Methyl Aminolaevulinate Photodynamic Therapy Research Articles

‘Efficacy and safety of imiquimod 5% cream for basal cell carcinoma: a meta‐analysis of randomized controlled trial’: a critical appraisal

Jia and He aimed 'to compare the efficacy and safety of imiquimod with other treatments in patients with basal cell carcinoma' (BCC). Meta-analysis of studies that included patients with histologically confirmed BCC treated with imiquimod 5% cream compared with all other treatments, including vehicle, excisional surgery, cryosurgery, fluorouracil and methyl aminolaevulinate photodynamic therapy. The main outcome measures included histological and composite clearance rates, success rates, complete response rates, tumour-free survival and adverse events. Thirteen studies with a total of 4265 patients were included in the review. Pooled analyses comparing imiquimod with all or any of the listed comparators, including vehicle, demonstrated higher histological clearance rates [risk ratio (RR) 9·28, 95% confidence interval (CI) 5·56-15·5; P < 0·001], higher composite clearance rates (RR 34·2, 95% CI 21·3, 55·1; P = 0·001), no significant difference in success rates (RR 0·98, 95% CI 0·89-1·08; P = 0·73), higher complete response rates (RR 3·15, 95% CI 1·55-6·38; P = 0·001), no significant difference in tumour-free survival (RR 1·15, 95% CI 0·98-1·35; P = 0·088) and increased incidence of adverse events (RR 2·00, 95% CI 1·39-2·88; P < 0·001). The authors state that 'imiquimod significantly exhibited benefit effect in improving the histological/composite clearance rates' compared with other treatments, and they suggest it could be used as the first-choice treatment for patients with BCC. The main concerns related to the article by Jia and He are that the research question is replicative, it makes little sense to combine all BCC types in a meta-analysis, and it also makes no sense to combine an active treatment against a combination of vehicle and other active treatments. There are also concerns about bias related to the use of the same study data more than once in a meta-analysis. Furthermore, we have identified an example of covert duplicate publication, which further compounds the profusion of misleading systematic reviews.

A trial-based cost-effectiveness analysis of topical 5-fluorouracil vs. imiquimod vs. ingenol mebutate vs. methyl aminolaevulinate conventional photodynamic therapy for the treatment of actinic keratosis in the head and neck area performed in the Netherlands.

SummaryBackgroundActinic keratosis (AK) is a common premalignant skin condition that might have the ability to progress into squamous cell carcinoma. Due to the high incidence of AK, treatment of this disease significantly impacts healthcare spending.ObjectivesTo determine which commonly prescribed field‐directed treatment is the most cost‐effective, when comparing 5‐fluorouracil (5‐FU) 5%, imiquimod (IMQ) 5%, ingenol mebutate (IM) 0·015% and methyl aminolaevulinate photodynamic therapy (MAL‐PDT) for AK in the head and neck region.MethodsWe performed an economic evaluation from a healthcare perspective. Data were collected alongside a single‐blinded, prospective, multicentre randomized controlled trial with 624 participants in the Netherlands. The outcome measure was expressed as the incremental cost‐effectiveness ratio, which is the incremental costs per additional patient with ≥ 75% lesion reduction compared with baseline. This trial was registered at ClinicalTrials.gov, number NCT02281682.ResultsThe trial showed that 5‐FU was the most effective field treatment for AK in the head and neck region. Twelve months post‐treatment, the total mean costs for 5‐FU were significantly lower (€433) than the €728, €775 and €1621 for IMQ, IM and MAL‐PDT, respectively. The results showed that 5‐FU was a dominant cost‐effective treatment (more effective and less expensive) compared with the other treatments, 12 months post‐treatment.ConclusionsBased on these results, we consider 5‐FU 5% cream as the first‐choice treatment option for multiple AKs in the head and neck area. What's already known about this topic? Due to the increasing incidence of actinic keratosis (AK), the recommended treatment results in a considerable socioeconomic burden for (dermatological) healthcare.Although cost‐effectiveness modelling studies have been performed in which different treatments for AK were compared, a prospective clinical trial comparing four frequently prescribed treatments on effectiveness and resource consumption within a time horizon of 12 months has never been conducted. What does this study add? This is the first study examining the cost‐effectiveness of 5‐fluorouracil 5% cream, imiquimod 5% cream, ingenol mebutate 0·015% gel and methyl aminolaevulinate photodynamic therapy, with data collected in a randomized controlled trial over a time horizon of 12 months.We found that 5‐fluorouracil was a dominant cost‐effective treatment (more effective and less costly), based on data from the Netherlands. Linked Comment: Steeb et al. Br J Dermatol 2020; 183:612.

