Daylight methyl‐aminolevulinate photodynamic therapy versus ingenol mebutate for the treatment of actinic keratoses: an intraindividual comparative analysis

Daylight‐photodynamic therapy (D‐PDT) and ingenol mebutate (IM) are novel therapies directed to actinic keratoses (AK). The purpose of our study was to compare effectiveness, tolerability, cosmetic outcome and patient preference of D‐PDT versus IM in the treatment of grade I and II AK. Twenty‐seven patients with AK on the face or scalp were enrolled. Each patient received, in a 25 cm² target area, D‐PDT on right side and IM on left side. Overall 323 AK were treated. Both target areas achieved complete response in 40.47% of the cases and average AK clearance rate was similar for D‐PDT and IM (p=0.74). In D‐PDT areas mean grade II AK clearance rate was lower compared with that of grade I AK (p=0.015). In IM areas grade I and II AK average clearance rates were similar (p=0.28). At week 1 and month 1, mean local skin responses (LSR) score were higher in areas treated with IM. IM areas showed more severe pain and cosmetic sequelae. D‐PDT had similar effectiveness to IM, even if IM demonstrated higher grade II AK clearance rate. Tolerability profile was superior for D‐PDT in terms of LSR and pain. D‐PDT was more cosmetically acceptable. Patients preferred D‐PDT to IM in most cases.     

Daylight‐mediated photodynamic therapy for actinic damage in Latin America: consensus recommendations

Although conventional photodynamic therapy (c‐PDT) using methyl aminolevulinate cream (MAL) is effective for the treatment of grade I‐II facial and scalp actinic keratosis (AK), it is associated with treatment‐related pain for some patients. Daylight‐mediated PDT (DL‐PDT) has shown similar efficacy to c‐PDT, was nearly painless, and was well tolerated. Overall, DL‐PDT effectively treats AK and offers a simpler and better tolerated treatment option than c‐PDT. This consensus panel provided recommendations on the use of DL‐PDT in Latin America (LATAM) for the treatment of actinic damage associated with few or multiple AKs. The panel was comprised of eight dermatologists from different LATAM countries who have experience using PDT for the treatment of actinic damage. The panel reviewed the relevant literature and provided personal expertise with regard to using DL‐PDT for the treatment of photodamage with or without AK. The recommendations formulated by the expert panel provide evidence‐based guidelines on all aspects of DL‐PDT for the treatment of actinic damage associated with AK in different regions of LATAM. These recommendations provide guidance for dermatologists to ensure maintenance of efficacy and safety of DL‐PDT when treating actinic damage, associated with few or multiple AKs in sun‐exposed skin.     

Daylight photodynamic therapy with MAL cream for large‐scale photodamaged skin based on the concept of ‘actinic field damage’: recommendations of an international expert group

Conventional PDT (c‐PDT) is a widely used and approved non‐invasive treatment for actinic keratosis (AK). Recent clinical, histological and immunohistochemical observations have shown that c‐PDT with methyl aminolevulinate (MAL) may also partially reverse the signs of photodamage. However, pain and the need for special light source equipment are limiting factors for its use, especially in the treatment of large areas. More recently, daylight PDT (DL‐PDT) has been shown to be similar to c‐PDT in the treatment of AK, nearly painless and more convenient to perform. To establish consensus on recommendations for the use of MAL DL‐PDT in patients with large‐scale photodamaged skin. The expert group was comprised of eight dermatologists. Consensus was developed based on the personal experience of the experts in c‐PDT and DL‐PDT, and results of an extensive literature review. MAL DL‐PDT for large areas of photodamaged skin was evaluated and recommendations based on broad clinical experience were provided. As supported by evidence‐based data from multicentre studies conducted in Australia and Europe, the authors defined the concept of ‘actinic field damage’ which refers to photodamage associated with actinic epidermal dysplasia, and provide comprehensive guidelines for the optimal use of DL‐PDT in the treatment of actinic field damage. The authors concluded that MAL DL‐PDT has a similar efficacy to c‐PDT at 3‐month (lesion complete response rate of 89% vs. 93% in the Australian study and 70% vs. 74% in the European study (95% C.I. = [?6.8;?0.3] and [?9.5;2.4] respectively) and 6‐month follow‐ups (97% maintenance of complete lesion response) in the treatment of AKs. The authors agree that DL‐PDT is not only efficacious but also nearly pain‐free and easy to perform, and therefore results in high patient acceptance especially for the treatment of areas of actinic field damage.     

