A randomized clinical comparative study of cryotherapy plus photodynamic therapy vs. cryotherapy in the treatment of multiple condylomata acuminata

Background: Cryotherapy cannot destroy subclinical human papillomavirus‐infected cells of condylomata acuminata (CA). The topical application of aminolevulinic acid (ALA) results in a shallow penetration depth in CA lesions ( 1 ). Objectives: To compare the efficacy and safety of cryotherapy plus ALA‐photodynamic therapy (PDT) with cryotherapy in the treatment of multiple CA. Methods: Eighty patients with multiple CA received cryotherapy plus ALA‐PDT (n=40) or cryotherapy plus placebo‐PDT (n=40). After cryotherapy, a 20% ALA or a placebo solution was applied to the CA area 3 h before illumination with red light (635 nm, 100 mW/cm², 100 J/cm²). The treatment was repeated 7 days after the first treatment if the lesions were not completely resolved. The complete response rate, recurrence rate and adverse effects in the two groups were analyzed. Results: After two treatments, the complete response rates in the combined group (cryotherapy plus ALA‐PDT) and cryotherapy group were 32.4% (36/111) and 32.6% (43/132) in the anal area (P>0.05), 100% (32/32) and 54.5% (18/33) in the urethral meatus (P<0.05), and 94.2% (129/137) and 50.5% (56/111) in the external genitals (P<0.05), respectively. The recurrence rates in the combined group and cryotherapy group were 24.3% (27/111) and 31.1% (41/132) in the anal area (P>0.05), 9.4% (3/32) and 39.4% (13/33) in the urethral meatus (P<0.05), and 3.6% (5/137) and 31.5% (35/111) in the external genitals (P<0.05), respectively. The adverse effects in each group included mild to moderate pain, edema, erosion and hypopigmentation, without any infection, ulcers, scarring or urethral malformations. Conclusion: Cryotherapy plus ALA‐PDT is a more effective regimen for the treatment of multiple CA compared with cryotherapy alone.     

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.     

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.     

Photodynamic therapy using topical 5‐aminolaevulinic acid vs. surgery for basal cell carcinoma

Background Photodynamic therapy (PDT) is an attractive modality for the treatment of BCC, based on its generally favorable efficacy, adverse effect profile and its excellent cosmetic outcome. Objectives The purpose of the study is to compare the efficacy and cosmetic outcome of photodynamic therapy with topical 5‐aminolaevulinic acid (ALA‐PDT) vs. simple excision surgery for superficial and nodular basal cell carcinoma (BCC). Methods A total of 72 patients, 32 with 48 lesions, were treated with ALA‐ PDT, and 40 with 46 lesions treated by excision were included in this prospective, comparative, controlled, clinical study. The patients have been followed for 16–37 months (mean 25 months). The PDT was performed in combination with 5‐aminolaevulinic acid twice, one month apart. Surgical excision was performed under local anesthesia with a 3‐mm margin, followed by histological examination. The cosmetic outcome was evaluated by the physician according to a 4‐point scale. Results Overall 94 BCC were treated. Complete healing rates did not differ significantly between groups, P = 0.64 (46/48 [95.83%] lesions treated with PDT vs. 44/46 [95.65%] lesions with surgery). In the first 12 months of follow‐up, 4 lesions had recurred, 2 of which were in the PDT group while 2 lesions after surgery. The mean follow‐up was 25 months. The recurrence rate in the ALA‐PDT group was 4.16% vs. 4.34% in the surgery group, p = 0.64. The cosmetic outcome was superior for ALA‐PDT at all time points. At 12 months, 100% lesions treated with ALA‐PDT had an excellent or good cosmetic outcome, according to the investigator, compared with 88.86% with surgery, P = 0.01. Conclusion ALA‐PDT offers a similarly high efficacy, and a better cosmetic outcome than simple excision surgery in the treatment of BCC.     

