety and efficacy of an anti-proliferative and anti-inflammatory drug inhibiting cytosolic phospholipase A2 (AVX001) was tested using 1%, 3% or vehicle gel in 60 patients with actinic keratosis (AK) and assessed in-clinic as well as remotely. Over the course of 12 weeks, patients were assessed in-clinic at baseline, end of treatment (EOT) and end of study (EOS), as well as 9 times remotely on a weekly to biweekly basis. Safety outcomes comprising local skin reactions (LSR; 0-5), adverse events (AE) and cosmesis, were graded in-clinic and remotely using patient-obtained smartphone photographs (PSPs) and questionnaires; efficacy was assessed in-clinic based on clinically visible clearance of AK target area of >50%. A total of 55 participants (91.7%) completed the treatment course. The average submission rate of PSPs was high (≥85%), of which 93% were of sufficient quality. No serious AE were reported and only two experienced temporary LSR >2 (scale 0-4) and cosmesis remained stable throughout the study. Based on the mild AE and LSR profile, daily application of AVX001 gel for 1 month appears safe, tolerable, and cosmetically acceptable for use in patients with AK. At EOT, AVX001 achieved a subtle treatment response with clearance of AK target area of >50% in 18% of patients. Remote and in-clinic assessments of LSRs were in high agreement, suggesting that the use of mobile health technologies in early-phase hybrid studies of AK does not compromise patient safety.

Therapeutic and fluorescence evaluation of 20% 5-aminolevulinic acid-mediated photodynamic therapy in actinic keratosis.

BACKGROUND: Actinic keratosis (AK) is a precancerous lesion that occurs in areas that are chronically exposed to sunlight and has the potential to develop into invasive cutaneous squamous cell carcinoma (cSCC). We investigated the efficacy of 20 % 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) with LED red light for the treatment of AK in Chinese patients by examining changes in dermoscopic features, histopathology and fluorescence after treatment. METHODS: Twenty-eight patients with fourty-six AK lesions from March 2022 to September 2023 were treated with 20 % ALA, and 3 h later, they were irradiated with LED red light (80-100 mW/cm2) for 20 min. A session of 20 % ALA-PDT was performed once a week for three consecutive weeks, and the dermoscopic, histopathological, fluorescent and photoaging outcomes were measured one week after the treatment. RESULTS: One week after ALA-PDT, complete remission (CR) was reached in 53.6 % of patients. The CR of Grade I AK lesions was 100 %, that of Grade II lesions was 71.4 %, and that of Grade III lesions was 38.1 %. There was a significant improvement in the dermoscopic features, epidermal thickness and fluorescence of the AK lesions. The presence of red fluorescence decreased, and there was an association between CR and post-PDT fluorescence intensity. ALA-PDT also exhibited efficacy in treating photoaging, including fine lines, sallowness, mottled pigmentation, erythema, and telangiectasias, and improved the global score for photoaging. There were no serious adverse effects during or after ALA-PDT, and 82.1 % of the patients were satisfied with the treatment. CONCLUSION: AK lesions can be safely and effectively treated with 20 % ALA-PDT with LED red light, which also alleviates photoaging in Chinese patients, including those with multiple AKs. This study highlights the possibility that fluorescence could be used to diagnose AK with peripheral field cancerization and evaluate the efficacy of ALA-PDT.

Efficacy and safety of 0.5% colchicine cream versus 5% 5-fluorouracil cream in the treatment of cutaneous field cancerization: a randomized clinical trial.