Consensus recommendations on the use of daylight photodynamic therapy with methyl aminolevulinate cream for actinic keratoses in Australia

Australia has the highest prevalence of actinic keratoses (AK) worldwide. Because of the risk of transformation of AK to invasive squamous cell carcinomas, consensus guidelines recommend that AK are removed using appropriate therapies to prevent progression to invasive disease. Daylight photodynamic therapy (PDT) is emerging as an efficacious treatment for AK, particularly for patients who require treatment of large areas of chronic actinic damage that can be exposed easily to daylight. Daylight PDT with methyl aminolevulinate (MAL) cream is a simple treatment for AK, almost painless, well tolerated and convenient, requiring minimal time in the clinic. Randomised controlled studies from northern Europe and Australia support the use of daylight PDT as an effective therapy for grade I and II AK on the face and scalp. There is sufficient daylight to conduct daylight PDT in Australia at any time of the year and during most weather conditions. Hence, daylight PDT with MAL can be included as an effective and well‐tolerated new treatment option for the treatment of AK in Australia. These consensus recommendations provide guidelines for Australian clinicians on the use of daylight PDT in the treatment of diagnosed AK.     

Treatment of post-transplant premalignant skin disease: a randomized intrapatient comparative study of 5-fluorouracil cream and topical photodynamic therapy

BACKGROUND: Organ transplant recipients (OTR) are at high risk of developing nonmelanoma skin cancer and premalignant epidermal dysplasia (carcinoma in situ/ Bowen's disease and actinic keratoses). Epidermal dysplasia is often widespread and there are few comparative studies of available treatments. OBJECTIVES: To compare topical methylaminolaevulinate (MAL) photodynamic therapy (PDT) with topical 5% fluorouracil (5-FU) cream in the treatment of post-transplant epidermal dysplasia. METHODS: Eight OTRs with epidermal dysplasia were recruited to an open-label, single-centre, randomized, intrapatient comparative study. Treatment with two cycles of topical MAL PDT 1 week apart was randomly assigned to one area of epidermal dysplasia, and 5-FU cream was applied twice daily for 3 weeks to a clinically and histologically comparable area. Patients were reviewed at 1, 3 and 6 months after treatment. The main outcome measures were complete resolution rate (CRR), overall reduction in lesional area, treatment-associated pain and erythema, cosmetic outcome and global patient preference. RESULTS: At all time points evaluated after completion of treatment, PDT was more effective than 5-FU in achieving complete resolution: eight of nine lesional areas cleared with PDT (CRR 89%, 95% CI: 0.52-0.99), compared with one of nine lesional areas treated with 5-FU (CRR 11%, 95% CI: 0.003-0.48) (P = 0.02). The mean lesional area reduction was also proportionately greater with PDT than with 5-FU (100% vs. 79% respectively). Cosmetic outcome and patient preference were also superior in the PDT-treated group. CONCLUSIONS: Compared with topical 5-FU, MAL PDT was a more effective and cosmetically acceptable treatment for epidermal dysplasia in OTRs and was preferred by patients. Further studies are now required to confirm these results and to examine the effect of treating epidermal dysplasia with PDT on subsequent development of squamous cell carcinoma in this high risk population.     

Photodynamic therapy with BF‐200 ALA for the treatment of actinic keratosis: results of a prospective,randomized, double‐blind,placebo‐controlled phase III study