A randomized,half‐side comparative study of aminolaevulinate photodynamic therapy vs. CO2 laser ablation in immunocompetent patients with multiple actinic keratoses

Background Photodynamic therapy (PDT) and laser ablation (LA) are frequently used treatment options for multiple actinic keratoses (AK), yet they have not been compared head to head. Objectives To compare PDT and carbon dioxide (CO₂) LA in the management of multiple AK using objective and subjective outcome measures. Methods A single‐centre, randomized, two‐treatment half‐side comparative study of PDT vs. CO₂ LA was performed. Patients with at least four bilateral (e.g., scalp, forearms) AK were included. The primary outcome measure was the reduction of AK 3 months (v3) after therapy. Secondary outcome measures included the reduction of AK 4 weeks (v2) after therapy, decrease of epidermal p53 and Ki‐67 protein expression, micromorphological changes as assessed by optical coherence tomography (OCT) in vivo, and investigators’ and patients’ satisfaction scoring. Results In total, 20 patients (18 men and 2 women) completed the study. Both treatments reduced AK quantity significantly. On v3, relative reduction of AK quantity was significantly higher following PDT (P = 0·0362). Ki‐67 and p53 protein expression was reduced significantly from baseline (Ki‐67, median 49·5%; p53, median 64·8%) to v2 by both procedures (PDT, median 18·5%, P < 0·0001; LA, median 16·2%, P < 0·0001). AK features as assessed by OCT imaging were also significantly reduced by both procedures. The investigators and patients rated the side‐effects and inconveniences of PDT as more severe, but both overall preferred PDT due to the superior clinical outcome. Conclusions CO₂ LA and PDT are both effective therapy options for multiple AK, yet PDT seems to be superior in terms of AK reduction and participants’ and investigators’ overall satisfaction.     

Comparative study of photodynamic therapy vs CO2 laser vaporization in treatment of condylomata acuminata: a randomized clinical trial

BACKGROUND: Most conventional therapies for condylomata acuminata (CA) are traumatic and have high recurrence rates. OBJECTIVES: To investigate the efficacy and safety of topical application of 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) for the treatment of CA. METHODS: Sixty-five patients with CA were allocated into the treatment (ALA-PDT) group and treated with 20% ALA solution under occlusive dressing for 3 h followed by irradiation with the helium-neon laser at a dose of 100 J cm(-2) and a power of 100 mW. Another 21 CA patients were allocated into the control group and treated with the CO(2) laser. The treatment was to be repeated 1 week later if the lesion was not completely removed after the first treatment. RESULTS: After one treatment, the complete removal rate was 95% in the ALA-PDT group and 100% in the control group. After two treatments with ALA-PDT, the complete removal rate in the treatment group was 100%. The recurrence rate for ALA-PDT group was 6.3% which was significantly lower than that in control group (19.1%, P < 0.05). Moreover, the proportion of patients with adverse effects in the ALA-PDT group (13.9%) was also significantly lower than that in control group (100%, P < 0.05). The side-effects in patients treated with ALA-PDT mainly included mild burning and/or stinging restricted to the illuminated area. CONCLUSIONS: The present study shows that topical application of ALA-PDT is a simpler, more effective and safer therapy with a lower recurrence for treatment of CA compared with conventional CO(2) laser therapy.     

Single vs. fractionated photodynamic therapy for face and scalp actinic keratoses: a randomized,intraindividual comparison trial with 12‐month follow‐up

Objective To compare the efficacy and tolerability of a single ALA‐PDT illumination scheme with that of a fractionated ALA‐PDT illumination scheme in face and scalp actinic keratoses (AKs). Methods Eligible patients received either a single ALA‐PDT illumination or a fractionated illumination scheme randomly allocated to alternate sides of face/scalp. The side allocated to a single illumination received 75 J/cm². This side received 2 sessions performed 7 days apart. Lesions on the fractionated illumination scheme side received 20 and 80 J/cm², 4 and 6 hours after a single ALA application. Patients were evaluated at baseline, at 3 and 12 months after treatment. Efficacy end point included the individual AK lesion clearance rate. Results Thirty three patients with 266 lesions were enrolled in the study. Three months after treatment the overall lesion complete response rate was 89.05% for the single scheme and 96.12% for the fractionation scheme while at the 12‐months follow‐up response rate decreased to 85.4% for the single illumination and to 93.79% for the fractionated illumination group. Looking at lesion response based on lesion grade fractionated photodynamic therapy (PDT) resulted in larger rates of cured grade I as well as grade II lesions. Recorded adverse events were transient and did not demand additional therapy. Conclusions Our results demonstrate that higher responses are achieved with fractionated PDT compared with single illumination PDT. The study data indicate that fewer treatment sessions may be needed with fractionated PDT increasing that way the comfort of the patient regarding number of visits, treatment cost and treatment‐related downtime.     