BACKGROUND: 5-Fluorouracil (5-FU) is a first-line drug to treat cutaneous field cancerization (CFC). There are few clinical trials with topical colchicine (COL). OBJECTIVE: To evaluate the effectiveness of 0.5% COL cream versus 5% 5-FU cream in the treatment of CFC. METHOD: This was a randomized, open, self-controlled clinical trial. Forty-five patients (90 forearms), with three to ten actinic keratoses (AK) on each forearm, used 0.5% COL cream 2×/day for seven days on one forearm, and 5% 5-FU cream 2× /day, for 21 days, on the other forearm. The dosages were defined based on previous clinical trials for each drug. Adverse effects were evaluated after 14 days and outcomes after 90 days of inclusion. The primary outcome was complete AK clearance and the secondary outcomes were: partial clearance (≥50%), reduction in AK count, assessment of the Forearm Photoaging Scale (FPS), AK Severity Score (AKSS), and adverse effects. RESULTS: After 90 days, there was complete clearance of AK in 37% (95% CI 24%-49%) and partial clearance in 85% (95% CI 76%-93%) of the forearms treated with 5-FU,versus 17% (95% CI 7%-27%) and 78% (95% CI 66%-88%) for COL (p > 0.07). There was a percentage reduction of 75% in the AK count of the forearms treated with 5-FU (95% CI 66%-83%) and 64% in those treated with COL (95% CI 55%-72%). Regarding FPS and AKSS, there was improvement in both groups, with no difference regarding FPS (p = 0.654), and 5-FU superiority for AKSS (p = 0.012). STUDY LIMITATIONS: Single-center study. CONCLUSIONS: 5-FU and COL are effective for treating CFC, with neither showing superiority regarding the reduction in AK counts.

Exploring Patient Pain Experiences during and after Conventional Red Light and Simulated Daylight Photodynamic Therapy for Actinic Keratosis: A Qualitative Interview Study.

Simulated daylight photodynamic therapy is a relatively new and potentially less painful alternative to conventional red light photodynamic therapy for actinic keratosis. Qualitative research exploring patient experiences of pain and skin reactions during these treatments is scarce. To address this, semi-structured interviews were conducted of 10 patients aged 60-81 years with symmetrically distributed actinic keratoses 4 weeks after split-face treatment with conventional red light photodynamic therapy and simulated daylight photodynamic therapy. The participants were recruited from an ongoing clinical randomized trial. Interviews (median length 35 min) were conducted between June 2022 and January 2023, audio-recorded, transcribed verbatim, and analysed qualitatively using content analysis, as described by Graneheim and Lundman. Participants reported that conventional red light photodynamic therapy was very painful during illumination and transiently painful in the post-treatment period, while simulated daylight photodynamic therapy was almost painless during illumination and led to minor post-treatment pain. Also, skin reactions were more intense and longer-lasting with conventional red light photodynamic therapy than with simulated daylight photodynamic therapy. Most participants expressed a treatment preference for simulated daylight photodynamic therapy but had reservations about its unestablished long-term effectiveness. This study underscores the considerable pain associated with conventional red light photodynamic therapy, and the pivotal importance of shared decision-making when selecting the most appropriate treatment.

Efficacy and tolerability of tirbanibulin 1% ointment in the treatment of cancerization field: a real-life Italian multicenter observational study of 250 patients.

BACKGROUND: Tirbanibulin 1% ointment is approved for the field treatment of Olsen grade I actinic keratoses (AKs) of the face and scalp. METHODS: We performed a multicenter retrospective study involving 15 dermatologic units in Italy to investigate the efficacy and tolerability of tirbanibulin in a real-life setting. 250 patients were enrolled. Tirbanibulin, 1% ointment, was applied daily for five consecutive days. The efficacy of treatment was measured with modifications of the Actinic Keratosis Area and Severity Index (AKASI). A satisfactory response was defined by complete (100% reduction in the number of lesions) or partial clearance (75-99%) of treated AKs. RESULTS: Overall, the AKASI score was significantly reduced in the studied population (mean, from 4.1 ± 2.7 to 1.4 ± 1.5; P < 0.001). A satisfactory response was observed in 222 (88.8%) cases. The proportion of satisfactory responses was higher when follow-up was performed after 8 weeks (34/35, 97.1%). The reduction in AKASI was significant in patients with Olsen grade II or III lesions (from 5.3 ± 2.8 to 1.6 ± 1.6; P < 0.001). A satisfactory response was observed in 91/104 (87.5%) cases. AKASI reduction was also significant in patients with trunk or limb AKs (from 7.0 ± 1.3 to 2.0 ± 1.6; P = 0.018) since a satisfactory response was observed in 7/8 (87.5%) cases. Tirbanibulin was well tolerated; all adverse events (AEs) included transient local reactions at the site of treatment. Overall, 231 patients had at least one AE. Only 7 (2.8%) grade 4 AEs were recorded. CONCLUSION: Our retrospective study confirmed that tirbanibulin 1% ointment is effective and well tolerated in a real-life setting and is also promising for Olsen grade II and grade III AKs and AKs localized on difficult-to-treat areas.