Background Photodynamic therapy (PDT) with 5‐aminolaevulinic acid (ALA) provides a therapeutic option for the treatment of actinic keratosis (AK). Different strategies are applied to overcome the chemical instability of ALA in solution and to improve skin penetration. A new stable nanoemulsion‐based ALA formulation, BF‐200 ALA, is currently in clinical development for PDT of AK. Objectives To evaluate the efficacy and safety of PDT of AK with BF‐200 ALA. Methods The study was performed as a randomized, multicentre, double‐blind, placebo‐controlled, interindividual, two‐armed trial with BF‐200 ALA and placebo. A total of 122 patients with four to eight mild to moderate AK lesions on the face and/or the bald scalp were included in eight German study centres. The efficacy of BF‐200 ALA after one and two PDT treatments was evaluated. BF‐200 ALA was used in combination with two different light sources under illumination conditions defined by European competent authorities. Results PDT with BF‐200 ALA was superior to placebo PDT with respect to patient complete clearance rate (per‐protocol group: 64% vs. 11%; P < 0·0001) and lesion complete clearance rate (per‐protocol group: 81% vs. 22%) after the last PDT treatment. Statistically significant differences in the patient and lesion complete clearance rates and adverse effect profiles were observed for the two light sources, Aktilite^® CL128 and PhotoDyn^® 750, at both time points of assessment. The patient and lesion complete clearance rates after illumination with the Aktilite^® CL128 were 96% and 99%, respectively. Conclusions BF‐200 ALA is a very effective new formulation for the treatment of AK with PDT. Marked differences between the efficacies and adverse effects were observed for the different light sources used. Thus, PDT efficacy is dependent both on the drug and on the characteristics of the light source and the illumination conditions used.     

Methyl aminolevulinate (Metvix) photodynamic therapy - practical pearls

Topical photodynamic therapy (PDT) is an effective treatment for certain non-melanoma skin cancers (NMSCs), including superficial and nodular basal cell carcinomas (sBCC and nBCC), actinic keratosis (AK) and Bowen's disease. Methyl aminolevulinate (MAL, Metvix) is licensed in Europe for use in PDT for sBCC, nBCC and thin or non-hyperkeratotic and non-pigmented AK on the face and scalp, where other therapies are unsuitable. Optimal PDT response can be achieved through appropriate patient selection and lesion preparation. Evidence of efficacy is reviewed from guidelines and clinical experience. Red light from an LED source offers a relatively efficient method of activating the photodynamic reaction. The most common side effect of PDT is pain, burning or stinging discomfort at the site of treatment, although most patients do not request pain relief. The incidental observation of surface fluorescence three hours after photosensitizer application can be utilized for tumour detection as well as delineation. Topical PDT using Metvix MAL offers a practical non-invasive therapy option with the potential for high efficacy and good cosmesis.     

Successful treatment of multiple actinic keratoses in organ transplant patients with topical 5% imiquimod: a report of six cases

BACKGROUND: Nonmelanoma skin cancer represents a significant cause of morbidity in organ transplant recipients (OTRs). Cutaneous malignancies, mainly invasive squamous cell carcinoma and its precursor actinic keratosis (AK), appear approximately 5-10 years after organ transplantation. Impaired wound healing and high recurrence rates in immunocompromised patients treated with destructive therapies such as cryosurgery or topical 5-fluorouracil represent frequently known complications. OBJECTIVES: To evaluate the safety and efficacy of imiqimod 5% in the treatment of AKs in OTRs. METHODS: Six OTRs (two kidney, two heart, one lung and one liver) with extensive AKs were treated with imiquimod 5% cream two to three times weekly in an open-label uncontrolled, nonrandomized pilot study. RESULTS: In five of six patients treated with imiquimod 5% cream all AK lesions were cleared after 12-16 weeks. One patient showed partial response. Local adverse events at the site of application included erythema, oedema and mild erosion. No wound infection or scarring was observed in any of these patients. All graft-related laboratory parameters were stable during and after treatment. Immunosuppressive therapy remained unchanged throughout the treatment. CONCLUSIONS: These results suggest that imiquimod 5% cream may be useful for the local treatment of precancerous AK lesions in OTRs.     

Pain during topical photodynamic therapy: uncomfortable and unpredictable

Background The major drawback of the widely used photodynamic therapy (PDT) is treatment‐related pain. Objective Gain insight into the intensity of and predictive factors for painful burning sensation associated with PDT. Methods A prospective cohort study was performed at the department of Dermatology in the Maastricht University Medical Centre in Maastricht, a reference centre for dermatological oncology in The Netherlands. A total of 141 lesions in 108 patients were included, treated from November 2008 until June 2009 with PDT for superficial basal cell carcinoma, Bowen’s disease (BD) or actinic keratosis (AK). Painful burning sensation was scored based on an 11‐point pain intensity numeric rating scale (PI‐NRS) (0 = no pain; 10 = worst possible pain). Results The percentage of patients with a PI‐NRS score over six was 32.6% and 37.9% during the primary and follow‐up PDT session respectively. A total of 76.6% (95/124) of the patients was consistent in pain intensity score reporting. Factors associated with higher PI‐NRS scores were treatment of AK or BD, tumour localization in the head/neck region, patient’s age over 70, Fitzpatrick skintype I/II, photosensitizer 5‐aminolevulinic acid and use of oral analgesics. After mutual adjustment of these factors, Fitzpatrick skintype remained the only independent predictor of PI‐NRS scores during PDT. Conclusion It remains difficult to decide which patients should be considered for pain relieving measures. The solution remains to support all patients treated with PDT with pain relieving techniques or to let the support of pain relieving measures depend on the reported pain score for the primary session.     