光动力联合CO2激光治疗对尖锐湿疣患者外周血T淋巴细胞亚群及炎性因子的影响

目的探讨光动力联合CO2激光治疗对尖锐湿疣患者外周血T淋巴细胞亚群及炎性因子的影响。方法选取2017年4月至2019年6月广州市皮肤病防治所诊治的90例尖锐湿疣患者作为研究对象。将其随机分为光动力治疗组(n=30)、CO2激光治疗组(n=30)及光动力联合CO2激光治疗组(n=30),并选择年龄相匹配的健康体检者作为对照组(n=30)。比较光动力治疗组、CO2激光治疗组和光动力联合CO2激光治疗组这三组的临床治疗效果、并发症引发情况以及3个月、6个月及1年的复发率,比较治疗前后患者外周血T淋巴细胞亚群和炎性因子的变化情况。结果光动力联合CO2激光治疗组的疣病变清除率显著大于光动力治疗组及CO2激光治疗组,差异具有统计学意义(P<0.05);光动力联合CO2激光治疗组的相关并发症发生情况发生率显著小于光动力治疗组及CO2激光治疗组,差异具有统计学意义(P<0.05);治疗后,光动力联合CO2激光治疗组尖锐湿疣患者的CD4^+、CD8^+以及CD4^ +/CD8^+、Th1/Th2比值显著高于光动力治疗组及CO2激光治疗组,差异具有统计学意义(P<0.05);治疗后,光动力联合CO2激光治疗组尖锐湿疣患者的IL-6、IL-8、TNF-α值显著低于光动力治疗组及CO2激光治疗组,差异具有统计学意义(P<0.05)。结论光动力联合CO2激光治疗对尖锐湿疣患者的治疗效果显著,且副作用小,值得在临床尖锐湿疣的治疗过程中推广使用。     

The impact of different fluence rates on pain and clinical outcome in patients with actinic keratoses treated with photodynamic therapy

Background/purpose: Literature data suggest that lower fluence rates are preferable in terms of clinical response and tolerability for treating patients with actinic keratoses (AKs). We aimed to clarify the impact of different fluence rates on pain during photodynamic therapy (PDT) for AKs, as well as on treatment outcome. Methods: Individuals with at least three discrete AKs were recruited. Each lesion was randomly allocated to 25, 50 or 75 mW/cm² of topical 5‐aminolevulinic acid (5‐ALA) PDT, using non‐coherent light source. Primary end point was pain during illumination, evaluated using a visual analogue scale (VAS). Secondary end points were clinical outcome and adverse events. Results: Fifty adults, with 150 AKs lesions were recruited in the study. Mean VAS score did not significantly differ between the groups of 25 and 50 mW/cm² (P=0.714). However, mean VAS was significantly higher at the group of 75 mW/cm² in comparison to the former ones (P=0.000). With respect to the clinical outcome and adverse events during the first year of follow‐up, no differences were observed between the three groups. Comparison between the 25 and the 50 mW/cm² (P=0.749), as well as between the former and the 75 mW/cm², did not show a dependence of complete response rate on fluence (P=0.749 and P=1.000, respectively). Conclusions: According to our observations a fluence rate between 25 and 50 mW/cm² is effective and better tolerated by patients treated with topical 5‐ALA PDT for AKs.     

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.     

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.     

The efficacy of fractional CO2 laser in acne scar treatment: A meta‐analysis

Fractional CO₂ laser is a good option for treating acne scars. However, the clinical efficacy of this treatment modality requires further evidence. To perform a meta‐analysis to assess clinical improvements in acne scars with fractional CO₂ laser and non‐CO₂ laser therapies. Databases (PubMed, Embase, Cochrane Library) were searched using the search strategy to identify eligible studies. All statistical analyses were performed using the Review Manager 5.0, and a meta‐analysis was conducted to assess the effects of fractional CO₂ laser used as a treatment for acne scars. Eight studies were included for further analysis. There was no significant difference between fractional CO₂ laser and non‐CO₂ laser therapies in terms of clinical improvement, observer assessment (P = .19), patient assessment (P = .91), and incidence of post‐inflammatory hyperpigmentation (P = .69). The subgroup analyses showed that the duration of follow‐up had little effect on the evaluation of treatment effect. The efficacy of fractional CO₂ laser therapy in acne scars appeared to be equal to that of non‐CO₂ laser therapies. More well designed randomized controlled trials and more credible and standard evaluation criteria are needed, and the efficiency of combination therapy requires further analysis.     