Viscum Album Lipophilic Extract in Actinic Keratosis, Cutaneous Squamous Cell Carcinoma, and Basal Cell Carcinoma: A Retrospective Case Series.

INTRODUCTION: Cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) belong to the group of keratinocyte carcinomas (KC). Actinic keratosis (AK) is a precursor lesion of cSCC. The incidences of cSCC, BCC, and AK are currently strongly increasing. Different standard therapies exist for these conditions but are not always applicable or successful. Hydrophilic Viscum album extracts have been used in anthroposophic cancer therapy since 1917. Viscum album lipophilic extract (VALE) is prepared by means of supercritical CO2 extraction. This retrospective case series assessed the safety and clinical effects of a topical application of 10% VALE in individual cases of cSCC, BCC, and AK. METHODS: For this retrospective case series, a positive vote was obtained from the Ethics Committee of the University of Witten/Herdecke (No. 146/2020). Eligible patients signed a declaration of consent prior to inclusion in the study. The main outcome parameters were the clinical response to treatment with VALE and adverse drug reactions. Risk factors, concomitant therapies and diseases, further diagnostic and therapeutic information were documented where available. Data analysis was performed on the level of patients and of individual lesions. RESULTS: The study population consisted of 55 patients with 74 skin lesions. Individual case analysis accompanied by photographic documentation revealed typical and promising treatment courses. Clinical response rates (complete + partial remissions) for individual lesions were 78% for cSCC, 70% for BCC, and 71% for AK. Complete remission rates for individual lesions were 56% for cSCC, 35% for BCC, and 15% for AK. In cSCC and BCC, shorter times to best clinical response were observed. Adverse drug reactions were reported in 5 patients including erythema and inflammatory reactions of mostly moderate severity that resolved completely. In one case, therapy was temporarily paused, in four cases it was continued without interruption. DISCUSSION/CONCLUSION: The results of this study suggest that VALE is a safe and tolerable extract under whose application complete and partial remissions of KC could be observed. To improve and assess the efficacy of VALE, prospective investigations are necessary.Das kutane Plattenepithelkarzinom (cSCC) und das Basalzellkarzinom (BCC) gehören zur Gruppe der Keratinozytenkarzinome (KC). Die aktinische Keratose (AK) ist eine Vorstufe des cSCC. Die Häufigkeit von cSCC, BCC und AK ist derzeit stark im Steigen begriffen. Es gibt verschiedene Standardtherapien für diese Erkrankungen, die jedoch nicht immer anwendbar oder erfolgreich sind. Hydrophile Viscum album-Extrakte werden seit 1917 in der anthroposophischen Krebstherapie eingesetzt. Viscum album Lipophilic Extract (VALE) wird mittels überkritischer CO2-Extraktion hergestellt. In dieser retrospektiven Fallserie wurden die Sicherheit und die klinischen Auswirkungen einer topischen Anwendung von 10% VALE bei einzelnen Fällen von cSCC, BCC und AK untersucht.Für diese retrospektive Fallserie wurde ein positives Votum der Ethikkommission der Universität Witten/Herdecke eingeholt (Nr. 146/2020). Die in Frage kommenden Patienten unterzeichneten vor der Aufnahme in die Studie eine Einverständniserklärung. Die wichtigsten Ergebnisparameter waren das klinische Ansprechen auf die Behandlung mit VALE und unerwünschte Arzneimittelwirkungen. Risikofaktoren, Begleittherapien und -erkrankungen sowie weitere diagnostische und therapeutische Informationen wurden, soweit vorhanden, dokumentiert. Die Datenanalyse wurde für jeden einzelnen Patienten und jeder einzelnen Läsion durchgeführt.Die Studienpopulation bestand aus 55 Patienten mit 74 Hautläsionen. Die Einzelfallanalyse mit Fotodokumentation ergab typische und vielversprechende Behandlungsverläufe. Die klinischen Ansprechraten (vollständige + partielle Remissionen) für einzelne Läsionen lagen bei 78% für cSCC, 70% für BCC und 71% für AK. Die Komplettremissionsraten für einzelne Läsionen lagen bei 56% für cSCC, 35% für BCC und 15% für AK. Bei cSCC und BCC wurden kürzere Zeiten bis zum besten klinischen Ansprechen beobachtet. Bei fünf Patienten wurden unerwünschte Arzneimittelwirkungen gemeldet, darunter Erytheme und Entzündungsreaktionen von meist mäßigem Schweregrad, die vollständig abklangen. In einem Fall wurde die Therapie vorübergehend pausiert, in vier Fällen wurde sie ohne Unterbrechung fortgesetzt.Die Ergebnisse dieser Studie deuten darauf hin, dass VALE ein sicherer und verträglicher Extrakt ist, bei dessen Anwendung vollständige und partielle Remissionen von KC beobachtet werden konnten. Um die Wirksamkeit der Therapie mit VALE weiterzuentwickeln und eingehender zu beurteilen, sind prospektive Untersuchungen erforderlich.

Home- vs clinic-based daylight photodynamic therapy with 5-aminolevulinic acid nanoemulsion (BF-200 ALA) for actinic keratosis: A randomized, single-blind, prospective study.

BACKGROUND: Daylight photodynamic therapy (DL-PDT) has become one of the most effective treatments for the resolution of actinic keratosis (AK) of Olsen grade 1 and 2. Generally, PDT it is carried out in a clinic setting, which involves the patient's and their caregivers commuting to the hospital as well as a significant use of resources to carry it out within the clinic setting. OBJECTIVES: To determine the efficacy and safety of a home-based treatment of AK with DL-PDT with the BF-200 ALA gel compared to a clinic-based setting. METHODS: The study was performed as a randomized, single-center, non-inferiority clinical trial with two parallel groups. 9 patients received one clinic-based DL-PDT (group 1) and 11 patients received one session of home-based DL-PDT (group 2). The primary endpoints were the mean AK clearance per patient and the total AK lesion clearance rate 12 weeks after treatment. The secondary endpoints were the number of remaining AKs and new AKs appearing in the treatment field 12 weeks after one PDT session. The pain during and 24 h after PDT as well as the local skin reactions were also assessed. RESULTS: The overall reduction of AK lesions per patient was similar in both groups with one PDT session. An overall AK clearance per patient of 10 ± 4.33 for group 1 versus 9.73 ± 2.9 for group 2 without statistically significant differences (p = 0.868). Regarding the clearance rate, although it was slightly higher in group 2 (71.58 ± 22.51 vs 82.1 ± 11.13), the analysis did not show statistically significant differences. The mild pain recorded during the treatment course and the mild local skin reactions were similar in both groups. Patient satisfaction was high for both groups without statistically significant differences. CONCLUSION: Self-performed home-based DL-PDT with BF-200 ALA gel is as effective as the one performed in a clinic-based setting, with a comparable safety profile, high levels of patient satisfaction and with advantages for the patients and their caregivers that can enhance patient´s adherence to the treatment.

The impact of occlusive vs non-occlusive application of methyl aminolevulinate on the efficacy and tolerability of daylight photodynamic therapy for actinic keratosis.

BACKGROUND: Conventional photodynamic therapy (c-PDT) is an effective treatment for actinic keratoses (AKs) and nonmelanoma skin cancer which exploits the photosensitizing properties of methyl aminolaevulinate (MAL). Daylight photodynamic therapy (DL-PDT) is an alternative to c-PDT which does not require the application of MAL in occlusion and that is better tolerated by patients. The impact of occlusion on the efficacy of DL-PD has not been investigated by previous studies. OBJECTIVE: To compare the efficacy and tolerability of occlusive and non-occlusive DL-PDT. METHODS: We conducted a prospective intraindividual left/right comparison study. AKs of the face or scalp were marked in two symmetrical treatment areas. The two target areas were randomly assigned to DL-PDT with occlusive and non-occlusive application of MAL. The efficacy and cosmetic outcome were determined by a "blinded" investigator. RESULTS: Lesions in occluded areas showed a better response in the clearance rate of the lesions (65.5% vs 35.0 %, p < 0.001 %), and cosmetic outcome (P < 0.001). There was no difference in phototoxicity or pain between occluded and non-occluded areas. CONCLUSION: The occlusive application of MAL improves the efficacy of DL-PDT in clearing AKs and does not increase the incidence of side effects.