Photodynamic therapy for the prevention and treatment of actinic keratosis/squamous cell carcinoma in solid organ transplant recipients: a systematic review and meta-analysis

Solid organ transplant recipients (sOTR) are at an increased risk of developing cutaneous cancers, especially squamous cell carcinoma (SCC). Photodynamic therapy (PDT) for the prevention and treatment of actinic keratosis (AK)/SCC in sOTR is increasingly prescribed given the increase in solid organ transplantations performed worldwide. PDT has added advantages of superior cosmetic outcomes and good safety profile compared to conventional surgical methods and other topical therapies. We aim to evaluate the role of PDT in the prevention and treatment of AK/SCC in sOTRs. The Cochrane Library, PubMed and EMBASE database were searched. Articles reporting PDT outcomes amongst sOTR with or without AK/SCC at baseline were selected. We classified the studies into two categories: (i) PDT as prevention measure and (ii) treatment of AK/SCC in sOTR. Primary outcome for the prevention category was 3-year incidence of AK/SCC and complete response (CR) of lesions after PDT exposure in the treatment category. Secondary outcomes were cosmesis and adverse reaction in both categories. Pooled results were expressed as risk difference (RD) with corresponding 95% confidence interval (95% CI). Twelve out of 641 articles met our eligibility criteria, out of which four RCTs reported the preventive effect of AK/SCC and another five RCTs reported the treatment effect of PDT in sOTR. One RCT did not report absolute number of lesions at baseline/end of study for results to be pooled in the quantitative analysis. The remaining three studies were cohort studies reporting treatment and preventive effect of PDT in sOTR. PDT group had a lower incidence as a preventive measure with pooled RD of 0.14 (95% CI 0.08–0.19). The CR in PDT was higher in the treatment group with a pooled RD of 0.77 (95% CI 0.6–0.94) and 0.50 (95% CI 0.22–0.79) in predivided lesional areas and number of lesions, respectively. In conclusion, PDT is efficacious for prevention and treatment of AK/SCC in sOTRs.     

Long‐term follow‐up of photodynamic therapy with a self‐adhesive 5‐aminolaevulinic acid patch: 12 months data

Background Photodynamic therapy with a self‐adhesive 5‐aminolaevulinic acid (5‐ALA) patch shows high efficacy rates in the treatment of mild to moderate actinic keratosis (AK) in short term trials. Objectives The purpose of the trial was to follow up patients after successful 5‐ALA patch‐PDT at 3 month intervals over a total period of 12 months. Patients who had received placebo‐PDT or cryosurgery served for comparison. Patients/methods Three months after therapy, 360 patients from two separate randomized parallel group phase III studies (one superiority trial vs. placebo‐PDT, one noninferiority trial vs. cryosurgery) were suitable for the follow‐up study. Patients had to show at least one successfully treated AK lesion after initial therapy. A total of 316 patients completed the follow‐up. Results Twelve months after a single treatment, 5‐ALA patch‐PDT still proved superior to placebo‐PDT and cryosurgery (P < 0·001 for all tests). On a lesion basis, efficacy rates were 63% and 79% for PDT, 63% for cryosurgery and 9% and 25% for placebo‐PDT. Recurrence rates of patch‐PDT proved superior to those of cryosurgery (per protocol set: P = 0·011, full analysis set: P = 0·049). While 31% of cryosurgery lesions were still hypopigmented after 1 year, the 5‐ALA patch‐PDT groups showed hypopigmentation in 0% (superiority trial) and 3% (noninferiority trial) of the treated lesions. Conclusion Twelve months after a single 5‐ALA patch‐PDT the majority of lesions were still cleared with an excellent cosmetic outcome. 5‐ALA patch‐PDT proved to be superior to cryosurgery in the noninferiority study setting.     

Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a multicentre, randomized, observer-blind phase III study in comparison with a registered methyl-5-aminolaevulinate cream and placebo

Background Photodynamic therapy (PDT) with 5‐aminolaevulinic acid (ALA) or its methylester [methyl‐5‐aminolaevulinate (MAL) or 5‐amino‐4‐oxopentanoate] was recently ranked as first‐line therapy for the treatment of actinic keratosis (AK) and is an accepted therapeutic option for the treatment of neoplastic skin diseases. BF‐200 ALA (Biofrontera Bioscience GmbH, Leverkusen, Germany) is a gel formulation of ALA with nanoemulsion for the treatment of AK which overcomes previous problems of ALA instability and improves skin penetration. Objectives To evaluate the efficacy and safety of PDT of AKs with BF‐200 ALA in comparison with a registered MAL cream and with placebo. Methods The study was performed as a randomized, multicentre, observer‐blind, placebo‐controlled, interindividual trial with BF‐200 ALA, a registered MAL cream and placebo in a ratio of 3 : 3 : 1. Six hundred patients, each with four to eight mild to moderate AK lesions on the face and/or the bald scalp, were enrolled in 26 study centres in Germany, Austria and Switzerland. Patients received one PDT. If residual lesions remained at 3 months after treatment, PDT was repeated. Results PDT with BF‐200 ALA was superior to placebo PDT with respect to patient complete clearance rate (78·2% vs. 17·1%; P < 0·0001) and lesion complete clearance rate (90·4% vs. 37·1%) at 3 months after the last PDT. Moreover, superiority was demonstrated over the MAL cream regarding the primary endpoint patient complete clearance (78·2% vs. 64·2%; P < 0·05). Significant differences in the patient and lesion complete clearance rates and severity of treatment‐related adverse events were observed for the narrow‐ and broad‐spectrum light sources. Conclusions BF‐200 ALA is a very effective, well‐tolerated new formulation for AK treatment with PDT and is superior to a registered MAL medication. Efficacies and adverse events vary greatly with the different light sources used.     

Photodynamische Therapie mit Methylaminooxopentanoat (Metvix®) und einer Breitbandlichtquelle (PhotoDyn 501): Praktische Erfahrungen bei Problem‐Patienten mit Aktinischen Keratosen und Basalzellkarzinomen

Background: Actinic keratoses (AK) and basal cell carcinomas (BCC) may represent a therapeutic challenge because of special subtypes, location, previous therapy or accompanying diseases. Photodynamic therapy (PDT) offers a semi‐conservative treatment option for selected indications. Patients and methods: 28 outpatients who had been admitted as complicated dermato‐oncologic cases because of AK (n = 22) and BCC (n = 6) were treated with PDT, using methylaminooxopentanoate (MAOP, Methyl‐Ala, Metvix®) and a broad band light source (PhotoDyn 501). The treatment was evaluated for efficacy and subjective tolerance (local discomfort and pain). Results: A complete remission (CR) was achieved in 11/22 AK (50 %) and 4/6 BCC (67 %) cases. All three cases of a superficial BCC subtype underwent a CR. Among responders, tolerance was good in 12/15 cases (80 %), as compared to 4/13 cases (31 %) in non‐responders. Focusing on 16/28 patients with good tolerance (57 %), there was a CR in 12 cases (75 % rate), whereas for the 12/28 patients with moderate to poor tolerance a CR was achieved in only 3 cases (25 % rate). In a subgroup of 8 patients who, partly due to secondary diseases, were taking systemic retinoids or immunosuppressive‐cytostatic medications, a CR was achieved in 3/8 cases (38 %) with a good tolerance in only 1/8 cases (13 %). Conclusion: These observations confirm a good efficacy and tolerance of PDT in ≥ 50 % of a AK/BCC problem patient cohort. We found indications for 1) a positive correlation between efficacy and subjective tolerance as well as 2) the presumptive existence of a retinoid‐dependent cutaneous PDT hyperalgesia. Effective pain control seems to be an essential cofactor for the success of PDT.     