Penetration enhancement of two topical 5‐aminolaevulinic acid formulations for photodynamic therapy by erbium:YAG laser ablation of the stratum corneum: continuous versus fractional ablation

Please cite this paper as: Penetration enhancement of two topical 5‐aminolaevulinic acid formulations for photodynamic therapy by erbium:YAG laser ablation of the stratum corneum: continuous versus fractional ablation. Experimental Dermatology 2010; 19 : 806–812. Abstract: 5‐Aminolaevulinic acid (ALA) is used in photodynamic therapy (PDT). Response rates of PDT vary widely, which may be because of the limited uptake of topically applied photosensitisers. We investigated skin penetration and fluorescence induction of protoporphyrin IX (PpIX) after applying either 20% ALA cream or 20% aminolaevulinic acid solution on laser‐stripped stratum corneum (SC) in an ex vivo full‐thickness porcine skin model. Both formulations are used in clinical practice. To enhance the skin penetration of ALA, we used two different 2940‐nm erbium:yttrium–aluminium–garnet (Er:YAG) laser systems to partially ablate the SC: continuous and fractional ablation. Different fluences were applied ranging from 0.5 to 1.5 J/cm² (continuous ablation) and from 4 to 24 J/cm² (fractional ablation). Fluorescence microscopy was used for detecting PpIX‐induced fluorescence. Compared to skin without laser pretreatment, mean fluorescence intensity (MFI) of PpIX was enhanced 13.8‐fold after continuous ablation with 1.0 J/cm² and 7.3‐fold after fractional ablation with 4 J/cm²; each laser procedure was followed by 4‐h incubation with lipophilic ALA cream. Optimal parameters for continuous ablation without damage to the epidermis were 1 J/cm² for both formulations, fractional ablation was best with 4 J/cm². Histological evaluations of laser‐treated skin showed necrosis and apoptosis, depending on light dose. In laser‐stripped skin, PpIX fluorescence was detected earlier and reached deeper epidermal layers than in untreated skin. Continuous laser ablation induced higher PpIX fluorescence levels than fractional ablation. This method offers a promising new tool for enhancing ALA penetration in PDT without damaging the underlying tissue.     

Topical aminolaevulinic acid- and aminolaevulinic acid methyl ester-based photodynamic therapy with red and violet light: influence of wavelength on pain and erythema

Background Photodynamic therapy (PDT) is based on the combination of an exogenously administered precursor of photosensitizer [protoporphyrin IX (PpIX)] synthesis and exposure to light. Choosing the optimal wavelength is important. Red light penetrates deeper into tissue, while violet light is more efficient in activating PpIX but does not penetrate so deeply. Objectives We studied PpIX formation and the PDT effect after application to human skin of creams containing aminolaevulinic acid (ALA) and aminolaevulinic acid methyl ester (MAL). The aim of the study was to investigate whether the wavelength of the light used has an influence on pain sensations during topical PDT with the different prodrugs. Methods ALA cream (10%) and MAL cream (10%) were topically applied on the skin of 10 healthy volunteers. After 24 h the application site was exposed to 8 mW cm⁻² violet laser or to 100 mW cm⁻² red laser light. The erythema index was monitored up to 24 h after light exposure. For the first time the pain during topical ALA‐ and MAL‐PDT was assessed by measuring the time taken for pain to occur. Also, for the first time, the intensities of the light sources were calibrated so as to have the same relative quantum efficiency. Results The pain sensation during ALA‐PDT with red light came 22 s sooner than during ALA‐PDT with violet light, which is statistically significant (P < 0·05). Moreover, ALA‐PDT with red light gave stronger and more persistent erythema than ALA‐PDT with violet light. ALA induced about three times more PpIX than MAL. No statistically significant differences were found for erythema, or for the time for pain to occur, in the case of MAL‐PDT with red vs. violet light. Conclusions Topical ALA‐PDT with violet light allows longer exposure times before pain is induced and gives less erythema as compared with topical ALA‐PDT with red light.     