Comparing the efficacy of field treatments for actinic keratosis: a critical appraisal of a randomized trial in the New England Journal of Medicine.

Jansen etal. conducted a randomized trial to compare the efficacy of four field treatments for actinic keratosis (AK). This was a multicentre, single-blind, randomized trial conducted in the dermatology departments of four Netherlands hospitals. Patients were not blinded. The investigator who evaluated the trial outcome was blinded. This study included adult patients with at least five AKs on the face or vertex scalp. Patients were randomized to treatment with fluorouracil 5% cream, imiquimod 5% cream, methyl aminolaevulinate photodynamic therapy (MAL-PDT) or ingenol mebutate 0·015% gel. The primary outcome was whether patients had ≥ 75% reduction in AK count 12 months after treatment. In total 624 patients participated. The likelihood of having ≥ 75% reduction in AK count 12 months after treatment was significantly higher (twice as high or greater) for fluorouracil than for any other therapy. Approximately 75% of patients treated with fluorouracil experienced ≥ 75% reduction in AK count at 12 months. Jansen etal. conclude that 1 year after treatment, fluorouracil was significantly more effective at AK reduction than imiquimod, MAL-PDT or ingenol mebutate.

Curettage and multiple needle puncture-assisted methyl-aminolaevulinate photodynamic therapy of basal cell carcinoma.

The use of skin puncture techniques may facilitate the delivery of topically applied drugs for photodynamic therapy (PDT). The main aim of this prospective study was to evaluate the efficacy and cosmetic outcome of curettage, multiple needle puncture, and methyl-aminolaevulinate (MAL)-PDT in basal cell carcinoma (BCC). All tumours received curettage and 15-20 needle punctures/cm2 before two sessions of MAL-PDT. The primary endpoint was clinically observed recurrence at follow-up. Overall, 284 patients with 299 histologically verified BCC (70 superficial, 190 nodular, 35 aggressive, and four not subtyped) were included. Following PDT, the mean follow-up period was 6.7 months. After follow-up, 274 (92%) of 299 treatment sites showed no clinical signs of recurrence, with >90% complete response for each BCC subtype. The cosmetic outcome was rated as excellent/good in 81% of cases. Good short-term treatment results were shown following curettage, multiple needle puncture, and MAL-PDT for BCC of different subtypes.

Local interventions for actinic keratosis in organ transplant recipients: a systematic review.

Actinic keratosis (AK) in organ transplant recipients (OTRs) has a high risk of progressing to invasive squamous cell carcinoma of the skin. Thus, early and consequent treatment of AKs is warranted in OTRs. To summarize the current evidence for nonsystemic treatments of AKs in OTRs. We performed a systematic literature search in MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) and hand-searched pertinent trial registers up to 22 August 2018. Randomized controlled trials (RCTs) evaluating nonsystemic interventions for AKs in OTRs were included. The risk of bias was estimated using the Cochrane Risk of Bias Tool. Of 663 records initially identified, eight RCTs with 242 OTRs were included in a qualitative synthesis. Most studies evaluated methyl aminolaevulinate photodynamic therapy (MAL-PDT), followed by ablative fractional laser (AFXL) and diclofenac sodium 3% in hyaluronic acid, imiquimod 5% cream and 5-fluorouracil 5% cream (5-FU). MAL-PDT showed the highest rates of participant complete clearance (40-76·4%), followed by imiquimod (27·5-62·1%), diclofenac (41%) and 5-FU (11%). Similar results were observed for lesion-specific clearance rates. Treatment with AFXL alone revealed low lesion clearance (5-31%). Local skin reactions were most intense in participants treated with a combination of AFXL and daylight MAL-PDT. There were no therapy-related transplant rejections or worsening of graft function in any trial. The overall risk of bias was high. Limited evidence is available for the treatment of AKs in OTRs. MAL-PDT is currently the best-studied intervention. Lesion-specific regimens may not be sufficient to achieve disease control. Field-directed regimens are preferable in this high-risk population.

Light therapies for acne: abridged Cochrane systematic review including GRADE assessments.