Photodynamic therapy of actinic keratoses with 8% and 16% methyl aminolaevulinate and home-based daylight exposure: a double-blinded randomized clinical trial

Background  Photodynamic therapy (PDT) is an effective but time-consuming and often painful treatment for actinic keratosis (AK). Home-based daylight–PDT has the potential to facilitate treatment procedure and to reduce associated pain due to continuous activation of small amounts of porphyrins. Moreover, a reduced methyl aminolaevulinate (MAL) concentration may reduce associated inflammation, making the treatment more tolerable for the patients.
Objectives  To compare response rates and adverse effects after PDT using conventional 16% and 8% MAL with home-based daylight exposure in treatment of AK.
Methods  Thirty patients with mostly thin-grade AK of the face or scalp were treated with 16% and 8% MAL–PDT in two symmetrical areas after application of sunscreen. Immediately after, patients left the hospital with instructions to spend the remaining day outside at home in daylight. Patients scored pain during treatment and light exposure was monitored with an electronic wristwatch dosimeter.
Results  The complete response rate after 3 months was 76·9% for 16% MAL and 79·5% for 8% MAL ( P  = 0·37). Patients spent a mean of 244 min outdoors and received a mean effective light dose of 30 J cm⁻². Light doses of 8–70 J cm⁻² induced similar response rates ( P  = 0·25). Patients experienced mild to moderate pain during daylight exposure (mean maximal pain score of 3·7). No differences in pain scores and erythema were seen between the areas treated with 16% MAL and with 8% MAL.
Conclusions  Home-based daylight-mediated MAL–PDT was an effective and well-tolerated treatment for AK. No differences in response rates or adverse events were found between the areas treated with 16% MAL and with 8% MAL.     

Comparative study for the effect of photodynamic therapy,imiquimod immunotherapy and combination of both therapies on 40 lesions of actinic keratosis in Japanese patients

We treated 12, 15 and 13 Japanese actinic keratosis (AK) lesions with 5‐aminolevulinic acid photodynamic therapy (PDT), 5% imiquimod cream and combination of both therapies, respectively, and compared the effects. Patients underwent the second course, when AK lesions remained after the first course. Efficacy was evaluated 1 month after each treatment. Combination therapy cleared all AK lesions only after the first course, while PDT and imiquimod therapy cleared 41.7% and 66.7% of AK lesions after the first course, respectively. All residual AK lesions after the first course were cleared by the second courses of PDT or imiquimod therapy. During the course, erosion and crust developed significantly more frequently in combination therapy (P < 0.001). Most Japanese AK lesions can be satisfactorily treated with either PDT or imiquimod monotherapy. However, only severe cases may better be treated with combination therapy, which show higher efficacy even though adverse events occur frequently.     

Photodynamic therapy for basal cell carcinomas in organ-transplant recipients

The incidence of nonmelanoma skin cancer is significantly increased in recipients of solid-organ transplants. Photodynamic therapy (PDT) is a well-documented treatment option for superficial and selected nodular basal cell carcinomas (BCCs) in immunocompetent patients, but there are few reports describing PDT of BCCs in organ-transplant recipients (OTRs). We report a study of 18 OTRs with BCC on the head and trunk, who were treated with PDT, using methyl aminolevulinate as photosensitizer. There was only one recurrence during a total follow-up period of 407 months. PDT seems to be an effective treatment option for BCC in immunosuppressed OTRs.     

Multicentre intraindividual randomized trial of topical methyl aminolaevulinate-photodynamic therapy vs. cryotherapy for multiple actinic keratoses on the extremities

Background  Methyl aminolaevulinate–photodynamic therapy (MAL‐PDT) is an effective treatment in facial/scalp actinic keratosis (AK). Objectives The aims of this study were to compare efficacy, safety, cosmetic outcome and patient preference of MAL‐PDT vs. cryotherapy in patients with AK at other locations. Methods A multicentre, controlled, randomized, open, intraindividual, right–left comparison was performed. Patients with nonhyperkeratotic AK were treated once with MAL‐PDT and cryotherapy on either side of the body. At week 12, lesions showing noncomplete response were retreated. The primary efficacy variable was the lesion response at week 24. Investigator’s assessment of cosmetic outcome, patient’s preference in terms of cosmetic outcome and a patient preference questionnaire were also analysed at week 24. Results In total, of 121 patients with 1343 lesions (98% located on the extremities and the remainder on the trunk and neck) were included. Both treatments provided a high mean percentage reduction in lesion count at week 24 with significantly higher efficacy for cryotherapy: 78% for MAL‐PDT and 88% for cryotherapy (P = 0·002, per protocol population). Investigator’s assessment of cosmetic outcome was significantly better for MAL‐PDT than cryotherapy (P < 0·001), 79% of lesions having an excellent cosmetic outcome with MAL‐PDT vs. 56% with cryotherapy at week 24. The cosmetic outcome achieved by MAL‐PDT compared with cryotherapy was also preferred by patients (50% vs. 22%, respectively, P < 0·001), and 59% of patients would prefer to have any new lesions treated with MAL‐PDT compared with 25% with cryotherapy (P < 0·001). Both treatment regimens were safe and well tolerated. Conclusions MAL‐PDT showed inferior efficacy for treatment of non‐face/scalp AK compared with cryotherapy. However, both treatments showed high efficacy, and MAL‐PDT conveyed the advantages of better cosmesis and higher patient preference.     