Fractionated 5-aminolaevulinic acid-photodynamic therapy vs. surgical excision in the treatment of nodular basal cell carcinoma: results of a randomized controlled trial

Background Skin cancer incidence rates have been increasing for decades and this increase is expected to continue. Surgical excision (SE) is the treatment of first choice for nodular basal cell carcinoma (nBCC). Photodynamic therapy (PDT) has proven to be an effective treatment for superficial basal cell carcinoma. Its long‐term efficacy in nBCC has not yet been established. Objectives Prospectively compare the efficacy of 5‐aminolaevulinic acid (ALA)–PDT and SE in terms of failure rates with long‐term follow‐up. Determinants of failure in the study population, such as the effect of tumour depth, were analysed retrospectively. Methods A randomized controlled trial in 173 primary nBCCs in 149 patients. Primary nBCCs were randomly assigned either to PDT (n = 85) or to SE (n = 88). Tumours treated with PDT were illuminated twice on the same day, 4 h after application of ALA cream, 3 weeks after debulking. SE was performed under local anaesthesia with a 3‐mm margin, followed by histological examination. An intention‐to‐treat analysis was performed. Results In total, 171 primary nBCCs in 149 patients were treated. A 3‐year interim analysis revealed that the cumulative incidence of failure was 2·3% for SE and 30·3% for PDT (P < 0·001). Tumour depth and other analysed determinants of failure were not significantly related to treatment failure. Conclusions SE proved to be significantly more effective than treatment with fractionated illumination ALA–PDT. Therefore, in the treatment of primary nBCC, SE is preferred over PDT following this treatment regimen.     

Treatment efficiency of combining photodynamic therapy and ionizing radiation for Bowen’s disease

Background Topical 5‐aminolevulinic acid photodynamic therapy (ALA‐PDT) is widely used for treating Bowen’s disease (BD), but recurrence and tumour cell persistence after ALA‐PDT is sometimes problematic. Radiation therapy (RT) is also effective for BD, but is limited by its side‐effects, such as refractory ulcers. Objective The objective of the study was to observe a synergic effect of combination therapy with ALA‐PDT and RT for BD cases that did not respond effectively to prior ALA‐PDT. Methods Subjects were BD patients whose lesion did not show complete remission or showed recurrence after prior ALA‐PDT. A total of four cases involving four lesions were studied (three male and one female, mean age 69.5). ALA ointment (20%) was applied to the lesions. After 4 to 6 h, subjects received combination therapy consisting of excimer‐pumped dye laser radiation at 630 nm (50 J/cm²) followed by electron‐beam radiation (3 Gy). The combination therapy was repeated every 2 to 3 days for a total of four treatments. The lesions were evaluated clinically or histologically after the final combination therapy session. Results Following combination therapy, all of the lesions disappeared. Recurrence was not detected during the observations periods, which averaged 14.0 months in duration. Conclusion Our results indicate that the cure rate of BD could be improved by combination therapy with ALA‐PDT and RT. Compared with conventional RT, the synergetic effect of this therapy might reduce the dose of radiation required, thereby also reducing skin side‐effects such as refractory ulcers.     

Fractionated aminolevulinic acid–photodynamic therapy provides additional evidence for the use of PDT for non-melanoma skin cancer

Background Photodynamic therapy (PDT) is an accepted treatment for superficial basal cel carcinoma (sBCC) and Bowens disease. In Rotterdam, extensive preclinical research has lead to an optimized twofold illumination scheme for aminolevulinic acid–PDT (ALA‐PDT). Objective To provide additional evidence of ALA‐PDT for sBCC, Bowens disease (BD), nodular BCC (nBCC) and actinic keratosis (AK) using a 2‐fold illumination scheme after a single application of ALA. Methods Five hundred fifty‐two lesions (430 sBCC, 20 nBCC, 32 BD, 70 AK) were treated with ALA‐PDT using a twofold illumination scheme. ALA was applied topically for 4 h. Lesions were treated with two light fractions of 20 and 80 J/cm² separated by a 2‐h dark interval. Results After a minimum follow‐up of 12 months, in average follow‐up of 2 years, an overall complete response of 95% was seen for all lesions. For sBCC, the complete response at 2 years was 97% (for AK 98%, for BD 84% and for nBCC 80% after 2 years). A sub‐analysis of the results of lesions larger than 2 cm showed CR at 2 years of 89% for all lesions (n = 57). Cosmetic outcome was good to excellent in 95% of the treated lesions. Conclusion ALA‐PDT using a twofold illumination scheme of 20 plus 80 J/cm² separated by a 2‐h dark interval leads to high complete response rates at 2 years and can be regarded as an evidence‐based treatment modality for superficial growing non‐melanoma skin cancer and the (pre)malignant AK. The Rotterdam fractionated approach should be included in future guidelines.     

Combination treatment by 10 600 nm ablative fractional carbon dioxide laser and narrowband ultraviolet B in refractory nonsegmental vitiligo: a prospective, randomized half-body comparative study

Background Vitiligo is a common acquired depigmentation disorder caused by the loss of melanocytes. Despite the numerous treatment modalities available for vitiligo, responses to treatment are still unsatisfactory. For this reason, new treatment modalities and approaches are needed. Objectives To investigate the effects of fractional carbon dioxide (CO₂) laser therapy followed by systemic narrowband ultraviolet B (NB‐UVB) phototherapy on nonsegmental vitiligo (NSV) as a prospective and randomized left‐right comparative study. Methods Ten patients with NSV who presented symmetrical vitiligo lesions with no further improvement despite more than 1 year of conventional treatment were enrolled. Two sessions of half‐body fractional CO₂ laser therapy were performed at a 2‐month interval. NB‐UVB phototherapy was then administered to the entire body 5 days after each fractional laser treatment twice a week, increasing the dose incrementally by 15% at each session. Objective clinical assessments were made by two blinded dermatologists using a quartile grading scale, and the patients’ overall satisfaction was evaluated using a 10‐point visual analogue scale. Results Two months after the last treatment, mean improvement scores, assessed by physicians, were significantly higher for those treated with half‐body fractional CO₂ laser therapy followed by NB‐UVB phototherapy, compared with those treated with NB‐UVB alone (P = 0·034). In addition, according to subjective assessment, the half‐body laser treatment followed by NB‐UVB showed significantly higher improvements compared with NB‐UVB treatment alone (P = 0·023). Noticeable adverse events, such as infection, scarring and Koebner phenomenon, were not found in any patient. Conclusions This study suggests that fractional CO₂ laser therapy followed by NB‐UVB phototherapy could be used effectively and safely as an alternative modality for the treatment of refractory vitiligo.     

光动力疗法治疗尿道口尖锐湿疣疗效观察

目的观察外用盐酸5-氨基酮戊酸(ALA)光动力疗法(PDT)治疗尿道口尖锐湿疣的安全性与疗效。方法将90例尖锐湿疣患者按就诊顺序随机分为ALA-PDT治疗组56例和CO2激光对照治疗组34例,比较两组的治愈率和复发率,以及有无不良反应和自觉不适。结果治疗组和对照组治愈率分别为92.86%和52.94%(P<0.01),治疗组治疗后总复发率(7.14%)较对照组(47.06%)显著降低(P<0.01),差异有显著性(P<0.01)。治疗组及对照组均未发生系统不良反应,局部不良反应发生率治疗组为3.57%,主要为局部轻微灼伤和刺激;对照组88.24%,主要为溃疡、疼痛及瘢痕形成,治疗组不良反应发生率明显低于对照组,差异有显著性(P<0.01)。结论外用ALA-PDT疗法治疗尿道口尖锐湿疣治愈率高,复发率低,安全性好。     

Surgical scar remodelling after photodynamic therapy using aminolaevulinic acid or its methylester: a retrospective, blinded study of patients with field cancerization

Summary Background Photodynamic therapy (PDT) is a nonsurgical alternative to conventional tumour excision for nonmelanoma skin cancers (NMSCs). Objectives We evaluated whether patients with field cancerization (multiple NMSCs) treated with aminolaevulinic acid (ALA) or its methylester (MAL) for that indication had PDT‐induced changes in surgical scars in the treatment field. Methods Six adult patients with multiple NMSCs and a total of 21 scars from previous excisions were studied in a retrospective blinded evaluation from clinical photographs of scar response to ALA/MAL‐PDT. After a 3‐h application of topical 20% ALA or 16·8% MAL under occlusion, each field was irradiated with 635‐nm light‐emitting diode light at the fluence of 200 J cm^?2. Patients underwent one to three PDT sessions per field at ～1 month intervals, to fields that included scars on the back, thigh, arms and neck. Pre‐ and post‐treatment digital photographs of scars were combined into 92 pairs that were independently and blindly evaluated by three board‐certified dermatologists. This study was performed at our academic practice at the Massachusetts General Hospital. Results PDT produced a statistically significant improvement in scar appearance. The degree of improvement correlated with the number of treatment sessions (two or three treatments; P < 0·05). Improvement after a single treatment was not statistically different from baseline ratings (P = 0·99). Conclusions Surgical scar remodelling and clinical improvement may be accomplished via ALA/MAL‐PDT, but may require repeated treatment sessions. Larger, prospective studies are necessary to confirm the effectiveness of PDT for this indication.