We undertook a Cochrane review of randomized controlled trials (RCTs) evaluating the effects of light-based interventions for acne vulgaris. We searched the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, ISI Web of Science and grey literature sources (September 2015). We used the Grading of Recommendations Assessment, Development and Evaluation Working Group approach to assess the quality of evidence (QoE). We included 71 RCTs (4211 participants, median sample size 31). Results from a single study (n = 266, low QoE) showed little or no difference in effectiveness on participants' assessment of improvement between 20% aminolaevulinic acid (ALA) photodynamic therapy (PDT), activated by blue light, vs. vehicle plus blue light, whereas another study (n = 180) comparing ALA-PDT (red light) concentrations showed that 20% ALA-PDT was no more effective than 15% ALA-PDT but better than 10% and 5% ALA-PDT. Pooled data from three studies (n = 360, moderate QoE) showed that methyl aminolaevulinate PDT, activated by red light, had a similar effect on changes in lesion counts vs. placebo cream with red light. Several studies compared yellow light with placebo or no treatment, infrared light with no treatment, gold microparticle suspension with vehicle and clindamycin/benzoyl peroxide (C/BPO) combined with pulsed dye laser with C/BPO alone. None of these showed any clinically significant effects. Most studies reported adverse effects, but inadequately, with scarring reported as absent, and blistering only in studies on intense pulsed light, infrared light and PDT (very low QoE). Carefully planned studies, using standardized outcome measures and common acne treatments as comparators, are needed.

Real-life Data on Patient Characteristics, Cost and Effectiveness of Field-directed Treatment for Actinic Keratoses: An Observational Study

Actinic keratoses (AK) occur frequently; however, real-life clinical data on personalized treatment choice and costs are scarce. This multicentre one-year observational study investigated patient-characteristics, cost and effectiveness of methylaminolaevulinate photodynamic therapy (MAL-PDT), imiquimod (IMI) and 5-fluorour-acil (5-FU) in patients with AKs on the face/scalp. A total of 104 patients preferred MAL-PDT, 106 preferred IMI and 110 preferred 5-FU. At baseline, significant differences between treatment groups were found; most patients were severely affected (mean 32.5 AK in PDT-group, 20.2 in IMI-group, 22.8 in 5-FU-group). A mean reduction in lesions of 81% after MAL-PDT, 82% after IMI and 88% after 5-FU was found after one year. Annual costs were €1,950 for MAL-PDT, €877 for IMI and €738 for 5-FU. These results show that, compared with clinical trials, in the real-life clinical setting AK patients are usually more severely affected and treatment costs are much higher. Furthermore, patient characteristics are important factors in treatment choice.

Topical corticosteroid reduces inflammation without compromising the efficacy of photodynamic therapy for actinic keratoses: a randomized clinical trial.

Photodynamic therapy (PDT) is an effective and established treatment for actinic keratoses (AK) and nonmelanoma skin cancer. The main side-effects of PDT are post-treatment erythema and oedema, and pain during illumination. Severe erythema after PDT enhances the down time associated with the treatment. To evaluate in a randomized intraindividual study whether use of a topical corticosteroid just before and just after PDT would reduce treatment-induced erythema compared with conventional PDT. Twenty-two patients with multiple AKs in the face and scalp were treated with methyl aminolaevulinate PDT in two symmetrical areas. One area was randomized to superpotent corticosteroid (clobetasol propionate) before and just after PDT. Objective and visual erythema, protoporphyrin IX (PpIX) fluorescence and pain were evaluated. Topical corticosteroid significantly reduced PDT-induced erythema (P = 0·012). The complete lesion response rate 3 months after PDT, and PpIX fluorescence prior to illumination did not differ significantly between the two treated areas. Superpotent corticosteroid before and just after PDT reduced the erythema 24 h after treatment of multiple AKs on the face and scalp. The use of topical corticosteroid did not affect the efficacy of PDT and may be an easy way to make PDT treatment of large visible areas more acceptable.

A randomized trial comparing methyl aminolaevulinate photodynamic therapy with and without Er:YAG ablative fractional laser treatment in Asian patients with lower extremity Bowen disease: results from a 12-month follow-up

Methyl aminolaevulinate photodynamic therapy (MAL-PDT) is an effective treatment for Bowen disease (BD) of the lower extremities. Er:YAG (erbium:yttrium-aluminium-garnet) ablative fractional laser (AFL) treatment removes the stratum corneum to increase MAL uptake and may improve efficacy. However, no studies have directly compared the efficacy of MAL-PDT with and without Er:YAG AFL therapy in treating BD of the lower extremities in Asians. To compare the efficacy, recurrence rate, cosmetic outcomes and safety between Er:YAG AFL-assisted MAL-PDT (Er:YAG AFL-PDT) and standard MAL-PDT. Twenty-one patients with a total of 58 BD lesions randomly received either one session of Er:YAG AFL-PDT or two sessions of MAL-PDT in two symmetrical areas. Er:YAG AFL therapy was performed with 550-600 μm ablation depth, level 1 coagulation, 22% treatment density and a single pulse. MAL cream was then applied under occlusion for 3 h and illuminated with a red light-emitting diode lamp at 37 J cm(-2) . A second session of MAL-PDT was administered 7 days later. Overall response rate, recurrence rate, cosmetic outcomes and safety were assessed at 1 week, 3 and 12 months after treatment. After 3 months, Er:YAG AFL-PDT was significantly more effective (93.8%) than MAL-PDT (73.1%; P = 0.031), and the recurrence rate was significantly lower for Er:YAG AFL-PDT (6.7%) than MAL-PDT (31.6%) at 12 months (P = 0.022). No significant difference was found between Er:YAG AFL-PDT and MAL-PDT in terms of cosmetic outcomes or safety. Er:YAG AFL-PDT showed significantly higher efficacy and lower recurrence rate than did standard MAL-PDT for treating lower extremity BD in an Asian population.

Oxygen saturation and perfusion changes during dermatological methylaminolaevulinate photodynamic therapy

Methylaminolaevulinate (MAL)-photodynamic therapy (PDT) is a successful topical treatment for a number of (pre)cancerous dermatological conditions. In combination, light of the appropriate wavelength, the photosensitizer protoporphyrin IX (PpIX) and tissue oxygen result in the production of singlet oxygen and reactive oxygen species inducing cell death. This study investigates real-time changes in localized tissue blood oxygen saturation and perfusion in conjunction with PpIX fluorescence monitoring for the first time during dermatological MAL-PDT. Oxygen saturation, perfusion and PpIX fluorescence were monitored noninvasively utilizing optical reflectance spectroscopy, laser Doppler perfusion imaging and a fluorescence imaging system, respectively. Patients attending for standard dermatological MAL-PDT were recruited to this ethically approved study and monitored prior to, during and after light irradiation. Significant reductions in mean blood oxygen saturation (P < 0·005) and PpIX fluorescence (P < 0·001) were observed within the first minute of irradiation (4·75 J cm(-2) ) while, in contrast, perfusion was observed to increase significantly (P < 0·01) during treatment. The changes in oxygen saturation and PpIX fluorescence were positively correlated during the initial phase of treatment (r(2) = 0·766). Rapid reductions in the localized blood oxygen saturation have been observed for the first time to occur clinically within the initial minutes of light irradiation and positively correlate with the concurrent PpIX photobleaching. Furthermore, perfusion increases, suggesting that the microvasculature compensates for the PDT-induced oxygen depletion.

Antibacterial Activity of Methyl Aminolevulinate Photodynamic Therapy in the Treatment of a Cutaneous Ulcer

We describe a 79-year-old female with a chronic venous ulceration infected by Staphylococcus aureus and Enterococcus faecalis and not responsive to conventional treatments. The patient was treated with Methyl-Aminolaevulinate Photodynamic Therapy (MAL-PDT). After four weeks the cutaneous swabs become negative and we observed a significant clinical improvement. Therefore we suppose that MALPDT could represent a valid therapeutic option in the treatment of infected chronic ulcers.

Tumor Thickness Predicts Long-Term Complete Response of Facial Basal Cell Carcinomas in Asian Skin Types IV/V Treated with Methyl Aminolaevulinate Photodynamic Therapy

Basal cell carcinoma (BCC) responds well to topical photodynamic therapy (PDT), with high clearance rates of 72-100%, although the therapy showed limited effectiveness for lesions > 2 mm thick. Tumor thickness is thought to be associated with therapeutic response. The purpose of this study was to investigate the efficacy, safety, and response depth of methyl aminolaevulinate (MAL) PDT for BCC. After application of MAL emulsion, each lesion was irradiated with 633-nm red light (total dose: 339 J/cm(2)). Complete response (CR) rates were assessed by histological examination at 6, 12, and 24 months. Forty-seven patients (95 lesions) with skin type IV/V were enrolled. Overall CR rate at 24 months was 75.8%. Superficial BCC was more responsive than other subtypes. Tumor thickness beyond subtype was significantly associated with CR rate. Three response depths are proposed: absolute CR (<1.3 mm), relative response (1.3 -1.8 mm) and no response (>1.8 mm). Although the recurrence rate (24%) is higher than with conventional surgical excision, 90.3% of patients were satisfied with the cosmetic outcome. MAL-PDT offers a noninvasive effective treatment; however, it is not the first option for most BCCs, except inoperable cases. The tumor thickness, independent of subtype, is predictive of PDT response.