Intensified photodynamic therapy of actinic keratoses with fractional CO2 laser: a randomized clinical trial

Background Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is effective for thin actinic keratoses (AKs) in field‐cancerized skin. Ablative fractional laser resurfacing (AFXL) creates vertical channels that facilitate MAL uptake and may improve PDT efficacy. Objectives To evaluate efficacy and safety of AFXL‐assisted PDT (AFXL‐PDT) compared with conventional PDT in field‐directed treatment of AK. Methods Fifteen patients with a total of 212 AKs (severity grade I–III) in field‐cancerized skin of the face and scalp were randomized to one treatment with PDT and one treatment with AFXL‐PDT in two symmetrical areas. Following curettage of both treatment areas, AFXL was applied to one area using 10 mJ per pulse, 0·12 mm spot, 5% density, single pulse (UltraPulse^®, DeepFx handpiece; Lumenis Inc., Santa Clara, CA, U.S.A.). MAL cream was then applied under occlusion for 3 h and illuminated with red light‐emitting diode light at 37 J cm^?2. Fluorescence photography quantified protoporphyrin IX (PpIX) before and after illumination. Results At 3‐month follow‐up, AFXL‐PDT was significantly more effective than PDT for all AK grades. Complete lesion response of grade II–III AK was 88% after AFXL‐PDT compared with 59% after PDT (P = 0·02). In grade I AK, 100% of lesions cleared after AFXL‐PDT compared with 80% after PDT (P = 0·04). AFXL‐PDT‐treated skin responded with significantly fewer new AK lesions (AFXL‐PDT n = 3, PDT n = 11; P = 0·04) and more improved photoageing (moderate vs. minor improvement, P = 0·007) than PDT‐treated skin. Pain scores during illumination (6·5 vs. 5·4; P = 0·02), erythema and crusting were more intense, and long‐term pigmentary changes more frequent from AFXL‐PDT than PDT (P = not significant). PpIX fluorescence was higher in AFXL‐pretreated skin [7528 vs. 12 816 arbitrary units (AU); P = 0·003] and photobleached to equal intensities after illumination (AFXL‐PDT 595 AU, PDT 454 AU; P = 0·59). Conclusions AFXL‐PDT is more effective than conventional PDT for treatment of AK in field‐cancerized skin.     

European Dermatology Forum guidelines on topical photodynamic therapy 2019 Part 1: treatment delivery and established indications – actinic keratoses,Bowen's disease and basal cell carcinomas

Topical photodynamic therapy (PDT) is a widely approved therapy for actinic keratoses, Bowen's disease (squamous cell carcinoma in situ), superficial and certain thin basal cell carcinomas. Recurrence rates when standard treatment protocols are used are typically equivalent to existing therapies, although inferior to surgery for nodular basal cell carcinoma. PDT can be used both as lesional and field therapies and has the potential to delay/reduce the development of new lesions. A protocol using daylight to treat actinic keratoses is widely practised, with conventional PDT using a red light after typically a 3‐h period of occlusion employed for other superficial skin cancer indications as well as for actinic keratoses when daylight therapy is not feasible. PDT is a well‐tolerated therapy although discomfort associated with conventional protocol may require pain‐reduction measures. PDT using daylight is associated with no or minimal pain and preferred by patient. There is an emerging literature on enhancing conventional PDT protocols or combined PDT with another treatment to increase response rates. This guideline, published over two parts, considers all current approved and emerging indications for the use of topical PDT in dermatology, prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence.