Daylight photodynamic therapy versus cryosurgery for the treatment and prophylaxis of actinic keratoses of the face - protocol of a multicenter, prospective, randomized, controlled, two-armed study.
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ABSTRACT: Photodynamic therapy with daylight (DL-PDT) is efficacious in treating actinic keratosis (AK), but the efficacy of field-directed, repetitive DL-PDT for the treatment and prophylaxis of AK in photodamaged facial skin has not yet been investigated.In this multicenter, prospective, randomized, controlled, two-armed, observer-blinded trial, patients with a minimum of 5 mild-to-moderate AK lesions on photodamaged facial skin are randomly allocated to two treatment groups: DL-PDT with methyl aminolevulinate (MAL) and cryosurgery. In the DL-PDT group (experimental group), 5 treatments of the entire face are conducted over the course of 18 months. After preparation of the lesion and within 30 min after MAL application, patients expose themselves to daylight for 2 h. In the control group, lesion-directed cryosurgery is conducted at the first visit and, in the case of uncleared or new AK lesions, also at visits 2 to 5. The efficacy of the treatment is evaluated at visits 2 to 6 by documenting all existing and new AK lesions in the face. Cosmetic results and improvement of photoaging parameters are evaluated by means of a modified Dover scale. Primary outcome parameter is the cumulative number of AK lesions observed between visits 2 and 6. Secondary outcome parameters are complete clearance of AK, new AK lesions since the previous visit, cosmetic results independently evaluated by both patient and physician, patient-reported pain (visual analogue scale), patient and physician satisfaction scores with cosmetic results, and patient-reported quality of life (Dermatology Life Quality Index). Safety parameters are also documented (adverse events and serious adverse events).This clinical trial will assess the efficacy of repetitive DL-PDT in preventing AK and investigate possible rejuvenating effects of this treatment. (Trial registration: ClinicalTrials.gov Identifier: NCT02736760).ClinicalTrials.gov Identifier: NCT02736760 . Study Code Daylight_01. EudraCT 2014-005121-13.
Daylight photodynamic therapy versus cryosurgery for the treatment and prophylaxis of actinic keratoses of the face - protocol of a multicenter, prospective, randomized, controlled, two-armed study.
<h4>Background</h4>Photodynamic therapy with daylight (DL-PDT) is efficacious in treating actinic keratosis (AK), but the efficacy of field-directed, repetitive DL-PDT for the treatment and prophylaxis of AK in photodamaged facial skin has not yet been investigated.<h4>Methods/design</h4>In this multicenter, prospective, randomized, controlled, two-armed, observer-blinded trial, patients with a minimum of 5 mild-to-moderate AK lesions on photodamaged facial skin are randomly allocated to two tre ...[more]
Project description:BackgroundGuidelines recommend treating actinic keratoses (AKs) as they are recognized as precursors of invasive squamous cell carcinoma.ObjectiveThe objective of this study was to collect real-world clinical data on the use of methyl aminolevulinate daylight photodynamic therapy (MAL DL-PDT) for the treatment of face and scalp AK in Europe.MethodsA prospective, multicenter, non-interventional study was conducted in six European countries in patients receiving a single treatment of MAL DL-PDT for face and/or scalp AK. Patient-reported outcomes were assessed by patient questionnaires at baseline and at 3 months after treatment, efficacy was assessed at 3 months using a 6-point global improvement scale, and adverse events (AE) were recorded at each visit.ResultsOverall, 325 patients were enrolled from 52 investigational centres, 314 of whom attended the 3-month visit. Most patients had multiple lesions (58.4% had >10 lesions) with lesions mainly located on the scalp (60.0%) and/or forehead (54.2%). AKs were predominantly grade I (39.4%) or grade II (33.2%), and 10.5% of patients had grade III lesions. The proportions of patients and physicians that were overall satisfied to very satisfied with the MAL DL-PDT treatment were 80.4% and 90.3%, respectively. The vast majority of patients (90.0%) would consider using MAL DL-PDT again if needed. Physician-assessed efficacy at 3 months was at least much improved in 83.5% of patients, with 45.9% of patients requiring no retreatment. Related AEs were reported in 15% of patients.ConclusionUse of MAL DL-PDT for multiple face and/or scalp AKs resulted in high levels of patient and physician satisfaction in clinical practice in Europe, reflecting the good efficacy and high tolerability of this convenient procedure.
Project description:Aminolevulinic acid photodynamic therapy (ALA-PDT) can be effective and well tolerated when applied over a broad area and for short drug incubation times.To evaluate the effect of short-incubation time and application method on the safety and efficacy of ALA-PDT versus vehicle (VEH-PDT) in the treatment of actinic keratoses (AKs) of the face or scalp.Aminolevulinic acid or VEH was applied to face or scalp as a broad area application for 1, 2, or 3 hours or as a spot application for 2 hours before blue light activation. An identical treatment was repeated at Week 8 if any AK lesions remained.Median AK clearance rate for ALA-treated subjects ranged from 68% to 79% at Week 12, compared with 7% of the VEH-treated group (p < .0001). Complete clearance rate for ALA-treated subjects ranged from 17% (8/46) to 30% (14/47) at Week 12, compared with 2% (1/46) of the VEH-treated group (p = .0041). The safety profile seen in this study is consistent with previously reported side effects of the therapy.Short-incubation ALA-PDT was found to be superior to VEH-PDT for AK lesion clearance. A second treatment improves efficacy.
Project description:BackgroundBlue light photodynamic therapy (PDT) is effective for actinic keratosis, but many patients experience stinging pain during illumination.ObjectiveTo compare a conventional regimen (1 hour of 5-aminolevulinic acid [ALA] preincubation, followed by blue light) versus a new modified regimen in which blue light is started immediately after ALA application.MethodsA clinical trial with a bilaterally controlled, intrapatient study design was conducted with 23 patients. Topical 20% ALA was applied to the entire face and/or scalp. On 1 side of the body, blue light was started immediately and continued for either 30, 45, or 60 minutes (simultaneous PDT). On the contralateral side, the blue light began 1 hour after ALA application and lasted 1000 seconds (conventional PDT). Pain was evaluated on a scale from 0 to 10. Actinic keratosis lesion counts were determined by clinical examination and photography.ResultsAll patients experienced significantly less pain during simultaneous illumination than during the conventional regimen. At 3 months after treatment, lesion clearance was nearly identical on the 2 sides, as determined by statistical testing of noninferiority ± 15% margin.LimitationsAlthough bilaterally controlled, the study was relatively small. Additional studies are recommended.ConclusionThe modified PDT regimen is essentially painless, yet it provides treatment efficacy similar to a conventional regimen.
Project description:Importance:Photodynamic therapy (PDT) is an effective and cosmetically favorable treatment modality for actinic keratoses (AKs). However, prolonged incubation times and pain associated with treatment are burdensome to the patient and a hindrance to widespread use of PDT as standard field therapy for AK. Objective:To evaluate efficacy and pain associated with microneedle expedited PDT. Design, Setting, and Participants:The Microneedle Photodynamic Therapy II (MNPDT-II) study was a randomized, single-blinded, split-face controlled, 2-arm clinical trial. Thirty-three participants with AK on the face were recruited in a university dermatology outpatient clinic from 2015 to 2016, and 32 participants completed the study. Interventions:Participants were randomized into 2 incubations arms, either 10-minute or 20-minute aminolevulinic acid (ALA) incubation times, after pretreatment with a microneedle roller (200 um) vs a sham roller. They were blinded to the laterality of microneedle and sham roller assignments. After incubation, they were exposed to blue light (Blu-U, Dusa Pharmaceuticals) for 1000 seconds for a total fluence of 10 J/cm2. Main Outcomes and Measures:The primary outcome was to quantitatively measure AK resolution, and the secondary outcome was to assess pain associated with microneedle pretreatment. Results:Thirty-three individuals were recruited and randomized to either the 20-minute or the 10-minute incubation arm. Thirty-two participants completed the study with a mean follow-up time of 34.5 days in the 20-minute group, and 30.2 days in the 10-minute group. For the 20-minute incubation arm, average AK clearance was 76% vs 58% on the sham side (P < .01), including 3 patients with complete clearance, although not statistically significant (P = .25). Pain assessment on the visual analog scale (VAS) during blue light illumination was not significantly different between the microneedle and sham sides (0.7 and 0.4; P = .28), respectively. For the 10-minute incubation arm AK clearance for the