Topical methyl aminolaevulinate-photodynamic therapy in erosive facial mycosis fungoides

Topical methyl aminolaevulinate-photodynamic therapy in erosive facial mycosis fungoides

Photodynamic therapy of multiple actinic keratoses: reduced pain through use of visible light plus water-filtered infrared A compared with light from light-emitting diodes

Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is an effective treatment for multiple actinic keratoses (AKs). Pain, however, is a major side-effect. To compare pain intensity, efficacy, safety and cosmetic outcome of MAL PDT with two different light sources in an investigator-initiated, randomized, double-blind study. Eighty patients with multiple AKs grade I-II were assigned to two groups: group 1, MAL PDT with visible light and water-filtered infrared A (VIS+wIRA); group 2, MAL PDT with light from light-emitting diodes (LEDs), with a further division into two subgroups: A, no spray cooling; B, spray cooling on demand. MAL was applied 3 h before light treatment. Pain was assessed before, during and after PDT. Efficacy, side-effects, cosmetic outcome and patient satisfaction were documented after 2 weeks and 3, 6 and 12 months. Where necessary, treatment was repeated after 3 months. Seventy-six of the 80 patients receiving MAL PDT completed the study. Patient assessment showed high efficacy, very good cosmetic outcome and high patient satisfaction. The efficacy of treatment was better in the group of patients without spray cooling (P=0·00022 at 3 months, P=0·0068 at 6 months) and showed no significant differences between VIS+wIRA and LED. VIS+wIRA was significantly less painful than LED: the median of maximum pain was lower in the VIS+wIRA group than in the LED group for PDT without spray cooling. Pain duration and severity assessed retrospectively were less with VIS+wIRA than with LED, irrespective of cooling. All treatments showed high efficacy with good cosmetic outcome and high patient satisfaction. Efficacy of treatment was better without spray cooling. VIS+wIRA PDT was less painful than LED PDT for PDT without spray cooling.

Guidelines for practical use of MAL‐PDT in non‐melanoma skin cancer

Methyl aminolaevulinate photodynamic therapy is increasingly practiced in the treatment of actinic keratoses, Bowen's disease and basal cell carcinomas. This method is particularly suitable for treating multiple lesions, field cancerization and lesions in areas where a good cosmetic outcome is of importance. Good treatment routines will contribute to a favourable result. The Norwegian photodynamic therapy (PDT) group consists of medical specialists with long and extensive PDT experience. With support in the literature, this group presents guidelines for the practical use of topical PDT in non-melanoma skin cancer.

Methyl aminolaevulinate photodynamic therapy for the treatment of hidradenitis suppurativa and pilonidal cysts

Hidradenitis suppurativa (HS) and pilonidal cysts are chronic, inflammatory skin conditions involving apocrine gland-bearing skin. Treatment is limited and unsatisfactory. Photodynamic therapy (PDT) has been reported to be safe and effective in the treatment of several off-label skin conditions. We report the case of a 29-year-old man affected by HS and pilonidal cysts since the age of 21. In the past, the patient was treated with antibiotics, corticosteroids and retinoids, without significant clinical improvement. Treatment with methyl aminolaevulinate (MAL)-PDT was started. A topical MAL cream (Metvix) was applied to the affected areas with an occlusive dressing for 3 h and irradiated with a red light source. Therapy was repeated every 15 days for a total of nine applications. The patient completed a 6-month follow-up and achieved an almost complete clinical remission of the skin lesions (80%) and complete resolution of the itching and discomfort. This is the first case of HS associated with pilonidal cysts treated with MAL-PDT. MAL-PDT was effective and well tolerated in our patient. The costs of this therapy represent an important limitation, taking into account the high number of sessions that were performed compared with non-melanoma skin cancers.

Methyl aminolaevulinate-photodynamic therapy for actinic keratoses, squamous cell carcinomain situand superficial basal cell carcinoma employing a square wave intense pulsed light device for photoactivation

Methyl aminolaevulinate-photodynamic therapy for actinic keratoses, squamous cell carcinoma<i>in situ</i>and superficial basal cell carcinoma employing a square wave intense pulsed light device for photoactivation

Erosive pustular dermatosis of the scalp following topical methylaminolaevulinate photodynamic therapy

Erosive pustular dermatosis of the scalp following topical methylaminolaevulinate photodynamic therapy

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

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

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

Methyl aminolaevulinate-photodynamic therapy (MAL-PDT) is an effective treatment in facial/scalp actinic keratosis (AK). 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. 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. 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. 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.