microneedle pretreated side was 43% compared with 38% on the sham side (P = .66). Pain during the blue light exposure was not significantly different between the microneedle and sham sides, 4.5 mm and 3.4 mm (P = .21), respectively. Conclusions and Relevance:Photodynamic therapy with microneedle pretreatment at a 20-minute ALA incubation time significantly improved AK clearance with efficacy similar to that of a conventional 1-hour ALA incubation time. The additional advantage to expedited treatment was that the procedure was virtually painless. However, expedited exposure of a 10-minute ALA incubation time did not reach significantly different AK clearance from the sham control. Trial Registration:clinicaltrials.gov Identifier: NCT02594644.
Project description:Reflectance confocal microscopy (RCM) presents a non-invasive method to image actinic keratosis (AK) at a cellular level. However, RCM criteria for AK response monitoring vary across studies and a universal, standardized approach is lacking. We aimed to identify reliable AK response criteria and to compare the clinical and RCM evaluation of responses across AK severity grades. Twenty patients were included and randomized to receive either cryotherapy (n = 10) or PDT (n = 10). Clinical assessment and RCM evaluation of 12 criteria were performed in AK lesions and photodamaged skin at baseline, 3 and 6 months. We identified the RCM criteria that reliably characterize AK at baseline and display significant reduction following treatment. Those with the highest baseline odds ratio (OR), good interobserver agreement, and most significant change over time were atypical honeycomb pattern (OR: 12.7, CI: 5.7-28.1), hyperkeratosis (OR: 13.6, CI: 5.3-34.9), stratum corneum disruption (OR: 7.8, CI: 3.5-17.3), and disarranged epidermal pattern (OR: 6.5, CI: 2.9-14.8). Clinical evaluation demonstrated a significant treatment response without relapse. However, in grade 2 AK, 10/12 RCM parameters increased from 3 to 6 months, which suggested early subclinical recurrence detection by RCM. Incorporating standardized RCM protocols for the assessment of AK may enable a more meaningful comparison across clinical trials, while allowing for the early detection of relapses and evaluation of biological responses to therapy over time.
Project description:BackgroundClinical diagnosis of actinic keratosis is known to have intra- and inter-observer variability, and there is currently no non-invasive and objective measure to diagnose these lesions.ObjectiveThe aim of this pilot study was to determine if automatically detecting and circumscribing actinic keratoses in clinical photographs is feasible.MethodsPhotographs of the face and dorsal forearms were acquired in 20 volunteers from two groups: the first with at least on actinic keratosis present on the face and each arm, the second with no actinic keratoses. The photographs were automatically analysed using colour space transforms and morphological features to detect erythema. The automated output was compared with a senior consultant dermatologist's assessment of the photographs, including the intra-observer variability. Performance was assessed by the correlation between total lesions detected by automated method and dermatologist, and whether the individual lesions detected were in the same location as the dermatologist identified lesions. Additionally, the ability to limit false positives was assessed by automatic assessment of the photographs from the no actinic keratosis group in comparison to the high actinic keratosis group.ResultsThe correlation between the automatic and dermatologist counts was 0.62 on the face and 0.51 on the arms, compared to the dermatologist's intra-observer variation of 0.83 and 0.93 for the same. Sensitivity of automatic detection was 39.5% on the face, 53.1% on the arms. Positive predictive values were 13.9% on the face and 39.8% on the arms. Significantly more lesions (p<0.0001) were detected in the high actinic keratosis group compared to the no actinic keratosis group.ConclusionsThe proposed method was inferior to assessment by the dermatologist in terms of sensitivity and positive predictive value. However, this pilot study used only a single simple feature and was still able to achieve sensitivity of detection of 53.1% on the arms.This suggests that image analysis is a feasible avenue of investigation for overcoming variability in clinical assessment. Future studies should focus on more sophisticated features to improve sensitivity for actinic keratoses without erythema and limit false positives associated with the anatomical structures on the face.
Project description:IntroductionActinic keratoses (AK) are treated to reduce the risk of progression to squamous cell carcinoma and for symptomatic and cosmetic benefits. The objective of this observational study was to generate real-life data on the use of daylight photodynamic therapy with methyl aminolevulinate cream (MAL DL-PDT) in treating mild to moderate facial/scalp AK.MethodsA multicenter, prospective, observational study was conducted in Australia in patients receiving a single treatment of MAL DL-PDT for mild to moderate AK. Efficacy was assessed 3 months after treatment by investigator-assessed improvement and patient- and physician-completed satisfaction questionnaires. Adverse events were recorded throughout the study.ResultsOverall, 81 patients were enrolled of mean age 62.7 years, mostly men (76.5%) with skin phototype I (64.2%) or II (35.8%) and a long history of AK (mean duration 16.8 years). Most had multiple lesions (82.7% had >10 lesions) of predominantly grade I (75.3%). At 3 months after treatment, almost half the patients (46.8%) required no further treatment. The proportions of patients and physicians satisfied to very satisfied with the MAL DL-PDT treatment were 79.7% and 83.3%, respectively. After receiving the treatment, 74.1% of patients indicated via the questionnaire that they were not bothered at all by the pain. Related AEs were reported in 48.1% of patients, mainly mild erythema (44.4%).ConclusionsIn clinical practice in Australia, the use of MAL DL-PDT in treating multiple mild to moderate non-hyperkeratotic AK of the face and/or scalp results in high levels of patient and physician satisfaction reflecting the good efficacy and tolerability of this almost painless, convenient procedure.Trial registrationClinicalTrials.gov identifier, NCT02674048.FundingGalderma R&D.
Project description:ObjectiveActinic keratoses (AKs) are cutaneous lesions that arise in sun-damaged skin. AKs may transform into squamous cell carcinoma in situ. Tirbanibulin 1% ointment is a new topical treatment for AKs, recently approved by the Food and Drug Administration.Data sourcesThe PubMed database was searched for articles published from 1960 to March 31, 2021, using the keywords tirbanibulin and Klisyri.Data extractionPhase 2 and phase 3 clinical trials were reviewed.Data synthesisIn phase 2 clinical trials, 43% of patients treated with tirbanibulin experienced complete clearance by day 57 (43% [95% CI = 32, 54]). Across two phase 3 clinical trials (pooled data), complete (100%) clearance occurred in 49% of patients in tirbanibulin groups and in only 9% of the vehicle groups (difference, 41% points; 95% CI = 35 to 47; P < 0.001). Although no comparative studies are available, tirbanibulin is applied for a shorter duration (5 days) compared with diclofenac 3% gel, fluorouracil 5% cream, and imiquimod 3.75% cream. Adverse events were mild and included pruritus, application site pain, and local skin reactions. Systemic adverse events such as necrosis and angioedema, observed with other AK treatments such as fluorouracil and imiquimod, were not observed with tirbanibulin, thus giving tirbanibulin a favorable safety profile.Relevance to patient care and clinical practiceTirbanibulin effectively reduces AK burden and recurrence and has a favorable safety profile with mild adverse events. In comparison, imiquimod, 5-flourouracil, and diclofenac can result in necrosis, angioedema, and arthralgias.ConclusionWith a favorable safety profile and short regimen, tirbanibulin is an efficacious treatment for clinicians to utilize in their treatment toolbox when treating AKs on the face and scalp.
